validation protocol


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Validation in the pharmaceutical industry is defined as the documented act of demonstrating that a procedure, process, and activity will consistently lead to the expected results. It often includes the qualification of systems and equipment. It is a requirement for Good Manufacturing Practices and other regulatory requirements VALIDATION


WHY? Validation is " Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes." (FDA 1987). A properly designed system will provide a high degree of assurance that every step, process, and change has been properly evaluated before its implementation. Testing a sample of a final product is not considered sufficient evidence that every product within a batch meets the required specification .


VALIDATION MASTER PLAN (VMP) is a document that describes how and when the validation program will be executed in a facility. it is the document that outlines the principles involved in the qualification of a facility, defines the areas and systems to be validated and provides a written program for achieving and maintaining a qualified facility with validated processes. It is the foundation for the validation program and should include process validation, facility and utility qualification and validation, equipment qualification, cleaning and computer validation. The regulations also set out an expectation that the different parts of the production process are well defined and controlled, such that the results of that production will not substantially change over time .

The validation process:

The validation process consists of identifying and testing all aspects of a process that could affect the final test or product. Prior to the testing of a process, the system must be properly qualified. Qualification includes common practice for equipment (IQ, OQ and PQ). The validation process

Activities need to be validated:

A ctivities need to be validated Cleaning Validation Process Validation Analytical Method Validation Computer System Validation

Activity of qualifying systems and equipment:

Activity of qualifying systems and equipment Design qualification (DQ) Component qualification (CQ) Installation qualification (IQ) Operational qualification (OQ) Performance qualification (PQ)

Process validation:

Process validation establishing by objective evidence that a process consistently produces a result or product meeting its predetermined requirements.

Steps in validating a Process :

Steps in validating a Process Establish team Determine validation activities Develop or write the validation protocol Specify the system development details Conduct installation qualification (IQ) Conduct operational qualification (OQ) Conduct performance qualification (PQ) Analyze results and reach conclusions Review periodically

Validation protocol:

Validation protocol A document stating how validation will be conducted, including test parameters, product characteristics, manufacturing equipment, and decision points on what constitutes acceptable test results . The Validation Protocol describes the procedure and the steps within the procedure that will be followed in order to validate the system. The Validation Protocol must also provide a high level description of the overall philosophy, intention and approach.

Validation protocol preparation:

Validation protocol preparation

Design qualification:

Defines the functional and operational specification of the instrument, program, or equipment and details the rationale for choosing the supplier. Design qualification

Installation qualification:

Demonstrates that the process or equipment meets all specifications, is installed correctly , and all required components and documentation needed for continued operation are installed and in place . establishing by objective evidence that all key aspects of the process equipment and ancillary system installation adhere to the manufacturer’s approved specification and that the recommendations of the supplier of the equipment are suitably considered. Installation qualification

Operational qualification:

Demonstrates that all facets of the process or equipment are operating correctly . establishing by objective evidence process control limits and action levels which result in product that meets all predetermined requirements. Operational qualification

Performance qualification:

Demonstrates that the process or equipment performs as intended in a consistent manner over time . establishing by objective evidence that the process, under anticipated conditions, consistently produces a product which meets all predetermined requirements. Performance qualification

Component qualification:

This term refers to the manufacturing of auxiliary components to ensure that they are manufactured to the correct design criteria . This could include packaging components such as folding cartons, shipping cases, labels or even phase change material. All of these components must have some type of random inspection to ensure that the third party manufacturer's process is consistently producing components that are used in the world of GMP at drug or biologic manufacturer. Component qualification

Members of the validation team:

Members of the validation team Quality Assurance Engineering Manufacturing Others depending on company organization and product types Laboratory Technical Services Research & Development Regulatory Affairs Clinical Engineering Purchasing/Planning

checklist to review validation activity:

checklist to review validation activity Form multi-functional team for validation Plan the approach and define the requirements Identify and describe the processes Specify process parameters and desired output Decide on verification and/or validation Create a master validation plan Select methods and tools for validation Create validation protocols Perform IQ, OQ, PQ and document results Determine continuous process controls Control the process continuously

Protocol includes:

Protocol includes Identification of the process to be validated Identification of device(s) to be manufactured using this process Objective and measurable criteria for a successful validation Length and duration of the validation Shifts, operators, equipment to be used in the process Identification of utilities for the process equipment and quality of the utilities Identification of operators and required operator qualification Complete description of the process Relevant specifications that relate to the product, components, manufacturing materials, etc. Contd …

Protocol includes:

Protocol includes Any special controls or conditions to be placed on preceding processes during the validation Process parameters to be monitored, and methods for controlling and monitoring Product characteristics to be monitored and method for monitoring Any subjective criteria used to evaluate the product Definition of what constitutes non-conformance for both measurable and subjective criteria Statistical methods for data collection and analysis Consideration of maintenance and repairs of manufacturing equipment Criteria for revalidation

For all three phases, IQ, OQ, and PQ, based on product/process requirements::

For all three phases, IQ, OQ, and PQ, based on product/process requirements: Determine what to verify/measure · Determine how to verify/measure · Determine how many to verify/measure, i.e. statistical significance · Determine when to verify/measure · Define acceptance/rejection criteria · Define required documentation

IQ considerations Is it installed correctly?:

IQ considerations Is it installed correctly? Equipment design features (i.e. materials of construction cleanability , etc.) Installation conditions (wiring, utilities, functionality, etc.) Calibration, preventative maintenance, cleaning schedules Safety features Supplier documentation, prints, drawings and manuals Software documentation Spare parts list Environmental conditions (such as clean room requirements, temperature, humidity)

OQ considerations To determine the robustness of the process in worst case conditions:

OQ considerations To determine the robustness of the process in worst case conditions Process control limits (time, temperature, pressure, line, speed, setup conditions, etc.) Software parameters Raw material specifications Process operating procedures Material handling requirements Process change control Training Short term stability and capability of the process, (latitude studies or control charts) Potential failure modes, action levels and worst-case conditions (Failure Mode and Effects Analysis, Fault Tree Analysis)

PQ considerations consistently produce acceptable product under normal operating conditions:

PQ considerations consistently produce acceptable product under normal operating conditions Actual product and process parameters and procedures established in OQ Acceptability of the product Assurance of process capability as established in OQ Process repeatability, long term process stability

controllable causes of variation from the OQ and PQ data:

controllable causes of variation from the OQ and PQ data Temperature Humidity Variations in electrical supply Vibration Environmental contaminants Purity of process water Light Human factors (training, ergonomic factors, stress, etc.) Variability of materials Wear and tear of equipment

Final report:

Final report

Revalidation may be necessary:

Revalidation may be necessary change(s) in the actual process that may affect quality or its validation status · negative trend(s) in quality indicators · change(s) in the product design which affects the process · transfer of processes from one facility to another · change of the application of the process

Thank you:

Thank you

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