In the complex and highly regulated realm of pharmaceutical manufacturing, validation specialists play a crucial role. But what exactly does process validation entail?
According to the European Medicines Agency (EMA), process validation is defined as:
“… documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes.”
In simpler terms, process validation is the act of proving, in line with the principles of Good Manufacturing Practice (GMP), that any procedure, process, activity, or system consistently leads to the expected results. In the context of pharmaceuticals, these expected results mean that the product consistently meets the quality standards appropriate for its intended use.
Validation specialists are, therefore, responsible for designing, implementing, and documenting procedures that demonstrate the consistency and repeatability of manufacturing processes. This process, known as validation, is a fundamental requirement for meeting regulatory standards.
The benefits of validation in pharmaceutical manufacturing are beyond complying with regulations, being the three most significant: improved product quality and safety, reduced rejections and reworks, and decreased process development time, which leads to faster time to market.
To better understand these benefits, let’s explore each one with some real-world examples.
1) How can validation improve quality and patient safety?
A notable example is the sterilization issues that Abbott faced with large-volume parenterals in the 1970s.
Over a single decade, more than 600 recalls of large-volume parenteral products occurred in the USA, primarily due to contamination. These incidents resulted in 54 deaths and over 400 injuries.
The FDA found that the root cause of these contaminations was the manufacturing process, which had three objectionable practices:
I) Product samples for sterility tests were taken immediately after the sterilization step (autoclave), but before the cooling and rinsing operations of the bottles.
II) The cooling step of the filled sterilized bottles was done with water containing more bacterial counts than permitted.
III) After the cooling step, the bottles were rinsed with non-filtered air.
These issues could have been prevented with a robust validation process, which includes a risk analysis that could have detected these risky operations before the incidents occurred. A validation could have also tested the reliability of the entire process by carefully evaluating three testing runs.
Thus, a comprehensive validation can significantly enhance product quality and patient safety, preventing catastrophic incidents like those just mentioned.
2) How can validation significantly reduce rejections and reworks in the manufacturing process?
An example of this is a company that manufactures a non-sterile intranasal dosage form. There was a suspicion that the autoclaving operation may be behind some rejections due to high impurities percentages in the final product.
Through a thorough risk analysis and validation process, they demonstrated that by adding a couple of microbiological controls, they could remove the autoclaving step safely.
This change not only reduced the impurities in the final product but also maintained a low risk of microbiological contamination even without the autoclaving step, reducing the risk of rejection and increasing the manufacturing plant throughput.
3) Can validation make the process development faster?
A case study involving the development of a generic pharmaceutical drug with two active pharmaceutical ingredients (APIs) in a solid dosage oral form illustrates this point.
The process began with a Criticality Assessment, which was instrumental in identifying the Critical Quality Attributes (CQAs). A list of 20 potential CQAs was compiled and evaluated using a scoring system that considered both uncertainty and impact. The higher the uncertainty and impact, the higher the score. This scoring system helped define the most critical quality attributes. Leveraging previous knowledge and experience, the manufacturing process was then designed with these critical attributes in mind. The manufacturing process was refined with the information gathered from a series of pilot batches.
This was followed by a Risk Analysis to identify the riskiest operations in the process to define the process control strategy. During the test batches, it was observed that some failure modes, initially thought to have a low probability of occurrence, were, in fact more common. This shows the importance of integrating the knowledge of each step of the product lifecycle into the Risk Analysis.
By adopting this comprehensive approach, a significant reduction of 30% in development and process validation time was achieved compared to a traditional approach.
Final words
In conclusion, the role of validation in pharmaceutical manufacturing is indispensable. It is a vital process that ensures the consistent production of safe, high-quality pharmaceutical products. As illustrated by the examples provided, validation not only enhances product quality and safety but also reduces rejections and reworks, and accelerates process development.
In essence, validation is not just a regulatory requirement but a key driver of business success and excellence in the pharmaceutical industry. By investing in robust validation processes, pharmaceutical companies can enhance their operational efficiency, competitiveness, and overall business performance. As the pharmaceutical industry continues to evolve, the role of validation will undoubtedly remain central to its success.
Curious to learn more? Dive into our latest article on this topic and mark your calendars for our upcoming webinar on Jun 27. In this webinar, we’ll discuss the benefits of validation and how it minimizes defects and errors, reducing rejections and reworks.
With a dedication to serving the pharmaceutical industry, Qualistery specializes in hosting informational webinars that support both professionals within the pharma sector and service providers. Our commitment lies in empowering businesses to maximize their impact through engaging virtual events and strategic webinar solutions. Additionally, Qualistery supports life science companies through private GxP training and compliance services.
