Verifying the suitability of test methods

Determining the appropriate parameters to establish the efficacy of compendial test methods can be confusing especially when performed using a particular lab’s analysts, instrumentation, and supplies. Moreover, the requirements for method verification are not well defined. The Current Good Manufacturing Practice (cGMP) regulations include a requirement to verify the suitability of testing methods under actual conditions of use, as listed in 21 CFR 211.194(a)(2). Although this is a long-standing part of the regulations, the meaning of this section is difficult to interpret. Like so many of the cGMP requirements, the expectations of the industry with regard to method verification have evolved over time. Melissa Mann, senior raw materials chemist, performs verification testing on compendial methods. USP recently proposed a new general information chapter, <1226> Verification of Compendial Procedures, to clarify guidelines for ensuring that a compendial method will give acceptable results. Although transfer protocols and method validation for finished products and active pharmaceutical ingredients are common in the contract laboratory setting, it is much less common to apply these same detailed principles to compendial methods on inactive ingredients or excipients. The proposed chapter recommends verification of tests that use liquid chromatography, gas chromatography, spectrophotometric, titrimetric, and thin-layer chromatography techniques. Verification is not required for USP general chapter tests, such as residue on ignition <281>, pH<791>, and heavy metals <231>. Microbiological procedures are also excluded from the proposal because they are covered in other USP chapters. Method verification typically includes a subset of the parameters evaluated when a complete validation is performed. Precision, specificity, and detection limit are among the characteristics checked when verifying a compendial method. No matter what parameters are to be verified, the study should proceed according to an approved protocol that defines the characteristics to be evaluated and sets acceptance criteria to be used in judging the results of the study. Data from a method verification study should be summarized in a final report that will serve as documentation of the lab’s ability to achieve reliable results for a given test. Lancaster Laboratories routinely tests raw materials using a wide variety of compendial methods, so demonstrating the suitability of multiple test methods is challenging. Since the FDA and industry expectations for method verification appear to be expanding, the Raw Materials Group at Lancaster Laboratories is in the process of performing formal method-verification studies for a number of frequently tested materials. These studies will generate data to establish that the people, equipment, and reagents employed in the laboratory produce acceptable results for these often-performed tests. Greg Kupp, Director of Pharmaceutical Chemistry, feels that taking this proactive approach to verifying the lab’s ability to perform compendial tests in accordance with the proposed chapter will result in savings for clients who submit samples. “If we can do the verification studies and make the data available for our overall client base, we can leverage the cost and ease the financial burden for individual companies,” explains Kupp. In addition to the method-verification studies for clients’ routinely performed compendial tests, Lancaster Laboratories can create and execute protocols to verify other methods upon client request. For more information about method verification studies, please contact Pharmaceutical Business Development at (717) 656-2300 or e-mail pha@lancasterlabs.com.