JP2002518981A - System and method for simulation, modeling and scheduling of process support operations in a biopharmaceutical batch process manufacturing facility - Google Patents

Abstract

(57) Abstract: A system and method for simulating, modeling and scheduling process support operations in a biopharmaceutical manufacturing facility. The process support operations include those associated with batch manufacturing facilities (eg, equipment maintenance and calibration, and quality control sampling and testing). The system and method for process support operations associated with the manufacturing facility includes ascertaining relevant data (eg, maintenance, calibration or testing) associated with the biopharmaceutical manufacturing process equipment (104). After confirming this data, the biopharmaceutical manufacturing process equipment is used to create a table of equipment and associated data. The device and data tables are then compared to a procedural timetable to determine the scheduling of operations for the devices in this biopharmaceutical manufacturing process (106). For process support operations associated with the manufacturing process in the facility, the system and method include identifying (108) the solution and its volume, or identifying the dirty device and its preparation procedure. . After confirmation, schedule creation information is confirmed based on the solution start date or device protocol (110). The duration of the solution preparation procedure is then determined based on the preparation vessel assignment and scheduling information (112). A device preparation timetable is also created based on the size and capacity of the preparation device and schedule creation information (112).

Description

DETAILED DESCRIPTION OF THE INVENTION                                 Background of the Invention Field of the invention   The present invention relates generally to the design of large-scale batch manufacturing facilities, and in particular, to biopharmaceuticals. The design of a batch process facility for drug production. Related technology   Biopharmaceutical plants produce biopharmaceutical products by biological methods. Typical raw Drug synthesis methods are mammalian cell culture, microbial fermentation, and insect cell culture . Biopharmaceutical products can be obtained from natural animal or plant sources or referred to as solid phase synthesis. Depending on the synthesis technique used. Mammalian cell culture, microbial fermentation, And insect cell cultures are used to grow live cells and Extraction of drug product. Solid phase synthesis and crude tissue extraction Is synthesized from chemicals or extracted from natural plant or animal tissues It is a process that is performed.   Biopharmaceutical manufacturing processes are complex. To produce end-product biopharmaceuticals In addition to basic synthesis, separation, purification, conditioning, and formulation Additional processing steps are required. Each of these processing steps may involve additional unit operations. Including work. For example, the purification step may include a product adsorption chromatography step, Product adsorption chromatography is high pressure liquid chromatography (HPLC), medium pressure liquid Body chromatography (MPLC), low pressure liquid chromatography (LPLC), etc. May be further included. The number, complexity, and number of possible synthesis methods and processing steps The production of biopharmaceuticals is complex due to and combination. Therefore, the biopharmaceutical factory Design is expensive.   Deficiencies in the design process during the biopharmaceutical plant design and construction phase Tens of millions of dollars can be wasted. The initial design of the biopharmaceutical manufacturing process And inefficiencies. Because the biopharmaceutical manufacturing process is modeled and And there is no effective tool to simulate. Initial processing Deficiencies in product design extend through all phases of biopharmaceutical plant design and construction continue. Errors in basic manufacturing process design are Phase, resulting in change orders near the end of the equipment development project Cost increases. For example, detailed piping and instrumentation diagrams (P & ID) are usually It costs thousands of dollars per piece. Issues in designing biopharmaceutical manufacturing processes are These detailed P & IDs are often forced to be revised. This is a biopharmaceutical factory design And substantially increase the total cost of construction.   In general, three phases of production coincide with different levels of drug approval by the FDA. There is a drug factory. Clinical phase I / II biopharmaceutical plants have up to hundreds of patients Supports both Phase I and Phase II clinical trials of the product, which may include Produce sufficient biopharmaceutical product. Clinical phase III biopharmaceutical plants Enough biopharmaceuticals to support a few thousand patients during Phase III clinical trials Produce agent product. The clinical phase III factory has also been Sufficient biopharmaceutical to support the initial commercial offering when the drug is licensed by To manufacture. Successive phases are full-scale commercial after product licensing Represents a continuously large biopharmaceutical facility to maintain production. Manufacturing process design , And is often repeated for each phase, resulting in each phase of factory development. Costs increase.   The design, construction, and engineering of biopharmaceutical plants is a factor in the complex nature of biopharmaceutical manufacturing. Is a multi-million dollar industry. Biopharmaceutical factory design occurs in separate phases . The first phase is a concept design phase. First step of conceptual design phase Is to identify the high-level steps of the process that produce the desired biopharmaceutical. Examples of high-level steps are synthesis, separation, purification, and conditioning. High After the level process steps have been identified, the unit operations associated with each of the high level Be identified. Unit operations are separate process steps that make up high-level process steps It is. For example, in the microbial fermentation process, synthesis, which is a high-level Made, It can include unit operations of flask growth, seed fermentation, and production fermentation.   Manufacturing processes at the unit operation level are typically designed by hand, so errors and And inefficiencies are likely to occur. In the conceptual design phase, the final manufacturing process is Often all specifications are not complete. Therefore, device design for various unit operations Do not estimate some of the parameters, unit operating yields, and actual production rates. I have to. These factors make mistakes in the initial design base of the manufacturing process. cause. In addition, the production process is designed by hand, which results in the production of biopharmaceutical products. Attempting to optimize the process for growth and efficiency is impractical. take time.   A scale calculation for each of the unit operations will determine the desired amount of product per batch. This is done to determine the size and capacity of the device needed to create it. Scale Included in the rule calculation is the amount needed to generate the required amount of biopharmaceutical product. Is the number of batches per year. The batch is a biopharmaceutical process that produces the product. One run of Roses. Increasing the size and capacity of the equipment will The amount of product produced increases. Batch cycle time is the production of one batch. The amount of time needed to produce a product. Therefore, per predetermined amount of time The amount of product produced depends on the amount produced per batch and the batch cycle time I do. Scale calculation is usually the size of the equipment required in each unit operation And performed manually to determine capacity. The scale calculation is based on the initial concept Because it is developed from the measured parameters, it can be used for the scale calculation as well as the initial conceptual design base. The same error as the inherent error is likely to occur.   Typically, after a scale calculation for a unit operation is performed, the process flow A figure is generated. Process flow diagram adapts the process to a given batch scale The process equipment, such as tanks and pumps, required to perform this is shown in the figure. Professional The process flow diagram shows different flows of products and materials through different unit operations. Generally, the process flow diagram is associated with each step in the biopharmaceutical manufacturing process. 4 is a material balance table showing the amount of material consumed and produced. Material balance The tables typically include rate information of raw material consumption and product production. Step Process flow diagrams and material balance tables provide the information needed to create a spare equipment list To provide a lot of. The spare equipment list performs all the unit operations in the manufacturing procedure. Indicates the equipment required to perform Process flow diagrams, material balance tables, and forecasts Since the equipment list is determined from the initial conceptual design parameters, these include: The same errors as those inherent in the initial concept design base are likely to occur.   Factory spare equipment layouts include process flow diagrams, material balance tables, and Created from equipment list. Spare equipment layouts usually involve different high-level processes. Indicate the space adjacent to the housing space and the size and square feet of the building space. Start with a factory plan or block diagram showing the space program. This information Thus, a factory spare equipment layout is prepared. Spare equipment layout, corridors, floors It is intended to show all spaces in the factory, including steps and the like. Mechanical, electrical And plumbing engineers are required to verify the utility requirements of the production equipment and the equipment design layer. Estimate the mechanical, electrical and plumbing requirements of the facility based on the outsourcing. Spare The preliminary layout is created because the layout is created from the initial conceptual design parameters. The same errors as those inherent in the initial concept design base are liable to occur.   Typically, the next phase of biopharmaceutical plant design is the preliminary plumbing and instrumentation (P & I) D) Design. The preliminary P & ID is the process flow obtained from the concept design phase. -Based on the diagram. Calculations for the process design are redone and preliminary Often incorporated into P & ID. Spare P & ID with spare equipment list Needed to incorporate information from material balance tables and perform manufacturing processes The basic piping and instrumentation to be used are shown.   Detailed design is the next phase of biopharmaceutical factory design. Sellers and contractors The plans and specifications to have the participant bid on parts of the biopharmaceutical plant were Made. Details that schematically represent every detail of the biopharmaceutical process system P & ID is created. Detailed P & IDs include, for example, process piping systems, machines Mechanical, electrical and plumbing systems, all tanks, instrumentation Device, management equipment, and hardware size and components. Equipment and Detailed specifications and material bills for all of the systems are available from P & ID Made. Detailed equipment architectural drawings matching detailed P & ID and equipment specifications are created You. Contractors and engineering with detailed P & IDs and equipment construction drawings Have the company bid on a biopharmaceutical factory project. Spare P & ID and detailed P Since & ID is created from the initial conceptual design parameters, these P & IDs However, the same errors as those inherent in the initial concept design base are likely to occur. Conceptual design phase If you revise the spare P & ID and detailed P & ID due to errors in the Can cost thousands of dollars.   Accurately model and simulate biopharmaceutical manufacturing processes (and the equipment itself) The inability to do so necessitates an incorrect initial design. These failures Due to changes in the blueprints and construction drawings at the factory construction site for accuracy, or , During the construction phase, factory restoration and rebuilding often occur, The result is an additional cost of millions of dollars.   Once the biopharmaceutical equipment is constructed and operated, the production equipment is Service required. Equipment maintenance to sustain the biopharmaceutical manufacturing process And instrument calibration is required. Required maintenance and calibration formats and And frequency are based on the specific equipment used in the facility and the frequency and nature of use. Is a function of Equipment involved in manufacturing process, solution preparation process, and equipment preparation All installations require regular maintenance during sustained operation. For a while For example, maintenance frequency and costs are considered in the design of biopharmaceutical manufacturing facilities. Not done. However, the cost of maintenance is It is an important part of the cost of production of the product. Equipment maintenance is typically scheduled Joules are set up, planned and managed manually, resulting in inefficiencies and And additional costs.   Manual switches typically used to plan equipment calibration and maintenance Schedule systems are generally inefficient and redundant. In production operations Requires different forms and frequencies of maintenance and calibration as a function of service There can be thousands of maintenance and calibration sites in all manufacturing plants. Machine Instrument maintenance or calibration errors can lead to critical process failures in manufacturing operations And may result in product loss.   Quality control in biopharmaceutical manufacturing facilities can improve the safety and quality of biopharmaceutical products. Necessary to guarantee. Quality at various points in the biopharmaceutical manufacturing process Control sampling and testing, manufacturing process, solution preparation and equipment preparation activities During this time, ensure that the product is free of contaminants. These sampling and testing procedures Moderate quality and sensitivity requires a significant amount of preparation and planning. But made Planning tools that support the integration between manufacturing operations and quality control activities do not actually exist. No.   The preparation of the solution will save capital and valuable resources in the construction and operation of biopharmaceutical facilities. One of the main consumers. Often, all of the processes in the facility can be supported Equipment and process designers must ensure that solution preparation is Embodies a device that needs many times what is needed to support it. apparatus , Availability and cost of the cleaning equipment are a function of the preparation and use of the solution. Thus, excess capacity results in waste of construction capital and continuous production during factory operation. Causes continuous losses.   After the biopharmaceutical manufacturing process and solution preparation process are designed, Equipment preparation procedures for cleaning equipment contaminated by process and solution preparation procedures The order must be determined. The protocol for cleaning contaminated equipment is Determined through experiments and tests. But once clean the contaminated equipment Once the protocols and procedures for determining Determine the equipment cleaning procedure schedule required to clean contaminated process equipment. It is difficult to determine. Often, biopharmaceutical equipment designers are Extra equipment preparation volume to the biopharmaceutical facility to ensure a stable supply of fungal equipment Design quantity.   Current methods for the design of equipment preparation procedures typically run in the equipment preparation area. It does not need to precisely define the relatively complicated procedures to be performed. As a result, Equipment and work areas associated with manufacturing are usually inefficiently designed. Equipment preparation activities The cleaning and sterilization of (preparation) equipment related to is capital and utility intensive, Inefficient designs result in increased costs of building and operating biopharmaceutical facilities.   Therefore, simulation of process support operations in biopharmaceutical manufacturing facilities, A system and method for modeling and scheduling is needed. This process support operation includes operations related to biopharmaceutical manufacturing facilities: (1) Maintenance and calibration; and (2) quality control sampling and testing; And operations associated with the batch manufacturing process in the facility; (3) solution preparation; and ( 4) Preparation of the device.                               Summary of the Invention   The present invention provides a process support operation in a biopharmaceutical production facility that satisfies the above needs. Systems and systems for simulation, modeling and scheduling of crops And method.   In system maintenance, the present systems and methods are useful in biopharmaceutical manufacturing processes. Identifying maintenance and calibration data for the storage device. Maintainer After the identification and calibration data have been identified, the biopharmaceutical manufacturing process equipment data is Used to generate tables of installation and maintenance and calibration data. apparatus After a table of maintenance and calibration data has been generated, the table is Determine calibration and maintenance schedules for equipment in process To be compared with the procedure timetable.   In quality control and sampling, the system and method Process to identify quality control sampling and test data Including the process. After quality control sampling and test data have been identified, Manufacturing process equipment data includes equipment and quality control sampling and test data. Used to generate a table. After the equipment and data tables have been generated, Table shows quality control samples for process operations in biopharmaceutical manufacturing processes. It is compared to a procedural timetable to determine the scheduling and testing schedule.   In the preparation of a solution, the present system and method includes the steps of: Identifying the capacity for After the solution for preparation has been identified, The predetermined start date and one consecutive start date in the solution preparation for Is determined. After the solution, start date and consecutive start dates have been identified, the solution is Assigned to. After the solution has been assigned to the preparation vessel and the duration of the solution preparation procedure An interval is determined and assigned to a solution preparation container.   In preparing an apparatus, the system and method may include cleaning contaminated process parts. And the preparation procedure of the equipment associated therewith. This contaminated professional After the process parts are identified, the contaminated process parts and their associated equipment A key list of the preparation procedures is prepared. Contaminated process parts and equipment preparation After the procedure has been identified, the instrument preparation procedure is scheduled based on the preparation instrument protocol. Is set up and an equipment preparation load summary table is created. Next, the size of the preparation equipment and And capacity are determined based on the information in the load summary table. Preparation equipment size and After the capacity and capacity are determined, an apparatus preparation timetable is created.   One advantage of the present invention is that maintenance and maintenance are more than previously possible. Calibration scheduling is linked directly and more accurately to cumulative instrument service time. It is to tie. As a result, more efficient equipment maintenance and calibration activities Good planning and scheduling and improved integration of manufacturing operations You.   Another advantage of the present invention is that designers are guided to factory design at the earliest stages. To be able to reduce the number of errors, to enable manufacturing process design And maximize the efficiency of the factory by finding the best equipment schematic. You. The present invention provides detailed specifications for the scheduling of equipment and solution preparation. Create, which facilitates the transition throughout the design phase, and Fix the cost of equipment design and construction. The invention also relates to a product for the product. Can be used to determine the cost of   Yet another advantage of the present invention is that resource requirements for quality control and other resources can be accurately determined. Enables process modeling ability to plan The present invention is a daily quality control operation Work flow efficiency, which ensures proper management of manufacturing systems .                             BRIEF DESCRIPTION OF THE FIGURES   The features and advantages of the invention will be apparent from the drawings, in which like reference numbers are identical or functionally identical. (Indicating similar elements) will be more apparent from the detailed description below. You. Additionally, the left-most digit (s) of a reference number identifies the drawing in which the reference number first appears. .   FIG. 1 is a block diagram illustrating a process for creating a block flow diagram and a process timetable according to the present invention. FIG. 4 shows a flow chart of the process.   FIG. 2 shows a flow diagram of a process for determining the required reactor volume according to the present invention. You.   FIG. 3 shows a unit operation list for the microbial fermentation process.   FIG. 4 shows a unit operation list for the mammalian cell culture process.   FIG. 5 illustrates a cross-reference of a unit operation list with a process parameter table according to the present invention. FIG. 3 shows a flowchart for the operation.   FIG. 6 shows an exemplary process parameter table.   FIG. 7 illustrates a process for creating a block flow diagram according to the present invention.   FIG. 8 shows an exemplary block flow diagram according to the present invention.   FIG. 9 is a block flow of a process for creating a process timetable according to the present invention. The figure is shown.   10 to 11 show high-level process timetables according to the present invention.   12A to 12H show detailed process timetables according to the present invention.   FIG. 13 is a diagram showing a schedule for preparing a solution in a biopharmaceutical manufacturing process and FIG. 3 is a block flow diagram illustrating an overview of a process for simulation.   FIG. 14 is a block diagram illustrating a process for determining the solution preparation time associated with each solution preparation container. It is a lock flow figure.   FIG. 15 shows an exemplary list of solution preparation parameters.   FIG. 16 shows the solution required by the biopharmaceutical manufacturing process as a specific solution preparation. It is a block flow figure which illustrates the process allocated to a container.   FIG. 17 shows an exemplary list of solution preparation procedure parameters.   FIG. 18 shows an exemplary brew container for a solution assignment list.   FIG. 19 illustrates an exemplary computer, according to an embodiment of the present invention.   FIG. 20 shows the calculated start date of preparation and the next solution preparation for each solution. It is a block flow figure which illustrates the process of determining a date of manufacture.   FIG. 21 shows an example of the main quality management protocol table.   FIG. 22 is a block diagram illustrating a process of preparing a quality control timetable for a solution preparation apparatus. FIG.   FIG. 23 is a block flow illustrating a process of creating a preparation device quality control timetable. FIG.   FIG. 24 determines the earliest solution preparation start date in each solution preparation container. FIG. 4 is a block flow diagram illustrating the steps of FIG.   FIG. 25 determines the latest solution preparation start date for each solution preparation container. FIG. 4 is a block flow diagram illustrating the steps of FIG.   FIG. 26 is a block diagram illustrating a process for calculating the time to use a solution preparation container. FIG.   FIG. 27 shows a process of calculating the cumulative solution preparation time in each solution preparation container. It is a block flow diagram which illustrates.   FIG. 28 is a block diagram illustrating a process for determining the utilization of each solution preparation container. FIG.   FIG. 29 is a block diagram illustrating the steps for creating an initial solution preparation shift schedule. FIG.   FIG. 30 illustrates the solution preparation in the initial solution preparation shift schedule. FIG. 4 is a block flow diagram illustrating a process of back scheduling.   FIG. 31 shows an exemplary initial solution preparation shift schedule.   FIG. 32 is a block diagram illustrating a process for creating a solution preparation schedule. FIG.   FIG. 33 is a diagram showing a schedule for preparing a solution in the biopharmaceutical manufacturing process FIG. 3 is a block flow diagram illustrating an overview of a process for performing and simulating.   FIG. 34 is a block flow diagram illustrating the steps for creating a preparation device protocol table. It is.   FIG. 35 is a block flow diagram illustrating a process of creating an apparatus preparation procedure table. .   36A-36H show an exemplary prep apparatus protocol table.   37A-37B show an exemplary apparatus preparation procedure table.   FIG. 38 is a block flow diagram illustrating a process of creating an apparatus size table.   FIG. 39 shows an exemplary device dimension table.   FIG. 40 is a block diagram illustrating the process of creating a key list of devices requiring preparation. FIG.   FIG. 41 is a block flow diagram illustrating a process of creating a device preparation load table. .   42A-42D show exemplary device preparation load tables.   FIG. 43 is a block flow diagram illustrating a process of creating a device preparation load summary table. is there.   FIG. 44 is a block flow diagram illustrating the process of determining the capacity of the preparation device. .   FIGS. 45A-45I illustrate exemplary process equipment quality control assay sample timetables. Show.   FIG. 46 is a block flow diagram illustrating a process of creating a device preparation timetable. .   FIG. 47 illustrates the process of creating a preparation device list with functional specifications and costs. FIG. 3 is a block flow diagram illustrating an example;   FIG. 48 is a block flow diagram illustrating a process of creating a preparation device use timetable. is there.   FIG. 49 is a block diagram illustrating a process of creating a process device maintenance table. FIG.   FIG. 50 is a block diagram illustrating a process of creating a process device maintenance timetable. FIG.   FIG. 51 is a block diagram illustrating a process of creating a solution preparation device maintenance table. FIG.   FIG. 52 is a block diagram illustrating a process of creating a solution preparation device maintenance timetable. FIG.   FIG. 53 is a block flow illustrating a process of creating a preparation device maintenance table. FIG.   FIG. 54 is a block diagram illustrating a process of creating a preparation device maintenance timetable. FIG.   FIG. 55 is a block flow diagram illustrating the steps for creating a process equipment calibration table. is there.   FIG. 56 is a block flow illustrating steps for creating a process device calibration timetable. FIG.   FIG. 57 is a block flow diagram illustrating a process of creating a solution preparation device calibration table. is there.   FIG. 58 is a block flow illustrating a step of creating a solution preparation device calibration timetable. FIG.   FIG. 59 is a block flow diagram illustrating a process of creating a preparation device calibration table. .   FIG. 60 is a block flow diagram illustrating a process of creating a preparation device calibration timetable. is there.   FIG. 61 is a block diagram illustrating a process of creating a main quality control protocol table. -It is a figure.   FIG. 62 is a block flow illustrating the steps for creating a key quality control sample table. FIG.   FIG. 63 is a block diagram illustrating a process of creating a process equipment quality control timetable. FIG.   64A-64AB illustrate an exemplary process equipment maintenance timetable.   Figures 65A-65G show a list of unit operations and their associated parameters. 4 shows a detailed example of a process parameter table.                       Detailed Description of the Preferred Embodiment 1. 0 Biopharmaceutical batch process simulator   FIG. 1 shows a high-level flow diagram of the preferred embodiment. The process includes step 102 Begin by determining the required volume of the reaction vessel. The reaction vessel contains the crude product Is the first container to be synthesized. For example, in a mammalian cell culture process, the reaction The container contains mammalian cells suspended in a growth medium. Next, in step 104, A unit operation sequence for production of a biopharmaceutical product is determined. Unit operation sea A cans is a sequence of unit operations required to produce a biopharmaceutical product . Each unit operation is an individual part of the biopharmaceutical manufacturing process using an associated set of manufacturing equipment. It is a process of. The unit operation list includes unit operations constituting a unit operation sequence, It is a list with sequence information related to these unit operations. Unit operation sequence Information about each unit operation in the unit operation list. This is information that defines the power cycle. The scheduling cycle is based on the unit operation Ke This is the repetition of the unit operation in the instance (one defect is (1)). Unit operation squirrel And the unit operation sequence information together define the unit operation sequence. Place The desired biopharmaceutical product is a specific unit operation and its Order. Some examples of unit operations include inoculum preparation, initial seeding of reaction vessels, Collection of solids by centrifugation, equalization at high pressure, dilution, etc.   Scheduling cycle for each of the unit operations of the biopharmaceutical manufacturing process And the cycle offset duration is determined in step 106. Schedule A cycle is a repetition of a unit operation in a unit operation sequence. Happens at the level of. Furthermore, each level of the scheduling cycle is consecutive The relevant time period between the beginning and the beginning of the scheduling cycle Offset duration.   "Cycles per unit operation" is the first level of the scheduling cycle It is. The cycle per unit operation is defined as the unit operation in the process. It is defined as the number of repetitions that are repeated independently before moving on to the work. For example, feeding Harvesting and feeding unit operations in animal cell culture processes are numerous per unit operation Cycle. Product-rich cultures during a single harvest and feed unit operation The ground is removed from the reaction vessel, and the nutrient-rich medium is supplied to the reaction vessel many times. . A large number of the product-rich reactor medium that has been removed is processed in the next unit operation. Pooled for.   The second level of the scheduling cycle is "cycles per batch" is there. A cycle per batch is a set of consecutive unit operations Repeated as a group after a set of operations and before moving on to the next unit operation It is defined as the number of times. A set of consecutive unit operations repeated as a group is Also called a subprocess. For example, in the microbial fermentation process, inoculum preparation, Flask growth, seed fermentation, production fermentation, heat exchange, and continuous centrifugation / whole cell harvesting The set of unit operations that are involved are often circulated together. Each of these six steps When run through, one harvest from the microbial fermentation reaction vessel is obtained. Sufficient amount Multiple harvests from the reaction vessel may be required to achieve a batch. Additional Each additional harvest is pooled with the previous harvest, and as a result, One batch of cell culture is obtained.   The third level of the scheduling cycle is "cycles per process" It is. Cycles per process use continuous or semi-continuous product synthesis. Is defined as the number of times the batch cycle is repeated for the process You. In such a case, a single biopharmaceutical manufacturing process can produce many batches of product. Can be obtained. For example, in a mammalian cell culture process, a single cell culture is typically Specifically, it is a continuous production for 60 to 90 days. During this period, a large number of crude product Collects are collected, pooled in batches, and processed to produce the final product biopharmaceutical. Is done. The pooling of many harvests into batches of material occurs several times during cell culture. This results in multiple batch cycles per process.   In step 108, all operation parameters for each unit operation in the unit operation list The process parameter table master list is referred to obtain the data. Process The parameter table contains all the unit operations needed to simulate a particular unit operation. Contains a list of operation and operating parameters. Examples of operating parameters are given for a specific unit operation. Solution, temperature, pressure, duration, agitation, scaling volume required for cropping (Scaling volume), and so on. In addition, the process parameter table contains Provides all of the individual tasks and task durations required in the position operation I do. For example, unit operations for inoculum preparation include setup, pre-incubation Including the individual tasks of incubation, incubation, and purification. For biopharmaceutical manufacturing FIG. 65A shows an example of the unit operations of the unit and the operation parameters related to these unit operations. ~ See Figure 65G.   In step 108, the unit operation list obtains operation parameters from the process parameter table. Thereafter, at step 110, a block flow diagram is generated. The block flow diagram is Each unit operation of the build process, both for incoming products and new materials With inputs for both processed and waste products Shown as a tick. The block flow diagram shows the equipment for a given process scale. Material flow through the process in a way that allows for sizing of many key parts of the process. It is a simple but convenient tool for quantifying raw.   The information in each block of the block flow diagram is Parameters and dimensioning ratios from the process parameter table and block flow diagram calculations Generated from the tuple. The calculation set is a set of algebraic equations. Parameters and calculations The set consists of the material input volume and product and waste output volume required for the unit operation. Is used to calculate based on the amount of product material received from the previous unit operation. Used. Similarly, the blocks in a given block flow diagram represent Calculate the amount of product transferred to the unit operation block. Further explained below As such, these calculations are based on the unit operation scheduling identified in step 106. Take into account the cycle.   After the block flow diagram has been generated in step 110, the process time line is generated in step 112. Is generated. The process timeline is a very useful feature of the present invention. process The time line is used for the unit operation list, tasks and processes related to each unit operation. Scheduling cycle and master process parameters for each unit operation Process parameters from data table and materials calculated from block flow diagram It is generated from the volume of the material. The process time line is relative to the start date of the manufacturing process. The time line is expressed in hours and minutes. The relative time is based on the biopharmaceutical drug manufacturing process. Start and end times for each unit operation and its related tasks for the entire process Converted to day and time to provide a timeline for the end time.   Process timelines are a very powerful tool for process design. Process The timeline calculates the flow rate from a known transfer time and calculates the transfer, filtration, or cooling Pumps and filters used in unit operations by calculating the volume of material to be pumped , And heat exchanger dimensions. Process time line Are labor, solution preparation, instrument cleaning, reagents, process utilities, preventive maintainers Precisely predict the burden on performance, quality control testing, etc.   FIG. 2 further illustrates step 102 of determining the required volume of the reaction vessel. Step 20 At 2, the amount of biopharmaceutical product produced in a predetermined amount of time is determined. Usually required Required biopharmaceutical product quantities are expressed in terms of quality quantities produced per year . In step 204, the number of reaction vessel runs per year for a particular biopharmaceutical product is determined. It is determined. In determining the number of reaction vessel cycles for a particular biopharmaceutical product Factors considered for example are the biopharmaceutical products produced in the reaction vessel of Number (ie, reaction vessels are shared to produce different products), reaction vessels Reaction time for each cycle of the reaction and the availability of reaction vessels for that year It is a percentage of up-time.   In step 206, the yield for each batch or reactor cycle is calculated. Each batch Or the yield from the reactor cycle is process dependent and is usually h) Expressed in grams of crude product per liter. Obtained from step 202 The amount of biopharmaceutical product required per year and the needs obtained from step 204 The number of reactor cycles available to produce the biopharmaceutical product Given the yield of each reactor cycle from step 06, step 208 The reactor volume required to produce the required amount of biopharmaceutical product is calculated .   FIG. 3 is a unit operation list for an exemplary microbial fermentation biopharmaceutical manufacturing process. Is shown. Column 302, the leftmost column, contains a column for each of the unit operations of the process. List the unit operation sequence numbers. An exemplary microbial fermentation unit operation list is 2 Includes three unit operations. Unit operation sequence numbers define the order in which unit operations occur. Set. For example, before the growth of the flask with unit operation sequence number 2, the unit operation sequence Preparation of inoculum No. 1 occurs first. Column 304 is a unit operation list unit operation. A unit operation identifier code associated with each of the works is shown (see step 108). Unit operation The identifier code converts the operation parameters from the process parameter table to the unit operation list. Used to transfer. For example, heat exchange, ie, unit operation list numbers 5, 8 and 10 has a unit operation identifier code 51.   As described above with reference to FIG. 1, at step 104 a particular biopharmaceutical manufacturing process After the unit operation sequence for the process has been determined, at step 106 Are determined. Columns 306, 310, and 318 is the number of scheduling cycles for the microbial fermentation process of FIG. Show. The scheduling cycle is the repetition of the unit operation in the unit operation sequence. It's recurring and happens on three levels. In addition, each of the scheduling cycles The levels are shown in columns 308, 316 and 324, in a continuous schedule. The associated offset duration, which governs the time between the beginning and the end of the cycle Have a pause. The latter two levels of the scheduling cycle are based on the related units It has an operation start point and a unit operation end point. That is, columns 312 and 314 Identify the start and end unit operations in each cycle per batch, and And columns 320 and 322 start in cycles per process, respectively. And the end unit operation.   Column 306 contains a column for each of the unit operations in the microbial fermentation unit operation sequence. List the number of cycles per unit operation of. Exemplary microbial fermentation unit operation sequence In each instance, each unit operation has only one cycle per unit operation. even here , The cycle per unit operation, the unit operation in the process, the next unit operation Defines the number of repetitions that are repeated independently before moving to.   Column 308 shows the cycle offset duration for the cycle per unit operation. List the time in hours. Each unit operation in the embodiment of the microbial fermentation of FIG. Since the operation has only one cycle per unit operation, any of the unit operations There is no cycle offset duration. Cycle offset duration is continuous Define the time between the beginning and the end of the scheduling cycle.   Column 310 contains a column for each of the unit operations in the microbial fermentation unit operation sequence. Enumerate cycles per batch. Unit operation sequence numbers 1 to 6 It is defined as having three cycles per switch. The cycle per batch is , Before proceeding to the next unit operation, a set of consecutive unit operations is repeated as a group Specify the number of repetitions. For example, in FIG. And the set of unit operations 1 to 6 as defined in column 314 of unit operation end Circulate together as a group (eg, for an exemplary microbial fermentation process The sequence of unit operations is 1, 2, 3, 4, 5, 6, 1, 2, 3, 4, 5, 6, , 1, 2, 3, 4, 5, 6, and 7). As defined in column 310, Unit operations 1-6 are grouped together as a group before the process continues to unit operation 7. Circulates once.   After the unit operation sequence numbers 1 to 6 are continuously circulated three times, The process comprises resuspending the cell paste with unit operation sequence number 7 (resuspensi on). After unit operation sequence number 7, the process continues with the unit operation sequence. Cycle Nos. 8 to 10 are performed 3 cycles per batch. Columns 310, 312 and 31 4, heat exchange, cell disruption and heat exchange The unit operation is continuously cycled three times. Unit operation sequence number 8 to 10 3 times After circulation, the microbial fermentation manufacturing process includes resuspension / detergent, unit operation sequence Continues with sense number 11.   Unit operation sequence, as defined by columns 310, 312 and 314 Numbers 11 and 12 circulate together twice. Unit operation sequence number 11 and After 12 circulations twice, the microbial fermentation production process proceeds to unit operation sequence number 1 13 to the unit operation sequence number 23 without cycling, End the process.   Columns 326-332 of FIG. 3 show stepwise recovery of product and total protein (SWR ) And the percentage of overall recovery (OAR). SWR is a row of SWR Protein recovery for each unit operation listed. OAR is O Up to and including the unit operation in which the AR is listed Recovery of proteins. The column for product recovery should be the solution in the process. 2 shows the recovery of their desired product protein. The row for protein recovery Represents the recovery of contaminating proteins from solution, resulting in a higher purity product solution .   FIG. 4 shows a unit operation list for an exemplary mammalian cell culture manufacturing process. Show. Column 402 lists unit operation sequence numbers 1 to 19. Unit operation sea Kens Nos. 1-19 are the order in which unit operations of the mammalian cell culture manufacturing process occur. Is specified. The microbial fermentation process of FIG. 3 and the mammalian cell culture process of FIG. The most notable difference between the two is that a large number of Cycle and a number of cycles per process of unit operation sequence numbers 8 to 18. With Kuru.   The unit operation sequence number 8 in FIG. 4 is a concept of a number of cycles per unit operation. Is shown. Unit operation sequence number 8 indicates the product abundance from the mammalian cell reaction vessel. Fresh growth medium and supply fresh growth medium to the mammalian cell reaction vessel Unit operation. In most mammalian cell culture processes, the product In the vessel, it is secreted by the cells into the surrounding growth medium. To collect the product At the same time, remove some of the product-rich growth medium from the reaction vessel and remove the product. And add an equal volume of fresh growth medium to the reaction vessel to Sustain in-vessel production. The process of sampling and feeding the reaction vessel is a single production The drug manufacturing process can last for several weeks. Unit operation sequence Number 8 is repeated 7 times per unit operation, that is, 7 cycles (for example, unit operation The sequence is 7, 8, 8, 8, 8, 8, 8, 8, 9). Note that the unit operation The offset duration of Sequence No. 8 is 24 hours. Offset duration Defines the time between cycles per unit operation. In the embodiment of FIG. Operation sequence number 8 is repeated 7 times (7 cycles per unit operation), and There must be a 24 hour or 1 day interval between each cycle and the next cycle. It is. This is a unit operation with a one week duration in which the harvesting / delivery process takes place daily. This corresponds to operation sequence number 8.   FIG. 4 also shows the features of multiple cycles per process. Per process Cycle in a given process using continuous or semi-continuous product synthesis It is defined as the number of times the batch cycle is repeated. Each batch cycle The result is a batch of product. Therefore, one biopharmaceutical manufacturing process As a result, multiple batches of product may be obtained. 4 of the mammalian cell culture process of FIG. In the embodiment, the unit operation sequence numbers 8 to 18 are repeated eight times together as a group. Returned (column 418). Each of these cycles of unit operation sequence numbers 8-18 Each produces one batch of product (columns 420-422). Unit operation sequence The offset between cycles numbered 8-18 is 168 hours or one week ( Column 424).   In the embodiment of FIG. 4, the unit operation sequence numbers 8 to 18 proceed as follows. The reaction vessel is sampled and fed once daily for 7 days. Collection / supply operation Crop results are pooled at the end of 7 days in unit operation sequence number 9. You. Next, the unit operations 9 to 18 are executed, and the process from the unit operation sequence number 8 is started. The collected harvested growth medium is processed. The unit operation sequence numbers 8 to 18 are weekly One additional cycle of harvested growth media from unit operation sequence number 8 circulated continuously once Process batches for days. At the end of eight weeks, the mammalian cell culture process has ended I do.   FIG. 5 shows a process for cross-referencing the unit operation sequence with the master process parameter table. Step 108 is further illustrated. Operation parameters in the process parameter table are specified This is a parameter required to simulate the unit operation of. Process parameters The parameters from the data table are used for each unit operation in the unit operation sequence. It defines key operation parameters and device sizing ratios. These parameters Values for parameters and ratios are based on different design scenarios for a given process scale. With variables that can be easily manipulated and ordered to model and evaluate is there. Examples of process parameters related to each unit operation are shown in FIGS. 65A to 65G. Is shown. But the list of unit operations, parameters, values and scaling ratios Note that is not exhaustive. One skilled in the art Meter tables can be used for other chemicals, specialty chemicals, beverages, and cosmetics. Expanded to include additional unit operations and manufacturing processes for multi-process industries obtain. With such an extension, the present invention provides a solution for other such batch processes. To simulate and schedule additional batch manufacturing processes for And become possible.   FIG. 5 illustrates a step 108 in which the unit operation list is cross-referenced with the process parameter table. Indicates the files needed to Exemplary unit operations for biopharmaceutical manufacturing processes The work list 502 and the process parameter table 504 are input to the process step 506. It is. In step 506, the unit operation identification code (see FIG. 3) is used. Cross-reference the list with the process parameter table. Parameter is the process parameter Is copied from the data table 504 to the unit operation list 502, and the unit operation list 508 is copied. Generate.   FIG. 6 further illustrates an exemplary process parameter table 504. Process parameters The operating parameters in the data table are required to simulate a particular unit operation. It is an important parameter. The unit operation identification code of the process parameter table 504 is In the cross-reference step 506, the parameters from the process parameter table 504 are unit-operated. Used to assign to the work list 502. Examples of operating parameters are specific to Solutions, temperatures, pressures, durations, agitation, scaling volumes, What is it? In addition, the process parameter table lists the individual tasks included in each unit operation. All tasks and task durations. However, those skilled in the art Meter tables for other chemicals, specialty chemicals, beverages, and cosmetics Expanded to include additional unit operations and manufacturing processes for the batch process industry Note that it can be stretched. With such extensions, the present invention Simulate additional batch manufacturing processes for such batch processes and Scheduling becomes possible.   FIG. 7 further illustrates a step 110 of generating a block flow diagram. Block flow -The diagram illustrates each unit operation in the biopharmaceutical manufacturing process with the incoming product and Inputs for both new material and both processed product and waste Are shown as blocks having the same outputs. Material flowing through each of the unit operation blocks The fee is quantified by the calculation set in each of the blocks in the block flow diagram . The unit operation block in the block flow diagram represents the unit operation graphically. A calculation set is a set of algebraic equations that show unit operations. Calculation set output Some examples are the process materials, equipment performance specifications, and And the process data output used for the next unit operation. Input to calculation set Some examples of are the amount (quality quantity) or volume (liters) of product from the previous unit operation. Other parameters and / or powers from the process parameter table The number and the design cycle defined in the unit operation list.   The block flow diagram 708 includes a unit operation list 508 and a block flow diagram meter. Generated from the arithmetic set 704. The block flow diagram calculation set 704 includes a unit operation List covering operation identifier codes and calculation sets associated with each unit operation identifier It is. The unit operation list 508 and the block flow diagram calculation set 704 are They are linked to each other based on the order operation identifier code.   Step 706 includes all of the relevant operating parameters from the process parameter table. From the unit operation list 508 including the Calculate material flow requirements for lock flow diagrams and basic equipment sizing requirements You. The block flow diagram 708 shows the key of the equipment for a given process scale. Sizing of many parts that The amount of material flow to each unit operation and And the amount of material flow from each unit operation is determined in step 706, so that each unit operation The capacity of a number of equipment items required in a crop can be determined. Block flow diagram Also indicates the percent recovery of product, percent purity, and It manages important information of the unit operation list 502 such as a purification factor. This information Helps identify steps in the process that may require optimization.   The following are tangential flow micro-filtration (TFMF) systems. 5 is an exemplary calculation set for stem unit operations. Tangential flow microfiltration This is an important process technology in the manufacture of drug products. This technology is useful for the storage life of filtration media. It greatly extends the life and reduces the cost of replacing expensive filters.   TFMF generally prepares membranes for each use and for storage after use. Requires the same steps to make. Design parameters for each unit operation such as TFMF Data has been developed for these general design requirements.   General parameters (variables) from the process parameter table     Device Design Type Plate & Frame     Membrane porosity 0. 2 microns     Membrane flux rate 125 liters / square meter / hour     Processing time 2 hours     Concentrated water / filtration rate 20-1     Flash volume 21. 5 liters / square meter     Prime volume 21. 5 liters / square meter     Wash volume 0. 5%     Regeneration volume 10. 8 liters / square meter     Storage volume 21. 5 liters / square meter     % Recovery of product 95%     % Recovery of total protein 80%     Cleaning in place (CIP) Yes     Steam in place (CIP) Yes   Input value from previous unit operation     Product volume 1,000 liters     Product amount 5kg     2. Total protein content 0Kg   The calculation set for this unit operation first takes the incoming process volume, The process volume is then based on the flux rate and the required processing time. Accordingly, it is used as a basis for sizing a filtration membrane for a filtration system.   1,000 liters / 125 L / SM / Hr / 2 hours = 0. 2 micron membrane 4. 0SM   After calculating the square meter (SM) of the membrane required by this unit operation, The volume of the holding solution can be calculated based on the volume ratio.     Flash volume 21. 5 liters / SM × 4. 0SM = 86 liters     Prime volume 21. 5 liters / SM × 4. 0SM = 86 liters     Washing volume 5% of 1,000 liters = 50 liters     Playback 21. 5 liters / SM × 4. 0SM = 86 liters     Storage 10. 8 liters / SM × 4. 0SM = 42 liters   The filtrate flow rate is calculated from the volume to be filtered and the required process time You.     1,000 liters / 2 hours = 8. 3 liters / minute   The flow rate of the retentate is calculated based on the retentate / filtration rate described above.     8. 3 liters / minute × 20 = 167 liters / minute   Based on the input of the process volume to this unit operation and the above parameters, the equipment Size, filtration equipment, retentate pumps, support linkages and related systems Can be measured.   In addition, the amount of product and contaminating protein received from the previous unit operation Input values, along with the recovery factors listed in the parameters, The cumulative recovery of product from the process and the percent purity and product And product purification factors. This information needs optimization Useful for identifying steps in a manufacturing process.   FIG. 8 shows the first five unit operations of the microbial fermentation process unit operation list of FIG. FIG. 4 shows an exemplary block flow diagram for the system. The unit operations 1 to 5 are performed in block 802. , 804, 806, 808 and 810. Input melting to each of the processes The liquid is shown as an arrow with solution identifier information from the unit operation list 508. You. The process stream to which these solutions are added in each unit operation is also a process stream. It is shown as an arrow with stream identifier information. Seed preparation in unit operation 1 Working from the initial process stream characteristics (P-101) in The volume of input material (solution) and subsequent process stream in each is Included in information from unit operation list 508 for each of the unit operations Determined using the scale-up ratio. For example, the unit operation block 802 in FIG. The volume of solution and process stream flowing into and out of each of ~ 810 , The initial start characteristic P-101 of the process stream, and the The volume of the related input material S-101 and the continuous unit operation And the scale-up ratio in each of the blocks 804-810 It is. The solution required in each of the unit operation blocks 802 to 810 is a unit operation block. Similar parts of information for each of the unit operations of the list 508.   FIG. 9 further illustrates a step 112 of generating a process time line. Process time line Is generated from the unit operation list 508 and the block flow diagram calculation set 704. (Steps 904 to 906). The unit operation list 508 includes information related to each unit operation. Detailed process timeline including start and stop times for most of the disks Contains enough input information to generate The duration of some unit operation tasks is Not scale dependent. However, the duration of other unit operation tasks is scaled Dependency. In the latter case, as the process scales up, unit operations The amount of time required to complete the work task increases. Holding unit operation task If the duration is scale dependent, the amount of material handled by the unit operation task To calculate, a block flow diagram calculation set 704 is required. Unit operation The duration of the unit operation task after the amount of material handled by the task has been determined Can be determined. An example of a scale-dependent task duration is a single storage tank The time required to pump the solution to another storage tank The amount of time required to heat or cool the solution in the vessel, generated from the solution The amount of time required to filter out contaminants or contaminants.   FIG. 10 is an example of a high level process timeline for a microbial fermentation process. . The unit operation sequence of the process time line in FIG. 10 corresponds to the unit operation list in FIG. Respond. The high-level process time line shown in FIG. Microbial fermentation unit operating system, designated as 2 illustrates two process cycles of the sequence. The process cycle is simply the process Complete run of the biopharmaceutical manufacturing process as defined by the It is.   The first two columns of the process time line in FIG. The order operation sequence number and the unit operation description are shown. The first three sets of unit operations are Three unit operation sequence numbers 1 to 6 correspond to three cycles per batch. unit Three cycles of operations 1 to 6 are performed, and the result is stored in the collection pool of unit operation 7. Is done. The two columns to the right of the duration column are specific for the first process cycle. Indicates the week and day on which the unit operation is taking place.   The day and week that each unit operation occurs is based on the start time of the process and each previous unit. Calculated from the cumulative duration of the position operation. In the example of FIG. 10, Sunday is the week Defined as the first day. In the example of FIG. 10, the process sequence is the first week Starts with the inoculum preparation which is the unit operation 1 on Friday. After unit operation 1 is completed (only Position operation 1 has a duration of 24 hours, so after 24 hours), unit operation on Saturday 2 is performed. The start time and end time of each successive unit operation are determined by the unit operation And the end time of the previous unit operation. FIG. 10 simply shows Calculated in days and weeks for illustrative purposes. Typically, the process time line is For each of the tasks associated with the unit operation, up to the minute is determined.   As shown in FIG. 10, the unit operation 7 is performed in the third week of the first process cycle. Happens on Monday. The third column from the left is the duration of each unit operation. Unit operation After three cycles 1 to 6 are pooled in unit operation 7, the process proceeds to unit operation 7. Follow heat exchange, cell destruction and heat exchange, crops 8-10. Unit operation 8 to 10 Each cycle is repeated three times and the relevant scheduling information is on the right side of the unit operation duration Column. As shown in column 3, each cycle of unit operations 8 to 10 is 0. With a five hour duration, each cycle starts on the third Monday of the process. This.   FIG. 11 shows the final unit operation of the treatment time line of the microbial fermentation process. Unit operation After the completion of the three cycles of 8 to 10, the unit operation sequence numbers 11 and 12 become Both cycle twice on the third Monday of the first process cycle. Unit operation After sequence numbers 11 and 12 circulate twice, the microbial fermentation production process is simply Continue from cycle operation sequence number 13 to unit operation sequence number 22 without cycling And terminate the microbial fermentation production process. The duration and the associated start time are Each of the unit operations 13 to 22 is listed.   12A-12H show a preferred embodiment of a detailed process timeline. FIG. The unit operation sequence of the process time line of FIGS. 2A to 12H is the unit operation list of FIG. Corresponding to the The process time lines in FIGS. 12A to 12H correspond to the microbial fermentation unit operation system. 1 illustrates a single process cycle of a sequence. Individual tasks associated with each unit operation Is included after the unit operation. For example, in FIG. 12A, the unit operation is 1A. Inoculum preparation involves setup, pre-incubation, incubation, and And the individual tasks of purification. Columns 11 to 14 show the tasks of each unit operation. The start date and start time and the end date and end time for each are shown. Set Setup and cleanup are not part of the actual process, so Cleaning does not directly affect the start and end times of subsequent unit operations . Start and end dates and open dates for each set-up and purification operation of the unit operation Beginning Time and end time are important. Because they follow the process timeline In this case, it is ensured that the device is available for each unit operation.   The process time lines in FIGS. 12A-12H are for calculating the task duration of a unit operation. Including examples. Line 2 of FIG. 12A corresponding to the seeding fermentation task of unit operation 3A. 0, column 15 is an example of duration calculation. As mentioned above, holding some unit operations Duration is process scale dependent (ie, duration is the volume to be processed) Depends on). The harvesting task in the unit operation of seed fermentation is scale-dependent in duration. It is an example of a task that is a viability process. In column 15, which is the column for calculation, the collection task The information shown for 50 liters, 1. 7 liters / minute (LPM) and And 0. 5 hours. 50 liters is the volume of material collected during the collection task Represents 1. 7 l / min represents the rate at which the solution is taken. Body to be collected Taking into account the product and the flow rate of the harvest, the duration of the harvest task is equal to 0. 5 hours Calculated as To generate the process time lines of FIGS. 12A-12H, The duration of each task of the unit operation that is volume dependent is calculated.   The process time lines in FIGS. 12A-12H may be in minutes and seconds, if necessary. Can be The accuracy of the process timeline is accurate for many aspects of the batch manufacturing process. Enables efficient planning and scheduling. Process time line schedule Ring information is effort, reagents, and reusable directly required by the manufacturing process For scheduling manufacturing resources such as materials, disposable materials, etc. Can be used for Needed to support core processes, labor, reagents, etc. Pre-process support activities such as solution preparation and instrument preparation and sterilization, including Can be scheduled, cost predicted, and prepared. Purification Product formulation, required to ship the product in a usable form Bacterial filling, freeze drying, vial capping, vial labeling, and Post-process support activities, such as packaging, can be added to the process timeline, and Can be managed. Based on the process timeline, these post process support functions The effort, reagents, etc. needed to support can be obtained and managed. The present invention One of the most important aspects of USP purified water for all of the manufacturing equipment, It is the determination of process utility charges such as injection water, pure steam, etc. process The time line is the peak utility loading and utility demand for the equipment Can be used to determine All manufacturing equipment, process areas and equipment Building steam, heating, ventilation, air conditioning, Building utility charges, such as equipment, equipment and equipment associated with each unit operation. And a process timeline. The process time line shows that the equipment Preventive maintenance of factory equipment, quality assurance activities (instrument calibration, automatic batch documentation) And quality control activities (including process system maintenance). Including raw materials, raw material testing, in-process testing, and final product testing Can be used to measure uptime for scheduling) You. 2. 0Solution preparation schedule creation module   A preferred embodiment of the present invention is a simulation, model, Computer-based system and method for optimization and scheduling . The preferred embodiment accurately addresses the complex manufacturing procedures of solution preparation in batch manufacturing. Based on the method for creating the information specified in. This schedule A more detailed and accurate style than was previously possible due to the scheduling system Thus, it is possible to define the manufacturing cost and the system. As a result, According to Ming, to reach the optimal process design early in the equipment development business, Fast and accurate evaluation of numerous batch manufacturing alternatives is possible. When doing so, Ming is a business cost that arises from inaccuracies that can be carried forward from the early stages of design to build. Minimizing overruns. The present invention also provides for solution preparation in an operating production plant. Precise scheduling of manufacturing operations (resources needed for solution preparation (e.g., , Labor, reagents, supplies, disposables, reusable supplies, usefulness, equipment maintenance And calibration).   The purpose of this solution preparation schedule creation module is to place each solution in a solution preparation container. Assign and create a solution preparation schedule for each solution preparation container It is in. By scheduling the solution preparation in each solution preparation container, Pharmaceutical manufacturing process designers must be able to inventory solution preparation containers, equipment costs, availability requirements, Manage, predict, and optimize the work associated with washing and preparation and other solution preparation It can be optimized.   Figure 13 shows a simulation of solution preparation in a biopharmaceutical manufacturing process. 5 is a flowchart that provides an overview of the process to be performed. Step 1302 is a process for preparing each solution. Determine the solution preparation time for the container. A solution preparation container is a biopharmaceutical manufacturing process. This is a container used for preparing a solution used in the process. In a preferred embodiment Each type of solution preparation container used in the biopharmaceutical manufacturing process has an associated solution preparation Has production time. The solution preparation time means that the solution is prepared in the solution preparation container. Is the amount of time it takes. Preparation of a solution in one solution preparation container Called Kulu. Each solution preparation container has an associated solution preparation parameter. Dissolution Solution preparation parameters are used when necessary to complete various steps in the solution preparation process. Describe the amount between.   Step 1304 divides the solution from this biopharmaceutical manufacturing process into specific solution preparation containers. Guess. For the solution, schedule and determine the loading amount for this solution preparation container To be assigned to a particular container. Step 1304 is the biopharmaceutical manufacturing process. Determine the total volume of each solution needed for the process and assign it to an appropriately sized preparation vessel Procedures. Large volumes of solution are prepared in multiple smaller solution preparation cycles And pooled to obtain a larger volume of the solution batch. vice versa, Smaller volumes of solution are batch prepared in larger prep volumes to Multiple process cycles, provided the shelf life of the solution allows for long storage Can be adapted to   Step 1306 determines a calculation start date and a next preparation date for each solution. For solution preparation The start date for the calculation is to prepare this solution for use in biopharmaceutical processes, This is the day to start preparing the solution. This calculation start date is required to prepare this solution. Consider the amount of time required and other key time factors required for solution preparation. Next key The production date is the earliest date on which the solution is prepared after the calculation start date. Next preparation The day is determined by adding the periodicity of the solution preparation to this calculation start date . The periodicity of the solution preparation is important to maintain the biopharmaceutical manufacturing process. About how often each solution must be prepared.   Step 1308 is the fastest solution in each solution preparation vessel for a given process cycle. Determine the preparation date. Each solution is assigned to a solution preparation container, and for each solution Since the calculation start date has been determined, step 1308 is calculated for each solution preparation container. Determine the earliest start date you did. Earliest start calculated in relation to solution preparation vessel The day is when the first solution is prepared in the container for a given process cycle Day. The earliest start date calculated for the solution preparation container is Check when the preparation vessel must be available in the cycle .   Step 1310 determines the next latest preparation date for each solution preparation container. Each solution The next latest preparation date for a preparation container is when the solution preparation container is This is the last date used for solution preparation to support the cycle. Process 13 Assignment of the solution determined in 04 to the solution preparation container, each solution determined in step 1306 Based on the earliest start date calculated for and the next preparation date for each solution, Step 1310 determines the next latest preparation date for each solution preparation container. Solution preparation The earliest start date and the next latest preparation date calculated for the container are Defines the use limit of the solution preparation container in the process cycle. Loading the solution preparation container During the time between this calculated earliest start date and the next latest preparation date, Can be done. Batch preparation to meet its usage limits for multiple process cycles If set by the solution to be used, the service limit of the tank is Process cycle. Therefore, the loading of the solution preparation container in this case is It also takes into account solutions from multiple process cycles.   First biopharmaceutical manufacturing process activities related to a given process and The duration between the last relevant biopharmaceutical manufacturing process operation is the production cycle and (I.e., multiple process cycles define a manufacturing cycle). If operations such as solution preparation are compatible with multiple process cycles, A vehicle consists of multiple process cycles. All work related to the process is 1 If only the process cycle fits, the manufacturing cycle is It consists only of icicles. Therefore, the production cycle is shared with the auxiliary work associated with them. Alternatively, it can consist of one or more process cycles.   Step 1311 calculates the duration of use for each solution preparation container. For each solution preparation Use duration refers to the time the solution preparation container occupies the solution preparation for the production cycle. It is the time that is possessed. For example, assigning multiple solutions to a single solution preparation vessel The duration of use of this solution preparation container is assigned to this solution preparation container. Based on the earliest start date and the next latest preparation date calculated for all Is determined. The total number of hours that this solution preparation container is occupied is Use duration (day) and shift time per day (e.g., A single shift operation is typically 8 hours per day).   Step 1312 calculates the cumulative solution preparation time for each solution preparation container. This accumulation Solution preparation time is defined as the time during which the solution preparation vessel The amount of time occupied by the product. Step 1312 prepares each solution based on: Calculate the cumulative solution preparation time for a container:   1) solution assigned to a particular container;   2) Duration of use of the preparation container;   3) duration of the process cycle;   4) number of solution preparations per process cycle; and   5) Solution preparation time. For example, if five solutions were prepared in a particular solution preparation vessel, each of which was 2 preparations per process cycle, 7 days pro If you need a solution cycle time of 3 hours, the solution preparation container Is 60 hours over a two week period.   Step 1314 determines the utilization of each solution preparation container. Utilization rate of each solution preparation container and The duration of use (e.g., That is, the ratio of the cumulative solution preparation time). This utilization rate is based on this process cycle Duration, cumulative solution preparation time and time per solution preparation shift Determined based on the number. For example, if the duration of use for the solution preparation container Is 14 days and if there is a shift time of 8 hours per day, this solution preparation container Has a full capacity of 112 hours. If calculated as above, this solution preparation volume If the cumulative solution preparation time for the vessel is 60 hours, the utilization of this solution preparation container Is about 54%. The utilization of each solution preparation container depends on the biopharmaceutical manufacturing process. The planner determines the level of use of this solution preparation device and Determined in step 1314 so that any adjustments in the tool or manufacturing cycle can be made. .   Step 1316 schedules an initial shift for each solution preparation container. This The initial shift schedule of a solution It is a schedule. Step 1316 includes a calculation start date for each solution, Based on the periodicity of solution preparation and the assignment of solutions to solution preparation vessels. Schedule a period shift.   Step 1318 schedules a solution preparation procedure that does not meet this shift schedule. Re-schedule (back scheduling) and check for system capacity issues. Schedule Recreating a solution means re-running the solution preparation cycle for a previous number of days or hours. This is the process of creating a schedule. This initial shift schedule is Created regardless of the number of hours a container occupies for a particular day. For example This initial shift schedule is scheduled for a 14 hour solution preparation May have a specific solution preparation container. Biopharmaceutical manufacturing process that operates 16 hours a day All solutions scheduled for this solution preparation container are compatible. Wear. However, if the biopharmaceutical manufacturing process is operated for 8 hours a day, If not, not all of the necessary solutions can be prepared on the day of the schedule. Engineering Step 1318 describes a solution preparation cycle that cannot be completed on the date , Reschedule on an earlier date. Schedule on available shifts Scheduling a reconstituted solution preparation cycle is based on all available schedules. Priority of the oldest reschedule date for the solution being rescheduled It is performed according to. The end result of step 1318 is that each preparation container (which Assign the appropriate solution for the shift volume and shift Schedule the preparation of each solution according to the duration of each preparation) To create the final shift schedule.   Step 1320 includes shift assignment and solution preparation in this final shift schedule According to the duration associated with each solution preparation step in the procedure table, each solution preparation container and Create a timetable for the associated device operations. Based on this timetable, Labor, reagents, disposables, reusables, usefulness, equipment maintenance, etc. The resources you need to do can be accurately scheduled.   FIG. 14 further illustrates step 1302, which is a solution for each solution preparation vessel. Determine the preparation time. Step 1302 is a setup time for the solution preparation container (setup time) Begin at step 1420, which determines Step 1420 is used in this biopharmaceutical manufacturing process. List 1402 of solution preparation containers available for use and their associated solution preparation Key identifiers for the production container identifiers and the solution preparation container identifiers and their associated set times. Compare with strike 1410. The solution identifier and the solution preparation container identifier are A key or tag for confirming the type of container and solution. When setting the solution preparation container An example in between is shown in column 1410 of FIG. A list of solution preparation containers 1402 is provided for each container. Minimum / maximum working volume as well as solution preparation needed to complete solution preparation Includes specific operations associated with the vessel and any process equipment. This solution preparation Operations and equipment are fully prepared for use in equipment preparation and scheduling. It can be included in production time 1428.   Next, step 1408 determines a water collection time for each preparation vessel. When collecting this water The interval is defined as the water collection rate 1404 and the maximum working capacity 1406 of this solution preparation vessel. The amount of time needed. Water collection rate 1404 means that this solution preparation container can be filled The speed that can be. The different solution preparation vessels have their specific water collection hardware Have different water collection rates. Step 1408 is based on its maximum working capacity of 1410 Approximate water collection time for each solution preparation vessel based on and water collection rate 1404 . In a preferred embodiment, the volume of water to be collected depends on the maximum working volume of the preparation vessel. Estimated to be 1406. In another embodiment, the volume of water to be collected is It may be the actual volume of the solution prepared in the preparation cycle. Water collection speed 1404, max Examples of working capacity 1406 and water collection time 1502 are shown in FIG. And column 1502.   Step 1414 defines the weighing and mixing times associated with each solution preparation container. Weighing And mixing time 1416 are necessary to weigh, mix and adjust the components of the solution. It is important time. The preparation container identifier 1402 is used to weigh and mix the associated preparation container. Matched between 1416. Associated with each solution preparation vessel in this biopharmaceutical manufacturing process The weighing and mixing time 1416 is thereby assigned to the associated solution preparation vessel identifier 1402. Assigned. Initial weighing and mixing time variables are determined by the designer of this process. Can be manipulated. Examples of weighing and mixing times 1416 are shown in FIG.   Next, step 1418 determines the time required to filter the solution in the preparation vessel. The time required to filter the solution in the preparation vessel The amount of time required for filtration and transfer after preparation of the solution. Step 1418 is a preparation vessel Identifier 1402, maximum working volume of preparation vessel 1406, filtration flow rate 1424 and surface area of filtration media Based on 1412, calculate the time required to filter the solution in the preparation vessel. Like In a preferred embodiment, the volume of solution to be filtered is the maximum working volume of the preparation vessel 1406. Presumed. In another embodiment, the volume of the solution to be filtered is May be the actual volume of the solution prepared in The surface area 1412 of the filtration medium As it moves out of the liquid preparation vessel, the surface of the filtration media used to filter this solution It is a product. Filtration flow rate 1424 is the unit area over which this solution can be filtered through this filtration medium. It is the speed of the rumble. Examples of filtration flow rate 1424 and filtration media surface area 1412 are respectively 15, columns 1424 and 1412.   Step 1426 calculates the adjusted filtration time. This adjusted filtration time is determined in step 1418. It is the value obtained by multiplying the determined filtration time by the filtration delay factor 1430. Filtration delay factor 1430 Typically, based on the additional filtration time required to operate the solution storage vessel on a full line. Is based on Step 1426 multiplies the filtration time calculated in step 1418 by a filtration delay factor 1430. Calculate the adjusted filtration time. FIG. 15, column 1430 shows the filtration delay factor. The representative value of 1430 is shown.   Step 1432 includes clean in place and cleanup associated with each solution preparation vessel. Determine the duration of steam in place. Positional cleaning duration 1422 And in-situ steam duration 1434 refers to the solution preparation used in the next solution preparation cycle. The duration of the washing procedure required to prepare the container. Step 1432 is for this biological drug. -Position cleaning duration associated with each of the solution preparation vessels used in the agent manufacturing process To determine 1422 and the positional steam duration 1434, the preparation vessel identifier 1402 is Match in-place cleaning duration 1422 and in-place steam duration 1434. Figure 15, Columns 1422 and 1434 indicate in-position cleaning duration 1422 and in-position steam, respectively. Shown are representative values for duration 1434.   Step 1436 is the time value calculated in steps 1420, 1408, 1414, 1418, 1426 and 1432. To calculate the total solution preparation time 1428 for each preparation container. all Solution preparation time 1428 adjusts the maximum working volume 1406 of the solution in a particular solution preparation container. It corresponds to the amount of time needed to However, those skilled in the art will appreciate that Whole solution preparation to include additional steps, factors or parameters other than It should be noted that the calculation of time 1428 can be extended. With these extensions, In the present invention, it is possible to more accurately calculate the total solution preparation time 1428 for the solution preparation container. Or other factors can be included in this calculation. Sa In addition, the calculation of the total solution preparation time 1428 for the solution preparation To accommodate a solution preparation working volume that is less than the maximum solution preparation working volume for the vessel Can be adjusted. Column 1428 in FIG. 15 provides representative values for total solution preparation time 1428. Offer.   FIG. 15 shows a representative list of solution preparation parameters. Such parameters Examples include minimum working capacity 1402, maximum working capacity 1406, set time 1410, water collection rate 14 04, water collection time 1502, weighing and mixing time 1416, surface area of filtration media (square area ) 1412, filter area per hour, volume per unit 1424 and solution There are post-preparation and wash procedure durations 1422, 1434.   The minimum working volume 1402 and the maximum working volume 1406 are the The minimum and maximum volume of liquid. Set time 1410 is the time for this solution preparation process. The amount of time required to prepare the solution preparation container. Water collection time 1404 The time required to fill the liquid preparation vessel with the maximum working volume of water 1406. Weighing and And mixing time 1416 is the time required to weigh and mix the components of a solution in a particular solution preparation vessel. It is necessary time. The surface area of the filtration media 1412 is related to the particular solution preparation vessel The area of the filter. Filter area per hour Volume per unit The volume 1424 is defined as the filter area per unit associated with a particular solution preparation vessel. Flow rate. Post-solution preparation and wash procedure durations 1422 and 1434 are one batch The time associated with preparing this solution preparation container after preparation of the solution.   FIG. 16 further illustrates step 1304, which is included in the biopharmaceutical manufacturing process. Thus, the required solution is assigned to a particular solution preparation container. Solution preparation cycle Each solution must be assigned to a solution preparation container in order to schedule I have to. Step 1304 begins with step 1602. Step 1602 is the solution to be prepared. Set the preparation cycle per batch for Preparation size per batch Kle 1608 is a solution preparation container that supports one product batch cycle. It is the number of times to prepare in. For example, if a biopharmaceutical manufacturing process 150 liters of solution 101 was required to make the product If it should be prepared in a 50 liter solution preparation container, solution 101 should be 50 Can be prepared in three preparation cycles per batch of Is obtained. Alternatively, solution 101 contains at least 37. 5 liter solution preparation container In each 37. Per 5 liter batch, Can be prepared in 4 preparation cycles No. In a preferred embodiment, The preparation cycle 1608 per batch of solution is: the first Is Set by designer. The preparation cycle 1608 per batch is As a whole hand, From the beginning of the solution preparation schedule creation module and the solution preparation procedure Affects the value up to now. Number of preparation cycles per batch for each solution 1608 is Determine the size of the solution preparation vessel and the time required to prepare a batch of solutions. decide.   Step 1606 is For each solution involved in this biopharmaceutical manufacturing process, 1 solution tone Determine 1610 days per cycle. 1610 days per solution preparation cycle Is Preparation cycle 1608 per batch and 16 days per batch cycle From 04, It is determined. This batch cycle time is Produce one batch of product Is the amount of time needed to 1604 days per batch cycle means Product continuity The number of days between batches. The number of days 1610 per preparation cycle is Open each solution preparation This is the number of days between the beginnings. The number of days per batch cycle Preparation service per batch Dividing by Icle 1608, 1610 days per preparation cycle are obtained. For example, Also And In the solution preparation container, With a working volume of 50 liters, One batch of product Or 150 liters of solution should be prepared, Preparation cycle per batch Le 1608 is Three times. if, One batch of biopharmaceutical product Generated every 6 days If The number of days per batch cycle is Six days. 1 for a specific solution There are three preparation cycles per batch, 6 days per batch cycle Et al., 1610 days per preparation cycle It is determined to be two days. That is, Between the start of each 50 liter solution preparation cycle, There are two days.   The decision step 1612 is For 1610 days per preparation cycle, Storage of this solution Inspect life. In preparing the solution, 1610 days per preparation cycle This May exceed the shelf life of the solution. In such a situation, Solution was held too long In order to "Expired" solutions may be subject to use in this biopharmaceutical manufacturing process . if, Decision step 1612, 1610 days per preparation cycle is from this shelf life If you decide it ’s long, Step 1304 continues at step 1602, here, One batch The number of preparation cycles 1608 is adjusted (preferably, Increased). 1 of this solution By adjusting the preparation cycle 1608 per batch, This solution preparation process The designer of To reduce 1610 days per preparation cycle determined in step 1606 Becomes possible. if, Decision step 1612, 1610 days per preparation cycle If you determine that the liquid is less than the shelf life, Step 1304 continues with step 1616.   Step 1616 is 1620 liters per cycle of solution preparation for each solution calculate. The number of liters per solution preparation cycle 1620 is: 1 for each solution 1618 total liters per batch, Adjustments per batch determined in step 1602 By dividing by 1608 manufacturing cycles, Is calculated. One batch for each solution The total liter number of 1618 is In this biopharmaceutical manufacturing process, One batch The amount of each solution type required to produce the product, this is, Stored in material balance table .   Step 1624 Determine the solution preparation container type for each solution preparation. Step 1624 Each solution Assigned to the solution preparation container in step 1624, To solution assignment list 1626 Make a preparation container for the product. Step 1624 Each solution One preparation cycle of solution Liters 1620 and based on the preparation vessel identifier and associated volume list 1402 And Assign to solution preparation container. The solution preparation container is One preparation cycle of solution The minimum working volume 1402 and the maximum working volume 1406 of the solution preparation vessel. To be within the range of Select from preparation vessel identifier and associated volume list 1402 Is done. Preparation vessel-solution assignment list 1626 This biopharmaceutical manufacturing process Solution to be prepared And a list of solution preparation containers associated therewith.   FIG. Representative values of the data for the present invention are shown. Column 1618 is For each solution Typical values of 1618 total liters per batch are shown. Column 1608 is 1 batch A typical value of 1608 preparation cycles per unit is shown. In this example, Shown in column 1608 All solutions are With one preparation cycle per batch, Prepared. Column 1604 is , Representative values for 1604 days per batch cycle are shown. Column 1610 is Engineering Shown is a typical value of 1610 days per preparation cycle determined in step 1606. The In the example, The number of preparation cycles per batch of solution 1608 is This solution manufacturing process Equal to for all solutions at 1610 days per preparation cycle , Equal to 1604 days per batch cycle. Column 1614 is Solution shelf life 1614 Are shown. Column 1706 is Shows representative values for the result of decision step 1612 And in this case, 1610 days per preparation cycle 1614 solution shelf life Be compared. Column 1618 in FIG. 17, 16 liters per batch for each solution 18 representative values are shown. 1608 preparation cycles per batch for each solution , In this example, Because it is 1, 1620 liters per cycle of solution preparation , Equal to 1618 total liters per batch for each solution.   Columns 1708 to 1728 in FIGS. 17 and 18 are: List of solution preparation container assignments for representative solutions 1626 is shown. The tank identifier is It is listed along the top of columns 1708-1728, Ma Was The solution identifier is It is described along the vertical axis, far to the left of the tables of FIGS. In FIG. 18, A typical solution preparation container identifier is On the opposite side of the horizontal from this solution identifier Are located in a certain column, this is, This preparation container Assigned to that solution To indicate that   FIG. FIG. 27 shows an exemplary preparation vessel-solution assignment list 1626. FIG. Column 1626 is , Shows preparation vessel-solution assignment. Column 1722 is Solution preparation container # 108 Solution S -0107, S-0108, S-0112, S-0115, Indicates related to S-0117 and S-0120 are doing. Similarly, Column 1724 is Solution preparation container # 109 is Solution S-0116, S-0118 and Indicates that it is related to S-0119. Column 1726 is Solution preparation container # 110, solution It indicates that it is related to S-0106 and S-0114. Column 1728 is Solution preparation container # 11 is It is shown that it is related to solutions S-0101 and S-0113.   FIG. Step 1306 is further illustrated; this is, Calculated for each solution preparation Determine the start date 2010 and the next preparation date 2022 for each solution. Next preparation day 20 22 is Based on the calculated start date 2010 and 1610 days per solution preparation cycle Have been. Step 1306 begins at step 2004, Start calculated for each solution preparation Determine the day ("the calculated start date") 2010. The calculated start date 2010 is This raw In order to prepare the solution in time for use in the drug manufacturing process, Until that day This is the day to start preparing the solution. The calculated start date 2010 is This biopharmaceutical In the manufacturing process, Recalculating from 2006, the earliest day the solution is needed, Use Measure the `` lead time '' needed to prepare and test a batch of solution before use By calculating It is determined. In a preferred embodiment, This recalculated value is , Total solution preparation time 1428 for the solution preparation container, Consider failed lot solutions 2002 and solution quality assurance and quality control (QA / QC) testing Hold days 2008 for experiments. if, A batch of a solution is If you do not pass the test, This solution is Have to be re-prepared, This preparation time Is As the number of reversion days 2002 to consider the solution of the failed lot, Is represented. Dissolution The earliest day 2006 when liquid is needed, According to this material balance table, This process time Obtained directly from the table. This material balance is List of solution preparation reagents and calculation settings And Each of them Related to unit operations. This material balance table is Of this solution According to the formulation All process flows and their structures in this block diagram 704 Includes the volume of the solution component. This material balance table also This process timetable 906 Follow the steps to schedule your data in Solutions are required for this manufacturing process. Check the required time.   After determining the calculated start date 2010 for the solution preparation, that is, Related solutions And assigned to the preparation vessel solution assignment list 1626, as a result, Of each solution A calculated start date 2010 for the preparation and its associated solution preparation container is obtained .   Process 2018 is After determining the calculated start date 2010 for each solution, Against batch By choosing the larger of the number of days to prepare or the days for preparation, Each solution Calculate the next solution preparation date for the solution. Process 2018 is Thereby, For each solution Calculate the next solution preparation date. The next solution day is In process 2018, Split into preparation containers On the calculated start date 2010 for the preparation of each applied solution, Per preparation cycle By adding 1610 days, Is calculated.   FIG. Step 1308 is further illustrated; this is, Each solution in the process cycle Determine the earliest solution preparation start date for the preparation container. Step 1308 is calculated Determine the solution preparation start date 2010, Assign it to each solution preparation vessel in step 2402 By doing Begin. Solution Preparation Container (`` Preparation Container '')-Solution Assignment List 1626 and And the calculated solution preparation start date 2010 for all solutions is: Cross-referenced Key A calculation and assignment solution preparation start date for the container 2404 is created. Step 2406 Are Earliest solution preparation start date for each solution preparation container ("earliest start date") 24 08 is created. The solution preparation start date 2404 calculated and assigned to the preparation container is: Process 24 Processed in 06, The earliest solution preparation start date associated with each preparation container is determined. From step 2406, The earliest preparation start date 2408 assigned to each preparation container is obtained. This list is Solution preparation containers and solution preparation required for this biopharmaceutical manufacturing process The container makes the earliest day necessary for the preparation of the solution in this process cycle.   FIG. Step 1310 is further illustrated; this is, Most for each solution preparation container Determine the late solution preparation start date. Step 1310 is Determine the next solution preparation date, It By assigning each solution preparation container in step 2502, Begin. Next solution preparation date Is After the earliest start date 2408, The solution preparation container is On the day needed to prepare the solution is there. This solution preparation vessel-solution assignment list 1626 and the next solution for each solution Liquid preparation day 2022, As determined in process 2018, Matched, In step 2502, A list of the next solution preparation dates for each preparation container is created. next, Step 2504 is Determine the latest next preparation start date 2506 associated with each preparation container. This slowest next The solution preparation start date of During the process cycle, Occurs in certain solution preparation vessels The date associated with the preparation vessel, meaning the last preparation of the solution procedure.   FIG. Step 1311 is further illustrated; this is, Solution for each solution preparation container The preparation container use time 2604 is calculated. Solution preparation container usage time for each preparation container 26 04 is For a particular production cycle, The time this container is occupied in the preparation of the solution It is. With the solution preparation container use time 2604, Earliest preparation start date 2408 and next latest Between the end of a new solution preparation cycle. Next slowest solution preparation The end of the kuru, Total solution preparation time 1428 for the solution preparation container, For each solution preparation container Calculated by adding to the next latest solution preparation start date 2506 for in addition Than, The date when this solution preparation container completed the solution preparation in the process cycle was obtained. It is. The solution preparation container use time 2604 for each solution preparation container is Fastest solution preparation Start date 2408, For the next latest solution preparation start date 2506 and each solution preparation container By comparing with the total of the total solution preparation time 1428, It is determined.   FIG. Step 1312 is further illustrated; this is, Cumulative for each solution preparation container Calculate solution preparation time 2708. Cumulative solution preparation time 2708 for each solution preparation container Is Each preparation container is actually, The amount of time occupied by the preparation of the solution. Basic , Cumulative solution preparation time is Total solution preparation time 1428 for the solution preparation container, this The solution preparation vessel is multiplied by the number of solution preparation cycles used in this manufacturing cycle. is there. For example, if, The total solution preparation time for the solution preparation container is One cycle And 6 hours This solution preparation container Used in the preparation of 6 cycles of the solution If The cumulative solution preparation time 2708 is 36 hours.   Step 1312 is The total solution preparation time for each solution preparation container is determined by the By assigning Begin. Total solution for each preparation vessel from step 1302 Preparation time 1428 is Matched with the preparation vessel-solution assignment list 1626. Preparation container, A list of associated solutions and their total solution preparation times can be found at: Enter in step 2704 Is done. Step 2704 is Total solution preparation time 1428 for this solution preparation container, 1 bag By multiplying the number of preparation cycles for each individual solution by 1608, For each solution Determine the cumulative solution preparation time. From step 2704, Each solution preparation container is Each specific The amount of time occupied by the preparation of the solution is obtained. Step 2706 is Each preparation container is actually , By summing the amount of time occupied in the preparation of this solution, Each solution preparation volume Determine the cumulative solution preparation time for the vessel 2708. From steps 2704 and 2706, Each key For container 2708, A list of cumulative solution preparation times is obtained.   FIG. Step 1314 is further illustrated; this is, Determine the utilization rate of each solution preparation container Set. The utilization rate of this solution preparation container is Cumulative total solution preparation for each solution preparation container Production time 2708, For the total time 2802 when the solution preparation container is available for solution preparation, Is the ratio this is, Expressed as a percentage. Use of each solution preparation container By determining the usage rate 2808, This process designer Advantages of this solution preparation device To maximize Change preparation cycle 1602 per batch of each solution It is possible, Thereby, Costs are minimized, And the efficiency is maximized. Process 1314 is To calculate the total number of hours that the solution preparation container is available in step 2802 Than, Begin. The total number of hours that the preparation vessel is available is The solution determined in step 2602 This is the product of the liquid preparation container use time 2604 and the time 2804 per one solution preparation shift. 1 The time 2804 per solution preparation shift is First biopharmaceutical manufacturing process Obtained from process design parameters. For example, if, This process is Two If designed as a shift process, This plant Normal, Operation 16 hours a day And The number of hours 2804 per one solution preparation shift is 16 hours.   Step 2802 is Solution preparation container use time 2604, One solution preparation shift per day It multiplies with 2804. From step 2802, The solution preparation container is The number of raw hours available for the process is obtained. For example, if, This solution Liquid preparation container use time 2604, 6 days And this biopharmaceutical manufacturing process , If you work with one shift per day (8 hours) This solution preparation container Made of this biopharmaceutical The number of hours available for use in the build process 48 hours. 48 hours is this The maximum number of hours that the solution preparation container is available for use. if, Such a solution The preparation container is actually, 24hours, If occupied by the preparation of the solution, Available The utilization rate 2808 of this solution preparation container during the 50%.   Step 2806 includes: Calculate the utilization of each solution preparation container. Usage rate 2808 is In step 2802 The total number of hours that solution preparation vessels are available as calculated and the By comparing the cumulative total solution preparation time 2708 to It is determined. Each solution preparation volume Cumulative total solution preparation time 2708 for the vessel Use a preparation vessel as calculated in step 2802. By dividing by the total number of hours available, As explained in the example above, Available The utilization 2808 of each preparation vessel during the active period is calculated.   FIG. Step 1316 is further illustrated, this is, Initial shift schedule 2910 Create What is the initial shift schedule 2910? In this biopharmaceutical manufacturing process Figure 3 is a table of dates for preparing a schedule for the preparation of a solution for use. Initial shift Schedule 2910 is For each of the solution preparation containers, Created. Solution preparation The initial shift schedule for containers is Solutions to prepare and their related Includes preparation date and days per preparation cycle. FIG. Initial shift schedule This is an example of the rule. Step 1316 begins with step 2902, This biopharmaceutical in step 2902 Starting from the earliest start preparation date of all solutions required by the drug manufacturing process Create a table. In a preferred embodiment, This timetable is Increased one day at a time hand, The date is predetermined by the system designer. In another embodiment, This time The table and shift schedule are At any of the most convenient time intervals, Increased Or delimited.   Step 2904 is Determine the solution preparation date 2404 for each solution, this, From step 2902 Match the date in the shift schedule timetable. Matched to solution preparation container Solution preparation day 2404 Shift schedule timetable for each of the solution preparation containers Can be put in. Starting from the calculated start date 2404, Step 2904 is 1 preparation cycle Based on 1610 days per le Continuous preparation for each solution associated with the preparation vessel Enter the production start date. For example, if, The specific solution assigned to the solution preparation container , Per preparation cycle, If you have two days, This solution is The solution preparation container Every two days after its calculated start date 2010 for preparation within Schedule creation Is done. From step 2904, Solution and associated preparation date for each solution preparation container Listing 2906 is obtained.   Step 2908 is The total number of solution preparation times for each solution is Each initial shift schedule Into the timetable. The result is For each solution preparation in this initial shift schedule Relevant daily hours of preparation. Step 2908 is Solution for each solution preparation container Preparation time 1428, Match the date assigned in each shift schedule timetable, An initial shift schedule 2910 is created. Each solution preparation container is day by day, This solution The total number of hours occupied by liquid preparation is Then Number of solution preparation times associated with each day By adding to the initial shift schedule timetable 2910, Can decide. Like In a preferred embodiment, The number of hours of solution preparation per day per one solution preparation container is Base Essentially, The number of solution preparation cycles, Total solution preparation time for this solution preparation container 14 It is the product of 28. For example, if, The solution preparation container is For 5 hours solution preparation container Having a total solution preparation time of 1428, Then, schedule the four solution preparation cycles If it has been This solution preparation container On that day, For 20 hours solution preparation Schedule is created. From step 2910, Assigned for each shift Initial shift schedule 2910 with solution identifiers and their solution preparation times can get.   FIG. 6 is an example of an initial shift schedule for the solution preparation container 101. Teens A tabular solution identifier is This is shown in column 3102. Column 3102 is This biopharmaceutical manufacturing professional 5 shows representative solution identifiers for the solutions used in the process. Solution identifier 31 02 is Have corresponding date registration. Representative for time per solution preparation shift Values are This is indicated by a frame 2804. Representative for days per preparation cycle value is, This is shown in column 1610. Typical values for the solution preparation date for each solution are: Shown in column 2906 Have been.   FIG. further, Step 1318 is shown, this is, This initial shift schedule Re-schedule solution preparation in The solution preparation is At first, Schedule Without considering potential conflicts for In steps 1302-1316, Scheduled It is. The re-scheduling of the solution preparation Competition in this solution preparation process To avoid Done. Schedule conflicts Fits in the amount of time available Schedule more solution preparation cycles in a solution preparation container than can be Arising from For example, Schedule conflicts if, Certain solution preparation containers are 16 On working days, If you schedule a 20-hour solution preparation, Occur. Departure Ming is Scheduled shifts or unprepared solution preparation cycles , Re-create the schedule. For example, if, The solution preparation container is 3 times of 3 hours each If the solution preparation cycle is scheduled, This solution preparation container 9 Scheduled time preparation activities. if, This manufacturing facility works 8 hours a day If it works, All solutions can be prepared as scheduled Do not mean. The present invention Schedule one of these solution preparation cycles Do it again One day, Complete the 6 hour solution preparation time. Schedule Solution preparation cycle This solution The schedule in this process timetable As created, Prepared for use in this biopharmaceutical manufacturing process So that Rescheduled to the first previously available shift. Process After 1318 is completed, This solution preparation timetable is Solution preparation and scheduling And a form suitable for use as a management tool.   Step 1318 begins with step 3002, this is, Date on initial shift schedule 2910 Or for each shift This solution preparation time is summed continuously. This solution tone The production time is To determine the total solution preparation time for each solution preparation container at each shift To Summed up. For the purpose of summing these solution preparation times, What is a shift? 1 organism Number of hours in the drug manufacturing process day (e.g., 8:00 for a single shift plant while, 16 hours for two shift shift plants). By step 2002, Each A list for each solution preparation container with a total solution preparation time of 3004 for It is. The total solution preparation time 3004 is Shift time available in step 3006 / Compared to day 2804. if, A total of 3004 scheduled solution preparation times are If the number of available shift hours exceeds 2804, The solution is "Re-schedule" Is marked, And for the first previously available shift, Reschedule creation Is done. From the previous example, One of the 3 hour solution preparation cycles was: First available before For a shift, Should be rescheduled, 6 hours solution preparation , Remain in the shift for 8 hours. if, First schedule for 9 hour solution preparation The day of success On Wednesday, This 3 hour solution preparation On Tuesday, Will be fixed. After re-scheduling the solution that does not fit on the day, that is, On the day Removed from schedule.   if, Step 3006 is Scheduled solution with 2804 available shift hours If you decide to exceed the total preparation time of 3004, Step 3010 is In the current shift, Either solution Determine if it is scheduled for preparation. if, Step 3010 is A solution is scheduled for preparation in the current shift If you decide Step 3012 is This solution is For preparation on this shift schedule Leave the schedule created.   if, Step 3010 is For the evaluated shift, Assign to this solution preparation container If you decide that there is no solution Step 1318 is Continuing to step 3014. Engineering About 3014, Either solution For preparation for later shifts, Schedule for current shift Determine if you have re-created the rule. if, Create a schedule for the current shift If there is no fixed solution preparation cycle, This process is Continued to step 3002, This Where The next shift is For re-scheduling, Will be analyzed. if, Process 30 14 is If you determine that the solution preparation cycle has been rescheduled, This Roses Continuing at step 3016. Step 3016 is Re-scheduled solution Regarding the preparation cycle, Find out the date when you first created the schedule, This schedule The day I recreated the rule, Date of first schedule creation-re-schedule Determine if it is faster than the periodicity of the solution. For example, if, This solution For four days, Continuously rescheduled (i.e. Preparation cycle for this solution Le To suit a certain shift, I have to reschedule 4 days ago Absent), If its periodicity is two days, The re-scheduled preparation the same Potentially interfere with the previously scheduled preparation of the solution, Thereby, Shifts Indicates an error in schedule performance.   if, Step 3016 is This solution was rescheduled beyond its periodicity If you decide There is a warning, In step 3020, There is a system performance problem Indicates that if, Step 3016 is This re-scheduled solution preparation cycle The date the file was orbitally scheduled-not earlier than its periodicity If you decide This solution preparation cycle In step 3018, The current shift A schedule is created.   FIG. further, Step 1320 is shown, this is, Solution preparation schedule 3210 Create Solution preparation schedule 3210, Shifts re-scheduled Based on schedule 3202 and solution preparation procedure 3212, This biopharmaceutical process Schedule each task related to the solution preparation to be performed. Solution preparation schedule 3210 is For each solution preparation container having an assigned solution, Created. Schedule The initial shift schedule 3202 that has been re-created As created in step 1318 , For each shift in the initial shift schedule 2910, Solution Preparation Container-Solution Includes prepared assignments. Step 1320 is Shift in initial shift schedule 2910 Implemented for each of the Thereby, For each solution preparation vessel at each shift All solution preparation operations are scheduled.   Step 1320 is Beginning at step 3206, this is, Initial shift re-scheduled Number of solution preparations scheduled for the current shift in the schedule 3202 To determine. if, Neither solution is scheduled for preparation If Step 1320 is Continuing to step 3204, this is, Rescheduled In the initial shift schedule 3202, Move on to the next shift. if, Against this current shift If there is a solution preparation scheduled Step 1320 is Continue to step 3208 Continued. Step 3208 is For each solution preparation scheduled in this shift , From the solution preparation procedure data 3212, A solution preparation schedule 3210 is created. For example , if, In the solution preparation container 101, Scheduled preparation of two solutions If it has been Each operation in each solution preparation procedure, To solution preparation schedule 3210 A schedule is created. An exemplary solution preparation procedure 3212, As shown in FIG. 14 (Step 1420 , 1408, 1414, 1418, 1426, 1432 and 1436).   FIG. As described above, Used to create solution preparation schedule 3210 Shown are representative solution preparation procedure data. Step 3208 is Each assigned to the current shift Each operation for solution preparation is scheduled. After step 3208 and, if, In the initial shift schedule 3202 that was re-created, Additional If a shift exists, Step 1320 is Continued at step 3204, this is, Schedule In the initial shift schedule 3202 that was recreated, Proceed to the next shift. Engineering About 1320, In this initial shift schedule that was re-created, all To schedule all solution preparations, repeat. Therefore, According to step 1320 And A solution preparation schedule 3210 is obtained, this is, Assigned to the solution preparation container 6 is a time table based on a shift for each solution preparation operation for each solution preparation. 3. 0 Module preparation schedule creation module   The purpose of this device preparation module is In this biopharmaceutical manufacturing process, apparatus Simulating the preparation and loading of Create a schedule, And model It is in. The equipment used in this biopharmaceutical manufacturing process It gets dirty, So To be reused Washing, Must be packaged and sterilized. Washing, Packaging And the sterilization process Known as device preparation. This biopharmaceutical manufacturing process The parts of the equipment that need to be prepared before they can be used and reused in the process Dirty process Parts. The preparation of the device To sustain this biopharmaceutical manufacturing process , Will be implemented.   Current methods for this design equipment preparation procedure include: Typically, In the equipment preparation area It has not reached the point where it specifies precisely the relatively complex procedures to be performed. As a result hand, The work area associated with this device and device preparation Normal, Inefficiently designed ing. Cleaning and sterilization (preparation) equipment related to equipment preparation work Capital and useful Because it is a collection of sex, Accurately model these areas of biopharmaceutical manufacturing facilities There is a need for an improved method of optimizing. A preferred embodiment is Conventional design method A more accurate and efficient tool for designing and scheduling equipment preparation operations. Provide a computer simulation method.   FIG. In the biopharmaceutical manufacturing process, Schedule the preparation of the equipment and simulate 5 is a flowchart outlining a process for rating. Step 3302 is Key Create a manufacturing equipment protocol table. The preparation device protocol is One part of the preparation equipment It is a protocol for operation. The preparation device protocol is: Normal, Multiple device preparation Including work. Preparation work, This is a step in the apparatus preparation process. For example, In the glassware dryer, Work is Installing this dryer, This dryer Preheating, Drying this glassware, Removing this dryer And so on. The preparation device protocol table is Cleaning dirty process parts A set of standard prep protocol. The preparation device protocol is: Normal, Through experiments and quality assurance tests, Be developed. Dirty process parts, Reuse for, The most efficient preparation equipment protocol to prepare to the required level of cleanliness is , This is the preparation device protocol.   The preparation device protocol is: It relates to a specific part of the preparation device. Example of preparation equipment In Bench sink, Washing station, Glassware washing machine, Gala Utensil dryer, Carboy cleaning machine, Carboy dryer, Autoclave, Steam sterilizer and so on. further, Per part of the preparation device, Multiple preparation device protocols available May be present. For example, 4 preparation protocols related to each type of bench sink Can exist, Each is Different combinations of bench sink cleaning work and duration Having. A preferred embodiment is A limited set of preparation equipment, Dirty process Although describing the parts and preparation equipment protocol, Those skilled in the art In this specification The description process Can be easily extended to any preparation equipment or dirty process parts You.   Step 3304 is Create a device preparation procedure table. The device preparation procedure Dirty process Parts are For reuse in this biopharmaceutical manufacturing process, Complex that is cleaned and sterilized This is a standard procedure that includes a number of preparation equipment protocols. For example, Against carboy The equipment preparation procedure Rinse at bench sink, Washing in the bench sink, Carb I washing, Carboy drying, Preparation equipment for sterilization in packaging and autoclave protocol May be included. Different types of dirty process parts This biopharmaceutical manufacturing process In preparation for reuse in Requires different combinations of preparation equipment protocols And Thereby, Different equipment preparation procedures are defined. Preparation protocol and Similarly, The device preparation procedure Experiment, With quality assurance and quality control, It is determined . Each type of equipment used in this biopharmaceutical manufacturing process Related equipment preparation hands Have order.   With the device preparation procedure table, List of preparation equipment protocols and related information And They are, For each of the dirty process part types, Defines equipment preparation procedure are doing. In a preferred embodiment, For each part of the dirty process parts, apparatus There is a preparation category. Equipment preparation tools associated with each type of dirty process component Instead of order, There is a device preparation procedure associated with each device preparation category. Strange The preparation equipment protocol associated with each of the equipment preparation categories Table format At Are placed together, Dirty processes assigned to the equipment preparation category For each part of the This procedure is provided.   Step 3306 is Create an equipment dimension table. Equipment dimensions Requires cleaning and sterilization Parts of the process equipment (e.g., beaker, flask, Carboy, stainless Length of steel fittings, etc.) Height and depth. This equipment dimension table is This biopharmaceutical All process equipment dimensions that potentially require cleaning after use in the manufacturing process Is specified. This equipment dimension table is Of the equipment used in this biopharmaceutical manufacturing process From the list, Determined directly. This equipment dimension table is This biopharmaceutical manufacturing process Providing a means for determining the volume of the device to be cleaned in Thereby, this The capacity of the preparation device can be calculated.   Step 3308 is Create a main list of equipment that may need to be prepared. This biological drug Each unit operation in the agent manufacturing process Associated with the preparation device. Step 3308 is this Create a major list of equipment related to biopharmaceutical manufacturing and solution preparation processes. To achieve. In a preferred embodiment, This biopharmaceutical manufacturing process and solution preparation The preparation equipment associated with each unit operation for both processes About these tasks When the unit operation of is specified, Stipulated. As described above, Biopharmaceutical manufacturing process Process equipment related to the unit operation of Incorporated into the manufacturing process timetable. Similarly, The tasks involved in each step of the solution preparation are: Confirmed in step 1302, And the solution Incorporated in total solution preparation time 1428 for preparation vessel.   Step 3310 is Create an equipment preparation loading table. This equipment preparation loading table This device dimensions Certain dirty process parts from the law table When, Describe what will be available for preparation Include the data you are doing. For example, Some information is This biopharmaceutical manufacturing process Dirty process parts from When, Professional to determine if it will be available for cleaning It is obtained from the work end time 906 in the access timetable. Step 3310 is This process By comparing the timetable schedule with the main equipment preparation list, This device style Create a loading table.   Step 3312 is Prepare the equipment preparation loading summary table. This equipment preparation loading summary table All of the biopharmaceutical manufacturing processes operating at this biopharmaceutical manufacturing facility This is the sum of the equipment preparation loading table. For example, Some facilities are In multiple processes, Multiple biopharmaceutical products can be manufactured. In such a case, This preparation device Multiple Deals with equipment preparation for the biopharmaceutical manufacturing process. Similarly, Some facilities are Duplicate It may have a number of solution preparation kits. In such a case, This preparation device Multiple melting Handles device preparation for a complete liquid preparation. Step 3312 is This biopharmaceutical manufacturing professional By combining the equipment preparation loading tables for all of the processes, All biological drugs Create a device preparation loading summary table for the total of the agent manufacturing process.   Step 3314 is Estimate the capacity of this preparation device. The capacity of this preparation device is This raw Product manufacturing facility, Enough capacity to handle loading of dirty process parts To provide It is determined. The preparation volume is Dirt compatible with this preparation device Flow rate of the process component. The prepared volume is Instrument flow from this preparation load summary table Based on speed Estimated. In this biopharmaceutical production facility, Dirty process department The speed at which goods are created This is a good estimate of the capacity of this preparation device.   Step 3316 is Determine the device preparation timetable. This device preparation timetable is This device style In each of the manufacturing procedures By each part of the preparation device, Schedule each dirty process part Including making joules. Usefulness of this preparation device and preparation device Functional specifications for sexual loading requirements are: It can be created from this device preparation timetable. Machine The functional specification is Identify and describe parts of the device. For example, Functional about pump The specifications are Pump type, Flow rate, Maximum and minimum input and output pressure, Input and output fitting size, Electrical requirements, Necessary security Includes temperature range and type and frequency of maintenance.   FIG. further, Step 3302 is shown, this is, This preparation equipment protocol table Create Step 3302 is Beginning at step 3404, this is, This preparation equipment protocol Create the identifier 3408. With the preparation device protocol identifier 3408, Prototyping equipment The key or code that identifies the col. By preparation device protocol identifier 3408 , Each preparation device protocol is: Confirmed in this device preparation module, And Allows it to be used to create this preparation equipment protocol table. Process 34 04 is Unique preparation equipment identifier 3408, Assigned to each of the preparation device protocols 3402 You. The preparation device protocol table 3402 also shows Tasks and tasks associated with each preparation device protocol And duration information. next, Step 3406 is Preparation device protocol Table 3410 Create Preparation device protocol table 3410 Preparation device protocol identifier 3408, By assigning to each preparation device protocol in preparation device protocol table 3402, Created.   Figures 36A-36H Representative Preparation Equipment Protocol Table 3410. 3408 in FIGS.36A-36H The column is A representative preparation device protocol identifier 3408 is shown. Preparation equipment protocol Table 3410 Contains information describing each preparation protocol. Preparation equipment proto The col identifiers BS-1 to BS-5 are Individual bench sink preparation protocol Confirm. For example, FIG. Protocol for this bench sink preparation device The work duration is shown. Protocol work duration is Preparation equipment protocol The amount of time associated with working with For example, The protocol BS-1 in FIG. 5 minutes With a loading duration of between. The bench sync protocol BS-1 Therefore, this Including the step of loading the bench sink, this is, It takes 5 minutes. Non-p otable) Pre-cleaning rinse using hot water (NPHW), Prewash using non-portable cold water (NPCW) Cleaning rinse, Detergent washing with reagents, Rinse after washing with NPHW and NPCW, Final Rinse and hold dry protocol work duration, Shown in Figure 36A I have. Columns 3602 and 3604 are It is an example of a protocol parameter. Protocol What is a parameter? A data element that describes a particular aspect of the preparation device protocol. In the example of FIG. 36A, To describe the detergent in this bench sink cleaning process , Protocol parameters for detergent cleaning reagents and reagents per cubic foot Ram numbers are used.   FIG. Shows a representative preparation equipment protocol table for the washing station . Column 3408 in FIG. Typical preparation equipment protocol identifier 3 for wash stations 408 is shown. FIG. Typical preparation equipment professional for glassware washer FIG. Column 3408 in FIG. Typical preparation for glassware washer The device protocol identifier 3408 is shown. FIG. About glassware dryer Shown is a representative preparative instrument protocol table 3410 of Column 3408 in FIG. Glass FIG. 35 illustrates an exemplary preparation device protocol identifier 3408 for an instrument dryer. FIG. , Typical duration of work for work related to this glassware dryer protocol Shows the interval. Some examples of work duration include: Shown in each of those columns Like Loading 3618, Heating 3620, Dried 3624, There is cooling 3626 and removal 3628 . Column 3622 is Figure 7 shows drying temperature protocol parameters. FIG. Carboy Shown is a representative preparation equipment protocol table 3410 for a washer. FIG. Shown is a representative preparation equipment protocol table 3410 for a carboy dryer.   FIG. Shows a representative preparation equipment protocol table for a steam sterilizer . Multiple protocol parameters related to the steam sterilizer preparation device protocol and For work duration, The preparation device protocol table of FIG. It is two-dimensional. 3608 The columns are Shown is a representative preparation equipment protocol identifier 3408 for this steam sterilizer. ing. This steam sterilizer preparation device protocol table 3410, As shown in column 3606 A number of protocol activities 1-33. Working with this steam sterilizer protocol Each of the 3608 column, 3610 column, 3612 column, Related as shown in columns 3614 and 3616 Was It has protocol parameters and protocol duration. In column 3606 of FIG. 32 columns Different steam sterilizer protocols (protocol identifier SS-1, SS-2 and S Representative values for the total time (minutes) required for each of S-3) are shown. FIG. Shown is a representative preparative instrument protocol table 3410 for a dry heat sterilizer.   FIG. The step 3304 of creating the apparatus preparation procedure table 3512 is shown. Equipment preparation procedure Table 3512 shows Including data related to each device preparation procedure, This includes Preparation equipment pro As well as the order of the tocols and their individual duration The entire procedure These cumulative durations are included. Step 3304 is Beginning at step 3506, this is, apparatus A preparation procedure identifier 3510 is created. The device preparation procedure identifier is Check equipment preparation procedure Tag or code. FIGS. 37A and 37B Representative instrument preparation procedures Table 3512 Is shown. Column 3702 is A representative device preparation procedure identifier 3510 is shown. EPC- 1, EPC-2, EPC-3, EPC-4, EPC-5, EPC-6 and EPC-7 are Check equipment preparation procedure Here is an example of the code.   Step 3508 is An apparatus preparation procedure table 3512 is created. Step 3508 is Equipment preparation protocol Table 3502, From the device preparation procedure 3504 and the device preparation procedure identifier 3510, Equipment preparation procedure Create Table 3512. The apparatus preparation procedure 3504 includes Specific equipment preparation procedures and equipment assignments Provide a list of preparation equipment protocols to confirm FIG. For example, apparatus Preparation procedure EPC-1 (As shown in the EPC-1 column), In FIG. 37B, Preparation equipment proto Col BS-1, BS-3, Shown to include GD-1 and SS-1. Equipment preparation procedure 3504 Was A device assignment for each of these device preparation procedures is included. Device allocation Guess is Dirty processes associated with or prepared by each equipment preparation procedure Specify the parts. For example, Specific equipment preparation procedures include: For cleaning carboy See Can be used. Step 3508 is Preparation equipment protocol and control in equipment preparation procedure 3504 It is compared with the manufacturing device protocol table 3502. The duration and program of these protocols The protocol parameters are The information in the device preparation procedure table 3512 is provided. Equipment tone The manufacturing procedure identifier 3510 is Instrument Preparation Procedure Assigned to each individual instrument preparation procedure in Table 3512 Can be   FIG.37A and FIG.37B A representative instrument preparation procedure table 3512 is shown. Column 3702 is Representative equipment preparation procedure identifier EPC-1, EPC-2, EPC-3, EPC-4, EPC-5, EPC-6 and EPC-7 is shown. The device preparation procedure identifier 3510 is About different classes of equipment Check the equipment preparation procedure. Typical, The device preparation procedure identifier EPC-5 is Cleaning stay (WS-1), Carboy cleaning machine (CW-1), Carboy dryer (CD-1) and steam sterilizer Includes autoclave 1 (SS-2) preparation equipment protocol. These preparation equipment professionals Each of the Tokor Work duration is relevant. Column 3704 is Equipment preparation procedure EPC- The work duration for 5 is shown. Each of these preparation equipment protocols The work duration for Totaled, Equipment preparation procedure duration for EPC-5 Is obtained. The cumulative total for this device preparation procedure duration is: Column 3706, 8 rows, 15 columns, 24 columns, 31 columns, 38 columns, 45 columns, 52 columns, 66 columns, Shown in columns 75 and 82. These cumulative durations are: All previous preparation equipment protocols in this equipment preparation procedure The total duration of the event.   FIG. further, Step 3306 is shown, this is, Create Equipment Dimension Table 3816 . Step 3306 is Beginning at step 3806, this is, Create Main Equipment Dimension List 3808 . Step 3806 includes: Using the required equipment list 3802 and equipment dimension list 3804 , Create the main device list 3806, this is, All equipment that can be cleaned by this equipment preparation procedure Specifies the dimensions of all process equipment. The list of required equipment 3802 is This creature It is a complete list of all devices used in the drug manufacturing process. Equipment required for preparation Listing 3802 of A process timetable 906 or a simple solution preparation schedule Can be created from position operations. Or, The list of required equipment 3802 is System Design By As a device used by design in this biopharmaceutical manufacturing process, Can be provided. Listing 3802 shows Prepared to complete this biopharmaceutical manufacturing process Identify the parts of the equipment that need to be Device Dimension List 3804 Made of this biopharmaceutical In the main list of equipment dimensions for all equipment available for use in the building process is there. often, The equipment size list 3804 is Seller or manufacture of this process equipment By the trader, Provided. The list of required equipment 3802 is The dimensions of these devices , To assign to the equipment used in this biopharmaceutical manufacturing process, Equipment dimensions Compared to strike 3804, The main device size list 3808 is obtained.   next, Step 3812 is Creates a device dimension table with the classified device preparation procedure identifiers I do. Step 3812 is This equipment list is This equipment preparation procedure and equipment allocation To the apparatus preparation procedure specified in Listing 3504. List of main equipment dimensions 3808 , According to the device preparation procedure identifier, In order to create the equipment dimension table 3816, Equipment preparation Based on the order identifier 3510, Are classified. The obtained device dimensions table 3816 is Specific professional A list of access devices and their associated device preparation procedure identifiers. Each feature Certain equipment preparation procedures (e.g., EPC-1, EPC-2, EPC-3) Assign to a specific device type Hit. Equipment dimension table 3816 also Includes the dimensions of the equipment to be prepared.   FIG. A representative device dimension table 3816 is shown. Column 3902 is Typical equipment preparation A procedure identifier 3510 is shown. The 3904 column is Involved in this equipment preparation process Check the dimensions of each specific type of device. The 3904 column is Should be cleaned in this equipment preparation procedure Representative values for the dimensions of the soiled process parts are shown. One of the 3904 rows is , Representative values (inches) for left and right dimensions (R / L) are shown. 2 rows of 3904 rows , A typical value (inch) for the front-rear dimension (F / B) is shown. The three rows of 3904 , Representative values (inch) for the top and bottom dimensions (T / B) are shown. 5 rows of 3904 rows , Representative values (cubic inches (CI)) for capacity are shown. 6 rows of 3904 Typical values for capacity (cubic feet (CF)) are shown. CI and CF are 39 From the linear dimension values in rows 1 to 3 of row 04, Directly, Calculated by computer.   Column 3906 is Typical dimension values for siphon tube equipment in equipment preparation procedure EPC-1 Is shown. Column 3908 is Pressure indicator (PI), Optical density probe and pH probe 2 shows representative dimensional values for instruments including. Column 3910 is T-shaped tube, elbow tube, Cross tube, Reducing joint, Fittings including hose barbs and clamps The table shows typical dimensional values for the brushes. Column 3912 is Small and medium plastic Typical dimensional values for hardware are shown. The 3914 column is Silicone and And representative dimensional values for butyl rubber stoppers. Column 3916 is small Representative dimensional values for molds and large flexible tubes are shown. Column 3918 is Small And typical dimensional values for medium glassware. The 3920 column is 1 li Torr, Typical about 20 liter and 45 liter polypropylene carboy The dimension values are shown. Column 3922 is 10 liters, 20 liter and 45 liter hoes Representative dimensions for a silicate glass carboy are shown.   FIG. further, Step 3308 is shown, this is, Equipment preparation main list 4004 create. The main equipment preparation list 4004 is Unit operation in this biopharmaceutical manufacturing process Includes process equipment that can be soiled by operations and solution preparation procedures. the above like, Each operation in the unit operation main list 508 is Has associated process equipment You. The process equipment associated with each unit operation is In step 4002, Main equipment preparation Added to strike 4004. Step 4002 is Using unit operation key list 508 this Create a major list of equipment that may require preparation after use in the biopharmaceutical manufacturing process. To achieve. Each part of the device It has the relevant dimensions specified in the equipment dimensions table 3816. Process 4002 is When the main equipment preparation list 4004 was created, Equipped with main unit operation list 508 Compared to the installation dimension table 3816, These device dimensions are used for the unit operation main list 508 device. assign. Step 4002 is When the main equipment preparation list 4004 was created, Solution preparation Industry list 4006 with the equipment dimensions table 3816, The dimensions of these devices are Assign to strike 4006. After step 4002, The main equipment preparation list 4004 is This biological drug Of the process equipment used in the agent manufacturing process Cleaning by this equipment preparation procedure Includes a list of potential dirty process parts that require   Figure 41 shows further, Step 3310 is shown, this is, Create equipment preparation loading table 4104 I do. The device preparation loading table 4104 is Dirty process section from equipment preparation main list 4004 Goods When, Includes data indicating whether it will be available from this biopharm Include. Step 4102 is Equipped with solution preparation schedule 3210 and process timetable 906 Combined with the main preparation list 4004, Create equipment preparation loading table 4104 You. The cumulative flow of equipment leaving this biopharmaceutical manufacturing process is: Solution preparation schedule 3210 and process timetable 906, Equipment Preparation Load Table 4104 To provide device dimensional information, This is compared with the main device preparation list 4004. Equipment tone Production loading table 4104 Dirty process parts, These dirty process parts When, apparatus Schedule of availability to preparation procedures, For each dirty process part Related dimensional information, And biopharmaceutical manufacturing or solution preparation processes Includes whether the operation resulted in dirty process parts. The device preparation loading table 4104 is this Equipment from the biopharmaceutical manufacturing process (this is Sustain continuous biopharmaceutical manufacturing In order to (Needs to be prepared for later use).   42A-42E A representative device preparation loading table 4104 is shown. Column 4202 is Typical Work titles. Work title 4202 Solution preparation procedure work or unit operation Work title. Column 4204 is It shows the end time of a typical operation. 42 The value in the 04 column is Various dirty process parts can be cleaned and prepared in equipment preparation procedures Represents the date and time of availability. Columns 4206-4216 of FIGS.42A and 42B , Representative of dirty process parts available for preparation in equipment preparation procedures Values are shown. In each of these fields, Each of these dirty process parts Is Includes figures and cubic feet associated with it. FIGS. 42C-43D are: this 3 illustrates additional work in the biopharmaceutical manufacturing process. As before, 42 in FIGS.42C-42D Columns 18 to 4228 are Identify dirty process parts that are available for preparation in the equipment preparation procedure. Are shown.   FIG. further, Step 3312 is shown. this is, Equipment Preparation Load Summary Table 4304 create. The device preparation loading table 4104 is Dirty processes from the equipment preparation main list 4004 Parts When, From all biopharmaceutical manufacturing processes operating on this biopharmaceutical facility Specifies whether it will be available. A single equipment preparation facility Multiple biopharmaceutical manufacturing professionals Because it can be shared across The device loading table 4104 is Equipment preparation loading required To create about Table 4304, Can be combined. According to the equipment preparation loading summary table 4304 , Schedule preparation and simulation of equipment preparation procedures for all biopharmaceutical manufacturing facilities Is possible.   FIG. further, Step 3314 is shown, this is, Determine capacity 4416 of preparation equipment I do. Step 3314 is Beginning with step 4404, this is, Initial equipment preparation schedule Create 4408. The initial equipment preparation schedule 4408 is Each equipment preparation procedure (EPC-1, EP C-2, EPC-3) Created. As mentioned above, Each equipment preparation procedure , Related to certain dirty process parts. Initial equipment preparation schedule 4408 , As obtained by the device preparation loading summary table 4304, Dirty process parts available Before the earliest day of noh, Begin.   The initial equipment preparation schedule 4408 is In each part of the preparation device, Dirty process This is the initial schedule for the arrival of parts. In each of these device preparation procedures Since the duration of each task in is known, Dirty process parts in various preparation equipment The time to reach is The duration of each operation from the Preparation Device Protocol Table 3410 is Equipment tone By adding to the loading summary table 4304, Calculated directly. Each dirty process section The time it takes for a product to reach a particular step in the Shown in Equipment Preparation Load Summary Table 4304 As has been Previous equipment preparation procedures and dirty process parts available Is the total time. Dirty process parts reaching each part of the preparation equipment By creating a schedule, Determining the peak loading on this preparation device It becomes possible. The peak loading of this preparation device is Then The size and size of this preparation device And can be used to determine capacity.   Step 4412, The peak cubic foot loading determined in step 4410 is Equipment dimensions table 3816 Compared to cubic feet of dirty process parts from Max. Step 4412, This equipment From the dimensions table, Cubic feet for this peak cubic foot load and maximum equipment item Choose the larger of the two.   Step 4414 is Using the larger peak CF value determined in step 4412, Preparation equipment Create capacity for 4416. The volume for the preparation device 4416 is This device preparation Handle peak cubic feet of dirty process parts that need to be prepared in steps Need to be high enough. The capacity determined in step 4414 and written in Table 4416 is Follow hand, Maximum capacity for this preparation device. Once The essentials for this preparation device Once the required capacity is determined, Device preparation timetable can be created.   FIG. further, Step 3316 is shown, this is, Device preparation timetable 4610 created I do. The device preparation timetable 4610, By each part of the preparation device in the device preparation procedure, each Includes schedule creation information for dirty process parts. Equipment preparation time Table 4610 shows A schedule of operations for each part of the preparation device is included. Equipment tone The timetable 4610 also Preparation device operation (labor, Usefulness, Disposable supplies, Reusable Supplies, Maintenance management, Specific aspects (including material loading for calibration, etc.) All schedule creation information. Along with the capacity data determined in step 4414, According to the device preparation timetable 4610, Functional specifications for the preparation device (including Cost And other data can be matched).   Step 3316 is Beginning with step 4606, this is, For each part of the preparation equipment Create a final equipment preparation shift schedule. As mentioned above, In step 3314, After determining the capacity of this preparation device, The maximum loading capacity of the preparation device 4602 is known. The volume for the preparation device 4416 is Specifies the maximum loading capacity for preparation equipment 4602 You. The minimum loading capacity for the preparation device 4604 is To maximize efficiency, Or As a confirmation of the device preparation procedure, Values set by the biopharmaceutical manufacturing process designer It is. For example, Designers of biopharmaceutical manufacturing processes The sterilizer is Its loading capacity If it is less than 50%, it can be determined that the operation should not be performed. This sterilizer, Therefore, sufficient Only when a large volume of dirty process parts accumulates Operated. Step 4606 is , Maximum loading capacity for preparation device 4602, Minimum loading capacity for preparation equipment 4604 , And based on the device preparation procedure table 3512, Final equipment preparation for each part of the equipment Create a shift schedule. This final equipment preparation shift schedule is: minimum Loading cycling by the preparation equipment governed by loading capacity 4604 and maximum loading capacity 4602 Including exercise. The maximum loading capacity 4602 and the minimum loading capacity 4604 are Equipment preparation procedure table Each specific protocol in 3512, Specify when to run. This final device The shift schedule made by Includes accurate scheduling of each operation.   Step 4608 is An apparatus preparation timetable 4610 is created. The device preparation timetable 4608 is Step 46 As determined in 06, Equipment Preparation Procedure Table 3512 related to the preparation equipment protocol. By providing detailed schedules for your business, Shift schedule for final equipment preparation Different from The device preparation timetable 4610, Device preparation procedure table 3512, Parts of the preparation device By comparing with the final equipment preparation shift schedule for minutes, Created You. The device preparation timetable 4610, Time data for specific operations and operations of instrument preparation Data.   FIG. Fig. 19 illustrates a process for creating a device preparation functional specification 4706. Equipment preparation Functional specification list 4706 is For each part of the preparation equipment used in this equipment preparation procedure Includes linked functional specifications and costs. The maximum loading capacity 4602 for the preparation device is , Used with the device preparation timetable 4610, Required for equipment preparation in this equipment preparation procedure Provide specifications. Step 4704 is Maximum loading capacity 4602 and equipment preparation timetable 4610 Compare the specifications, Which preparation unit of the main unit and cost list 4702 , Determine what is needed for these equipment preparation procedures. Main equipment and cost squirrel To 4702, Functional preparation of all available preparation equipment and their associated costs Including The preparation device is Equipment preparation timetable 4610 and maximum loading capacity 46 for the preparation equipment 02 Based on the functional specifications that match Selected from main equipment and cost list 4702 . The result of step 4704 is Preparation equipment list 4706 with functional specifications and cost And this is, It is a subset of the main device and cost list 4702. Functional specifications Preparation equipment list 4706 with cost and The necessary preparation equipment, Detailed cost And other data (for example, Usefulness, Maintenance management, calibration, Quality assurance and quality control trials To provide a more accurate match to the load for testing.   FIG. Figure 39 illustrates a process for creating a preparation device availability timetable 4810. Preparation equipment The installation availability timetable 4810 It provides usability requirements for this device preparation process. Preparation device availability timetable 4810, Availability requirements for each part of the preparation equipment and this Includes relevant dates and times for requirements. Preparation equipment availability timetable 4810 Than, Calculation of the utility cost associated with each part of the preparation device, And raw The designer of the product manufacturing facility Determining the required availability supply for this preparation device Becomes possible. The process of creating the preparation device availability timetable 4810 includes: Beginning at step 4804 ball, This preparation equipment utility table is created. This preparation equipment utility table is: Preparation equipment A list 4706 of preparation equipment functional specifications from the strike, Preparation equipment usefulness data 48 Packages that match the availability data for each part of the preparation device as indicated by 02 Include. The preparation device usefulness data 4802 is During each operation of the preparation equipment protocol Requirements for each part of the preparation device. Examples of usefulness data include: Power requirements , Portable and non-portable hot and cold water requirements, Wastewater requirements, There are steam requirements, etc. Engineering About 4804 is The data from the device preparation device list 4706 is Preparation equipment based on preparation equipment On the table, By matching the preparation device availability data 4802, Preparation equipment usefulness table Create 4806.   Step 4808 is Prepare the preparation device availability timetable 4810. Step 4808 is Preparation equipment available By matching the data in the utility table 4806 with the device preparation time table 4610, Preparation equipment availability time Create Table 4810. Preparation device availability timetable 4810, In this preparation device protocol For each task, Schedule availability requirements for each part of the preparation equipment . Each of the operations in the device preparation timetable 4610, Preparation equipment availability Table 4806 and data Be matched. Equipment preparation timetable 4610, And preparation equipment usefulness as described in Table 4806 Based on the availability requirements for each part of the preparation device, Useful for each of the preparation equipment sex Requirements, In the preparation device availability timetable 4810, A schedule is created. Availability time Table 4810 shows that Other manufacturing operations (e.g., Biopharmaceutical manufacturing, (From solution preparation) Combined with the engraving, Provides peak loading data for the exact size of the utility You. According to the detailed data of this device timetable, Well recorded operation schedule By the analysis of Confirmation and optimization of utility peak loading and costs You. Four. 0 Device maintenance management schedule creation module   Equipment maintenance at the biopharmaceutical manufacturing facility can sustain this biopharmaceutical manufacturing process. It is necessary to make The type and frequency of maintenance required are used by this facility. It is a function of the frequency and nature of use as well as the particular device. This manufacturing process, The equipment involved in the solution preparation process and equipment preparation are all , Periodic maintenance is required. Often, the frequency and cost of maintenance It is not considered in the design of biopharmaceutical manufacturing facilities. However, maintenance management The strike is a key factor in the cost of operating this biopharmaceutical production facility to produce biopharmaceutical products. Part. Maintenance is a significant cost of operating biopharmaceutical manufacturing facilities. Create schedule for maintenance management of process equipment, solution preparation equipment and preparation equipment The modeling and modeling system and method allow the designer of this biopharmaceutical manufacturing facility to: It is possible to predict maintenance management costs and minimize them. In addition, biological drugs By scheduling and modeling the maintenance of the More complete modeling of drug manufacturing facilities is possible.   Modeling and scheduling the maintenance of biopharmaceutical manufacturing facilities Based on the functional specifications and applications of the biopharmaceutical manufacturing process equipment. Parts of the device The minutes have associated maintenance parameters. For example, certain pumps may have a certain number After operating hours, new drive belts, seals and lubrication may be required. fill The filtration media in the filter must change after a certain number of hours of use. Predetermined Equipment functional specifications, equipment maintenance and management requirements, and biopharmaceutical manufacturing process equipment Equipment maintenance management by scheduling Rules can be created.   FIG. 49 shows a method of creating the process device maintenance management table 4906. Process Table 4906 shows the maintenance procedure, maintenance duration (that is, The amount of time required to perform maintenance), reusable supplies (i.e., Maintenance items that must be replaced), disposable items (i.e., Maintenance items that must be replaced), maintenance periods (that is, Used before it must be managed), and complete maintenance work on this equipment. Includes the number of hours required to tie.   Step 4904 lists the process equipment list and functional specifications 4908 and process equipment A process device maintenance management table 4906 is created from the maintenance management data 4902. Process equipment The list 4908 is created from the unit operation list 508. The unit operation list 508 is a unit Includes process equipment associated with each operation in the operation. Process equipment list 4908 Therefore, the unit operation list 508 includes a list of (form) process devices. The process device list 4908 also lists each of the process devices in the process device list 4908. Includes functional specifications related to the part. Functional specifications identify and identify equipment parts. Has been described. For example, functional specifications for a pump include pump type, flow rate, maximum And minimum input and output pressure, input and output fitting size, electrical requirements Includes conditions, temperature range and type and frequency of maintenance required.   The functional specifications associated with each part of the process equipment can be found in Block Diagram 704, Process Determined from the time table 906 and the device data sheet. The equipment data sheet is Usually supplied by the seller or the manufacturer, but not specified in this biopharmaceutical manufacturing process. A device specification that provides capacity and functional specifications for a device that can be used . Each unit operation has an associated process device. The functional specifications of this device are However, it depends on speed and time. The block flow chart 704 shows each unit operation. Defines the volume of solution and biopharmaceutical products handled by the crop. Process time Table 906 shows the rates at which solutions and biopharmaceutical products are handled in each unit operation. Stipulate. Capacity and speed information from this block flow diagram and process timetable The information thus defines the operational parameters of this process device. This process The functional specifications of the storage device specify the capacity and speed parameters for this device in the device data. Determined directly by matching the capacity and speed parameters in the You. The functional specifications of the equipment from this equipment data sheet are then In addition to the list, a process equipment list 4908 having functional specifications is formed.   Step 4904 includes a process device list 4908 having functional specifications and a process device list. A process device maintenance management table 4906 is created from the maintenance management data 4902. Process equipment Maintenance data 4902 contains functional specifications for each part of the process equipment and Includes maintenance management information related to them. Process equipment maintenance management data 4902 Replaceable items, resale items, labor, cycle life and cost Includes Some examples of replaceable and reusable items include: : Filters, gaskets, bearings, seals, belts, crankshafts, Lubricant and heat carrier. Each maintenance item is the number and identifier of this item, quality, Cycle life (ie, amount of time or usage before replacement), and Costs are relevant. In addition, process equipment maintenance management data 4902 contains Amount of effort associated with the control item and the dollar per cycle for this effort Numbers are included.   Step 4904 stores the process equipment list 4908 having the functional specifications in the process equipment maintenance. A process device maintenance management table 4906 is created in accordance with the management data 4902. functional The process device list 4908 having specifications is the process device list 4908 and the process Process equipment based on a comparison of functional specifications in This is matched with the maintenance management data 4902. Step 4904 is the process in process equipment list 4908. The process equipment maintenance management data 4902 for each part of the process equipment is copied and As a result, a process device maintenance management table 4906 is created.   64A-64AB illustrate a representative process equipment maintenance management table 4906. 6402 column The typical unit operations and their operations as determined from the process equipment list 4908 The process equipment associated with them is shown. FIGS.64A-64E are as shown in the column 6402. 2 shows process device maintenance management data for the unit operations 1 to 6.   The column 6404 in FIG. 64A is representative maintenance data for this filter maintenance item. Data values. Column 6404 contains the number of items, quantity, and cycle of this filter material. Life, unit cost of this filter material, one cycle of this filter material Dollars, the amount of time required to repair this filter media, and Effort includes dollars per cycle. The number of items is Check the stock number or part number of the item used in the management procedure. The size of this material The life of the vehicle confirms the effective life of the maintenance item. The amount of this maintenance procedure Check the quantity of maintenance management items used in. The unit cost is the maintenance management item Is the cost per unit. The number of dollars per cycle means these maintenance It is an index of the cost of the managed item and the cycle life of the maintenance item.   Column 6406 shows typical maintenance data for gasket maintenance items. I have. Columns 6408 in FIGS. 64A and 64B are representative maintenance management items for bearing maintenance items. Shows the data. Column 6410 in FIG. 64B is a representative maintenance pipe for seal maintenance items. It shows the physical data. Columns 6412 in FIGS. 64B and 64D are representative of belt maintenance items. It shows typical maintenance management data. Column 6416 in FIG. 64C shows the crankshaft maintenance pipe. It shows representative maintenance management data of physical items. Columns 6418 in FIGS. 64C and 64D 9 shows typical maintenance data of lubricant maintenance items. Column 6420 in FIG. 9 shows typical maintenance management data of a heat medium maintenance management item. Figures 64E and 64AB Indicates the same maintenance / management item described in columns 6404 to 6420 in relation to unit operations 7 to 22. are doing.   FIG. 50 shows a process for creating the process device maintenance management timetable 5004. The process equipment maintenance management timetable 5004 shows the process equipment in this biopharmaceutical manufacturing process. This is a schedule maintenance management item or procedure for the device. Step 5002 is a process Device schedule creation data from the device timetable 906 data is transferred to the process device maintenance A process device maintenance management timetable 5004 is created by applying the process table 4906 to the process table 4906. Step 5002 calculates the cumulative use time for each piece of equipment and At the time specified in the maintenance management table 4906, maintenance management for this device is scheduled. Create a rule. Process device maintenance management timetable 5004 contains process maintenance management data Process equipment maintenance data from 4906 and repair parts of process equipment The specific time and date to be included. Step 5002 is, therefore, a maintenance management Cycle life being evaluated for this maintenance item to induce Determine the number of unit operations or process cycles required to achieve.   FIG. 51 shows a process of creating the solution preparation device maintenance management table 5106. solution The preparation equipment maintenance table 5106 contains the maintenance procedure, maintenance duration (that is, The amount of time required to perform maintenance), reusable supplies (i.e., Maintenance items that must be replaced), disposable items (i.e., Maintenance items that must be replaced), maintenance periods (that is, Used before it must be managed), and complete maintenance work on this equipment. Includes the number of hours required to tie.   Step 5104 is a list of solution preparation devices and functional specifications 5108 and solution preparation device storage. A solution management system maintenance management table 5106 is created from the security management data 5102. Solution preparation equipment The list 5108 is created from the preparation container identifier and the associated volume list 1402. The preparation container identifier and associated volume list 1402 contains the solution associated with each solution preparation container. A liquid preparation device is included. The solution preparation equipment list 5108 therefore contains the preparation vessel identifier and And a list of solution preparation devices from the associated volume list 1402. Solution preparation The equipment list 5108 also lists each part of the solution preparation equipment in the solution preparation equipment list 4809. Includes functional specifications associated with Each solution preparation container and its associated solution preparation The functional specification for the device, when specified, shall dictate the preparation vessel identifier and associated Included in the capacity list 1402.   Step 5104 includes a solution preparation device list 5108 having functional specifications and a solution preparation device A solution preparation device maintenance management table 5106 is created from the maintenance management data 5102. Solution preparation equipment The maintenance data 5102 contains the functional specifications for each part of the Includes maintenance management information related to them. Solution preparation equipment maintenance management data 5102 is Replaceable items, resale items, labor, cycle life and cost Includes Some examples of replaceable and reusable items include: : Filters, gaskets, bearings, seals, belts, crankshafts, Lubricant and heat carrier. Each maintenance item is the number and identifier of this item, quality, Cycle life (ie, amount of time or usage before replacement), and Costs are relevant. In addition, the solution management system maintenance management data 5102 contains Amount of effort associated with the control item and the dollar per cycle for this effort Numbers are included.   Step 5104 includes maintaining the solution preparation device list 5108 having functional specifications in the solution preparation device list. A solution preparation apparatus maintenance management table 5106 is created in accordance with the management data 5102. functional The solution preparation device list 5108 having the specifications is the solution preparation device list 5108 and the solution preparation device list. Based on a comparison of the functional specifications in the This is matched with the maintenance management data 5102. Step 5104 is a solution preparation device list 5108 The solution preparation device maintenance management data 5102 for each part of the solution preparation device is copied and Thereby, a solution preparation apparatus maintenance management table 5106 is created.   FIG. 52 shows a process of creating the solution preparation device maintenance management timetable 5204. The solution preparation equipment maintenance management timetable 5204 shows the solution preparation equipment for this biopharmaceutical manufacturing process. This is a schedule maintenance management item or procedure for the device. Step 5202 is a solution preparation step The device schedule creation data from the device timetable 3210 is transferred to the solution preparation device maintenance management table 51. By applying this to 06, a process device maintenance management timetable 5204 is created. Step 52 02 calculates the cumulative use time for each part of the device, and Schedule maintenance management for this device at the time specified in Table 5106. create. The solution preparation device maintenance management timetable 5204 is based on the process maintenance management data 5106. Solution management equipment maintenance data and the characteristics of each part of the solution preparation equipment to be repaired. Includes fixed times and dates. Step 5202 therefore defines this maintenance process. Achieve the cycle life being evaluated for this maintenance item to trigger Determine the number of unit operations or process cycles required to perform   FIG. 53 shows a process for creating the preparation apparatus maintenance management table 5306. Preparation equipment The maintenance table 5306 includes the maintenance procedure, the maintenance duration (that is, the maintenance The amount of time required to carry out reusable supplies (i.e., Maintenance items), disposable items (i.e. Maintenance items that must be maintained), maintenance periods (i.e. And the maintenance work on this equipment is completed. Includes the number of hours required for   Step 5304 includes a preparation apparatus list 4706 having functional specifications and preparation apparatus maintenance management. From the data 5302, a preparation apparatus maintenance management table 5306 is created. Preparation Equipment List 4706 Also, include the functional specifications associated with each part of the preparation device as determined in step 3314. You. The preparation equipment maintenance management data 5302 contains functional specifications and information for each part of the preparation equipment. And maintenance information related to them. Preparation device maintenance management data 5302 is Replacement items, resale items, labor, cycle life and cost of related maintenance items Include strikes.   Step 5304 is a step of storing a preparation apparatus list 4706 having functional specifications in the preparation apparatus maintenance management data. The preparation apparatus maintenance management table 5306 is created in accordance with the data 5302. Has functional specifications The preparation device list 4706 includes the preparation device list 4706 and the preparation device maintenance management data 5302. Based on the comparison of functional specifications in the preparation equipment maintenance management data 5302 You. Step 5304 is a step of storing the preparation apparatus for each part of the preparation apparatus in the preparation apparatus list 4706. Copy the maintenance management data 5302, thereby creating the preparation apparatus maintenance management table 5306. You.   FIG. 54 shows a process for creating the preparation apparatus maintenance management timetable 5404. Preparation The device maintenance management timetable 5404 shows the schedule for the preparation device in this biopharmaceutical manufacturing process. Scheduled maintenance items or procedures. Step 5402 is a preparation apparatus timetable 4610 data. Apply the equipment schedule creation data from the data to the preparation equipment maintenance management table 5306. Thus, a process device maintenance management timetable 5404 is created. Step 5402 is performed for each of the devices. Calculate the cumulative usage time for the portion and identify the preparation equipment maintenance table 5306 At this point, a maintenance schedule for this device is created. Preparation equipment The maintenance management timetable 5404 contains the preparation equipment maintenance management data from the process maintenance management data 5306. Data and specific times and dates at which parts of the preparation equipment are to be repaired. Step 5402 is, therefore, performed in order to trigger this maintenance process. Unit operations or processes necessary to achieve the cycle life being evaluated for the eye Determine the number of access cycles. Five. 0 Instrument calibration module   Equipment calibration at a biopharmaceutical manufacturing facility can sustain this biopharmaceutical manufacturing process. Is necessary for Instrument calibration is necessary for accurate measurement and control of all critical manufacturing operations. Su. Instruments such as pressure indicators, temperature indicators, flow meters, loading cells, etc. At the heart of most manufacturing systems. These instruments and the professionals they can help The reliability of the process relies on a punctual and consistent calibration program. Necessary comparison Positive types and frequencies are based on the frequency of use as well as the specific equipment used in this facility. And a function of nature. This manufacturing process, solution preparation process and equipment preparation All equipment involved requires periodic calibration during sustained operation. Shiba Frequently, the frequency and cost of calibration are considered in the design of biopharmaceutical manufacturing facilities. Absent. However, the cost and schedule of calibration is It is an important part of the cost of operating a manufacturing facility to produce biopharmaceutical products. Calibration is Process equipment, solution preparation, because of the significant cost of operating biopharmaceutical manufacturing facilities System and method for scheduling and modeling calibration of equipment and preparation equipment The method allows the designer of this biopharmaceutical facility to estimate the cost of calibrating the It is possible to make it smaller. In addition, schedule the calibration of the biopharmaceutical manufacturing process. A more reliable calibration program by creating and modeling Enables to ensure proper and consistent performance of all manufacturing systems.   Modeling and scheduling the calibration of biopharmaceutical manufacturing equipment is Based on the functional specification and application of the drug manufacturing process equipment. Each part of the device , With associated calibration points. These calibration points are typically a pressure indicator and Includes transmission devices, temperature indicators and transmission devices, level sensors, flow meters, and the like. All of these calibration points require reliable operation of these process systems. is there. Equipment functional specifications, equipment calibration requirements, and biopharmaceutical manufacturing process equipment Modeling and calibrating equipment calibration by giving Files can be created.   FIG. 55 illustrates a process for creating a process equipment calibration table 5506. Process Calibration table 5506 for the calibration procedure, calibration duration (i.e., performing this calibration). Amount of time required to perform the calibration), the calibration period (i.e. Before use), and when necessary to complete calibration work for this instrument Inclusive.   Step 5504 includes the process device list 4908 having the functional specification and the process device list. From the calibration data 5502, a process equipment calibration table 5506 is created. Process equipment calibration data Data 5502 provides functional specifications for each part of the process equipment and their associated Contains calibration information. Process equipment calibration data 5502 is used to replace related calibration items Includes possible supplies, resale, labor, cycle life and cost. Said above As such, some examples of replaceable and reusable supplies include: Luters, gaskets, bearings, seals, belts, crankshafts, lubricants And heat medium. Each calibration item is the number and identifier of this item, quality and cycle life. Life (ie amount of time or usage before replacement), and cost per cycle Is relevant. In addition, process equipment calibration data 5502 includes information related to each calibration item. It also includes the amount of work done and the number of dollars per cycle for this work.   Step 5504 stores the process equipment list 4908 having the functional specifications in the process equipment calibration. A process equipment calibration table 5506 is created to match the data 5502. Has functional specifications Process device list 4908 is a list of process device list 4908 and process device comparison. Based on the comparison of the functional specifications in the positive data 5502, the process equipment calibration data 55 Matches 02. Step 5504 corresponds to each part of the process equipment in the process equipment list 4908. Copy the process equipment calibration data 5502 for the Create a calibration table 5506.   FIG. 56 illustrates a process for creating a process device calibration timetable 5604. Professional The Process Equipment Calibration Timetable 5604 describes the process equipment for this biopharmaceutical manufacturing process. Schedule calibration item or procedure. Step 5602 is a process device timetable 90. 6 Apply the equipment schedule creation data from the data to the process equipment calibration table 5566. Thus, a process device calibration timetable 5604 is created. Step 5602 is performed for each of the devices. Calculate the cumulative usage time for the part and identify it in the process equipment calibration table 5566. At this point, a calibration is scheduled for this device. Process equipment Calibration timetable 5604 contains process equipment calibration data from process calibration data 5566, And specific times and dates at which parts of the process equipment should be repaired. Process 5602 will therefore review this calibration item to trigger this calibration process. Unit operations or process cycles required to achieve the expected cycle life Determine the number of   FIG. 57 shows a process for creating the solution preparation device calibration table 5706. Solution preparation The device calibration table 5706 contains the calibration procedure, calibration duration (i.e., Reusable supplies (i.e., have to be replaced regularly). Items that need to be replaced after each use. Genuine item), calibration period (i.e. use before this device must be repaired) Volume), and the number of hours required to complete the calibration work for this instrument. You.   Step 5704 includes the solution preparation device list and functional specifications 5108 and the solution preparation device comparison. From the positive data 5702, a solution preparation device calibration table 5706 is created. Solution Preparation Equipment List 51 08 is created from the preparation vessel identifier and the associated volume list 1402. Preparation container The identifier and associated volume list 1402 contains the solution preparation equipment associated with each solution preparation container. Position. The solution preparation equipment list 5108 will therefore include the preparation vessel identifier and associated A list of solution preparation devices from the list of volumes 1402 included. Solution preparation equipment squirrel 5108 also associates each part of the solution preparation device in the solution preparation device list 4809. Functional specifications. For each solution preparation container and its associated solution preparation equipment The functional specification that specifies, when specified, the preparation vessel identifier and the associated volume Included in strike 1402.   Step 5704 includes selecting a solution preparation device list 5108 having functional specifications and a solution preparation device From the calibration data 5702, a solution preparation device calibration table 5706 is created. Solution preparation equipment calibration data Data 5702 provides functional specifications for each part of the solution preparation device and their associated specifications. Includes calibration data.   Step 5704 stores the solution preparation device list and functional specifications 5108 in the solution preparation device calibration data. A solution preparation apparatus calibration table 5706 is created in accordance with the data 5702. Has functional specifications The solution preparation device list 5108 contains the solution preparation device list 5108 and the solution preparation device calibration. Based on the comparison of functional specifications in data 5702, solution preparation device calibration data 5702 Is matched with Step 5704 is for each part of the solution preparation device in the solution preparation device list 5108. Copy the solution preparation device calibration data 5702 for the Create the calibration table 5706.   FIG. 58 shows a method of creating the solution preparation device calibration timetable 5804. Solution preparation The device calibration timetable 5804 compares the solution preparation devices for this biopharmaceutical manufacturing process. It is a schedule of regular items and procedures. Step 5802 is a solution preparation device timetable 3210 To apply the equipment schedule creation data from the to the solution preparation equipment calibration table 5706 Then, a process device calibration timetable 5804 is created. Step 5802 covers each part of the device. Calculate the cumulative use time to perform, and at the time specified in Solution Preparation Equipment Calibration Table 5706 A recalibration schedule is created for this device. During calibration of solution preparation equipment Envelope 5804 contains solution preparation equipment calibration data from process calibration data 5706, and Includes the specific time and date when each part of the liquid preparation device should be calibrated. Step 5802 is Therefore, an evaluation is made on the calibration of the device in order to trigger a re-calibration of this device. Determine the number of unit operations or process cycles required to achieve Set.   FIG. 59 illustrates a method for creating the preparation device calibration table 5906. Preparation equipment calibration table 59 06 is the calibration procedure, the calibration duration (i.e., the time required to perform this calibration) Volume), calibration period (i.e. usage before this device has to be repaired) , And the number of hours required to complete the calibration operation for this device.   Step 5904 includes the preparation equipment list 4706 with functional specifications and the preparation equipment calibration data. The preparation apparatus calibration table 5906 is created from the data 5902. Preparation equipment list 4706 also includes Includes functional specifications associated with each part of the preparation device as determined in 3314. Preparation Equipment calibration data 5902 provides functional specifications for each part of the preparation equipment and their related Includes a series of calibration data. Preparation equipment calibration data 5902 Includes associated cycle life.   Step 5904 converts the preparation equipment list and functional specification 4706 to the preparation equipment calibration data 5902. And prepare a preparation device calibration table 5906. Preparation equipment with functional specifications The strike 4706 is the functional list in the preparation equipment list 4706 and the preparation equipment calibration data 5902. Based on the specification comparison, it is matched with the preparation equipment calibration data 5902. Step 5904 is Copy the preparation equipment calibration data 5902 for each part of the preparation equipment in the production equipment list 4706. Thus, a preparation apparatus calibration table 5906 is created.   FIG. 60 shows a method of creating the preparation device calibration timetable 6004. Preparation equipment calibration Timetable 6004 shows the calibration schedule for the preparation equipment in this biopharmaceutical manufacturing process. Calibration. Step 6002 is an apparatus schedule from the preparation apparatus timetable 4610 data. By applying the created data to the preparation equipment calibration table 5906, the process equipment calibration time Create Table 6004. Step 6002 calculates the cumulative use time for each part of the device, At the time specified in the Preparation Equipment Calibration Table 5906, calibration for this equipment was performed. Create a schedule. The preparation equipment calibration timetable 6004 shows the process calibration data 5906 Preparation equipment calibration data, and the specific time and And date. Step 6002 is, therefore, to trigger this calibration process Unit operations required to achieve the cycle life being evaluated for this calibration item Or determine the number of process cycles. 6. 0 Quality control module   Quality control of biopharmaceutical manufacturing facilities ensures the safety and quality of this biopharmaceutical product It is necessary to do. Quality control sun at various points in the biopharmaceutical manufacturing process During the process, solution preparation and equipment preparation, coupling and testing Guarantee a product free of stains. Quality Control Sampling Required for Biopharmaceutical Manufacturing Process The type and frequency of testing and testing depend on the particular equipment used in this process, The frequency and nature of the installation and the specific process or operation Function. Often, quality control testing, frequency and cost Before the design was not planned. However, quality control, sampling and And testing play an important role in scheduling the operation of biopharmaceutical manufacturing facilities. Fulfill. Model quality control sampling and testing at biopharmaceutical manufacturing facilities Creating a schedule defines the basic steps in this biopharmaceutical manufacturing process. It is based on righteousness. The quality control testing and sampling process depends on the manufacturing process. , Solution preparation processes and equipment preparation protocols.   FIG. 61 shows a method of creating the main quality management protocol table 6110. Quality tube Management protocols include assays and assays related to quality control sampling and testing. And test procedures. Quality control protocol 6102 is designed by the designer of this biopharmaceutical manufacturing facility. As defined by, determined by tests and experiments, or Specified by the vendor of the equipment in the agent manufacturing facility. Quality control protocol 6102 Contains management protocol parameters. Quality control parameters are quality control updates. It is the value that defines the sie. Examples of quality control parameters include the category of this assay. And title, set time for this assay, time required to withdraw each sample, The time required to clean these specimens after removal and waste samples after testing There is waste material needed to discard.   Step 6104 is for each of the quality control protocols 6102, Create Besshi 6108. The quality management protocol identifier 6108 is an individual quality management protocol. A tag or code that identifies Col 6102. Step 6106 is a quality control protocol. Identifier 6108 is assigned to quality management protocol 6102, and the main quality management protocol Table 6110 is obtained. The main quality control protocols Table 6110 shows the quality control protocols 6102 and Unique quality control protocol identifier associated with each of the quality control protocols 6102 6108.   FIG. 21 shows a representative key quality control protocol table 6110. Column 2102 is 3 Representative categories of quality control protocols, including environmental, analytical and (Including biological quality control protocols). Column 2104 is a representative The quality management protocol identifier 6108 is shown. Column 2106 is the quality control protocol Representative values for the parameters are shown. More specifically, column 2106 contains the setting Sample, withdraw each sample, and perform sampling operations associated with each quality control protocol. Indicates the quality control protocol parameters for the number of steps required to clean the crop. ing. Setup and cleaning parameters are set before sampling the quality control protocol. It specifies the amount of time required to perform the subsequent cleaning. Quality per sample Control protocol parameters specify the amount of time required to withdraw each sample. You. For example, 10 samples of temperature (quality control protocol identifier E-1) have a setting of 0. 5 man-hours To sample, 1. 0 man-hours (0. 1 hour / sample x 10 samples) and 0 for washing. 5 workers Need a number.   FIG. 62 illustrates a method for creating the Main Quality Control Protocol Sample Table 6208. main Quality Control Samples Table 6208 shows the work and quality control services associated with the production of biopharmaceutical products. Includes all of the sampling protocols. Each operation in this process timetable or Process, solution preparation schedule or preparation equipment timetable (this is (With protocol 6102) is included in the Primary Operations List 6206. Main unit Each operation or step in the order operation list 6206 also includes a quality control protocol. . Key quality control protocol The quality control protocol parameters in Table 6110 are To Used to create a key quality control sample list. Main quality control sample squirrels 6202 has all the codes of the quality control protocol from the main QC protocol table 6110. They are listed. Step 6204 uses this key quality control sample list to sample Assigning a running assay to each step in the main unit operation list 6206, and A quality control protocol is assigned to each step in the main unit operation list 6206. The result of step 6204 is Primary QC Sample Table 6208, which is the biopharmaceutical manufacturing process. Quality as well as all processes in solution, solution and equipment preparation, as well as Includes management protocol and sample list.   FIG. 63 shows a method of creating the process device quality control timetable 6304. quality The management process device timetable 6304 includes all the units related to the process device timetable 906. Quality control assays and sample schedules associated with each, as well as position operations It is a table of. Step 6302 creates a process equipment quality control timetable 6304. Process 63 02 matches the process steps 906 of the process equipment with the main unit operation list 6206 Which assays need to be assigned to the activities in the process equipment timetable 906 To determine. Step 6302 includes each of the relevant operations from Key Quality Control Sample Table 6208. A quality control sample to be removed is assigned to each of the operations in the process equipment timetable 906. Then, a process equipment quality control timetable 6304 is obtained.   45A-45I show a representative process equipment quality control timetable 6304. FIG. Figure 45 A indicates unit operations 1A to 6A in column 4502. Each operation in unit operation 1A to 6A Each schedule is shown in column 4504. Columns 4506 in FIGS. Figure 9 shows the quality control assay from Quality Control Protocol Table 6110. Column 4506 is blank However, if the quality control sample is scheduled for unit operations 1A to 6A in column 4502, If created, column 4506 shall be as specified in Table 6208 for Primary Quality Control Samples. Contains the number of samples to be removed at the scheduled time. Figures 45C-45I Shows the balance of work and unit operations for the process equipment quality control timetable 6304. ing.   FIG. 22 shows a method of creating the solution preparation apparatus quality control timetable 2204. quality The management solution preparation device timetable 2204 includes all the solutions related to the solution preparation schedule 3210. Schedules for quality control assays and samples associated with each task as well as tasks It is a table of. Step 2202 creates a solution preparation device quality control timetable 2204. Process 22 02, the solution preparation operation 3210 of the solution preparation schedule is What assays need to be assigned to the tasks in solution preparation schedule 3210? Determine if it is necessary. Step 2202 is a related product from Key Quality Control Sample Table 6208. The quality control samples to be removed in each of the operations Each process is assigned to obtain a process equipment quality control timetable 2204.   FIG. 23 shows a method of creating the preparation apparatus quality control timetable 2304. quality management Preparation device timetable 2304 is not only all the work related to preparation device timetable 4610, but also The quality control assays and samples associated with each task in this prep protocol. It is a table of a schedule. Step 2302 creates a preparation device quality control timetable 2304 . In step 2302, the apparatus preparation operation of the preparation apparatus timetable 4610 is referred to as a main unit operation list 6206. Which assays need to be assigned to the tasks in the preparation machine timetable 4610 Determine if there is. Step 2302 is for related work from Key Quality Control Sample Table 6208. The quality control samples to be removed by each are assigned to each of the operations in the process equipment timetable 906. By allocating, the process equipment quality control timetable 2304 is obtained. 7. 0 Environment   The present invention uses hardware, software or a combination thereof Can run and can run on computer systems or other processing systems . In fact, in one embodiment, the present invention is capable of performing the functions described herein. It is aimed at computer systems that can be turned on. An example computer system 1901 is shown in FIG. Computer system 1901 may include one or more computers. A processor (eg, processor 1904). Processor 1904 is a communiqué Connected to the application bus 1902. About the computer system in this example Various software embodiments have been described. After reading this description, Those skilled in the art will recognize other computer systems and / or computer configurations. It will be clear how to implement the invention using the structure.   Computer system 1902 also includes a main memory 1906 (preferably a run And a secondary memory 1908. Secondary memory 1908 may include, for example, hard disk drive 1910 and / or Removable storage drive 1912 (typically floppy disk drives, magnetic Tape drive, optical disk drive, etc.). Removable Storage drive 1912 reads from removable storage unit 1914 in well-known fashion. And / or write to it. Representative of the removable storage unit 1914 Include floppy disks, magnetic tapes, optical disks, etc. Readable and writable by the removable storage drive 1912. As you can see, Bubble storage unit 1914 contains computer software and / or It includes a computer usable storage medium storing data.   In another embodiment, the secondary memory 1908 is a computer program or other Other similar to allow loading of instructions into computer system 1901 Means may be included. Such means include, for example, removable storage units. 1922 and interface 1920. Example of something like this Includes a program cartridge and a cartridge interface (e.g., Video game devices), removable memory chips (e.g. EPRO M or PROM) and associated sockets, and other removable storage units 19 22 and interface 1920 (this removes software and data, Moving from bubble storage unit 1922 to computer system 1901 Can).   The computer system 1901 also has a communication interface 19 24 can also be included. Communication interface 1924 Data and data between computer system 1901 and external devices To Examples of communication interface 1924 include modem, network Network interface (for example, Ethernet card), communication port, PCMCIA slots and cards can be mentioned. Communication Software and data moved through interface 1924 Is an electrical signal, electromagnetic signal, optical signal or communication interface 1924). These signals 1926 Provided to the communication interface, via channel 1928 . This channel 1928 carries the signal 1926 and can be wired or , Telephone lines, mobile phone links, RF links and other communication channels You can do this using a channel.   In this document, the terms "computer program media" and "computer use The term `` usable medium '' generally refers to a removable storage device 1912, Hard disk installed on the drive 1910 and media such as signal 1926 Used to mean body. These computer program products A means for supplying software to the computer system 1901.   Computer programs (this is also a computer control logic Is also stored in main memory and / or secondary memory 1908. You. The computer program also has a communication interface 19 Via 24 is acceptable. When such a computer program runs, Computer system 1901 implements the features of the present invention discussed herein. To be able to In particular, when running these computer programs Then, the processor 1904 can implement the features of the present invention. So this Such as computer program controller for computer system 1901 Equivalent to   In embodiments where the present invention is implemented using software, this software Stored in a computer program product, and Drive 1912, hard drive 1910 or communication interface 1924 Can be loaded into the computer system 1901. Control logic When the (software) is executed by the processor 1904, the The features of the invention described in the specification are implemented.   In other embodiments, the invention primarily relates to, for example, hardware components (e.g., For example, using application-specific integrated circuits (ASICs)) A. Hardware to perform the functions described herein. Implementation of a hardware state machine will be apparent to those skilled in the relevant arts. You.   In yet another embodiment, the invention relates to both hardware and software. Performed using a combination of 8. 0 Conclusion   The invention has been particularly shown and described in connection with their preferred embodiments. However, without departing from the spirit and scope of the present invention, It will be understood by those skilled in the art that various changes in form and detail may be made.

────────────────────────────────────────────────── ─── Continuation of front page    (31) Priority claim number 60 / 050,294 (32) Priority Date June 20, 1997 (June 20, 1997) (33) Priority country United States (US) (31) Priority claim number 60 / 050,299 (32) Priority Date June 20, 1997 (June 20, 1997) (33) Priority country United States (US) (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, I T, LU, MC, NL, PT, SE), OA (BF, BJ , CF, CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, L S, MW, SD, SZ, UG, ZW), EA (AM, AZ , BY, KG, KZ, MD, RU, TJ, TM), AL , AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, E E, ES, FI, GB, GE, GH, GM, GW, HU , ID, IL, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, M D, MG, MK, MN, MW, MX, NO, NZ, PL , PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, UZ, V N, YU, ZW [Continuation of summary] In addition, the Based on this, the duration of this solution preparation procedure is determined (1 12). The device preparation timetable also contains the preparation device and schedule. Created based on the size and capacity of the (112).

Claims (1)

[Claims]   1. A method of scheduling and simulating solution preparation, wherein the solution is , For use in a biopharmaceutical manufacturing process, the method comprising the steps of: RU:   (1) identifying at least one solution for preparation and its associated volume ;   (2) a predetermined start date for the preparation of said at least one solution and said at least Identifying at least one next start date for the preparation of one solution;   (3) assigning the at least one solution to a preparation vessel;   (4) based on the step of assigning the at least one solution to a preparation vessel, Determining the duration of the liquid preparation procedure.   2. The at least one solution required in step (1) in one process cycle; 2. The method of claim 1, comprising calculating the total capacity of the.   3. The step (2) is timed for use in the biopharmaceutical process. In the preparation of said at least one solution required for the preparation of said at least one solution to be The method of claim 1, comprising calculating a latest start date for the.   4. How to schedule and simulate equipment quality control sampling. Wherein the method comprises the following steps:   (1) checking quality control sampling data related to the equipment;   (2) preparing a table of the apparatus and the quality control sampling data; and And   (3) Compare the table with the procedure timetable to determine the quality of the device in the biopharmaceutical manufacturing process. Determining a schedule for administrative sampling.   5. A method for scheduling and simulating maintenance of an apparatus, the method comprising: The method includes the following steps:   (1) checking maintenance and calibration data related to the equipment;   (2) creating a table of the device and the maintenance and calibration data; and   (3) Compare the table with the procedure timetable to calibrate the device in the biopharmaceutical manufacturing process And the process of determining the maintenance schedule.   6. A method of scheduling and simulating device preparation, the method comprising: Comprising the following steps:   (1) determining an apparatus preparation procedure associated with the preparation apparatus;   (2) Make a major list of dirty process parts to be prepared by the equipment preparation procedure. Forming step;   (3) Create equipment preparation loading table based on work in biopharmaceutical manufacturing process Process; and   (4) In the device preparation procedure, when preparing the device preparation schedule The process of creating a timetable.