Bioprocess Validation: Process Design and Process Characterization

 

Bioprocess Validation 

The first step in bioprocess validation involves thorough characterization of the production process. Process engineers will develop the process design based on laboratory research and manufacturing requirements. They design the production steps, equipment used, materials required and operating parameters. Effect of various process parameters on product quality is studied. Experiments are performed to understand the relationship between inputs like media composition, inoculum size, temperature and outputs like product yield, impurities level etc. Operating ranges are established for critical process parameters within which the process is capable of consistently producing product meeting predefined specifications.

Process Qualification

Once the process design is finalized, process qualification experiments are performed to prove that the process is capable of reproducible commercial manufacturing under normal conditions. Equipment qualification is also done to ensure installed equipment, supports and utilities are capable of reliably performing their intended functions as per design. Qualification batches are manufactured under CGMP following the commercial process procedure. Bioprocess Validation It is demonstrated that the process is robust and capable of producing product meeting predefined specifications and quality attributes. Sources of variability are identified and process controls are established.

Process Validation

Bioprocess validation involves collecting and analyzing data from multiple commercial-scale batches to scientifically prove the process is capable of consistently delivering quality product complying with predetermined specifications and quality standards. Three consecutive commercial-scale batches are generally used for validation. In-process controls (IPCs) and finished product test parameters are evaluated. Additionally, the overall performance of the process is observed. The data is statistically analyzed to establish process is in a state of control.

Ongoing Process Verification

Even after initial bioprocess validation the manufacturing process requires continuous monitoring and verification. As the process gains experience, additional production data from commercial batches is reviewed. The purpose is to demonstrate that the process remains in a state of control and any changes to facilities, equipment, materials etc. do not adversely impact the process capability. Statistical tools are used to review batch records on an ongoing basis. Process or product related deviations and corrective actions are also evaluated as part of ongoing verification. It helps identify any trends requiring process enhancement actions.

Clean In Place (CIP) Process Validation

Equipment and facility cleaning processes are integral part of bio manufacturing since they remove residuals from previous batches and prevent cross-contamination. CIP validation involves qualifying cleaning procedures, validating cleaning agents and limits, establishing rinse effectiveness and verifying absence of residuals and carryover. Appropriate sampling methods and analytical tests are established to ensure cleaning acceptance criteria are met. Equipment design also ensures effective cleaning and drainage. CIP validation ensures manufacturing areas, surfaces and equipment are sufficiently cleaned between batches.

Sterilization Process Validation

Terminal sterilization using heat, radiation, filtration or aseptic processing are commonly employed sterilization techniques in bioprocessing. The sterilization process needs to be validated to demonstrate its ability to achieve required sterilizing value (Fo, D-value etc) under defined manufacturing conditions. Parameters like time, temperature, pressure are studied. Biological indicators are used to verify sterilizing conditions achieve desired level of sterility assurance. Process simulation studies using physical/chemical indicators also help establish sterilization efficacy. Sterilization validation provides assurance that all microorganisms are eliminated from product, containers and equipment after the sterilization process.

Process Validation Summary Report

Finally, a bioprocess validation master plan and summary report is prepared documenting all aspects of validation. It summarizes key validation protocols, describes experiments performed, discusses results achieved, identifies any deviations observed, details statistical analysis, concludes process is capable and establishes ongoing monitoring plan. The report along with batch manufacturing records and supporting data forms integral part of regulatory submissions to health authorities in seeking marketing approval. It provides health authorities assurance that quality manufacturing process is in place for consistent commercial production of product meeting all quality requirements.

 

Get more insights on Bioprocess Validation

 

About Author:

Ravina Pandya, Content Writer, has a strong foothold in the market research industry. She specializes in writing well-researched articles from different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. (https://www.linkedin.com/in/ravina-pandya-1a3984191)