The message was loud and clear: patients need better access to generic drugs. At the FDA's July 18th Public Meeting Administering the Hatch-Waxman Amendments: Ensuring a Balance Between Innovation and Access, a variety of industry stakeholders provided clear statements of how they believe the FDA can enable this increased access. These groups want to do it by gaining access for manufacturers to samples of reference products for bioequivalence testing, access to Risk Evaluation and Mitigation Strategies (REMS), and access to priority reviews of Abbreviated New Drug Applications (ANDA). This meeting was held in support of the FDA's new "Drug Competition Action Plan" and was designed specifically to allow organizations to provide their perspective on how to reduce anti-competitive practices within the generic pharmaceutical market.
FDA Commissioner Gottlieb blogged about this topic prior to the meeting, calling out two very specific items of interest:
- The statutory requirement for a single Risk Evaluation and Mitigation System (REMS) program across all versions – branded or generic – of a product
- Using limited distribution to restrict the availability of samples of the reference product required for comparative testing
These topics were heavily covered by the presenters, but they were not the only items of interest. We heard passionate pleas regarding the following:
- Evergreening strategies through either reformulation or combinations
- "Pay for Delay" settlements
- Perceived abuse of "Citizen Petitions" to block generic entrants
- Recommendation for eLabeling for generics
- Pending Generic Drug User Fee Amendments II (GDUFA II) legislation
Consistency Across Stakeholder Responses
The overall consistency in responses from the presenters was interesting. Presenters, spanning academia, payers, providers, manufacturers, and patient advocacy groups, all pushed for changes to regulations and administrative actions that currently act as barriers to entry. Each of the recommended changes, on their own merit, make sense for the industry and will affect the generic market in a way that should allow for greater patient access.
The current requirement for a single REMS solution was a nearly universal topic. Branded manufacturers often do not readily allow generic manufacturers to integrate into existing REMS solutions, which effectively blocks a generic drug from being sold into the market due to a single REMS requirement. Additionally, the stringent distribution requirements imposed by a REMS program have been used to prevent a generic manufacturer from securing sufficient samples to conduct bioequivalence testing. Fortunately, members of Congress are already acting on this recommendation.
The Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act of 2017, currently in front of the Senate, provides the ability for a generic manufacturer to bring civil suit against the branded manufacturers when they have "(1) declined to make available sufficient quantities of the approved medication for the developer's testing; or (2) failed to agree on, or refused to allow the developer to join, a single, shared system of elements to assure safe use (ETASU) of the medication."
The Fair Access for Safe and Timely (FAST) Generics Act of 2017 looks to accomplish nearly the same goals. Interesting, though not surprising, multiple stakeholder groups spoke out in support of these acts: The Blue Cross Blue Shield Association and Association for Affordable Medicines in their statements at the meeting, and CVS Health in submitted statements. If enacted, these acts should remove some of the current barriers to providing the access needed to develop and market generics.
Patent Protection and Extension
Of all the other ideas discussed, the most interesting idea warranting future exploration was noted by the majority presenters: the desire to reduce evergreening, or the extension of patent protection through reformulation or combination products. From the perspective of someone focused on branded products, evergreening is appealing and it is a lever to drive economic benefit through modest changes to a products. However, you have to look at the limited therapeutic benefit being brought to the table. When comparing to the economic benefit for the patient population of having access to a generic, the therapeutic benefit is often minimal.
What makes this concept so interesting and complex is the method the FDA would use to determine the line between legitimate therapeutic advantage and minor technical change to differentiate in product alone. The recent settlement against Namenda was cited directly by the FDA, and while it demonstrates their attention is focused on this critical issue, it also highlights the complexity with which these evergreening situations are evaluated. Namenda was found to have pushed this approach too far, extending the life of a product through reformulation. The complicating factor was the decision to release the new, extended release version in advance of patent expiry to switch patients over prior to generic competition. This was designed to limit the desire for all customer groups to switch back to the generic version of the instant release. Namenda was not only the first major instance of pushback on this concept, it has become the reference for future pushback against this method of restricting generic access.
The challenge is the implementation of each change. In our preview of the meeting, we stressed the importance of caution and a focus on maintaining safety requirements when implementing any changes. Pushing generic products to market is good for competition, but it must not be done at the expense of patient safety. We are very intrigued to see which of these ideas takes hold and are pursued by the FDA or Congress and just how effective the changes are in enabling better access to generics. Time will tell, but many of these changes should have an immediate, lasting impact on the marketplace.