Today, The Hill hosted a webinar called “Complex Generics & the Prescription Drug Landscape.”  Many thanks to The Hill for their efforts.  The takeaway messages from the program participants are important, especially as the current Generic Drug User Fee Amendments III (GDUFA III) negotiations are revving up for the Office of Generic Drugs’ review and approval process.

An evaluation conducted by Dr. Alex Brill, Resident Fellow at the American Enterprise Institute, concluded that if just seven complex generic products not currently approved in the U.S. were to be approved in the U.S. now, patients and the U.S. government would save $1.3 billion a year.

Costs are certainly drivers for improvement in the OGD review and approval process for complex generics.  Dr. Brill indicated that the most important things, which should be the highest priority in the FDA review and approval process, are that the Agency should have clear guidance and the process should be adequately resourced.  When asked what is the single most important question that should be asked to Congress regarding the review and approval of complex generics, Brill said, “why are things taking longer now” to be approved?

Christine Baeder, Senior Vice President and COO for U.S. Generics at Teva, provided a bit of background on what makes some generics “complex.”  She noted that complex generic products come from all therapeutic areas, but they all have unique characteristics that may include the complexity of the active pharmaceutical ingredient, the drug device combination, the dosage form, or the delivery system.  When asked about the significance and impact of getting these complex products approved more quickly, she referred to Dr. Brill’s economic assessment of the cost savings that could be realized as the most important issue.  It all goes to the affordability of drugs and how generics can respond to that need.

Ms. Baeder noted that we can no longer wait forty-four or more months for a complex generic to be approved and she outlined three issues that are most important for increasing efficiency in the FDA review and approval process:

  1. Increased transparency – the FDA needs to be more proactive and timelier in providing advice
  2. Predictability – the industry needs to know when reviews will be completed and when products are nearing approval to be ready to launch them and meet market demand.
  3. Better guidance practices – to provide the most current information and FDA thinking for specific products.

Ms. Baeder noted that, with the GDUFA III reauthorization around the corner, this is the perfect time to address some of the policy issues surrounding complex generics.  This was also echoed by Representative Brett Guthrie (R-KY).  He noted that the original Hatch-Waxman Act was designed for simple generics but it has evolved over time as some of the products took on this “complex” generic status.  Rep. Guthrie said that the FDA must not compromise its safety and efficacy evaluations, but there also needs to be more efficiency built into the process so as not to present unnecessary roadblocks.  The more information the applicant has going into the Agency, the better the quality of the application will be, and that will depend upon continued improvement in communication between the FDA and industry.

Tonya Winders, President and CEO of the Allergy and Asthma Network, hit the nail on the head.  The overall goal is to reduce the number of review cycles and communication, and clear, unambiguous advice from the regulators to industry is the way to do that.  Reliable Agency guidance coupled with application quality is essential in trying to reduce the number of Agency review cycles.  She pointed out that the generic EpiPen took ten years to gain approval.

All of these points (if translated into an action plan in GDUFA III) may help with the process of moving complex generic products through the ANDA review and approval process faster.  However, it must be recognized that, if an NDA approval for a new chemical entity and/or complex product can be granted in ten months, there needs to be a more efficient process for approving a duplicate of that product in an ANDA.

This may involve more meetings with potential sponsors and ensuring that the FDA staff is fully knowledgeable as to how to compare reference listed drugs to generic products prior to receipt of the first ANDAs.  While the FDA is catching up in this area, in the past, they relied on learning along with the ANDA applicants as submissions were made to the Agency.  There must be improved communication for these complex products as well as for generics for which there is currently no competition.  There should be additional touchpoints with the industry to resolve perceived problems arising during review of applications from both the FDA and industry perspectives.  In my opinion, the controlled correspondence (CC) process as it currently stands is woefully inadequate for the purpose of clarifying submission requirements and will be as long as the OGD continues to respond piecemeal (or not at all) to bioequivalence recommendations and reference standard requests.  This is especially true when an applicant wants to bring an old NDA product back to the market when there is no NDA or ANDA product still on the market.  Some CCs asking for BE recommendations have been languishing for well over 2.5 years with no response or product-specific guidance posted.  Perhaps GDUFA III can address some of these issues, but the Agency must look for ways to interact outside of the CC process when deeper dialog is needed to resolve an issue.  In such a case, the Agency should reach out to the industry to initiate a dialog for a complex or unusual situation or issue.  Turning down a CC request is not a solution to the problem nor is letting it sit on the shelf for a prolonged period of time.  I am hopeful but doubtful that these kinds of policy issues and progress can all be incorporated into the GDUFA III reauthorization.  One last thing: It is of utmost importance to ensure that the Agency and the industry have the same understanding of the terms of the goals letter before agreeing on its contents.