New Impurities Guidance May Speed Generic Approvals
The US Food and Drug Administration (Rockville, MD,
http://www.fda.gov/) released a new draft guidance that may speed generic approvals. The guidance, ANDAs: Impurities in Drug Products, describes the degradation-product information that generic drug manufacturers should include in their abbreviated new drug
applications (ANDAs). This clarification, FDA officials say, will help companies submit the correct information, thus increasing
the likelihood that their generic drugs will be approved, and approved more quickly.
"Deficiencies related to impurity specifications probably occur more often than any other deficiency in applications we see,"
says Gary Buehler, director of FDA"s Office of Generic Drugs (OGD). Those deficiencies result in a lot of "back-and-forth"
discussions, Buehler says, between the agency and the sponsor company. Such dialogue means a longer review—often months longer—and
Buehler says that the new guidance will help reduce those discussions. "Our intention in putting out this guidance is to provide
more predictability to the generic industry as to how they should prepare their applications," he says.
The draft guidance helps manufacturers understand which degradation products they should list in their ANDAs, how to set acceptance
criteria, and what thresholds and procedures to apply when qualifying degradation products. The new guidance applies to generic
drugs the guidelines established in the International Conference on Harmonization's Nov. 2003 guidance, Q3B(R) Impurities in Drug Products. "We want to make sure the policy for generic drugs is the same as [the policy for] innovator drugs," says Lawrence Yu, director
for science at OGD.
Buehler says the guidance will also help ensure consistency among the 11 teams in OGD. "Because we hadn't clearly spelled
out our policies with respect to impurities, we had difficulty sometimes with the interpretation of [those impurities] from
division to division," he explains. "This gives [manufacturers] a clearer idea of what we would expect and also gives our
own reviewers a clearer idea of what the office expects with respect to evaluating applications."
In some areas, the new guidance sets stricter standards for generic manufacturers, because some Q3B(R) thresholds are lower
than the standards set in United States Pharmacopeia monographs, particularly for unspecified and unknown impurities. Nonetheless, Buehler and Yu don't expect a lot of industry
comments on the draft. "The Office of Generic Drugs has been communicating with stakeholders and industry, so I think the
industry will understand the approach and welcome a clear policy for impurities in generic drugs," says Yu.
Improving Manufacturing Science Is Key, According to CDER Report
The FDA's Center for Drug Evaluation and Research (CDER,
http://www.fda.gov/cder/, Rockville, MD) issued its 2004 report to the nation, citing the center's key initiatives: improving the science of drug
manufacturing, streamlining the path for developing new drugs, and improving methods for identifying and analyzing drug safety
The report says that the center's overhaul of the pharmaceutical good manufacturing practices "encourages manufacturers
to modernize their methods, equipment, and facilities to eliminate both production inefficiencies and undue risks for consumers."
It also says the risk-based approach to inspections makes "better use of limited resources."
The 66-page report, Improving Public Health through Human Drugs, says CDER developed initiatives to improve drug safety, protect against bioterrorism, and accelerate drug development while
maintaining its performance in reviewing new drugs and overseeing the safety of marketed drugs. During 2004, CDER approved
119 new medicines and 380 generic versions of existing drugs, and evaluated more than 400,000 reports of adverse drug events,
including more than 20,000 submitted directly by individuals.