Year in Review: Top U.S. Biosimilars-Related Regulatory Developments of 2021

As 2021 comes to a close, Big Molecule Watch reviews the top five biosimilar regulatory developments of the year:

1. President Biden Signs Orange Book Transparency Act

In January, we reported that President Biden signed H.R. 1503 (the Orange Book Transparency Act of 2020). The Orange Book Transparency Act requires NDA holders to notify FDA if a patent listed in the Orange Book is invalidated by the PTAB or a court, within 14 days of a final decision. The Act also requires that, if such a patent is invalidated, FDA remove or amend the patent information in the Orange Book in accordance with the decision, but not before the expiration of any 180-day exclusivity period that relies on a paragraph IV certification that such a patent is invalid.

2. FDA’s Purple Book

In July, we reported on the FDA’s Purple Book database. As we previously reported, the Consolidated Appropriations Act, enacted in December 2020, contained a provision that required FDA to create a searchable, electronic database of biologics and to update it with patent information provided by the Reference Product Sponsor to an applicant during the patent dance. In 2021, the FDA’s Purple Book went live, providing a searchable database of licensed biological products, including the patent information provided to biosimilar applicants during the patent dance. As of December 29, 2021, the Purple Book database lists patents for Humira, Avastin, and Lucentis.

3. President Biden Issues Executive Order with Provisions to Promote Generic Drug and Biosimilar Competition in American Economy

In July, President Biden issued an Executive Order addressing competition in various sectors of the United States economy, including the healthcare market. Among the initiatives set forth were instructions charging various agencies with tasks to promote generic and biosimilar competition. The Order instructed the FDA to make the process for approving generic drugs and biosimilars more transparent, including by clarifying the standards for interchangeability of biological products and by developing educational materials for providers, patients, and caregivers. The U.S. Federal Trade Commission (FTC) was instructed to target misleading and deceptive statements made about the safety and effectiveness of generics and biosimilars. The Order also contained a controversial proposal to ban many patent settlements that delay the market entry of generic drugs or biosimilars. The U.S. Department of Health and Human Services (HHS) was instructed to support the market entry of lower-cost generic drugs and biosimilars by helping product developers obtain brand-drug samples pursuant to the CREATES Act of 2019. Finally, the Centers for Medicare and Medicaid Services (CMS) were instructed to prepare interchangeable biological products for Medicare and Medicaid coverage, and to create payment models to support increased utilization of generic drugs and biosimilars.

4. FDA Issues Revised Guidance on Biosimilar Development and BPCIA

In September, the FDA issued a revised final guidance for industry entitled “Questions and Answers on Biosimilar Development and the BPCI Act” and a third revision to its draft guidance entitled “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act.” The guidance documents were intended to provide answers to questions from prospective applicants and other interested parties regarding the BPCIA, as well as explain FDA’s interpretation of certain statutory requirements. The FDA also finalized its guidance on issues such as the nature and type of information that a sponsor should provide to support a postapproval manufacturing change for a licensed biosimilar product; whether a sponsor may seek approval of a route of administration, a dosage form, or a strength that is different from the reference product; and whether a sponsor may seek approval for a condition of use that has not been approved for the reference product.

5. FDA’s Woodcock Reviews Patents Practices as a Way to Effect Drug Pricing

In September, we reported that on September 10, 2021, Janet Woodcock, the acting FDA Commissioner of Food and Drugs, sent a letter to Andrew Hirshfield, Under Secretary of Commerce for Intellectual Property and Director of the United States Patent and Trademark Office (USPTO), pursuant to Executive Order 14036. The Order instructed FDA to enumerate and describe relevant concerns to ensure that the patent system does not unduly delay generic drug and biosimilar competition. Commissioner Woodcock flagged the use of continuation patent applications, which “can allow companies to create ‘patent thickets’ by obtaining multiple patents on different aspects of the same product with a patent application,” and the practice of filing patent applications on “post-approval” or “secondary” drug formulations or delivery systems, or new indications, which could “effectively extend[] protection against competition.”

Commissioner Woodcock also outlined suggestions for potential collaboration between the FDA and USPTO, including FDA-offered training to assist USPTO examiners in locating pertinent prior art references in FDA’s public information and databases, and joint training for FDA and USPTO in determining a product’s eligibility for patent term extension. The letter also noted that the FDA would be interested in the USPTO’s perspective on the use of the patent continuation process to engage in possible patent misuse (patent thickets, product hopping, and evergreening), as well as its perspective on whether pharmaceutical patents should be given additional time and resources during the examination process, due to the complex nature of their subject matter. Finally, Commissioner Woodcock noted that the FDA would be interested in data on the impact of post-grant review and IPR proceedings on Orange-Book listed patents and/or patents covering biological products.