The generic pharmaceutical sector is calling on the US Food and Drug Administration (FDA) to make changes to a proposed policy that would make it easier for regulators to prioritize the review of some new generic drug products for which there is no previously approved generic.
In August 2014, FDA released a new policy that proposed a major change to the agency's generic drug review policies. Traditionally, FDA has mostly operated on a first-to-file system in which the first application the agency received would be reviewed first, regardless of its potential impact on patients.
FDA's new policy, MAPP 5240.3 Rev. 1, overturns the first-to-file system in favor of one in which FDA is able to push important applications to the front of the review line. "Potential first generic products for which there are no blocking patents or exclusivities on the reference listed drug may receive expedited review," FDA wrote in the policy.
But the words "first generic" has generated a significant amount of confusion within the generic pharmaceutical industry. In response to that confusion, FDA proposed a new definition for the term "first generic" in November 2014:
A first generic application is any received ANDA:
(1) That is a first-to-file ANDA eligible for 180-day exclusivity, or for which there are no blocking patents or exclusivities; and
(2) for which there is no previously-approved ANDA for the drug product.
FDA said it hoped the newly proposed criteria would "appropriately focus FDA’s resources on approving as quickly as possible, new safe and effective generic drug products for patient use." Implied in that statement is that other criteria—the priority review of a company's "top priority" ANDA, for example—might be substantially more burdensome to implement.
Read our in-depth explanation of FDA's policy proposal in our November 2014 story, "How Should FDA Prioritize the Review of Important New Generic Drugs? Agency Wants to Know."
Industry Feedback: Good Start, But Give us More
Now the generic pharmaceutical industry is weighing in on FDA's proposal, offering both praise and suggestions for how FDA might broaden the definition even further.
For example, the Generic Pharmaceutical Association (GPhA), the generic drug industry's main trade body, told FDA that it was in favor of a definition that defined "a first generic application" as any ANDA:
- that is first to file and eligible for 180-days exclusivity for which there are no blocking patents or exclusivity,
- that is first to file and eligible for 180-days exclusivity which has either been sued or not (all such ANDAs may resolve its legal challenges at any time during the 30-month stay)
- for which there is no other approved marketed ANDA and for which there are no blocking patents or exclusivity
- submitted for drug products that are designated by FDA as drug shortage medicines at the time the ANDA is received.
That definition is similar in two respects to FDA's own definition, but also includes mention of drug shortages and generic drugs not expected to be encumbered by lawsuits. The trade group also mentioned in its comments that FDA should take into account the "undue economic hardship" that lack of generic competition might cause in certain cases. The group also spoke out in favor of assigning "target action dates" (TADs) to applications, calling them "crucial to managing the review process of all abbreviated new drug applications (ANDAs)."
Other generic drug companies offered similar requests to expand FDA's proposed definition. Dr. Reddy's, an Indian generic pharmaceutical company, proposed a six-part definition in its comments to FDA:
- Any ANDA(s) filed for which (i) there are no blocking patents or exclusivities and (ii) other approved ANDA (s) exists but are not commercialized or are discontinued.
- Any ANDA(s) filed for which (i) there are no blocking patents or exclusivities and (ii) other approved applications are approved as 505 b2 applications and not a 505 (j) approval
- Any ANDA(s) filed for which (i) there are no blocking patents or exclusivities and (ii) other approved ANDA (s) exists and are commercialized but there is still a market shortage
- Any ANDA(s) filed for which (i) there are no blocking patents or exclusivities and (ii) the first to file ANDA is not approvable due to a quality/compliance issues
- Any ANDA(s) filed for which ANDA(s) is not approved due to blocking patents but there is a potential for shortage or emergency due to epidemic.
- Generic applications with a paragraph III certification for which there are no approved generics and the associated patent or exclusivity is expiring on or before the assigned GDUFA goal date for the given cohort year.
As with GPhA, Dr. Reddy's comments call on FDA to accommodate market shortages and "quality/compliance issues" that might preclude the approval of another company's generic pharmaceutical products. Such a definition might prove problematic for some Indian drug manufacturers, who have been plagued by quality problems that have in some cases prevented them from bringing new generic drugs to market.
Another generic company, Apotex, had similar recommendations, including an especially notable one:
Submissions that contain a Paragraph IV certification, that are submitted on the first day that any valid Paragraph IV application for the drug in question is submitted, and that are received as substantially complete (i.e. submissions that have “first filer” status). Review of these submissions in a manner that would permit tentative or final approval within 30 months of filing (or 40, as specified by GDUFA).
Such a definition would permit FDA to work on the review of multiple high-value submissions at the same time, regardless of whether one of those submissions would be eligible for first-to-file status.
Read all Comments to FDA