The amendment– detailed in the Federal register earlier this month – eliminates specified test methods for culture media, some filtration procedures for certain products and sterility analysis requirements for 'most' bulk materials.
It also changes repeat test requirements, limiting them to only once per product lot if it can be determined that any microbial contamination detected during initial analysis is due to lab error or faulty testing materials. Other revisions focus on the storage of test organisms, sample size and data interpretation.
The Food and Drug Administration (FDA) cited technical advances in analysis methods as the basis for the revisions - which are final and due to come into effect on June 4 – and said the changes will benefit patients and biologics producers alike.
“Advances in technology in recent years have allowed the development of new sterility test methods that yield accurate and reliable test results in less time and with less operator intervention than the currently prescribed methods.”
The agency cited methods like adenosine triphosphate bioluminescence, chemiluminescence and carbon dioxide head space measurement among the innovations and suggested: “Manufacturers may benefit from using such sterility test methods with rapid and advanced detection capabilities.”
The FDA also detailed some of the industry feedback it received about the amended rules, reporting that the 17 letters it received were broadly supportive of the initiative.
“Many of the comments agreed that the proposed amendments would provide manufacturers of biological products greater flexibility and would promote improvement and innovation in the development of sterility test methods.”
Despite this support, there were some concerns. One unidentified firm suggested that the focus should be on ensuring good manufacturing practices (GMP) compliance for aseptic manufacturing processes “as opposed to the perceived assurance that sterility testing of samples provides.”
In its response the FDA acknowledged that sterility testing does not provide ‘absolute assurance’ a biologic drug is sterile but argued that properly validated aseptic processes testing – using media fills and process simulations – combined with sterility testing and controls are sufficient.
“We believe this final rule, together with the other applicable regulations and Agency guidance, provide manufacturers appropriate latitude to determine how to achieve the level of control necessary for compliance.”
Environmental conditions and cross contamination
Other worries focused on the lack of recognition of the importance of environmental conditions in sterility testing – particularly in avoiding cross-contamination – and proposed that the FDA adopt wording similar to that detailed in the European Pharmacopoeia 2.6.1.
The FDA said that it would not adopt such wording, arguing that such concerns are address in cGMP requirements (part 210, 211 and 600 to 680 and suggesting that manufacturers should look to other relevant agency guidance documents and USP Chapter 71 for additional information.