LABORATORY MASTER VALIDATION PLAN FOR LIQUIDS

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MASTER PLAN OF

VALIDATION

LABORATORY XXXX.
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SIGNATURE SHEET
ELABORATION
Name Cargo Date Signature

REVIEW
Name Cargo Date Signature

AUTHORIZATION
Name Cargo Date Signature

EFFECTIVE DATE OF THE DOCUMENT: .........................................

DOCUMENT REVISION
Version Description of change Date

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I. INTRODUCTION
LABORATORIO XXXXXX founded in the year ......................................is located
located in the district of .............. in the city of LIMA.

LABORATORIO XXXXXXXX is dedicated to the production of NON-STERILE pharmaceutical

products for human use and among these we have :

1. Liquid Pharmaceutical Forms:

- Syrups

- Drops

- Suspensions

2. Semisolid Pharmaceutical Forms :

- Creams

- Ointments

It consists of :

General Management,

Plant Management .

Technical Management

Quality Assurance Manager

Production Manager

Quality Control Manager

Logistics Manager

Finance Manager

LABORATORIOS XXXXX has .............................workers

XXXXX LABORATORIES . convinced of the importance of compliance with the BPM. establishes
this master validation plan for LIQUID and SEMISOLID non-sterile dosage forms, which describes
the guidelines for the implementation and execution of this plan.

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II. CORPORATE PURPOSE

MISSION:
VISION:

POLICY :

QUALITY

OCCUPATIONAL HEALTH AND SAFETY

ENVIRONMENT

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III. XXXXXXXX LABORATORIES POLICY REGARDING VALIDATION OF NON-STERILE

LIQUID AND SEMI-SOLID PHARMACEUTICAL PRODUCTS

Senior Management will allocate financial and human resources for the development and
compliance with the Validation Plan for LIQUID AND SEMISOLID non-sterile dosage forms,
complying with national and international quality standards.

IV. OBJECTIVE

• Verify that the manufacturing process of non-sterile LIQUID AND SEMISOLID dosage forms
complies with the established parameters and is consistent and reproducible from batch to
batch.

• Ensure that the finished product meets critical quality attributes and critical process
parameters.

V. SCOPE

This process is applicable to non-sterile LIQUID AND SEMISOLID dosage forms:

The master plan covers all aspects included in the production processes as well as those related
to it:
> Equipment
> Facilities (Areas)
 > Critical Support Systems
> Analytical methods
> Cleaning and Sanitizing
> Materials
> Suppliers
> Staff
> Documentation
> Automated handling systems

VI. FOUNDATION

Since it is a Quality Policy to manufacture products in compliance with Good Manufacturing

Practices regulations and within this policy it is indicated that all critical processes must be
validated, the present plan is developed.
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VII. ABBREVIATIONS

Abbreviation Meaning
URS User Requirement

CQA Critical Quality Attributes

CPP Critical Process Parameters

DQ Design Qualification

IQ Installation Qualification

OQ Operation Qualification

PQ Performance Rating

HVAC Heating, Ventilation and Air Conditioner

PMV Validation Master Plan
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VIII. RESPONSIBILITIES

• Head of the Non-Sterile Liquids and Semi-Solids Production Area: Responsible for the
elaboration of production flows.
• Production Manager: In charge of Production Supervision.
• Maintenance Manager: in charge of preventive and/or corrective maintenance of
equipment.
• Validation Manager : In charge of the qualification and calibration of instruments and
equipment as applicable.
• Quality Control Manager: Responsible for the development and validation of analytical
methodologies, sampling and approval of the results obtained.
• Technical Director: Responsible for approving process validation protocols and verifying
compliance with the PMV.
• Plant Manager : Approves and facilitates the procurement of the necessary resources to
implement the validation program.

IX. VALIDATION STRATEGY

XXXXXX Laboratories ' strategy to comply with the Validation Plan will begin with the :

• Qualification of the production areas of LIQUID and SEMISOLID non-sterile pharmaceutical

forms.
• Qualification of systems and services: water, air.
• Equipment qualification, according to ANNEX I.

At the same time, the analytical methodology and supplier qualification will be validated.
After the respective qualifications we will proceed to :
a) List the products that are produced in the Liquid and Semi-solid areas.
b) Review the formulas to group them according to their manufacturing process.
c) to validate the production and packaging processes.
d) Cleaning Validation

The validation method to be developed is of the concurrent type.

IX. A. AREA QUALIFICATION

It is carried out with the purpose of verifying that the installations meet the design and user
requirements based on architectural specifications.
The MANUFACTURING AND PACKAGING area must comply with an ISO 8 (Class D) classification,
and the packing area with an ISO 9 classification.
It starts with :
1) Verification of the dimensions of the area,
2) Distribution of services and installation of equipment, according to the plans that have been
designed in Annex Nº 2.
3) Characteristics of floors, walls and ceilings:
4) Water and sewage services:
5) Doors and Windows:
6) Lighting:
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7) Air flow :

Facilities involved in the manufacture, storage or control of products need to be qualified

including all four phases:

a) Design (DQ)

b) Installation,(IQ)

c) Operational (OQ)

d) Performance,(PQ)

e) Maintenance and Monitoring

a) Design (DQ)
Facility design is extremely important because it affects equipment location, capacity, personnel
and material flow. Considerations include:

1. Area, space distribution and size, construction materials

2. Finishes that minimize contamination (walls, floors, ceilings and supply lines)
3. Personnel, materials, process flow and safety
4. Clear and concise agreements and specifications with suppliers and contractors

b) Installation Qualification (IQ)

The requirements for facility (plant) qualification involve verifying that the construction meets
the design criteria or agreed upon modifications. It includes the following information:
1. A protocol and documented results
2. Verification of grade, type of materials used and quality of installation
3. Verification of the quality of finishes (floors, walls, ceilings, doors, windows, incoming
and outgoing material supply, etc.).

c) Operation and Performance Qualification:

Operational qualification and performance requirements include demonstrating that finishes,
personnel, material, process flow, are adequate during worst-case or normal conditions. This can
be done during routine operations and include:
A documented environmental protocol and results (feasible, non-feasible)

d) Maintenance and Monitoring -

They must include:
1. Definition of preventive and routine maintenance procedure / schedules (scheduling)
2. Periodic calibration and monitoring of equipment
3. Environmental performance monitors (feasible, non-feasible)
4. Including facility changes in the change control system

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IX. B. QUALIFICATION OF CRITICAL SYSTEMS AND EQUIPMENT

Support systems that must operate at a certain level in order to maintain the required level of
product quality must be qualified. That will include HVAC or ambient air supply, water supply
system and steam.
The qualification of critical plant systems includes: design (DQ), installation (IQ), operational
(OQ), performance (PQ), monitoring and maintenance.

WATER TREATMENT SYSTEM.

SCHEME

RESI
N

Finio mi
Filter 5 mi

PRETREATMEN
T
PURIFIED
WATER USP

Description of the Water Treatment System -

The purified water treatment system is Reverse Osmosis which has the following characteristics:
The process begins with the collection of drinking water taken from the public network, this is
subjected to filtration through a multimedia equipment consisting of a quartz filter where coarse
particles are retained, then the water passes through the softener to remove calcium and
magnesium salts, then sodium bisulfite is added to the incoming water to remove the chlorine
present in the water, then the water is made to enter through a 1 um filter, then it is passed
through a UV lamp, the next step is to enter the Reverse Osmosis equipment, the output water
can again pass through a reverse osmosis equipment (reverse osmosis osmosis).The next step is to
enter the Reverse Osmosis equipment, the output water can again pass through a reverse osmosis
equipment (double pass osmosis) or pass through a mixed ion exchange resin in order to further
lower the conductivity, finally the water will pass through a filter of 0.45u obtaining purified
water grade 0.45u filter to obtain pharmaceutical grade purified water which will be stored in a
tank from which it will be fed to the different points of use forming a recirculation ring to
maintain the water quality conditions.

Qualification of the Water Procurement System -

• Rating fromInstallation
• Rating from operation
• Rating fromperformance

Installation Qualification -
Verify that the equipment has been installed according to specifications, key elements,
engineering design based on the installation drawings.

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• List of equipment or system components

• List of materials in contact with the product
• List of points of use
• List of spare parts
• List of filters
• Preventive maintenance
• Training documentation
 • List of system instruments
• List of Standard Operating Procedures

Operation Qualification -
• Evaluation of the correct operation of the equipment (reproducibility)
• Individual evaluation of the system (pumps, filters, etc...)
• The operation of the controls is verified.
• Verification of instruments in operation.
• Valve verification.
• Alarm verification.
• Verification of safety devices.
• Verification of the functionality of instruments and system components.
Performance appraisal
• Monitoring plan for operational parameters.
• Sampling plan (size, quantity and location of sampling)
• Analysis plan ( Physical, Chemical and Microbiological Tests )
System validation. Phase 1
• Duration from 2 to 4 weeks.
• Under chemical and microbiological tests according to a defined plan.
• Sample inlet daily to verify quality.
• Sample after each step in the purification process daily.
• Sample at each point of use and at other daily defined sampling points (pretreatment,
treatment, storage and distribution).
• Develop appropriate operating ranges.
• Develop and finalize operating, cleaning and maintenance procedures.
• Demonstrate production and delivery of water in the required quantity and quality.
• Verification of provisional action and alert levels.
• Develop and polish the failure procedure.
System validation. Phase 2
• Duration between 2 to 4 weeks.
• Involves monitoring of procedures after completion of phase 1.
• The sampling scheme is generally the same as Phase 1.
• Water can be used for manufacturing purposes during this stage.
• Consistency in the operation with the established ranges must be demonstrated.
• Demonstrate consistent production and delivery of water of required quality when the
system is operating according to procedures.

System validation. Phase 3

• Duration of one year after successful completion of phase 2. Water can be used for
manufacturing.
• Periodic sampling and testing is performed to demonstrate the operational and control
status of the system.
• Demonstrate reliable equipment performance over time.
• Minimum frequency once a week at the points of use.
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• Change Control, evaluation of the impact on the validated system (membranes,
distribution network, new equipment).

Water Treatment System Maintenance -

Procedures:
• System operation.
• System cleaning .
• System sanitization
• Corrective actions for out-of-specification results
• Physical, chemical and microbiological water analysis
• Training.
• Calibration programs
• Sampling program
• System maintenance program.
• Change control
• Nonconformities

AIR TREATMENT SYSTEM.

SCHEME

VALIDATION PLAN FOR NON-STERILE LIQUIDS AND SEMI-SOLIDS AREAS

The purpose of the HVAC system is :

• Consistently provide environmental conditions required for the manufacturing process
• Demonstrate that its generation and handling is reliable, effective, reproducible and does
not represent a source of contamination.

Parameters influencing Protection Levels:

•
Number of particles in the air
•
Number of microorganisms in the air
•
Number of air changes
•
Air velocity
•
Filters (type, position)
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• Air pressure differentials between areas

• Temperature and humidity

Installation Qualification -
It verifies what has been installed according to your specifications: PRE-FILTER BANK
• ASHRAE 30% Efficiency Dust Filters
• ASRHAE 85% Efficiency Dust Filters
• Terminal filter banks
• Air injection, return and recirculation fans
• Air ducts
• Heat coil
• Cooling coil
• Indicator instruments.

AIR HANDLING UNIT: UMA

• Constructed of material that does not mildew and does not release particles.
• Fan: drives the amount of air inside the system
• Condensate or dehumidifier water should not accumulate inside the unit.
• Verify the sealing of the filters when assembled to ensure airtightness
• Percentage of air replaced
• Position the necessary instruments
• Alarm system

DISTRIBUTION PIPELINES
• Ensure that the duct joints are tightly sealed.
• It must be of a solid structure to maintain pressure.
• The returns must be located 30 cm above the floor.

FILTERS
Consisting of Pre-filters, Bag Filters and Terminal Filters.
• Each filter class has a different design and construction.
• Filters should be selected for their ability to retain particles of appropriate size.

1 . Environmental control monitoring

non-viable particles
viable particles
2 Number of air renewals
3 Environmental temperature and relative humidity control
4 Differential pressures
5 Illumination level
6 Area Performance Rating
7 Area grading (floors, walls, etc.)
8.Documentation
•Viable particles control procedure
•Non-viable particles control procedure
•Filter change procedure
•Air renewal procedure
•Temperature and humidity control procedure
•Procedure differential pressures
•Lighting procedure
•Area qualification procedure

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FILTERS
TERMINAL FILTERS (AMBIENT)
AIR FLOW RATE
PURPOSE :
Check the outlet air flow rate. Demonstrate that the air system is balanced and capable of
delivering sufficient air volume.
EQUIPMENT : Velometer , Anemometer (analog , digital)
PROCEDURE: Velometer readings should be taken 6 inches from the filter surface and the reading
interval should be at least every 15 seconds.

AIR RENEWAL TEST

PURPOSE:
Demonstrate that the air flow rate circulating through a clean area is adequate to ensure the air
quality of each area.
EQUIPMENT: Velometer , Anemometer (analog , digital)
PROCEDURE :
1 . Determine the air flow rate supplied by each filter.
Flow rate = Average air velocity x filter area
= ft /min x ft 2
= ft 3 / min (CFM)
= (foot 3 / min) x (60 min / 1 hour)
= ft 3 / hour

2 The total flow will be the sum of the individual flows of the area.
Calculate the hourly renewals as follows:

Hourly changes = Total flow rate

Room volume

Changes Hour = ft 3 / hour ft 3 (LxWxH)

Changes Hour = N/ hour

ACCEPTANCE CRITERIA :

PRESSURE DIFFERENTIALS

PURPOSE :
Demonstrate that between two adjacent areas there is a difference in pressures that ensures
compliance with the established air flow direction to avoid cross contamination.
EQUIPMENT: Multimeter or Magnaghelic or differential pressure gauges.
METHOD :Record the comparison between the pressures of two adjacent environments using two
output channels of the equipment used.
ACCEPTANCE CRITERIA:
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NON-VIABLE PARTICLE COUNT

PURPOSE :
Demonstrate that the particle count is adequate according to the classification established for
each environment.
They can be taken at rest/ At rest or in operation.
Alert and action levels are determined.
EQUIPMENT : Particle counter with current calibration certificate
METHOD
1. Perform counting under At Rest conditions and in operation.
Determine the number of sampling points within a room ( N= square root of the area) 2. Program
the equipment to count particles of : 0.5 microns and 5.0 microns, 3.Take each sample with a
duration of 60 seconds (2L/min) at the working height.

Acceptance criteria: WHO Report 36

GRADE AT REST IN OPERATION

Maximum number of Maximum number of

particlesallowed/m3 particlesallowed/m3

0.5 - 5 .0 um > 5.0 um 0.5 - 5 .0 um > 5.0 um

A 3500 0 3500 0

B 3500 0 350000 2000

C 350000 2000 3500000 20000

D 3500000 20000 Not defined Not defined

HUMIDITY AND TEMPERATURE

PURPOSE :
Demonstrate that the required humidity and temperature conditions are maintained in the
different production rooms to minimize microbial growth and ensure adequate preservation of
the manufactured products.
EQUIPMENT :Digital thermo-hygrometer

PARAMETER LIQUIDS, CREAMS

Temperature Less than 22+ 2 °C
Humidity Less than 60

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QUALIFICATION OF PRODUCTION EQUIPMENT

All equipment involved in any phase of manufacturing (from dispensing to packaging) must be
qualified. The qualification includes 5 phases; design, installation (IQ), operation (OQ),
performance (PQ) and maintenance/monitoring.

Among the equipment to be considered :

 • Manufacturing tank
• Storage tank.
• Reactor with jacket
• Tanks with built-in agitators
• Packaging machine

DESIGN QUALIFICATION.
Design considerations focus on consistent and reliable performance. This includes:
• Filling current and future needs (capacity)
• Ease of maintenance, cleanliness and service available
• Materials of construction/contact are not additive or reactive to the product
• Presence of controllers for key attributes (sensors, switches, logic circuits, gauges,
recorders)
• There must be clear and concise specifications, drawings and agreements with suppliers
and contractors.

QUALIFICATION OF THE INSTALLATION.

Installation qualification requirements include verifying that what was purchased and installed is
what was designed or specified. This includes:
• A protocol and documented results
• Verification of model, capacity, etc.
• Verification of materials of construction (grades/types) and quality of finish (welding,
smoothness etc.)
• Verification of the presence of sensors, alarms, switches, regulators, safety mechanisms,
etc.
• Schematic and isometric installation drawings where required.

OPERATION QUALIFICATION.
Operational Qualification (OQ) requirements include demonstrating that the equipment and its
performance are consistent with the design criteria during operation. This is usually done during
the initial operation of the equipment, which can be dry (no product) and/or placebo operation
(inactive ingredients). This includes:
• A protocol and documented results
• Verify equipment parameters such as speed or RPM, cycle time, etc. and their variability.
• Challenging and verifying that all sensors, regulators, logic circuits, gauges, safety
mechanisms graphs and monitors are functioning properly and are calibrated.
• Verify equipment performance or product attributes such as weight, dimensions,
uniformity, mix and variability meet product specifications/process capability.

PERFORMANCE RATING (PQ)

Performance qualification requirements include demonstrating that the equipment meets
acceptable design criteria during normal or worse case conditions. This is usually done during the
validation process. This includes:

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• Verify equipment and product attributes listed in OQ under normal or worst case
conditions (capacity, load, speed, pressure, etc.).
• Determine the operating ranges of the equipment parameters that control the product
variables.

MAINTENANCE AND MONITORING.

• Definition and performance of preventive, predictive and routine maintenance.
• Periodic calibration of monitoring/control mechanisms.
• Periodic verification of process capability.
 • Include the team in the change control process.
• Define revalidation schedules (programs).

IX. C. VALIDATION OF MANUFACTURING AND PACKAGING PROCESSES

The primary reason for the validation process is to identify critical process parameters, establish
an acceptable range for those parameters and provide a means of control for them.
Description of the process:
• Flowchart
• Determination of critical points
• Establishment of parameters for validation of critical points
• Acceptance criteria

At LABORATORIOS XXXXXXX the validation plan contemplates the following stages:

a) List of liquid and semi-solid dosage forms

b) List of liquid and semi-solid dosage forms to be manufactured during the year .
c) Group liquid dosage forms according to their manufacturing process:

SYRUP
Syrups with sugar.
Syrups with Lycasin
Syrups with Sorbitol
Others.
For these processes, they were grouped according to the vehicle used in the formulation,
knowing that their manufacturing process is similar.

SUCROSE SYRUPS
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SYRUPS WITH LYCASIN

SYRUPS WITH SORBITOL

SUSPENSIONS
Sucrose + Sorbitol Suspensions
Sorbitol Suspensions

SUCROSE + SORBITOL SUSPENSIONS

SORBITOL SUSPENSIONS

DROPS

Water vehicle drops+ glycerin

Water vehicle drops+ propylene glycol
Water vehicle drops+ propylene glycol + sucrose
Water vehicle drops+ Ethyl alcohol
Water vehicle drops+ sorbitol + alcohol
Water vehicle drops
WATER + GLYCERIN DROPS

WATER +PROPYLENE GLYCOL DROPS

WATER + PROPYLENE GLYCOL + SUCROSE DROPS

WATER + ETHYL ALCOHOL DROPS

WATER +SORBITOL + ALCOHOL DROPS

In the case of syrups, as 3 groups have been determined, it has been considered to evaluate one
product from each group, the products being :
a) Nnnn
b) Nnnnn
c) Nnnnn
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In the case of Suspensions, as 2 groups have been determined, it has been considered to evaluate
one product from each group, the products being :
a) Nnnn
b) Nnnnn
In the case of drops, as 5 groups have been determined, it has been considered to evaluate one
product from each group, the products being :
a) Nnnn
b) Nnnnn
c) Nnnnn
d) Nnnnn
e) Nnnnn

Before designing the validation procedure, a review of the critical steps in the non-sterile liquid
manufacturing process will be necessary.
In order to draft the process validation protocol, it is important to consider the following points:
> What are the critical phases (establish points for monitoring these phases).
> Equipment to be used in each phase (Meeting the qualification requirements).
> Possible problems (study them on the basis of the worst case scenario)
> Controls to be complied with (know the control status, control parameters, and margins
of error).
> Sampling plans (representative of the lot)
> Analysis plans (based on size, risks, etc.)
> Acceptance criteria
> Relevant process information
> Reference controls or specifications (given by official monographs)
> Summary and/or conclusion for validation
> Process validation covers initial process validation, subsequent validation of modified
processes and revalidation.
> Process validation will normally be performed during systematic production (concurrent
validation).
> The flow charts corresponding to the manufacturing processes of the non-sterile liquid
dosage forms are shown below.
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LIQUID FORMS

FLOWCHART AND OPERATIONAL PHASES

I. I.

Manufacturing stage (Preparation of

sugar syrup) - Addition of preservatives.

Addition of the active ingredient and

other excipients

Syrup Coloring
Addition of Flavoring

Shake
________________ pH control
Clarifying Filtration
Quality Control Sample

Container and Packaging

Material
Washing - Drying
Bottles IN-PROCESS
Cap Preparation Bulk Packag CONTROL
Approval ing Volume Control 2.
Tightness Control

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Insert IN-PROCESS
CONTROL
Appearance control

Packing Carton
Coding
Pack
 Quality control
1. Manufacturing Registration Review
2. Packaging Record Review - Packaging
3. Physical, Chemical and Microbiological
Analysis Protocol Revision

Product Release

Finished Product Warehouse

IX. D. VALIDATION OF CLEANING PROCESSES

In compliance with corporate policy, the cleaning process of all equipment involved in manufacturing
is validated. The cleaning validation study will be developed under the concept of "Product Matrix",
where those products considered as very critical, either because they are more difficult to clean, less
soluble and/or more toxic, will be selected.
The purpose of cleaning validation is to demonstrate and document that the cleaning procedure and
critical parameters of the cleaning process are capable of effectively and reproducibly reducing
residues of active products, excipients, cleaning agents and microorganisms to pre-established levels.

IX. E. VALIDATION OF COMPUTERIZED SYSTEMS

The computerized system is validated according to the appropriate level for its use and application.
This is important in production as well as in quality control. The purpose of the computerized
validation system is to ensure a degree of documented evidence and new confidential data (a rigorous
archive of pre-determined specifications).

Aspects to be validated include system specifications and functional specifications. Procedures for
monitoring, change control, data and program security, calibration and maintenance, personnel
training, and periodic re-evaluation should be described.

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IX. F. VALIDATION OF ANALYTICAL METHODS

The main purpose of analytical validation is to ensure that the analytical procedure provides
reproducible and reliable results, which must be fit for purpose (attempted). Therefore, it is necessary
to properly define the conditions under which the procedure is to be used, with the purpose for which
it is intended.
These principles apply to all procedures described in a pharmacopoeia or not, when it is the case of
those that are of proprietary technique.
As far as the USP pharmacopoeias are concerned, the codified methods are valid and the only
requirement is compliance with the Adequacy Test, indicated in each monograph.
Relative retention time, asymmetry, theoretical plates and reproducibility are found; linearity is also
important.
The validation of analytical theories will be carried out based on the validation protocol for analytical
techniques.
According to the parameters established by WHO and pharmacopoeias: accuracy, precision,
reproducibility, robustness, linearity, range, selectivity, limit of detection, limit of quantification.

Objective:
> Demonstrate from laboratory studies that the functional characteristics of a test make it
suitable for the intended analytical application.
> All equipment must be validated prior to validation of an analytical titration.
> The validation report of an analytical assessment should be submitted to the QA for evaluation
and approval.

IX. G. SUPPLIER QUALIFICATION

The SUPPLIER QUALIFICATION regulates the qualification and evaluation of the performance of
suppliers of goods and services of XXXXXXXXXX laboratories.
For this purpose, the supplier's performance in the development of a specific contract will be
measured; this qualification will be assigned by the person responsible for contracting based on the
appropriate records and established criteria.

In the aforementioned qualification, suppliers are subjected to evaluation programs not only because
it is a regulatory requirement, but also and above all because of the reliability that this means and the
advantages in the acquisition of inputs, analysis flows and impact on processes that this
represents.This is why the generation of evaluation systems is taken into account, since depending on
the nature of the supplier, the level of demand depends on the nature of the supplier.
In addition to complying with the applicable legal provisions, drug manufacturers must issue the
corresponding certificate of analysis, signed by the health officer, to verify that the quality of the
drugs they manufacture complies with the specifications established in the current edition of the
official pharmacopoeias.In addition to the current edition of the official pharmacopoeias, the
pharmacopoeias of other countries whose analysis procedures are carried out according to the
specifications of specialized organizations or other internationally recognized scientific literature may
be used.
• They must comply with Good Manufacturing Practices.

• Document evidence of analyses, tests and evaluations performed for each batch at different
stages of the process.

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• Keep the identification documentation of the operations carried out.

• Labelthe containers of the product being marketed with the name and address of the
manufacturer, the lot number and the name of the product.

• It shall issue the corresponding certificate of analysis, when requested.

• In the case of an importer, the importer must demonstrate that the manufacturer it markets
complies with the sanitary provisions of the country of origin and demonstrate that it has the
manufacturer's original certificate of analysis.

• It must demonstrate that the manufacturer complies with Good Manufacturing Practices for the
input it markets.

• You must have the technical release documentation for each batch, for the products that you
commercialize.
 • It shall have documented evidence of the studies it conducts in accordance with its own quality
control process.

• If requested by the buyer, he shall issue a true copy of the original certificates and, if
applicable, the certificate of analysis performed.

• You must keep the identification documentation of the operations you carry out.

XI. SCHEDULE OF ACTIVITIES

XII. REZONING-REVALIDATION

Facilities, systems and equipment and processes including cleanliness should be evaluated periodically
to confirm that they remain valid. Likewise, in the event of any change, the revalidation will be
carried out.
When no significant changes have occurred with respect to the validated status, this need for
revalidation will be covered by a review that demonstrates that the facilities, systems, equipment and
processes comply with the mandatory requirements.

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XIII. VALIDATED STATE SUPPORT AND MAINTENANCE PROGRAMS

XIV. GLOSSARY

Risk analysis
Method to evaluate and classify the fundamental parameters of the functionality of a piece of
equipment or process.
Installation qualification
Documented verification that the premises, systems and equipment, as installed or modified, conform
to the approved design and manufacturer's recommendations.
Design qualification
Documented verification that the proposed design of the premises, systems and equipment is adequate
for the purpose for which they are intended.
Rating of results
Documented verification that the premises, systems and equipment, in the way they are connected
together, can deliver effective and reproducible results based on the approved processing method and
product specifications.
Operation qualification
Documented verification that the premises, systems and equipment, as installed or modified, perform
as expected under all anticipated operating circumstances.
Worst case
A condition or set of conditions covering the maximum and minimum processing limits, as well as the
circumstances within standard processing procedures, that pose the greatest potential for failure of
the product or process compared to ideal conditions. These conditions do not necessarily result in
product or process failure.
Change control
A formal system whereby qualified representatives from appropriate disciplines review proposed or
implemented changes that may influence the validated status of the premises, systems, equipment or
processes. Its objective is to determine the actions necessary to ensure and document that the system
is maintained in a validated state.
Revalidation
Repeat process validation to ensure that process or equipment changes introduced in accordance with
change control procedures do not adversely affect process characteristics or product quality.

LABORATORY MASTER VALIDATION PLAN FOR LIQUIDS

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Product simulation
Material whose physical and, where appropriate, chemical characteristics (p. e.g., viscosity, particle
size, pH, etc.) are very similar to those of the product to be validated. In many cases, these
characteristics are met by a placebo product batch.
System
Set of equipment with a common purpose.
Concurrent validation
Validation carried out during the systematic production of products intended for sale.
Validation of cleanliness
Cleaning validation is documented proof that an approved cleaning procedure will provide adequate
equipment for drug processing.
Process validation
Documented verification that the process, performed within established parameters, can provide
effective and reproducible results to produce a drug that meets its predetermined specifications and
quality attributes.
Prospective validation
Validation carried out prior to the systematic production of products intended for sale.
Retrospective validation
Validation of a process for a product that has already been commercialized, based on accumulated
manufacturing, testing and control batch data.

XV. ANNEXES