FDA's Catch-22 Problem

Although the generic drug approval process was intended to be streamlined and efficient, Abbreviated New Drug Applications (ANDAs) often run a gauntlet of unnecessary and senseless regulatory hazards during the review process. One of the biggest is FDA’s “Catch-22” policy regarding qualitative and quantitative (Q1/Q2) sameness. On the one hand, many generic drugs – particularly injectables and complex generics – cannot be approved unless they contain the same inactive ingredients in the same amounts as the reference listed drug (RLD). This is what Q1/Q2 sameness means. On the other hand, if FDA identifies a deficiency regarding a proposed generic drug’s Q1/Q2 sameness, it will not disclose any details about the deficiency to the ANDA applicant – not the direction or size of the deviation and not even the identity of the ingredient or ingredients at issue. Hence the Catch-22: no approval unless the drug is Q1/Q2 the same; no information about Q1/Q2 sameness unless the drug is approved.

FDA’s review process for Q1/Q2 sameness has not always been so murky. In the past, when FDA determined that a proposed generic drug was not Q1/Q2 the same as the RLD, FDA’s practice was to fully disclose the deficiency. Specifically, FDA would identify the ingredient or ingredients at issue and the general direction of the deviation by telling the applicant, essentially, that “the amount of Ingredient A in your formulation is too high.” This practice allowed ANDA applicants to quickly address the deviation, thereby facilitating timely approval of competing generic drugs. In recent years, however, FDA has changed its disclosure policies in a manner that delays generic drug approval and access. Specifically, where Q1/Q2 deficiencies are identified, FDA will no longer disclose either the ingredient at issue or the general direction of the deviation. Generic drug applicants thus are left guessing on what they can do to get their ANDA approved.

Problems With FDA's Current Q1/Q2 Disclosure Policy

There are several major problems with FDA’s new policy, which was implemented without warning or notice to the generic drug industry. First, it violates FDA’s own regulations, which require the Agency to disclose to the ANDA applicant “all of the specific deficiencies that the agency has identified” and the recommended actions the applicant can take to obtain approval. 21 C.F.R. § 314.110(a)(1), (4). Simply stating that Q1/Q2 sameness has not been established, without more, does not meet the regulatory requirement to describe specific deficiencies or to provide guidance on actions that could be taken to address Q1/Q2 deficiencies. Second, FDA’s new policy delays access to cost-effective generic drugs, contrary to the intent of the Hatch-Waxman Act. By refusing to disclose the specific basis for Q1/Q2 deficiencies, FDA’s new policy severely hampers generic drug development by turning the ANDA process into a guessing game for the applicants.

FDA surely understands these problems but nevertheless appears to be worried about insulating itself from future trade secret related lawsuits, no matter how frivolous. But this concern is misguided. Both the statute and FDA regulations already require the labeling of many brand drugs, particularly injectables, to bear the names and quantity or proportion of all inactive ingredients. See 21 U.S.C. §§ 355(e), (n)(2); 21 C.F.R. § 201.100(d). This demonstrates that information about a brand drug’s formulation and inactive ingredients is not considered to be secret or confidential and is routinely disclosed by brand sponsors in drug labeling. Moreover, FDA routinely discloses to ANDA applicants that a proposed generic formulation is Q1/Q2 the same as the RLD, thereby disclosing, at least indirectly, the brand’s formulation. Disclosing Q1/Q2 deficiencies provides exactly the same information, no more and no less, and thus should be equally acceptable under the statute and FDA regulations.

Potential Congressional Fix

Luckily, Congress is considering legislation that would restore FDA’s prior disclosure policy regarding Q1/Q2 deficiencies. In the recently released bipartisan House Energy and Commerce Committee legislation reauthorizing the various user fee programs, Congress added a provision – section 601 – that would require the Agency to fully disclose the basis for a Q1/Q2 deficiency to the affected ANDA applicant. According to the new provision, if FDA determines that a proposed generic drug is not Q1/Q2 the same as the RLD, it must identify and disclose both the ingredient or ingredients at issue and the amount of any quantitative deviation, thereby allowing the applicant to correct the problem and obtain timely approval. Moreover, the proposed legislation specifies that such disclosures are “authorized by law” under 18 U.S.C. § 1905, thereby removing any concerns the FDA may have about lawsuits alleging an unauthorized disclosure of trade secret or confidential commercial information.

If passed, section 601 would go a long way to extracting both FDA and the generic drug industry from the unproductive Catch-22 in which they’ve been trapped the last few years. If enacted, this provision will enable patients to benefit from timely complex generic drug approvals and ultimately experience lower out-of-pocket costs at the pharmacy counter. Catch-22 is a wonderful work of American fiction, but it is no way to speed the approval of generic drugs.

Categories: Other