FDA Exploring Whether Public Shaming Can Stop REMS Abuses

The US FDA may resort to using its bully pulpit to lessen REMS abuses that prevent generic entry.

Agency letters to brand companies indicating it is acceptable under a Risk Evaluation and Mitigation Strategy (REMS) to sell samples to a generic company for testing may be made public, Commissioner Scott Gottlieb said during the July 18 public meeting on ensuring the Hatch-Waxman Act continues to balance access and innovation.

FDA called the meeting to explore whether changes to generic laws and policy are needed amid problems with rising drug prices.

Generic firms have long complained that brand companies with products covered by a REMS often refuse to allow them to purchase product for sampling because it would violate aspects of the plan.

In 2014 draft guidance, FDA said it would officially notify a brand company in writing that it was not a REMS violation to allow the sale to the generic company. (Also see "Generics REMS Hurdles Lowered Somewhat By FDA Protocol Letters" - Pink Sheet, 4 Dec, 2014.)

The program has not met with widespread success. Gottlieb told meeting attendees that the agency is reviewing the guidance and "actively considering whether it achieves its goals."

REMS letters to brand companies could be released "to make more widely known the instances where generic drug makers may be having trouble getting access to branded drugs," Gottlieb said.

Whether releasing the letters would break the log-jams is unclear. The hope seems to be that disclosure (and the resulting public pressure) may help generic sponsors gain access to the products and potentially curb abusive practices.

"These letters could contain important information that can help inform broader discussions about access and competition," Gottlieb said. "Their public release could be one step to help ensure that unnecessary hurdles to generic drug development are removed."

FDA did not offer a timeline for when a decision on publicizing the letters will be made.

The idea follows on Gottlieb's interest in agency transparency. He also has suggested releasing complete response letters, in part because they could help inform the public about FDA's review process. (Also see "Gottlieb Q&A: Confirmation Is Nearing, Will Complete Response Letters Finally Get Released?" - Pink Sheet, 5 May, 2017.)

What has become known as REMS abuse is not a new problem, but finding a solution to it has been a challenge for the generic industry. In 2012, an early draft of the FDA Safety and Innovation Act included a REMS abuse provision, but it was removed after lobbying by the brand industry. (Also see "REMS Abuse Legislation: GPhA and PhRMA Set To Battle Again" - Pink Sheet, 15 Jun, 2016.)

A representative of the Pharmaceutical Research and Manufacturers of America (PhRMA) did not offer an opinion of the idea when asked by FDA officials at the meeting.

In a later presentation, PhRMA suggested that REMS abuse was not a serious problem in need of reform because there are some generics that have come to market with a REMS. Publicizing the agency's letters could deflate that argument by highlighting instances where generics have not been able to come to market, but the policy shift probably won't dent another industry argument against REMS reforms – providing large quantities of samples is a burden for small firms. (See sidebar.)

REMS letters could become part of the agency's Drug Competition Action Plan, intended to use agency resources to increase competition and potentially help bring down drug prices.

FDA announced in June that the plan also included a change to internal policy to prioritize ANDAs for reference products where there are fewer than three approved applications. (Also see "FDA Drug Pricing Policy Offers Short-Term PR Gain, More Long-Term Actual Benefit" - Pink Sheet, 27 Jun, 2017.)

FDA Also A Problem With REMS Letters

Not surprisingly, many stakeholders raised the problem of REMS being used to prevent generic entry during the meeting.

Michael Carrier, distinguished professor at Rutgers Law School, agreed that the letters should be made public, in part because brand companies sometimes simply ignore them.

But FDA also was implicated as a potential barrier. Candis Edwards, senior VP of clinical regulatory affairs at Amneal Pharmaceuticals LLC, said the company has submitted seven requests for REMS letters since 2015.

Edwards said on average the agency review to determine whether a letter is warranted has taken 18 months. She said FDA has sent two letters sponsors, and of those requests, one was resulted in receiving product.

Edwards asked that the agency commit to a formal review timeline for the reviews, suggesting three to six months.

Submission Guidance, ANDA Assessment Practices Being Developed

FDA also intends to update to its internal policy on ANDA review again, as well as offer industry more guidance on the submission practices.

Gottlieb said that a Manual of Policies and Procedures document on Good ANDA Assessment Practices will be released outlining how the agency can streamline the review process, including eliminating duplicative procedures.

The MaPP will include several new changes to the ANDA review process.

Primary ANDA assessments should focus on "need-to-know" regulatory requirements. Gottlieb also said practice will change such that supervisors will validate, rather than re-do the assessment, and their scrutiny will "vary according to the experience level of the primary reviewer and risk and complexity of the product." If a complete response letter is required, it should "clearly state what needs to be fixed" and if it is not clear, the reviewer should follow-up and explain the issues over the phone, he said.

Gottlieb indicated that GDUFA II review goals will not change because "truncating [the] review prevents applicants from fixing their submissions and getting them approved."

At the same time, FDA also is preparing guidance for sponsors on Good ANDA Submission Practices that should include many familiar items. Gottlieb said it will state "common, recurring deficiencies that we see in applications and provide advice on how these problems can be avoided."

Both documents are expected by the end of the year and intended to help cut the number of ANDA review cycles. Many now require three or more cycles before approval. FDA would prefer the average be one or two. (Also see "ANDA Reviews: First-Cycle Desired, But Two-Cycles OK?" - Pink Sheet, 27 Jul, 2015.)

FDA has argued that submission quality also must improve. (Also see "Generic Drugs: First-Cycle Review Times Improve, But Hundreds Of ANDAs Still Pending" - Pink Sheet, 4 Jul, 2017.)