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FDA is encouraging alternative insulins and challenging anticompetitive practices.
The 10th anniversary of the enactment of the Biologics Price Competition & Innovation Act (BPCI) in March 2020 has focused attention on the advances made over the past decade and main challenges ahead. Despite general disappointment over the slow pace of consumers gaining access to less costly biotech therapies, new FDA guidance and clarified policies provide added support for biosimilar development and approval, particularly for diabetes treatments. FDA also has teamed up with the Federal Trade Commission (FTC) to counter anticompetitive practices that thwart development and raise concerns about biosimilar safety and effectiveness.
A positive sign is that the pace of FDA approvals of biosimilars has picked up in recent months, with more than 26 approved products as of early February 2020-10 approved in 2019-and more than a dozen competitors on the market. In addition, the World Health Organization has begun to prequalify biosimilar versions of “essential medicines” to make these treatments more available and affordable in less developed countries.
An important FDA initiative aims to encourage manufacturers to prepare the data needed to support applications for follow-on versions of insulins now deemed to be licensed as biologics and thus eligible for competition from biosimilar or interchangeable therapies. In February 2020, FDA issued a final rule defining the new process, as established by the BPCI and revised in legislation to clarify that the deeming process applies to insulin, human growth hormone, and most proteins-specifically any alpha amino acid polymer with the specific, defined sequence greater than 40 amino acids in size (1). The new rule aims to “bring down prices and help patients have access to more choices for these life-saving drugs,” said FDA Commissioner Stephen Hahn. FDA also issued explanatory documents for consumers (2) and physicians (3) to clarify that treatments approved under the new program will be just as safe and effective and accessible as brand insulin reference therapies.
Efforts to bring insulin competitors to market builds on FDA guidance issued in November 2019 outlining a streamlined development pathway for these long-established therapies (4). That advisory proposes reduced clinical immunogenicity studies for products that present strong comparative analytical assessments demonstrating high similarity to the reference drug, and no residual uncertainty regarding immunogenicity. In May 2019, FDA provided detailed advice on designing and evaluating such analytical studies and on providing scientific and technical information for the chemistry, manufacturing, and controls (CMC) portions of an application for a biosimilar in draft guidance (5). At that same time, FDA published long-awaited guidance on developing interchangeable biosimilars, again noting the importance of analyzing critical quality attributes and identifying analytical differences between the reference product and the proposed interchangeable (6).
The FDA–FTC initiative further aims to encourage prescribing and reimbursement for biosimilars by taking aim at “misinformation” campaigns backed by brands to discourage biosimilar uptake. The regulators outline how they will work together to promote competitive markets for biological products that “contribute significantly to drug costs,” noted Commissioner Hahn (7).
The two agencies also offered to help biosimilar makers gain ready access to samples of reference products needed to develop and test follow-ons-a difficulty that also has plagued the broader generic-drug industry. And FTC is taking a close look at patent settlement agreements involving biologics and biosimilars to detect any antitrust violations. A joint public workshop held on March 9, 2020 addressed these efforts and other strategies to build a more competitive market for biological products.
In a related move, FDA also published guidance in February 2020 outlining the process for seeking FDA approval of a subset of approved indications of a reference product. This approach applies when patent and exclusivity provisions may prevent a newly licensed biosimilar from including all indications of a reference product on the label, a situation that often involves pediatric or orphan disease treatments. But once those limitations expire, FDA encourages the follow-on manufacturer to file a supplemental application with data supporting the expanded uses, as seen in an advisory outlining how data and labeling should be presented to add previously omitted conditions of use (8). FDA says it will review such supplements within six months, much faster than the usual 10-month timeframe set for supplements to biologics license applications (BLAs).
And to ensure that promotional messages related to biosimilars by both brands and competitors are truthful, non-misleading and balanced, FDA draft guidance issued Feb. 3, 2020 instructs brands to avoid implying in its messages that a reference product is safer or more effective than an approved biosimilar, or that the follow-on is “not highly similar” to the reference product, even if the competitor is not licensed for all indications (9). The guidance emphasizes that a biosimilar product is not required to be identical to the brand to be licensed, but just that it be “highly similar” and without “clinically meaningful differences” in terms of safety, purity, and potency. An added proposal is that the FTC take antitrust action against brand manufacturers that make misleading claims to counter competitions.
1. FDA, 21 CFR Part 600, Federal Register, 85 (35), Feb. 21, 2020.
2. FDA, Information for Patients About Regulatory Changes for Certain Biological Product Medications, FDA.gov, undated, accessed March 5, 2020.
3. FDA, Information for Health Care Providers About Regulatory Changes for Certain Biological Product Medications, FDA.gov, undated, accessed March 5, 2020.
4. FDA, Clinical Immunogenicity Considerations for Biosimilar and Interchangeable Insulin Products, Draft Guidance(CDER, November 2019).
5. FDA, Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations, Draft Guidance(CDER, CBER, May 2019).
6. FDA, Considerations in Demonstrating Interchangeability with a Reference Product, Guidance for Industry (CDER, CBER, May 2019).
7. FDA, “FDA and FTC Announce New Efforts to Further Deter Anti-Competitive Business Practices, Support Competitive Market for Biological Products to Help Americans,” Press Release, Feb. 3, 2020.
8. FDA, Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use for Which the Reference Product Has Been Licensed, Draft Guidance (CDER, CBER, February 2020). 9. FDA, Promotional Labeling and Advertising Considerations for Prescription Biological Reference and Biosimilar Products, Questions and Answers, Draft Guidance (CDER, CBER, February 2020).
Vol. 33, No. 4
When referring to this article, please cite it as J. Wechsler, "Biosimilars Poised for Gains in US Market," BioPharm International 33 (4) 2020.