Drugmakers Say FDA Draft Guidance Not Clear on Reporting Timeframe

August 6, 2015

Drugmakers want to know when changes to chemical, manufacturing and controls in NDAs, ANDAs and BLAs must be reported to the FDA, saying draft guidance lacks clear criteria and examples.

AstraZeneca argues that changes to the maintenance strategy for a process or equipment should be considered part of continuous quality improvement and not subject to reporting. The company was among 13 that weighed in on the May guidance.

The confusion centers on the FDA’s definition of an “established condition,” which, if changed following approval, must be reported to the FDA.

As part of the application process, the FDA said it will assess established conditions in conjunction with the level of understanding about the product and process, the applicant’s risk assessment activities and the proposed control strategy.

Glenmark Pharmaceuticals wants to know how this will apply for products awaiting approval and how the FDA will communicate assessments to applicants.

AZ also wants to know whether approval might be delayed if applications don’t include a summary of established conditions.

Drugmakers also raise harmonization concerns. AZ questions the timing of the guidance, noting the International Conference on Harmonisation is developing ICH Q12, covering similar issues. And Pfizer points out that the guidance talks extensively about control strategy without referencing ICH Q8, 10 and 11, which address this concern.

Pfizer also disagrees with a requirement that updated batch records be submitted following changes to the process or control strategy. These are not considered established conditions and shouldn’t need to be submitted, especially as they are available during FDA inspections, the drugmaker says. The company also wants the FDA to provide an example of when an established condition would no longer be necessary.

The FDA should also define “legacy product” and how established conditions for these drugs would be described in applications, drugmakers say.

Leo Pharma says the definition should include the month and year a product could be classified as legacy and criteria to determine whether a legacy product must be reported to the agency.

AZ suggests it might be more practical to delineate the established conditions after legacy products have been approved when additional data is available to show risk mitigation. In general, legacy products are ones that are no longer under development but haven’t been retired from a company’s drug development program.

The FDA has not indicated when it will issue final guidance. To view the draft guidance, go to www.fdanews.com/05-29-15-CMCguidance.pdf. — Kellen Owings