What Is The Difference Between Method Verification And Method Validation?

Posted by Wellspring Pharma Services

stockvault-chemistry150636Clients have come to us in the past asking "We need 'method validation'.” Sometimes they'll use the term “validation” or “verification” but it seems apparent they're not really clear on what the difference is between the two. For the most part it’s not that well-known that method validation is a much more rigorous process. What’s really needed, more likely, is the establishment of a verification regime that assures analytical methods perform reliably, accurately, and precisely for its intended application.

Method validations are performed for new methods that have just been developed or instituted, and that require revisions because they've been significantly changed. So oftentimes its “re-validation” that is really required in the wake of making significant changes to a method, equipment, or conditions of the analysis. Examples include: changes in the formulation, changes in the instrumentation that’s intended to be used—perhaps chromatographic conditions for each PLC, sample preps, filters, etc.

It Is Important To Review Methodologies To Ensure They Adhere To Current Standards And Guidances

Assuring-Pharmaceutical-Technology-Transfer-Success-eBook By necessity, revalidation would be required for a previously validated method that was updated to meet current regulatory requirements. We see a lot of this in our industry, where many of our clients come to us with older ANDA or NDA products that were approved some 20 or even 30 years ago. It only takes a brief review of those methodologies for one to realize that they were validated to a whole lot of different standards back then. Now we need to really ensure that the validations adhere to current International Conference on Harmonisation (ICH) guidance. These testing requirements are determined individually based on the types of changes that are needed.

Method “verification” or method “transfers” are materially different and a little more limited, and not as robust or rigorous as a method “validation". Regardless, verification is needed in order to verify that a lab is capable of performing an analytical method reliably and precisely for its intended use. Method verifications are really performed for compendial methods, where there's already an existing method in a compendia, like USP, NFBP or EP. It is showing or proving that a given lab is capable of performing that particular test reliably and precisely.

Method transfers on the other hand, are performed for validated methods, where a method may have already been validated and it's being transferred to a new laboratory or a new facility. It's a validated method - but there’s no need to ensure that the lab is capable of performing that method. There is a process that needs to be followed and in place, to ensure that the transferring lab can perform that test reliably and accurately.

Have Proper Documentation That Proves Testing Capabilities

WS-12-2013_47-1If you think you can go ahead and test release a pharmaceutical product without doing any method validation or verification, you should think again. There have been clients that have come to us in a rush to get a product on the market, and they need the test to be done - even if either their current lab can't do it or they think their methodologies are fine. Regardless, you can’t just go ahead and test without doing validation or verification in advance.

If you didn’t that would be frowned upon by regulatory authorities because you really haven't proven that the laboratory that's executing these tests can actually perform those tests accurately and precisely. What is needed is a protocol, indicating what tests are going to be performed to accomplish method verification. Then, by doing those tests, you've proven that you can accurately perform this test reliably with precision, with accuracy, and then you can prove to the regulatory authorities that your lab is capable of running this test day in and day out without any issues.

The Bottom Line: Testing Must Prove Reliable, Accurate, And Precise

There are a lot of tests that need to be performed to establish method veracity and these should all be written in your protocol prior to actually conducting the tests. The list of tests likely includes a system suitability requirement, precision, intermediate precision, accuracy, linearity, limited detection, limited quantification, specificity and robustness. One might also challenge solution stability and this may prompt some stress testing of the method to see how variable or what kind of chromatograph conditions that might be able to change to ensure that it's still accurate and precise.

That might seem like a lot of tests but for a method validation, there’s no getting around it. Now, for a method transfer, there would be other tests that you wouldn't have to do because those methods have already been validated and you're only really proving that the new lab is able to do those tests. So you still want to do things like system suitability, precision, intermediate precision, linearity, and specificity. Those tests would be required for a method transfer.

Before you can test a pharmaceutical product and release it to market, either method verification or a method validation would have to occur, because it is a minimum requirement that the regulatory authorities would expect you to have in place before you start testing and releasing product to the market place.

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Topics: Quality & Regulatory

WellSpring Pharma Services is a full-service provider of pharmaceutical contract manufacturing and packaging outsourcing solutions for solids, semi-solids, and non-sterile liquids. WellSpring offers full-service contract cGMP manufacturing, packaging and analytical testing services from a single FDA inspected and Health Canada licensed facility.

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