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

       Explain  different types of validation  and its importance

       Describe validation master plan


       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


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


For compliance to current good manufacturing practices validation is essential


       Documentation associated with validation includes

       Standard operating procedures (SOPs)


        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


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)



       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


Required when there is a change in:

       Any of the critical process parameters


       Primary packaging components

       Raw material fabricators

       Major equipment or premises

       Failure to meet product specifications and process specifications in sequential batches


       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


       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


       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


       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


                       Installation qualification

                       Operational qualification

                       Process qualification



       Preventive maintenance

       Charge control





       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


       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




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