Department of Pharmacy, Shree Dev Bhoomi Institute of Science & Technology, Dehradun, Uttarakhand.
This review aims to outline the effects of effective process validation in the pharmaceutical sector. Pharmaceutical tablets are the solid oral dosage form widely used for the prevention, diagnosis, and mitigation of disease. Process validation refers to the documented proof that a manufacturing process reliably yields a product that meets established specifications and quality attributes. The main objective of process validation is to guarantee that pharmaceutical products are consistently safe, effective, and of superior quality. This process focuses on enhancing the safety and quality of the dosage forms produced in the pharmaceutical industry.
Process validation ensures that the manufacturing process consistently produces high-quality products that meet regulatory requirements and align with industry standards. It offers uniformity, weight, and dosage across batches, complies with quality benchmarks for attributes such as dissolution and hardness, and ensures regulatory adherence through documented evidence of reliability. In summary, process validation is essential for maintaining consistency, quality, and compliance in tablet manufacturing. Drug product development is a sophisticated process that involves drug discovery, laboratory testing, animal studies, clinical trials, and regulatory registration. Process controls include inspection of raw materials and packing materials, in-process controls, and targets for the final product. Process validation includes monitoring each process involved in the whole manufacturing process to produce high-quality, efficient, and safe products. Process validation is an integral part of CGMPs (Current Good Manufacturing Practices). The requirement of process validation appears as the regulatory agency's requirement to ensure that the product manufactured is consistent, safe, and reliable throughout its lifecycle.
Validation
Validation is the documented act proving that any procedure, process, equipment, material, activity, or system leads to the expected result. Validation as defined in ICH Q7 - ‘Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.’ Validation defined in ICH Q8(R2)/Q11 - Continuous Process Verification is an alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated.
ISO definition - Validation is the confirmation by examination and the provision of objective evidence that the requirements for a specific intended use are fulfilled.
According to the Food and Drug Administration (FDA), the goal of validation is to:
Establish documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.
Importance of Validation
Types Of Validation
There are several different types of validation:
Process Validation
In pharmaceutical manufacturing, process validation refers to the documented evidence ensuring that the manufacturing process consistently produces a product that meets predetermined specifications and quality attributes. This process plays a critical role in meeting regulatory requirements set by agencies such as the FDA, EMA, and ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
Cleaning Validation
Cleaning validation is the documented evidence that assures that the cleaning process is effective in removing all residues of the product that was manufactured and cleaning agents that were used during the cleaning process, and preventing contamination.
Equipment and Instrument Validation
Equipment validation ensures that every piece of equipment used in the manufacturing process performs as expected, producing high-quality products.
Analytical Method Validation
According to ICH Q2 (R1), method validation can be defined as, ‘‘Establishing a documented proof, which provides a high degree of assurance that a specific process will consistently produce a desired result at its prearranged specifications and quality characteristics.”
Computer Software Validation
Computer Systems Validation (CSV) is a process used to test, validate, and formally document that a regulated computer-based system does exactly what it is designed to do consistently and accurately that is secure, reliable, and traceable in highly regulated sectors that impact public health and safety such as the pharmaceutical and medical device industries.
Process Validation
Process validation is a step-by-step procedure designed to ensure that a manufacturing process can consistently produce quality products. Generally, process validation is carried out before releasing a new product, or when applying any change to an existing product, and for periodically verifying the process.
History of Process Validation
This concept was first introduced in the mid-1970s for improving the quality of pharmaceuticals by two Food and Drug Administration (FDA) officers, Ted Byers and Bud Loftus [1] In 1987, the FDA released the first process validation guidance.[4] The fundamental approach was testing the process to ensure it worked, along with periodic retesting of the manufacturing process to ensure it was continuing to work. In the mid-2000s, regulatory agencies developed ICH Q8 – Pharmaceutical Development to provide foundational concepts required for companies to develop high-quality manufacturing processes. The final 2009 guidance provided several definitions intended to provide the basis for very important concepts for building processes [5]
The most important PV concepts begin with the following terms defined in ICH Q8 (R2):
In addition, acknowledging that developing and manufacturing pharmaceuticals was primarily a risk management and control exercise, regulatory agencies in 2006 developed and issued ICH Q9 – Quality Risk Management [6]
Types of Process Validation
Figure 1: Types of Process Validation
Prospective process validation- also known as pre-market validation. Prospective process validation is executed after the completion of the R&D trial to produce the product for commercial purposes. This type of validation is generally connected with the introduction of new drug products into the market and involves studies of all their manufacturing processes.
Retrospective process validation- The Retrospective process validation establishes documented evidence that a system does what it is supposed to do based on a review and analysis of historical information. It is normally conducted on a product already being commercially distributed and is based on accumulated production, testing, and control data.
Concurrent process validation- Concurrent validation is a type of validation that occurs during the routine production of the product. It involves collecting and analyzing data from each batch or lot to verify that the process or system is operating within the specified limits and producing consistent results. Concurrent validation can also be used as an alternative to prospective validation in some cases, such as when there is a lack of historical data, when the product has a short shelf life, or when the product is urgently needed.
Revalidation process validation- Revalidation means repeating the original validation. Revalidation is performed if there is any sort of change in the batch size, or formulation or when the consecutive batches of the manufacturing unit don't meet specifications as stated in its product, when changes are made in the site location, equipment size, and capacity or new advance equipment are introduced for further processing or when new manufacturing methods and control are to be followed or changes are made in them.
Approaches in Process Validation
Figure 2: Approaches of Process Validation
Stage-1 Process Design:
The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.7 This stage also involves process control and planning strategies to reduce input variation and/or adjust for it during manufacturing. The following are sources and methods to capture process information:
Stage-2 Process Performance:
During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.7 This stage has two elements:
Proper design of a manufacturing facility is required under part 211, subpart C, of the CGMP regulations on Buildings and Facilities. Activities performed to ensure proper facility design and commissioning must precede PPQ. Qualification of utilities and equipment generally includes the following activities:
— A description of the statistical methods to be used in analyzing all collected data (e.g., statistical metrics defining both intra-batch and inter-batch variability).
— Provision for addressing deviations from expected conditions and handling of nonconforming data. Data should not be excluded from further consideration in terms of PPQ without a documented, science-based justification.
Stage-3 Continuous Process Verification:
Ongoing assurance is gained during routine production that the process remains in a state of control. The goal of the third validation stage is to continually ensure that the process remains in a state of control (the validated state) during commercial manufacture should include:
Elements of Effective Validation
Validation Master Plan - A validation program must clearly outline essential elements in a validation master plan (VMP) or similar documents. The VMP specifies the scope and objectives of the validation. It comprises the following components:
CONCLUSION
Validation is a dependable approach to ensure the creation of a safe, high-quality product. The study mentioned above indicates that Pharmaceutical Process Validation is a crucial regulatory requirement for agencies to achieve a high-quality, efficient, and safe product. Process validation involves a series of activities that occur throughout the lifecycle of the product and process.
REFERENCES
Pratibha Thapliyal*, Neha Sodiyal, Shivanand Patil, A Review on Process Validation of Pharmaceutical Tablet, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 4393-4401. https://doi.org/10.5281/zenodo.15518879
10.5281/zenodo.15518879
