Pharma Companies Warn of Regulatory ‘Dead Zone’ With FDA’s Interpretation of BPCIA

Regulatory NewsRegulatory News | 27 May 2016 |  By 

Sanofi, Mylan, Novo Nordisk, and industry groups PhRMA and the Biosimilars Council are all calling on the US Food and Drug Administration (FDA) to amend its interpretation of the "deemed to be a license" provision of the Biologics Price Competition and Innovation Act (BPCIA) of 2010 as some are saying the current draft guidance could halt biosimilar development for a prolonged period.

The provision in the BPCIA in question states that: "An approved application for a biological product under section 505 of the Federal Food, Drug, and Cosmetic Act [FD&C] (21 U.S.C. 355) shall be deemed to be a license for the biological product under such section 351 [of the Public Health Service Act (PHS)] on the date that is 10 years after the date of enactment of [the BPCIA]."

FDA interprets this provision to mean that on 23 March 2020, applications for biologics that have been approved under section 505 of the FD&C Act will no longer exist as New Drug Applications (NDAs) (or, as applicable, Abbreviated New Drug Applications (ANDAs)) and will be replaced by approved Biologics License Applications (BLAs) under section 351(a) or 351(k) of the PHS Act, as appropriate.

Rob Cerwinski, a partner in Goodwin Procter's IP Litigation Group, previously told Focus that with the guidance, FDA wanted to get ahead of companies that might be investing in a decision to file under an NDA or 505(b)2 or ANDA pathway that FDA has typically allowed.

In comments submitted on the March draft guidance, industry groups and a number of companies impacted by the provision are calling for a complete shift in FDA’s interpretation of the statute.

PhRMA, for instance, said that FDA’s proposal that NDAs pending on 23 March 2020—including tentatively approved NDAs, “would not be finally approved and would need to be withdrawn and resubmitted under the PHSA is contrary to the plain language of the BPCIA. The statute preserves sponsors’ ability to submit applications under section 505 of the FDCA until March 23, 2020. FDA’s proposed interpretation also is unduly burdensome and would unnecessarily delay patient access to new medical treatments.”

‘Dead Zone’

PhRMA joins a number of companies in saying the proposal “would create a blackout period during which applicants would be unable to submit either NDAs or BLAs for their proposed medicines. For instance, the sponsor of a follow-on transition biological product would be unable to submit a biosimilar application (due to the lack of a reference product, the originator application having not yet been ‘deemed licensed’) and unable to submit a section 505(b)(2) application (because there is insufficient time to secure approval). Similarly, because FDA’s proposed approach seemingly would apply to pending supplemental NDAs, it could hamper efforts by sponsors to introduce product improvements and ensure consistent drug supply in the lead up to March 23, 2020.”

Similarly, GPhA and its Biosimilars Council noted that “delays caused by this regulatory ‘dead zone’ not only will have a ‘significant impact’ on ongoing biosimilar development plans but also will have a major negative impact on the U.S. healthcare system.”

For example, the groups pointed to the insulin market, where they say FDA’s proposed policy could result in $6.65 billion in lost savings annually in the US. Sanofi’s Lantus and Lantus Solostar products are daily, chronic use medications widely prescribed to a growing diabetes population. In the year ending in October 2015 alone, Sanofi Aventis “realized almost $9 billion dollars in sales – much of which was borne by state and federal drug purchase and insurance programs – and the price is skyrocketing.

“A biosimilar or interchangeable insulin product approved to compete with the Lantus products can result in $18.3 million in daily savings to the U.S. healthcare system,” GPhA and its council wrote.

Mylan also highlighted the way in which FDA’s current interpretation “creates a regulatory ‘dead zone’ that could already be disrupting development programs for transitional biologic products... The scope of this regulatory dead zone may vary but is likely to be lengthy. At a minimum, it will extend at least a year, i.e., from March 2019 to March 2020, because of FDA’s 10-month user fee goal for reviewing 505(b)(2) applications and ANDAs. Reasonable sponsors are unlikely to submit applications within, or even close to, this 10-month review period because of the unlikelihood, and in some cases impossibility, of receiving FDA approval by March 23, 2020. This one-year period, however, is only a minimum: FDA’s review times for complex products historically have extended well beyond a year.”

For example, Mylan says the review times for Basaglar (insulin glargine injection), Omnitrope (somatropin [rDNA origin] for injection), and enoxaparin were 2 years, 4½ years and 5 years, respectively.

“Reasonable sponsors will factor these historical review times into their planning and make submission decisions accordingly. They also will consider Hatch-Waxman patent and exclusivity protections, which could block approvals for 30 months or more if innovator products are protected by patents or non-patent exclusivity. Consequently, for many transitional biological products, a more realistic estimate is that the regulatory dead zone will last anywhere from two to four years,” Mylan added.


Sanofi, meanwhile, could stand to lose some of its exclusivity under the draft interpretation and is calling for patent protections to be preserved.

“While the transition statute mandates that biological products approved under the FDCA must be transitioned to the PHSA, it does not grant FDA the authority to extinguish the value of the regulatory exclusivity and other rights that have been lawfully awarded to the sponsors of products approved under the FDCA. To revoke those rights without express statutory authority and without compensating the holder would be contrary to law. In particular, terminating the Hatch-Waxman exclusivity without compensating the holder would create a significant Fifth Amendment constitutional issue,” Sanofi said.

FDA, however, has made clear its thoughts on exclusivity, noting: "Nothing in the BPCI Act suggests that Congress intended to grant biological products approved under section 505 of the FD&C Act — some of which were approved decades ago — a period of exclusivity upon being deemed to have a license under the PHS Act that would impede biosimilar or interchangeable product competition in several product classes until the year 2032.”

PhRMA, meanwhile, offered alternative ways for FDA to interpret the “first licensure” date from which reference product exclusivity runs, including: “(1) the date on which the NDA is deemed to be a biologics license application (BLA); (2) the date on which FDA approved the NDA for the transition biological product; or (3) the date that provides reference product exclusivity that would expire on the date that Hatch-Waxman exclusivity would have expired.

“The agency’s reading is by far the least natural reading of the BPCIA. It is inconsistent with other parts of the Draft Guidance and statutory provisions. The Draft Guidance also raises constitutional issues concerning a taking of private property without just compensation in violation of the Fifth Amendment and threatens the nation’s compliance with its free trade agreements,” PhRMA said. “The most natural reading of the BPCIA is that the first licensure occurs on the date on which a transition biological product is deemed licensed under the PHSA. We understand FDA has concerns with this literal reading of the statute and therefore urge FDA to embrace a compromise approach—one that harmonizes the BPCIA with the FDCA.”

But GPhA and its Biosimilars Council took FDA’s side on the issue of exclusivity, saying that “awarding new 4- and 12-year exclusivity periods to such products would result in a massive, undeserved windfall to many previously-approved biological products that have been marketed for years and already have benefitted from the Hatch-Waxman exclusivity and patent listing protections, including the 30-month stay provision.”

Goodwin Procter’s Cerwinski also previously told us: “Companies that made the choice to file NDAs rather than BLAs understood the exclusivity, those expectations haven't been altered.”



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