US FDA, USP Collaborate To Promote Generic Development In Reversal Of Biosimilar Clash

Talks remain in early stages, but both sides thinking 'outside the box' to come up with potential policy updates to generate more generic competition and bring down drug prices.

The US FDA and the US Pharmacopeia may be at odds over biosimilar policies, but the two are trying to work together to encourage more small molecule generics to enter the market.

The organizations remain in the early stage of talks about how USP's monograph system could be used to generate more generic competition for drugs currently without competition, said Maryll Toufanian, acting director of FDA's Office of Generic Drug Policy within its Office of Generic Drugs.

Toufanian said the talks are part of FDA's effort to "think creatively" about the issue.

"We started a conversation with them," she said during a May 3 session at the Food and Drug Law Institute Annual Conference. "What can they do in their monograph development and modernization that can be targeted to help development of these off-patent, off-exclusivity products. So we're really trying to think outside the box as much as we can on this."

FDA wants USP to modernize compendial standards primarily to help firms develop generics for drugs on its off-patent, off-exclusivity list. When the talks were announced in December, FDA said USP may use the list as a reference for drugs to consider developing or updating its standards.

Elizabeth Miller, USP VP of US Regulatory Affairs, told the Pink Sheet that USP supports the "intended outcomes" of FDA's Drug Competition Action Plan (DCAP) and is "actively engaging" with FDA.

Toufanian said after the FDLI session that no ideas were ready for prime time yet. But it is potentially another avenue for helping create more competition to help lower drug prices.

President Trump and HHS Secretary Alex Azar unveiled their drug pricing plan May 11, which includes many proposals, such as moving drugs in Medicare Part B to Part D to facilitate price negotiation. (See sidebar.)

The plan also said the administration will consider requiring drug companies to include their prices in DTC advertising. (Also see "How Drug Promotion Might Change Under Trump's Rx Pricing Plan" - Pink Sheet, 14 May, 2018.)

FDA's role in the fight against high drug prices has largely been finding ways to increase competition, namely by encouraging generic development.

The agency targeted drugs without generic competition in 2017 when it published a list of NDAs with no blocking patents or exclusivity preventing competition. (Also see "Generic Industry Gets 267 Reasons From FDA To Pursue ANDA Development" - Pink Sheet, 27 Jun, 2017.) But it turned out there were few takers early on, likely because most generic companies already had determined that the drugs on the list were not worth pursuing. (Also see "FDA's Off-Patent, Off-Exclusivity List Draws Few Takers Early On" - Pink Sheet, 4 Aug, 2017.)

Looking Beyond Monographs

Miller said that "everything is on the table and being considered" in the talks with FDA.

That includes how USP policies can help companies develop generics for the off-patent, off-exclusivity list, "where we are exploring how to develop and revise standards," she said.

Miller also said USP and FDA are considering "other mechanisms to continue to provide helpful, supportive information, resources, and tools to facilitate development of important generic medicines."

"We are being innovative in our thinking, looking beyond our usual mechanisms (monographs, general chapters) seeking to identify opportunities for collaboration among FDA, USP, industry, and other stakeholders to support and contribute to expanded availability and access of needed generics for patients," she said.

Among the keys to the effort may be to add more detail and specifications on impurities and other characteristics to the monographs. Robert Pollock, senior VP at Lachman Consultants, told the Pink Sheet that many monographs are missing specifics on impurities and other items that may be useful. Absent that information, generic sponsors often are left guessing, which can hinder development.

USP standard changes should fit with other FDA policies intended to ease the burden of generic drug development.

FDA Commissioner Scott Gottlieb has said he wants to adjust the instructions for use regulations for combination products to allow generics on the market faster. (Also see "Generic Combination Products May Be Permitted Delivery Device Variations" - Pink Sheet, 4 Jun, 2017.)

The agency also is considering adjusting regulations of 180-day exclusivity to eliminate efforts to prevent other generics from entering, as well as adjustments to Risk Evaluation and Mitigation Strategy rules so generic companies are not blocked from obtaining samples. (Also see "Are 180-Day Exclusivity Changes Moving Out Of Drug Pricing Plans?" - Pink Sheet, 10 May, 2018.) In addition, Gottlieb has called on industry to stand up against inappropriate behavior, saying tolerance for increasing drug prices is running thin. (Also see "Gottlieb: Real Risk Of Congressional Action If Anti-Competitive Actions Continue" - Pink Sheet, 3 May, 2018.)

FDA, USP Clashed Over Biosimilars

The FDA/USP collaboration on small-molecule generic drugs represents a much different climate than the two organizations created in relation to biosimilar regulation, another area that the administration hopes will help bring down drug prices.

FDA publicly criticized USP for its stance on how the monograph system should handle biologics. In April, FDA released a letter sent to USP stating that it was against a USP proposal to align the suffix naming system with the biologic monographs and worried that the change could potentially hurt biosimilar development. (Also see "US FDA Vs. USP: Regulator Sees Biologic Product Monographs As Barrier To Biosimilars" - Pink Sheet, 2 Apr, 2018.) USP ended up holding implementation pending additional work on the proposal's implications. (Also see "USP Backs Down From Biologic Monograph Naming Plan Amid US FDA Objections" - Pink Sheet, 30 Apr, 2018.)

Gottlieb said FDA will release a plan to encourage more biosimilar development soon and has suggested it may include changes to the standards for interchangeability. (Also see "US FDA Biosimilar Guidance Update Will Relax Interchangeability Standards" - Pink Sheet, 21 Apr, 2018.)