The Price Is Right May be All Wrong
By Terri-Lee Nataline | April 28, 2016
So you think you can always get a Q1/Q2 (qualitative and quantitative sameness) determination from the Office of Generic Drugs (OGD) through a Controlled Correspondence? Well, think again. If a non-Q1/Q2 formulation is permissible for the product in question, then OGD will decline to make that Q1/Q2 determination.
For example, let’s say that the firm plans to pursue a biowaiver for a certain BCS Class 3 drug product. In order to do so, the firm must typically demonstrate that “the test product formulation is qualitatively the same and quantitatively very similar, e.g., falls within scale-up and post-approval changes (SUPAC) IR level 1 and 2 changes, in composition to the reference.” (see Guidance here). In addition, certain other products (such as topical products) that have an in vitro or in vivo option for BE testing, if not Q1/Q2, could be impacted, as well as certain other products for which the FDA requires Q1 and Q2 sameness to avoid the conduct of in vivo studies.
Well, getting this information from FDA may be easier said than done. In many instances, there are inactive ingredients present in the RLD that defy standard measurement. The only way to obtain certainty that the proposed product is quantitatively similar to the RLD formulation is by requesting OGD's determination via Controlled Correspondence. That request, however, will likely be denied on the basis set forth in FDA's Guidance on Controlled Correspondence Related to Generic Drug Development which states, “FDA does not intend to review proposed formulations that are not required or FDA-recommended in guidance to be Q1/Q2 to the RLD.”
FDA’s position places firms in a quandary: either take a gamble that the product is quantitatively similar to the RLD formulation and proceed down the BCS biowaiver pathway, knowing that the biowaiver could be rejected, or worse yet, the ANDA Refuse to Received (RTR’d), or avoid the risk altogether and conduct what could turn out to be an unnecessary bioequivalence study. The first option kicks the can down the road by having the Q1/Q2 assessment done post-filing. This is really a waste of scarce Agency resources, as OGD will need to conduct the same review upon resubmission. It would also waste firms’ resources should the FDA not concur with the Q1/Q2 nature of the formulation as firms may be required to reformulate and conduct new 6-month stability studies. The second option would be to conduct an in vivo pharmacokinetic (pK) or clinical endpoint study on the failed Q1/Q2 formulation that may have been otherwise avoided if OGD had performed a pre-submission review of the formulation. This second option runs counter to one of the basic tenets of Hatch-Waxman Act, which is to avoid unnecessary duplicative human testing and could have been avoided if FDA performed the Q1/Q2 assessment pre-submission like it does for other dosage forms (parenteral or ophthalmic).
OGD should seriously reconsider its position relative to when it will perform Q1/Q2 determinations. Providing firms with the necessary formulation feedback in advance of an ANDA submission is consistent with yet another tenet of Hatch-Waxman – namely to help speed generics to the market. So we are in a “you can pay me now or pay me later” catch 22, but the ultimate payment is made by the American public that will have to wait longer for a generic version of a product to come to market in the current state of affairs.
Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act)
Mandatory Reading:
Regulatory Affairs (Reg)
Intellectual Property (IP)
Quality Assurance (QA)
Legal Department
Work Suggestions:
Reg: Ensure the company's drug applications comply with the new drug application procedures and bioequivalence standards.
IP: Monitor patent term extensions and the impact on the company's patent strategy.
QA: Verify that manufacturing processes meet the identity, strength, quality, and purity requirements.
Legal Department: Advise on patent infringement issues and the legal implications of abbreviated new drug applications.
Scope of Application: The Drug Price Competition and Patent Term Restoration Act of 1984 applies to chemical drugs, including new molecular entities and generic drugs, in the United States. It is intended for regulatory bodies, pharmaceutical companies, and legal entities involved in drug development and approval processes.
Key Points Summary:
Abbreviated New Drug Applications (ANDAs): The Act allows for the streamlined approval of generic drugs by submitting abbreviated applications showing bioequivalence to the listed drug, without repeating costly and time-consuming clinical trials.
Patent Term Restoration: Offers a mechanism to extend the effective patent life of a drug to partially compensate for the time lost during the regulatory review process, up to a maximum of five years.
Data Exclusivity: Provides a period of data exclusivity, during which the FDA cannot approve ANDAs for other companies that rely on the innovator's safety and efficacy data.
Patent Certification: Requires ANDA applicants to certify about the listed drug's patents or periods of exclusivity, which can trigger a patent infringement lawsuit.
Regulatory Review Period: Defines the regulatory review period for calculating patent term extensions and sets rules for due diligence during the application process.
Conclusion: The Drug Price Competition and Patent Term Restoration Act of 1984 is a landmark legislation that balances the need for accessible, affordable medications with the incentive for innovation. It has significantly impacted the pharmaceutical industry by fostering competition and ensuring that both innovator and generic drug companies have clear pathways to market. The above points are not exhaustive; for comprehensive understanding, the full text of the Act should be consulted.
