Process Validation


Process Validation

Successful  Process Validation gives assurance about produced Drug Quality . which is Drug should be fit for its intended use.

  • Quality ,  safety and efficacy should be built into the product.
  • Only in-process test & finished products tests can not give assurance of product quality.
  • because of it every step of product manufacturing process should be controlled & assure that finished product passes all test as per specifications.

So How should we proceed for Process validation as per USFDA Guideline of Process Validation as per follows;

  1. Stage 1- Process Design : The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale up activities.
  2. Stage 2 – Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.
  3. Stage 3 – Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

A successful validation depends on information & all small details of Product and Product Development.for this manufacturer should look after;

  • Source of variation which could play a role in compromising Intended quality of product and understand it properly which will help in below study.
  • Detect the variation.
  • Detect the degree of variation.
  • Detect & understand the impact of variation on process & ultimately on  product.
  •  Control The Variation.

Types of Process Validation.

1 Prospective Validation.

it is performed before production batches & during Products Development . it gives clear idea about risk during production of particular product  which helps in risk analysis. it also gives clear idea about critical steps in product manufacturing process.

  • Evaluate individual risk for each one
  • investigate the same
  • Find potential cause 
  • check for solutions.
  • find out effects
  • set the trail
  • all should cover in validation. 

which will gives proper idea about validation which will help in actual production of product.

2  Concurrent Validation.

its comes when first  three batches of product being  manufactured on production scale very closely. it will gives all data required for assessing the batch manufacturing on production scale. this data collected during batch manufacturing will give precise & in depth idea about its fundamentals. and with the help of trend analysis & test results manufacturing process time , stability one can perform concurrent validation through out products shelf life to extent the same.

3 Retrospective Validation.

Retrospective validations is done on ongoing processes and process controls which have not gone through Concurrent Validation process. for this validation we can use historical data of manufactured batched with proper documentary evidence which shows  process is working as it is intended to work . because of it this type of validation is only acceptable in well -established process. it cannot be performed when there is any change in API vendor, formulation changes, manufacturing process changes or equipment changes.

4 Re-validation:-

Re-validation is needed to ensure that changes in the process and/or in the process environment, whether intentional or unintentional, do not adversely affect process characteristics and product quality.( WHO)

It can be divided into two types;

A) Re-validation after any change that shows effect on product quality.

  • Site to Site Transfer of product.
  • changes in the plant,the product , the manufacturing Process, the cleaning process or other changes which cause direct & indirect effects.
  •  change in batch size ( Increase & Decrease ).
  • Unexpected changes and deviations may be observed during self-inspection or audit, or during the continuous trend analysis of process data.

B)  Second is Periodic Re-validation carried out on specified schedule.

  • equipment wear may also cause gradual changes.
  • basis on review of historical data,trends should be evaluated.
  •  some times it is done in-house like for 1st 3 batches of production year.

Validation protocol should contain;as per (WHO)

A suggested scheme for the validation protocol and subsequent report concerning a particular process is shown below:

Part 1. Purpose (the validation) and prerequisites
Part 2. Presentation of the entire process and subprocesses, flow diagram, critical steps/risks
Part 3. Validation protocol, approval
Part 4. Installation qualification, drawings
Part 5. Qualification protocol/report

5.1 Subprocess 1

5.1.1 Purpose

5.1.2 Methods/procedures, list of manufacturing methods, SOPs, and written procedures, as applicable

5.1.3 Sampling and testing procedures, acceptance criteria (detailed description of, or reference to, established procedures, as described in pharmacopoeias)

5.1.4 Reporting Calibration of test equipment used in the production process Test data (raw data) Results (summary)

5.1.5 Approval and requalification procedure

5.2 Subprocess 2 (same as for Subprocess 1) Sub-process 

Part 6. Product characteristics, test data from validation batches

Part 7. Evaluation, including comparison with the acceptance criteria and recommendations (including frequency of revalidation/requalification)

Part 8. Certification (approval)

Part 9. If applicable, preparation of an abbreviated version of the validation report for external use, for example by the regulatory authority

The validation protocol and report may also include copies of the product stability report or a summary of it, validation documentation on cleaning, and analytical methods.


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