FDA Moves on Voluntary Consensus Standards; Launches Pilot for Post-Approval Mfg ChangesBy
The US Food and Drug Administration (FDA) has issued a draft guidance to promote development and appropriate use of consensus standards in pharmaceutical quality and also has launched a pilot program to engage with the industry on post-approval manufacturing changes.
The draft guidance, CDER’s Program for the Recognition of Voluntary Consensus Standards Related to Pharmaceutical Quality, proposes a program in which stakeholders and FDA staff will have the opportunity to propose pharmaceutical quality standards for potential recognition by the FDA to provide the industry with additional options for pharmaceutical development and manufacturing.
The FDA says that the overall goal of this program is to promote development and appropriate use of consensus standards to help expedite pharmaceutical development and streamline the review of drug product applications. “By providing a list of recognized standards on our website, we will provide transparency regarding our thinking on a particular standard, which will help industry compile information for applications, can streamline the FDA’s assessment and allow us to focus our efforts on developing guidance on other quality topics,” said Scott Gottlieb in a February 13, 2019 agency statement.
”Our recognition of a standard may also reduce regulatory uncertainty, allowing applicants and manufacturers to utilize new or innovative approaches within their development programs,” he said in the statement. “Once we’ve recognized a standard, applicants will generally not have to validate the approach outlined in the standard and can instead focus on appropriate use of the method and the acceptance criteria. We’ll similarly be able to streamline assessment of applications that reference recognized standards. Our hope is that establishing this program will also encourage the development of standards for emerging technologies that can improve drug quality and reduce manufacturing costs. This includes continuous manufacturing. Informally recognized standards related to pharmaceutical quality will also be publicly available on our website.“
The FDA points out that the program doesn’t change the requirements of the law and standards that are already legally binding, such as provisions of the Federal Food, Drug, and Cosmetic Act and the United States Pharmacopeia. The program is intended for all drugs, both brand and generics.
Gottlieb pointed out the proposed program is in keeping with other initiatives by the FDA to support efficiency of drug development and manufacturing. To that end, the FDA has launched an Established Conditions Pilot Program to propose explicit established conditions (ECs) to be considered in post-approval manufacturing changes as part of an original new drug application (NDA), abbreviated new drug application (ANDA), biologics license application (BLA), or as a prior approval supplement (PAS) to any of these. The concept of ECs was first described in the FDA draft guidance Established Conditions: Reportable CMC Changes for Approved Drug and Biologic Products, issued in May 2015, and further discussed in the FDA’s draft guidance Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, which the agency issued in 2018, and which is based on International Council for Harmonisation’s (ICH) Q12 guideline.
This draft guidance provides a risk-based approach to regulatory oversight of post-approval manufacturing changes. The framework in the guidance provides a mechanism for applicants to gain agreement with the agency on the established conditions (ECs) necessary to ensure product quality and to facilitate post-approval changes to those established conditions with a level of regulatory oversight commensurate with the applicant’s knowledge about their product and manufacturing process. Examples of ECs can include manufacturing and testing facilities and certain process parameters and specifications.
The new pilot program is intended to help the FDA gain experience receiving, assessing, and engaging with applicants regarding proposed explicit ECs. Gottlieb said that once the ICH Q12 guideline is finalized and implemented, the use of ECs is intended to help reduce submissions of unnecessary postapproval supplement applications and encourage manufacturers to continually improve their processes using the agreed-upon ECs as their guardrails. “This can help promote manufacturing innovations that can improve the quality and safety of drug manufacturing, and potentially lower the cost of finished drug products,” he said in the statement.
FDA will accept nine requests for participation in the pilot program that are submitted before May 30, 2019 from applicants intending to submit NDAs, ANDAs, or BLAs, either original applications or prior approval supplements, with proposed ECs.