The Boston Marathon is one of the world's most prestigious racing events. It has distinguished itself from other races in
many ways, one of which is the method of entry. Not only must each applicant meet a defined set of prerequisites in order
to qualify as an entrant and compete in the race, but each entrant's qualifications are subject to verification prior to the
race date. This qualification process coupled with the runner's own preparations for the race help to ensure that only experienced,
capable, and well-trained athletes are competing on the streets of Boston on race day.
Just as the race entrant must meet a well defined set of race prerequisites, train adequately, and have the right equipment
ready prior to the race, so too must a pharmaceutical or biopharmaceutical company meet a predefined set of prerequisites
before embarking on the course towards process validation. This Part I article will focus on the value of incorporating prerequisites
into a process validation protocol.
The quality systems approach to process validation
Developing a drug product is a lengthy process. Prior to commercial distribution, the US Food and Drug Administration requires
that the manufacturing process for the product be validated. Process validation is defined as the accumulation of documented
evidence that demonstrates with a high degree of assurance that a process can consistently meet its predetermined specifications
and quality attributes. Not only does process validation satisfy regulatory requirements, it is good business practice to
have the confidence that a manufacturing process is repeatable and will yield a quality product on a consistent basis.
Most companies understand the requirement for process validation. However, the way companies go about process validation oftentimes
lacks the business-related benefits that may result from truly challenging the entire process.
Simply repeating the normal manufacturing process a series of times, collecting routine samples, and analyzing the samples
for in-process and finished-product specifications is not sufficient to demonstrate that a process is validated. Performing
validation in this manner only shows that at that particular date and time the technical aspects of the manufacturing process
may or may not have been successful. In order to demonstrate repeatability, ensure a robust process after the process validation
report is approved, and hence obtain a business-related benefit from the process validation activity, the quality systems
contributing to the technical aspects of the process must be in a state of control. If these manufacturing support systems
are not in control and sufficiently thorough, these so-called quality systems cannot be counted on to ensure the same process
results. This is where the value of incorporating prerequisites comes into play.
Just as the marathon applicant must prove he or she meets the technical requirements to compete at the high standards the
Boston Marathon requires, if accepted, the runner still makes sure to have eaten the right foods prior to the race and that
his or her gear is in top condition and ready to go prior to starting the race. The same situation applies to the pharmaceutical
or biopharmaceutical manufacturer during process validation. The company should prove that they have addressed and controlled
all supporting process-related variables prior to starting the process validation production runs.
Process validation prerequisites 101
What are prerequsities? A prerequisite is defined within the context of this article as a documented verification in a process
validation protocol, which, when met satisfactorily, is intended to demonstrate readiness for execution of a manufacturing
run. A process that is not performed the same way every time cannot be considered validated. This is the core concept behind
using prerequisite verifications during process validation. Any area that could lead to variation in a manufacturing process
or in the analysis of the manufacturing process should be included in the prerequisite verifications section of the process
validation protocol. The following is a brief description of the most common areas that should be verified, as these areas
often lead to variation in the process.
Master batch record status verification.
Using the example of the Boston Marathon runner, if the map has changed prior to the race and without notice, the runner may
very well need a change of strategy and may even get to the intended destination without a considerable loss in valuable race
time. The MBR is a road map for the manufacturing process. In this prerequisite, the effective version of the master batch
record (MBR) is verified as the latest, approved version of the document and agrees with the version listed in the approved