FDA´s Pilot Program for Established Conditions

Last year, the US Food and Drug Administration (FDA) published ICH´s draft Q12 guidance for industry titled, “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management”. This guidance provides a risk-based approach to regulatory oversight of post-approval changes and a mechanism for applicants to gain agreement with the agency on the established conditions (ECs). Once the ICH Q12 guideline is finalized and implemented, the use of ECs is intended to help reduce submissions of unnecessary postapproval supplement applications. This can help promote manufacturing innovations and potentially lower the cost of finished drug products. However, the use of ECs is currently highly discussed in pharmaceutical industry as shown in the comments recently provided by EMA.

Identifying "Established Conditions" for Manufacture and Control

According to FDA, examples of ECs can include manufacturing and testing facilities, and certain process parameters and specifications. In the 2015 FDA draft guidance on ECs and reportable chemistry, manufacturing, and controls (CMC) changes, the agency defines ECs as “the description of the product, manufacturing process, facilities and equipment, and elements of the associated control strategy as defined in an application, that assure process performance and quality of an approved product.” Changes to such ECs must be reported to FDA. This definition aligns with ICH’s Q12 guidance, which notes that: “ECs are legally binding information (or approved matters) considered necessary to assure product quality. Consequently, any change to ECs necessitates a submission to the regulatory authority.”

In addition, the ICH Q12 draft guidance describes how an applicant can identify and propose so-called “explicit” ECs in which the EC itself or the reporting category for the EC, if changed, differs from existing requirements as described in regulations and guidance. “Such explicit ECs should be supported by an appropriate justification that takes into consideration the applicant’s development approach and risk to product quality. FDA recognizes that this process will be new for both applicants and Agency staff.”, the Federal Register states.

Therefore, the details of a new pilot program to gain experience receiving, assessing, and engaging with applicants regarding proposed ECs have been announced.

FDA´s Pilot

FDA´s Center for Drug Evaluation and Research (CDER) announced the new pilot program where sponsors can propose ECs 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). “FDA will accept nine requests submitted before May 30, 2019 from applicants intending to submit NDAs, ANDAs, or BLAs, either original applications or prior approval supplements, with proposed ECs,” the agency said. The submission of the application should be sent to FDA no later than 1 July 2019. FDA identifies four objectives for the pilot:

• gaining experience in assessing explicit ECs,
• engaging with applicants during the review cycle to refine such ECs,
• ensuring assessment decisions are made without negatively impacting the ability to meet user fee timeframes, and
• identifying agreed-upon ECs at the time of approval.

Furthermore, FDA encourages applicants who are accepted into this pilot to pursue pre-submission meetings with the agency. And, although FDA’s Center for Biologics Evaluation and Research (CBER) is not involved in the pilot, FDA said the CBER intends to leverage CDER’s experience as CBER assesses explicit ECs in future submissions.

To learn more about how to participate in the pilot, please see the notice in the Federal Register.