Biological test methods validation process in pharmaceuticals

Kazi
Last modified: July 31, 2024

Introduction

This article is designed to guide the validation practices of non-compendial or alternate biological test methods and the verification of concurrent biological test methods. It aims to demonstrate that a test method suits its intended purpose in GMP operations.

Responsibility in validation

Validating biological test methods is a significant responsibility. These methods must be developed, documented, and detailed enough for a qualified laboratory analyst to accurately perform the test in an environment suitable for the test methods and using the required test methods materials. Your role in maintaining all test methods under change control is crucial to the validation process.

Scope of the article

The scope of this article applies to all GMP operations responsible for the validation of biological test methods associated with products in or intended for the marketplace, including tests performed for release or stability evaluation of:

– Regulatory starting materials,

– Active pharmaceutical ingredients (API),

– Intermediates,

– In-process materials,

– Drug products,

– Biologics,

– Medical devices,

– Raw materials (RM).

This article does not address validating a Bacterial Endotoxin test (BET).

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Validation and verification

Biological test methods shall be validated unless the method employed is included in the current edition of an official pharmacopeia (e.g., EP, JP, or USP) or other recognized standard references.

Verifying a compendial biological test method must demonstrate its suitability for its intended purpose.

Examples of biological test methods

This guidance applies to biological test methods. The following are examples of biological test methods:

– Microbiological assay of antibiotics.

– Potency Bioassays (e.g., vitamins).

– Immunochemical assays [e.g. Enzyme Linked Immunosorbent Assay (ELISA)]

– Virus titration.

– In vivo and in vitro (cell-based) biological assays.

Specificity and verification

Specificity must be demonstrated to verify all compendial (e.g., EP, JP, USP) biological test methods under actual laboratory use conditions, including any minor variations in the test methods.

Validation characteristics

Non-compendial or alternate biological test methods shall be validated and shown to be equivalent to the compendial or regulatory filing method. Validation shall include consideration of the following validation characteristics applicable to the method:

– Accuracy,

– Precision,

– Repeatability,

– Intermediate precision (intra-laboratory), and

– Reproducibility (inter-laboratory),

– Specificity, and

– Quantitation limit (QL).

Robustness

If the robustness of the biological test method is not addressed during method development, it shall be considered during method validation.

When required, validated alternate biological test methods shall be submitted to the Regulatory Authority before implementation.

Documentation and protocol

Biological test method validation or verification studies shall be performed and documented according to an approved protocol that defines the evaluated parameters, the acceptance criteria for each parameter, and the test methods.

The laboratory manager must approve the protocol before the validation studies are executed. A method validation or verification report shall be prepared that documents the results of the validation or verification study, including the evaluation of each parameter and comparison against acceptance criteria.

Any deviations from the protocol must be documented, and the impact must be discussed in the report.

Roles and responsibilities

Qualified Personnel shall be identified with the following roles and responsibilities regarding biological test method validation or verification:

– The laboratory manager at the site conducting the validation or verification is responsible for assuring that the biological methods are validated or verified and reviewing and approving the final report.

– The quality authority, independent of the laboratory manager, at the site conducting the validation or verification study is responsible for reviewing and approving the final report for compliance with applicable site policies and procedures.

Computerized systems

Automated systems used in biological test methods and computerized laboratory systems shall include validation of the computerized system.

Qualified personnel shall perform:

– Validation studies, and

– Verification of compendial methods.

Procedures and equipment

Written and approved procedures shall describe the preparation, laboratory labeling, storage, and use of laboratory reagents, solutions, buffers, and reference standards.

Test equipment for executing the biological test method protocol must be qualified and have a current calibration status.

Record retention and revalidation

Biological test method validation and verification studies shall be documented and retained by site record retention requirements.

The laboratory manager shall determine the need for and degree of revalidation.

Changes to be considered in determining the need for and extent of revalidation include, and are not limited to:

– Changes to the biological test method (e.g., new or modified sample preparation procedure, change to detection conditions, change to instrument settings and operating -conditions)

– Changes to the sample being tested (e.g., process change for API or change in composition of the product)

– Changes in compendial or regulatory requirements (e.g., ICH, EMEA).

Legacy methods

The need to validate a legacy biological method that has not been previously validated or is not a compendial method shall be based on an impact assessment by the responsible quality team.

Legacy methods shall be assessed against this guidance to ensure available method documentation is current and reflects the method. A retrospective validation approach may be used to support the biological validation method.

Conclusion

Ensuring the validity and reliability of biological test methods helps maintain the integrity of GMP operations.

By adhering to stringent validation and verification protocols, GMP laboratories can guarantee that their test methods are suitable for their intended purposes, comply with regulatory standards, and produce consistent, accurate results.

This safeguards product quality and enhances trust with regulatory authorities and customers.

Remember, meticulous documentation, qualified personnel, and rigorous protocol adherence are critical to successful validation processes.

By following these guidelines, your organization can maintain high quality and efficacy standards in all biological testing operations.

Author: Kazi Hasan

Kazi is a seasoned pharmaceutical industry professional with over 20 years of experience specializing in production operations, quality management, and process validation.

Kazi has worked with several global pharmaceutical companies to streamline production processes, ensure product quality, and validate operations complying with international regulatory standards and best practices.

Kazi holds several pharmaceutical industry certifications including post-graduate degrees in Engineering Management and Business Administration.