Validation

Validation

Objective

•       At the end of this session , student will be able to

•       Explain  different types of validation  and its importance

•       Describe validation master plan

Validation

•       Validation is a key process for effective quality assurance

•       Validation is establishing documented evidence which provides a high degree of assurances

•       That a specific process or equipment will consistently produce a product

•       Or result meeting its predetermined specifications and quality attributes

The Major Reasons for Validation

Quality assurance:

Validation checks the accuracy and reliability of a system or a process to meet the predetermined criteria. A successful validation provides high degree of assurance that a consistent level of quality is maintained in each unit of the finished product from one batch to another batch

Economics:

Due to successful validation, there is a decrease in sampling and testing procedures and there are less number of product rejections and retesting. This leads to cost-saving benefits

Compliance:

For compliance to current good manufacturing practices validation is essential

Documentation

•       Documentation associated with validation includes

•       Standard operating procedures (SOPs)

•        Specifications

•        Validation master plan (VMP) 

•       Qualification protocols and reports

•       Validation protocols and reports

Types of Validation

•       Prospective validation (also called premarket validation)

•       Retrospective validation

•       Concurrent validation

•       Re-validation

Prospective Validation

•       Conducted prior to the distribution of either a new product

•       A product made under a modified production process

•       Where the modifications are significant and may affect the product’s characteristics

It is a pre-planned scientific approach. and includes:

•       The initial stages of formulation development

•       Process development

•       Setting of process specifications

•       Developing in-process tests

•       Sampling plans

•       Designing of batch records

•       Defining raw material specifications

•       Transfer of technology from scale-up batches to commercial

•       size batches

•       Listing major process equipment and environmental controls

The Implementation of Validation work Requires Considerable Resources

•       Time: generally validation work is subject to rigorous time schedules

•       Financial: validation often requires the time of specialized personnel and expensive technology

•       Human: validation requires the collaboration of experts from various disciplines

•       e.g. a multidisciplinary team, comprising quality assurance, engineering, manufacturing and other disciplines, depending on the product and process to be validated

Retrospective Validation

•       The retrospective validation option is chosen for established products whose manufacturing processes are considered stable. and when on the basis of economic considerations alone and resource limitations, prospective validation programs cannot be justified

•       Wherein the numerical in-process and/or end-product test data of historic production batches are subjected to statistical analysis

Using either data-based computer systems or manual methods, retrospective validation may be conducted in the following manner:

1. Gather the numerical data from the completed batch record and include assay values, end-product test results, and in-process data
2. Organize these data in a chronological sequence according to batch manufacturing data, using a spreadsheet format
3. Include data from at least the last 20–30 manufactured batches for analysis
4. Trim the data by eliminating test results from noncritical processing steps and delete all gratuitous numerical information
5. Subject the resultant data to statistical analysis and evaluation
6. Draw conclusions as to the state of control of the manufacturing process based on the analysis of retrospective validation data.
7. Issue a report of your findings (documented evidence)

Retrospective Validation

•       One or more critical measured responses being evaluated, and selected for statistical analysis.

•       Solid Dosage Forms

•       Content uniformity testing

•       Hardness values

•       Thickness values

•       Weight variation

•       Dissolution time or disintegration time

•       Moisture content

•       Semisolid and Liquid Dosage Forms

•       pH value (aqueous system)

•       Viscosity

•       Density

•       Color or clarity values

•       Average particle size or distribution

•        Unit weight variation and/or potency values

Concurrent Validation

• A process where current production batches are used to monitor processing parameters
• It gives assurance of the present batch being studied

Note: offers limited assurance regarding consistency of quality from batch to batch

Re-validation

Required when there is a change in:

•       Any of the critical process parameters

•       Formulation

•       Primary packaging components

•       Raw material fabricators

•       Major equipment or premises

•       Failure to meet product specifications and process specifications in sequential batches

Calibration

•       The set of operations that establish, under specified conditions

•       The relationship between values indicated by an instrument or system for measuring

•       For example, weight, temperature and ph

                Recording controlling

•        The values represented by a material measure,

•       The corresponding known values of a reference standard.

•       Limits for acceptance of the results of measuring should be established

Computer Validation

•       Documented evidence which provides a high degree of assurance

•       Computerized system analyses

•       Controls and records data correctly

•       Data processing complies with predetermined specifications

Commissioning

•       The setting up, adjustment and testing of equipment or a system

•       To ensure that it meets all the requirements

•       As specified in the user requirement

•       Capacities as specifi ed by the designer or developer

•       Commissioning is carried out before qualifi cation and validation

Concurrent Validation

•       Validation carried out during routine production of products intended for sale

Cleaning Validation

•       Documented evidence to establish

•       cleaning procedures are removing residues to predetermined levels of acceptability

•       Taking into consideration

•       Factors such as batch size, dosing, toxicology and equipment size

Design Qualification (DQ)

•       Documented evidence that the premises, supporting systems, utilities, equipment

•       Processes have been designed in accordance with the requirements of GMP

Good Engineering Practices (GEP)

•       Established engineering methods and standards

•       that are applied throughout the project life-cycle to deliver appropriate, cost-effective solutions

Installation Qualification (IQ)

•       The performance of tests to ensure that the installations

•       Such as machines,measuring devices, utilities and manufacturing areas

•       Used in a manufacturing process are appropriately selected and correctly installed

•       Operate in accordance with established specifications

Operational Qualification (OQ)

•       Documented verification that the system or subsystem performs

•       As intended over all anticipated operating ranges

Performance Qualification (PQ)

•       Documented verification that the equipment or system operates consistently

•       Gives reproducibility within defined specifications and parameters for prolonged periods

Qualification

•       Action of proving and documenting that any premises, systems and equipment

•       Properly installed, and/or work correctly and lead to the expected results

•       Qualification is often a part (the initial stage) of validation

•       Individual qualification steps alone do not constitute process validation

Standard Operating Procedure (SOP)

•       An authorized written procedure giving instructions for performing operations

•       Not necessarily specific to a given product or material but of a more general nature

•       e.g. equipment operation, maintenance and cleaning; validation

•       Cleaning of premises and environmental control

•       Sampling and inspection

Validation

•       Action of proving and documenting that any process, procedure or method

•       Actually and consistently leads to the expected results

Validation protocol (or plan) (VP)

•       A document describing the activities to be performed in a validation

•       Including the acceptance criteria for the approval of a manufacturing process  or a part thereof — for routine use

Validation report (VR)

•       A document in which the records, results and evaluation of a completed

•       Validation program me are assembled and summarized

•        It may also contain proposals for the improvement of processes and/or equipment

Validation master plan (VMP)

•       The VMP is a high-level document that establishes an umbrella validation plan for the entire project

•        Summarizes the manufacturer’s overall philosophy and approach

•       To be used for establishing performance adequacy

•       It provides information on the manufacturer’s validation work program

•       Defines details of and timescales for the validation work to be performed

•       Including a statement of the responsibilities of those implementing the plan

•       Introduction methodology

•       Qualification

•                       Installation qualification

•                       Operational qualification

•                       Process qualification

•       Personnel

•       Schedule

•       Preventive maintenance

•       Charge control

•       Procedures

•       Documentation

•       Appendixes

Verification

•       The application of methods, procedures, tests and other evaluations

•       In addition to monitoring, to determine compliance with the GMP principles

Worst Case

•       A condition or set of conditions encompassing the upper and lower processing

•       Limits for operating parameters and circumstances, within SOPs, which pose

•       The greatest chance of product or process failure when compared to ideal conditions

•       Such conditions do not necessarily include product or process failure

Encapsulation speed-

The formulation should be encapsulated at a wide range of speeds to determine the operating range of the encapsulator

Summary

•       Validation is a key process for effective quality assurance

•       Validation checks the accuracy and reliability of a system or a process to meet the predetermined criteria

•        Different types of validation are prospective validation , retrospective validation , concurrent validation  and revalidation

•       The VMP is a high-level document that establishes an umbrella validation plan for the entire project

REFERENCE-

•       http//www.pharmainfo.net/reviews/guidelines-general-principles-validation-solid-dosage.

•       www.google.com