The FDA’s Good Laboratory Practice (GLP) regulations have led to some misconceptions for medical device manufacturers (MDMs). To better understand the misconceptions about when to apply GLP testing, I think it’s important to first look at what the FDA GLPs actually say:
(a) This part prescribes good laboratory practices for conducting nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the Food and Drug Administration, including food and color additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products. Compliance with this part is intended to assure the quality and integrity of the safety data filed pursuant to sections 406, 408, 409, 502, 503, 505, 506, 507, 510, 512-516, 518-520, 706, and 801 of the Federal Food, Drug, and Cosmetic Act and sections 351 and 354-360F of the Public Health Service Act.
Okay, maybe it makes sense to run chemistry studies GLP, but before we make a final decision, how is a nonclinical laboratory study defined?
(d) Nonclinical laboratory study means in vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety. The term does not include studies utilizing human subjects or clinical studies or field trials in animals. The term does not include basic exploratory studies carried out to determine whether a test article has any potential utility or to determine physical or chemical characteristics of a test article.
The regulation seems pretty clear that chemical characterization studies are out of scope. But if you need further proof, look at how the regulations define the “test system.”
(i) Test system means any animal, plant, microorganism, or subparts thereof to which the test or control article is administered or added for study. Test system also includes appropriate groups or components of the system not treated with the test or control articles.
Still not convinced? Under GLP regulations, quality translates to consistency in practice and reliability of the test result; GLP tests are very prescriptive and direct. But in chemistry study, specifically under ISO 10993-18, there are many unpredictable variables at play. It is crucial to ask questions, explore different paths, and make real-time adaptations throughout the chemical characterization study – but under the parameters of GLP, this process is stymied. In short, GLP puts undue requirements on chemistry, resulting in restrictive studies and added costs.
Chemistry studies are highly investigative. Chemists are looking to identify potential risks to patients, including both chemicals they’re expecting to see and chemicals they’re not anticipating in the test article (like impurities and contaminants). The study must be agile, but the rigidity of GLP doesn’t allow this flexibility.
Bottom line: requiring chemistry studies to be conducted under GLP regulations puts devices at risk for incomplete analysis, lengthy delays and unnecessary additional costs. Furthermore, it’s a common misconception that regulators require chemistry studies to be conducted under GLP. Not only is it not required – it’s not best practice.
Employing FDA GLP in a chemistry study won’t lend it more credibility. But just because you aren’t following FDA GLPs doesn’t mean that you can’t and shouldn’t employ good laboratory practices to ensure quality and credibility of your chemistry study. Consider ISO 17025 accreditation. Internationally recognized, this accreditation indicates a lab’s competency and furthers its geographical reach. An ISO 17025 accreditation achieves comparable quality and consistency objectives as GLP, but in a manner that considers the critical quality attributes of chemical testing laboratories, which allows labs to flex their investigative skills to produce a comprehensive chemistry report – with no unknown substances.
If you are hiring a lab to conduct a chemical characterization study, I encourage you to consider how the study could be stunted by GLP. Don’t get me wrong: I believe in GLP regulations and admire what they’ve done for nonclinical laboratory testing – it’s just not the right path for chemistry.
Sandi Schaible is the Senior Director of Analytical Chemistry and Regulatory Toxicology at WuXi Medical Device Testing, located in St. Paul, Minn. She specializes in extractables and leachables studies. Sandi is a U.S. delegate and international delegate for ISO 10993 part 18 in chemical characterization. She is also a U.S. delegate for ISO 10993 part 13 and the particulates committee (TIR42). WuXi Medical Device Testing offers testing services in St. Paul, Minn., Atlanta, Ga., and Suzhou, China.