Day 2 of the Generic Pharmaceutical Association ("GPhA's") annual Fall Technical Conference focused on RTR issues, FDA's efforts to update the inactive ingredient database, stability, Uhl's OGD update, and closing remarks.Some of the key take aways for RTRs is that once year three of GDUFA kicks in, FDA will take a closer look at RTR issues such as DMFs, which need to be accepted for referencing rather than just filed prior to the ANDA. In the past, many sponsors had filed their ANDAs close in time--and sometime simultaneously--with the ANDA to prevent competitors and referenced drug holders alike from suspecting their ANDA filing in advance of a patent challenge notice. Now FDA is recommending that DMFs be filed at least six months in advance to permit a completeness assessment for filing. FDA's recommendation is based on an observation that it typically takes between two to five months for DMF holders to address submission deficiencies.
Johnny Young, M.A.L.A., Regulatory Health Project Manager, OGD, explained that OGD has been viewing excipients more critically than before, e.g., ophthalmic drugs need to be Q/Q even though the current regulations provide certain exceptions, based on what has been learned. Young also noted that there are new microbiology and stability requirements for ANDA that may also lead to RTRs, and he recommended that industry take a careful look at the new RTR guidance as well as ANDA checklist, which is regularly updated. Representing industry's viewpoint, Robert Pollock, M.S., R.Ph., Senior Advisor and Member of the Board, Lachman Consultant Services, Inc. said that the proposed five-day turn around to remedy a RTR prior to its issuance (from the current 10-day scheme) may prove to be difficult for industry to meet. Pollock also thought that it would be important for ANDA applicants to submit higher-quality ANDAs at the onset rather than hoping to fix them later, even when there is a rush to be the first patent challenger for 180-day exclusivity, because a RTR could remove that incentive.
During a question-and-answer period, FDA explained that its new RTR guidance put into writing many of the policies it had been following, so not that much in it was particularly new. Ian Margand, R.Ph., Regulatory Support Management, OGD, explained that for GDUFA to work, ANDA applicants have to take a greater responsibility for their DMF holders. In particular, ANDA applicants need to provide time for their DMF holders to provide an adequate DMF for their ANDA to be filed. Regarding labeling carve-outs to attempt to avoid certain Orange Book-listed patents with method-of-use claims or unexpired exclusivity, Young said that like other RTR issues, FDA will provide ANDA applicants with five days to fix prior to receiving an RTR, if the carve out is not in line with the Agency's expectations of appropriate carve outs.