Process validation is an important part of pharmaceutical product manufacturing. Where a scientific evidence is to be established that the process is capable of consistently delivering quality product.


As per FDA,

Process validation is the collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.

Process validation involves a series of activities taking place over the lifecycle of the product and process. As per FDA these activities can describe in three stages:

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



General Considerations for Process Validation

1. An integrated team where includes expertise from a variety of disciplines (e.g., process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing, and quality assurance) along with the full support of senior management, are essential elements for success.

2. Throughout the product lifecycle, various studies can be initiated to discover, observe, correlate, or confirm information about the product and process. All studies should be planned and conducted according to sound scientific principles, appropriately documented, and approved in accordance with the established procedure appropriate for the stage of the lifecycle

3. A written protocol that specifies the manufacturing conditions, controls, testing, and expected outcomes is essential for process validation, where may include – 

  • Objective and scope of the process validation activities.
  • The manufacturing conditions, including operating parameters, processing limits, and component (raw material) inputs.
  • The data to be collected and when and how it will be evaluated. 
  • Tests to be performed (in-process, release, characterization) and acceptance criteria for each significant processing step.
  • The sampling plan, including sampling points, number of samples, and the frequency of sampling for each unit operation and attribute. The number of samples should be adequate to provide sufficient statistical confidence of quality both within a batch and between batches. The confidence level selected can be based on risk analysis as itrelates to the particular attribute under examination. Sampling during this stage should be more extensive than is typical during routine production.
  • Criteria and process performance indicators that allow for a science- and risk-based decision about the ability of the process to consistently produce quality products.
  • Design of facilities and the qualification of utilities and equipment, personnel training and qualification, and verification of material sources (components and container/closures), if not previously accomplished.
  • Status of the validation of analytical methods used in measuring the process, in-process materials, and the product.
  • Review and approval of the protocol by appropriate departments and the quality unit.


A report documenting and assessing adherence to the written process validation protocol should be prepared in a timely manner after the completion of batches. This report should include:

  • Discuss and cross-reference all aspects of the protocol.
  • Summarize data collected and analyze the data, as specified by the protocol.
  • Evaluate any unexpected observations and additional data not specified in the protocol.
  • Summarize and discuss all manufacturing nonconformances such as deviations, aberrant test results, or other information that has bearing on the validity of the process.
  • Describe in sufficient detail any corrective actions or changes that should be made to existing procedures and controls.
  • State a clear conclusion as to whether the data indicates the process met the conditions established in the protocol and whether the process is considered to be in a state of control. If not, the report should state what should be accomplished before such a conclusion can be reached. This conclusion should be based on a documented justification for the approval of the process, and release of lots produced by it to the market in consideration of the entire compilation of knowledge and information gained from the design stage through the process validation stage.
  • Include all appropriate department and quality unit review and approvals.


FAQs

How many types of validation are there in pharmaceuticals?

There are four types of validation in pharmaceutical industry: Prospective validation, Concurrent validation, Retrospective validation & Revalidation


What are the stages of process validation?

As per FDA, there are three stages of process validation: Stage 1 – Process Design, Stage 2 – Process Qualification & Stage 3 – Continued Process Verification.


Why is process validation important in pharmaceutical?

process validation is important to ensure that the process is capable of reproducible commercial manufacturing.


Why are there (3) batches for process validation?

Consideration of validation batches fewer than three will require more statistical and scientific data to prove the consistency of process to meet quality standards. Therefore, minimum three consecutive batches are evaluated for validation of manufacturing process and cleaning procedures.

Only reference to magic number 3 you can find in EMA guidance on process validation of finished products. The guidance does not mandate minimum of 3 batches but seen many interpret this as requiring 3 batches and to meet both FDA and EMA requirements they default to 3 batches.


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