No slow-down for
generics
Because of all the complexities associated with follow-on proteins, FDA
review and approval of FOPP applications probably will be handled by
CDER’s new drug review office, as opposed to the Office of Generic
Drugs (OGD). That’s fine with OGD staffers, who continue to struggle
with an increasing number of abbreviated new drug applications (ANDAs).
OGD received more than 600 ANDAs in 2004—double the volume of 2001—and
there’s no slow-down in sight, according to OGD director Gary Buehler.
OGD has managed to reduce median ANDA approval times to less than 16
months (from more than 20 months in the mid-1990s) and is testing
further innovations to improve the process. But new challenges and
tight budgets may make it hard to cut review times much more.
One new OGD assignment is to provide expedited reviews for new generic
AIDS therapies. These generic submissions are coming in response to the
President’s Emergency Plan for AIDS Relief (PEPFAR); FDA approval of
generics made in India and other counties makes them eligible for
purchase by PEPFAR for distribution to developing nations. Buehler
anticipates processing 40 or 50 applications for AIDS drugs in the
coming months. He expects to process ANDAs for single entity and
combination AIDS drugs in only four to five months by starting a review
before receipt of full stability data; if an application comes in with
complete stability testing, the review could be completed in two
months. Shifting PEPFAR applications to the top of the queue, however,
may slow the processing of some ANDAs not related to AIDs.
To offset delays, Buehler is continuing efforts to streamline the ANDA
review system. A main goal is to help manufacturers submit
more-complete applications that the agency may evaluate in one or two
review cycles. A prime initiative is to reduce delays caused by
inadequate drug master files. FDA is testing a process for identifying
and reviewing drug master files before an ANDA comes up for review. OGD
also is urging manufacturers to calculate product specifications more
carefully to reduce the time OGD staff must spend negotiating tighter
limits. And the agency is seeking ways to improve the process for
dealing with citizen petitions, which absorb considerable time and
resources and may delay final ANDA market approval.
Other generic drug streamlining strategies include:
• Encouraging manufacturers to submit dissolution data early in the
process so that OGD may resolve dissolution issues early on.
• Testing a question-based review of manufacturing quality and
formulation data. This strategy involves eliminating nonscientific
specifications that have no relation to product quality.
• Continuing a pilot cluster review process. When a large group of
applications for the same product come in, OGD wants to assign a
special review team to process all the ANDAs together. This approach
has proven to be more efficient, even though it raises some eyebrows by
violating OGD’s “first-in, first-reviewed” policy. FDA is considering
issuing an internal memo that would clarify when the cluster review
approach is appropriate and procedures for implementing it.
OGD benefited from additional funding in recent years, which has
allowed Buehler to establish a third chemistry review division and
expand bioequivalence teams. OGD also has worked hard to help
manufacturers improve the quality of their applications, with some
success: Less than 10% of applications now fall into the refuse-to-file
category. But FDA’s budget is slated to be very tight next year, with
most additional funds targeted to drug safety activities. The prospect
is dim that OGD will be able to add more people to handle the office’s
growing workload, placing even more importance on identifying and
implementing more-efficient approaches. PT
