Joy McElroy is co-owner of Maynard Consulting Company. She offers 14 years of experience as a consultant and over 20 years’ total experience in the pharmaceutical and biotech industries in quality control, clinical settings, and good manufacturing practice (GMP) auditing as well as validation engineering. McElroy specializes in equipment qualification, cleaning validation, sterilization, environmental monitoring, GMP compliance auditing, good documentation practices, and GMP and good laboratory practice training. She has written and executed equipment qualification and validation protocols for numerous companies, such as Mallinckrodt, Wyeth Lederle, Merck, BioMérieux, Catalent, Phillips-Medisize, Xcelience, and Novartis.
Q: What are some of the latest changes or trends in analytical method validation?
A: With analytical method validation, there’s something that’s really big called “use of integrated life cycle.” It’s basically looking at the method and monitoring that method through its life cycle. [It involves] trending of all your method parameters . . . because you want to be sure that you’re evaluating the performance of your method through time. We’re validating because we want to prove that the method is consistent and repeatable and that we get a consistent result, but you want to also do trending to make sure that there are no changes that are needed or that have occurred in your testing. You want to demonstrate whether it needs to be optimized or revalidated and, of course, that will depend too on your product, the needs of your product, and the testing that requires. The analytical method validation, as far as looking at the life cycle, provides evidence that your method is suitable and you want to be sure that it is always performed for its intended purpose. It also allows you to continuously review your SOPs as far as your equipment and your method. You have to make sure there is a need for revalidation and, if there is, what changes are implemented and what type of revalidation is needed. That’s a big thing that I’m seeing as far as trends. Also for analytical method validation, the requirements are for very robust testing and very specific parameters, because in the past there hasn’t been much robustness in the method validation. So they’re looking at the requirements and pushing for more robust testing.
Q: How are these changes impacting labs?
A: One thing is that labs, when they’re looking at implementing more robust testing in their method validation and they’re looking at their revalidation needs and their trending, there’s also a need to conduct risk assessment for system suitability or actual system suitability testing. You have to submit your method development data. It’s not only “this is the validation” or “this is the PQ (process qualification) process validation,” but anything that goes into developing that data needs to be in that packet with your protocol. The biggest thing is doing risk assessment and grouping your analytical equipment, and grouping your methods as well, and figuring out what your highest-risk methods are. That takes a little bit of time and labs tend to be very busy with their day-to-day testing.
Q: What are the key benefits of these changes to analytical method validation?
A: With the life cycle management that is being instituted, it provides a framework for defining the criteria and for the development of your actual analytical procedure. It also provides greater assurance that the quality attributes of the tested product can be and are reliably measured, because that’s our goal—to measure the quality attribute [so that] it provides us more accurate, reliable testing and we’re sure that these quality parameters have been tested.
Q: What are the major challenges lab managers are facing with method validation because of these changes?
A: A lot of times what I’m hearing and what I’m seeing [are that] the actual staffing that is available to train and to actually design the experiment or carry out the initial design for the method validation and the actual validation [can be a challenge]. You have your regular production or your manufacturing activities, and now you need people to have time to evaluate methods, to look at trending,and to develop the method even further. Then that requires writing protocols and getting your testing just right for your analytical method to make sure that it is suitable for what you are doing. So, just the staffing and the time it takes to implement this life cycle management are the main [challenges].
Q: What are some of the things labs can do to handle those challenges?
A: I think the most effective thing that you can do for analytical method development is have strict, solid SOPs in place and strict schedules for review and evaluation. Staying on top of your method validation takes review and time. Internal audits are also important—having someone come in and audit your lab or your method development SOPs if you don’t have time for your staff to do it. Then [the auditor] can point out any deficiencies and you can work to put a team together to effectively handle those and get your methods up to date and anything else that needs to be done.
Q: What other changes do you expect to see in the future in analytical method validation?
A: I expect to see more specific requirements for testing, more of a push to build quality into the analytical method development with stricter documentation guidelines and stricter revalidation requirements.
Q: What advice would you have for lab managers who are not familiar with analytical method development but are just starting to get involved in it?
A: There’s lots of information and [there are] reference guides that they can read on the Internet. There’s the U.S. FDA [Food and Drug Administration] Guidance for Industry on Analytical Procedures and Method Validation. It was published in August 2000 and it’s a very good guide. It takes you through the life cycle management; it’s very detailed in telling you what’s expected for analytical equipment validation. ISO 17025 general requirements for the competence of testing and calibration laboratories—that’s another good guide that they can read. And just referring to [the FDA’s] 21 CFR Part 11 is also useful. The ICH [International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use] Q2(R1) is a section on validation of analytical methods. All these are very good references. Also, there are always webinars and seminars. I have a webinar that I give myself on analytical equipment validation and we also do some on method validation. There are also different articles that are published. For example, I get an email every month from the FDA that has good information on the latest changes as far as analytical method validation. So just keeping current on all the requirements and with these guides that I just suggested is very good. That’s where I would start. Also, researching and working with other labs, asking what’s going on, and networking with other managers [are] very helpful.
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