Pharma Focus Asia

The Significance of Process Validation in Pharmaceutical Industry

Edward Simpson, Technical Engineer, RS Calibration Inc

The documented verification of specific processes and systems against required specifications is known as process validation. Validation is an integrated process in the pharmaceutical industry as it is mandatory to comply with national and international standards of FDA and EMA. Validation ensures that all the processes are in compliance with the established CGMP standards. Any validation process requires complete documentation that complies with standard operating procedures and ongoing operations. This includes production plans, validation protocols, development reports, and analytical documents. Each and every step of the manufacturing process including subsequent processes and modifications is irrefutably verified to ensure complete safety of the pharmaceutical products that people rely on in their everyday life. Process control validation helps in bridging the gap between the ever-changing quality standards and dynamic market forces.

The Fundamental Requirements of Pharmaceutical CGMP

Good manufacturing practice is concerned with quality control and production which requires:

•    Trained, qualified, and competent personnel
•    Adequate production space
•    Appropriate equipment
•    Correct labels and containers
•    Suitable storage space
•    Safe transportation facilities
•    Adherence to approved procedures

Upcoming Validation Technologies in Pharma Manufacturing

According to the latest validation guide, the entire life cycle of the product is bifurcated into three stages. The first step is process design where all the knowledge is gathered during the scale-up. The second step is process qualification wherein the manufacturing system is validated at strategic points. The final step is continued verification which is an ongoing process. These three principles are essential for ensuring consistent quality and production throughout. Pharmaceutical companies are implementing the following approaches to improve efficiency and increase productivity.  

The PAT Framework

Process Analytical Technology is designed to assess and control manufacturing procedures and packaging processes for timely and efficient operations. This concept emphasizes the need to ensure predefined quality while reducing the product cycle time. PAT fundamentally enables manufacturers to control processes for reduced scrap and wastage. This concept requires tight collaboration between suppliers and customers during the design process. This innovative concept is gradually taking off with the advent of smart machines that come with integrated controls and sensors.

The Consistency of Validation Program

When different manufacturers apply their customized validation procedures, the end-user may get confused due to different structures and complicated vocabularies. Consistency plays a vital role in improving operations and it can be achieved through across the board integration. As original equipment manufacturers adopt software solutions to validate the subroutine, the whole packaging line is improving drastically.  

Factory Acceptance Testing

FAT is designed to ensure that quality systems are running at peak efficiency. It reduces the overall validation burden on pharmaceutical companies by involving suppliers in the infrastructure deployment process. Every company has a different validation procedure which makes it important to follow a standardized practice and track it on a regular basis. As machines and processes collaborate, single-use systems will become a norm and companies will achieve greater success. The set-up times will become shorter, cross-contamination risks will reduce dramatically and operational costs will come down significantly.


Pharmaceutical manufacturing is now being outsourced to third party service providers for higher production yields. Disposable technology is being widely used in drug development for bringing down production costs. Single use bioreactors have made processes more flexible and dramatically reduced the risk of cross-contamination. This results in reliable produce and accelerates the time to market. Disposable technology is facilitating the full integration of pharmaceutical production for consistent products while consuming fewer resources. This has made it necessary to establish an ongoing monitoring process that ensures strict adherence to regulatory compliance.

CGMP Documentation

Today process flow diagrams need to clearly describe each unit along with its placement and operational role in the overall process. From monitoring and control points to material inputs and output, every element of the production process needs to be described in detail. It is also important to record and preserve process flows to facilitate decision making and comparison. The documentation requirements become essential during process qualification and continued verification. This new practice is already becoming a compliance expectation for validation.

Equipment Cleaning and Maintenance Program

The structural integrity and efficiency of any equipment change over time due to extensive usage. As chemical and detergent residues deposit, cleaning becomes difficult. Repairing a non-functional piece or installing a part can create more problems by giving rise to new stress centers. All these issues are now giving rise to a new equipment maintenance program that entails the following points:

•    Strict enforcement of standard operating procedures
•    Regular functionality checks
•    Routine mechanical maintenance
•    An evaluation program that checks for cleanability, repairs, and replacements.

Good Manufacturing Practices

Pharmaceutical industries have realized the cost benefits of having a compliant CAPA system. This not only keeps bio-meds and pharma companies on track but also reduces consumer complaints. Adhering to all the CAPA protocols and associated documents is mandatory to carry out the validation task. Good manufacturing practices require that any changes in critical components, modifications in the plant, and changes in batch size need to be validated to conform to process specifications. Good manufacturing practice has been in place for more than a decade now and it ensures that all the products meet the accepted production and quality regulations consistently. This is an essential mechanism which needs to be executed from time to time.

Revision of the Validation Process

The pharmaceutical industry is moving ahead from the traditional three-batch validation approach to an ongoing monitoring process which runs regular quality assurance checks. The success of any validation program depends on the accuracy of the knowledge that further determines the effectiveness of the product. The use of critical utility systems plays a crucial role in the quality of the end product. This is why it is important to monitor every routine operation right from design and construction to deployment and qualification. The pharma manufacturing standards must meet both qualitative and quantitative regulations to achieve satisfactory results. This knowledge-intensive approach gives a clear sense of direction for effective and accurate validation.

Edward Simpson

Edward Simpson is a seasoned Calibration and Technical Engineer working for RS Calibration Inc. Edward has a knack for finding faults in machines and does not rest until they are rectified to perfection. He lives in Pleasanton, CA and can be contacted anytime for matters related to machines. He also invites people to visit his company to learn more about the type of calibration work he does.

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