Pilot plant scale-up techniques are essential for transitioning experimental formulations from R&D to larger production volumes while maintaining product quality and efficacy. Key considerations include personnel qualifications, space requirements, equipment selection, and production rates. The process involves several steps, including pre-engineering, modeling, fabrication, testing, and training, with a focus on minimizing costs through approaches like miniplant technology.
Pilot plant scale-up techniques are essential for transitioning experimental formulations from R&D to larger production volumes while maintaining product quality and efficacy. Key considerations include personnel qualifications, space requirements, equipment selection, and production rates. The process involves several steps, including pre-engineering, modeling, fabrication, testing, and training, with a focus on minimizing costs through approaches like miniplant technology.
Pilot plant scale-up techniques are essential for transitioning experimental formulations from R&D to larger production volumes while maintaining product quality and efficacy. Key considerations include personnel qualifications, space requirements, equipment selection, and production rates. The process involves several steps, including pre-engineering, modeling, fabrication, testing, and training, with a focus on minimizing costs through approaches like miniplant technology.
Pilot plant scale-up techniques are essential for transitioning experimental formulations from R&D to larger production volumes while maintaining product quality and efficacy. Key considerations include personnel qualifications, space requirements, equipment selection, and production rates. The process involves several steps, including pre-engineering, modeling, fabrication, testing, and training, with a focus on minimizing costs through approaches like miniplant technology.
Pilot plant scale-up techniques involve reproducible manufacture of an experimental formulation
on high-speed production equipment, in a cost-effective manner. It is a part of the pharmaceutical industry where the same processes used during Research and Development (R&D) of dosage forms are applied to different output volumes; usually greater than that obtained during R&D.
This is achieved by determining the ability of formula to withstand batch-scale and process modification.
Understand what makes these processes similar, identify and eliminate many scale-up problems before investing large sum of money on a production unit Maintain the chemical attributes of the product, its quality and efficacy even though the production processes are modified as a result of sample size increase, and equipment changes.
Pilot plant scale-up must include:
A close examination of the formula to determine its ability to withstand large scale and process modification. A review of a range of relevant processing equipment to determine which would be most compatible with the formulation as well as the most economical, simple, and reliable in producing the product. General considerations during pilot plant scale up:
1. Reporting responsibilities: In order to facilitate smooth transfer of products from a laboratory scale to a commercial scale, there is need for be adequate records and reporting arrangement. How effective a pilot plant is may be determined by the ease with which new products or processes are brought into routine production.
2. Personnel Requirement: Those employed during the scale up process should be individuals with qualifications required for position in a pilot plant organization. It should be a blend of good theoretical
knowledge of pharmacy and some practical experience in the pharmaceutical industry.
Practical experience in pilot plant operations is also invaluable.
3. Space Requirements The space requirements of a pilot plant are of four types:
a. Administrative and information processing
There should be adequate office and desk space for both the scientists and technicians to facilitate proper documentation of their activities and observations. This should be adjacent to the work area but sufficiently isolated to permit people to work without undue distraction.
b. Physical Testing Area
There should be an adequate working area where the analysis and physical testing of samples can be performed (in-process quality control analysis) which helps in early identification of production error. This area should provide permanent bench top space for routinely used physical testing equipment like balances, pH meters, viscometers etc.
c. Standard pilot plant equipment floor space
This has to do with where all the relevant equipment used in the pilot plant scale up techniques is kept. The equipment should be available in a variety of sizes known to the representative of all production capability. This arrangement helps make sure of the quality of the scale up data collected, as well as being prudent with expensive materials.
4. Raw Materials One responsibility of pilot plant operation is to approve and validate the active and excipient raw materials used in the formulation of pharmaceutical products. This should not be taken for granted. This is because pilot scale up, in itself, does not guarantee a smooth transition. 5. Relevant Processing Equipment During scale-up, alternative manufacturing equipment should be considered since most development work has been performed on small and simple laboratory equipment. The equipment that promises to be the most economical, the simplest, the most efficient and the most capable of consistently producing products within the proposed specifications should be evaluated based on the known processing characteristics of the product.
6. Production Rates The immediate and future market demands of a product should be considered when determining production rates and the type/sizes of production equipment to be used in the production process. The size of the equipment and its utilization should be proportional to each other.
7. Preparation of Master Manufacturing Procedure
This is concerned with the manner of presentation of the manufacturing procedures to facilitate easy compliance and understanding by the processing technicians. The procedures include; manufacturing directives, chemicals weigh sheet, sampling directions, in-process, and finished product specifications
8. Transfer of Analytical Methods to Quality Assurance
All analytical test methods developed in research during scale up of a new product, must be transferred to the quality assurance department. The quality assurance staff should review the process to make sure that the proper analytical instrumentation is available and that personnel are trained to perform the tasks. Steps to creating a custom pilot plant Custom pilot plants are commonly designed either for research or commercial purposes. They can range in size from a small system with no automation and low flow, to a highly automated system producing relatively large amounts of products in a day. No matter the size, the steps to designing and fabricating a working pilot plant are the same. They are:
1. Pre-engineering - completing a process flow diagram (PFD), basic piping and
instrumentation diagrams (P&ID's) and initial equipment layouts. 2. Engineering modeling and optimization - 2D and 3D models are created, using a simulation software to model the process parameters and scale the chemical processes. These modeling software help determine system limitations, non-linear chemical and physical changes, and potential equipment sizing. Mass and energy balances, finalized P&ID's and general arrangement drawings are produced. 3. Automation strategies for the system are developed (if needed). Controls system programming begins and will continue through fabrication and assembly 4. Fabrication and assembly - after an optimized design has been determined, the custom pilot is fabricated and assembled. Pilot plants can either be assembled on-site or off-site as modular skids that will be constructed and tested in a controlled environment. 5. Testing - testing of completed systems, including system controls, is conducted to ensure proper system function. 6. Installation and startup - if constructed offsite, pilot skids are installed onsite. After all equipment is in place, full system startup is completed by integrating the system with existing plant utilities and controls. Full operation is tested and affirmed. 7. Training - operator training is complete and full system documentation is handed over.
Other factors Other factors that may change during the transformation to a production scale include:
3D model of a multi-purpose pilot plant
Reaction kinetics Chemical equilibrium Material properties Fluid dynamics Thermodynamics Equipment selection Agitation Uniformity / homogeneity After data has been collected from operation of a pilot plant, a larger production-scale facility may be built. Alternatively, a demonstration plant, which is typically bigger than a pilot plant, but smaller than a full-scale production plant, may be built to demonstrate the commercial feasibility of the process. Businesses sometimes continue to operate the pilot plant in order to test ideas for new products, new feedstocks, or different operating conditions. Alternatively, they may be operated as production facilities, augmenting production from the main plant. Recent trends try to keep the size of the plant a small as possible to save costs. This approach is called miniplant technology. The flow chemistry takes up this trend and uses flow miniplant technology for small-scale manufacturing.
