Purple Book

FDA says the database covers biological products regulated by its Center for Drug Evaluation and Research, and the FDA-licensed allergenic, cellular and gene therapy, hematologic and vaccine products regulated by the Center for Biologics Evaluation and Research¹. A product may be shown as determined by FDA to be biosimilar to or interchangeable with a reference biological product¹.

Under 42 U.S.C. 262(k)(9)(A), the list is published in a searchable, electronic format and includes²:

• each licensed biological product by nonproprietary (proper name), with the date of licensure of the marketing application, the application number, the licensure status and, as available, the marketing status²;
• patent information: the reference product sponsor must provide the list of patents and their expiry dates to FDA not later than 30 days after providing the list to a biosimilar applicant under subsection (l)(3)(A), or a supplement under (l)(7)², and the sponsor must update that information within 30 days of giving a list or supplement to any later applicant²;
• and each exclusivity period under paragraph (6) or (7) for which FDA has determined the product eligible and that has not concluded².

The statute requires FDA to revise the list every 30 days to add newly licensed products². FDA's database says patent information appears for certain licensed biological products¹.

These terms are defined in 42 U.S.C. 262(i)²:

To be found interchangeable, the product must be biosimilar, must be expected to produce the same clinical result as the reference product in any given patient, and, if administered more than once to an individual, the risk of alternating or switching between it and the reference product must not be greater than the risk of using the reference product without switching (262(k)(4))². A biosimilar application must show biosimilarity based on data derived from analytical studies, an assessment of toxicity and a clinical study or studies, although FDA may determine that an element is unnecessary (262(k)(2)(A))².

• 12-year period. Approval of a biosimilar application may not be made effective until 12 years after the date on which the reference product was first licensed under subsection (a) (42 U.S.C. 262(k)(7)(A))².
• 4-year filing bar. A biosimilar application may not be submitted until 4 years after the reference product was first licensed (262(k)(7)(B))².
• Limits. These periods do not apply to a supplement for the reference product, or to a later application by the same sponsor for certain changes, such as a new indication, route, dosing schedule, dosage form, delivery system, device or strength (262(k)(7)(C))².

FDA's database shows the expiration date of applicable exclusivity for products determined eligible for reference product exclusivity¹. FDA's database also shows first interchangeable exclusivity under section 351(k)(6) where FDA has determined a product eligible¹. This is a separate barrier from patents, as with drugs. See Patent cliff.

Subsection (l) sets out a sequence of information exchanges between a biosimilar applicant and the reference product sponsor, which the Congressional Research Service notes are often called the patent dance⁵. The steps below follow the statute². The Supreme Court has held that the applicant's duty to provide its application and manufacturing information under paragraph (2)(A) is not enforceable by injunction under federal law, the sponsor's remedy being a declaratory judgment action under paragraph (9)(C), and that the notice of commercial marketing under paragraph (8)(A) may be given before licensure⁶.

1. Application and manufacturing informationNot later than 20 days after FDA notifies the applicant that the application was accepted for review, the applicant shall give the sponsor a copy of the application and information describing the manufacturing process (262(l)(2)(A)). Access is subject to the confidentiality terms of paragraph (1)².
2. Sponsor's patent listNot later than 60 days after receipt, the sponsor shall give the applicant a list of patents for which it believes an infringement claim could reasonably be asserted if an unlicensed person made, used, sold or imported the product, and identify those it would be prepared to license (262(l)(3)(A))².
3. Applicant's responseNot later than 60 days after receiving the list, the applicant may give the sponsor a list of further patents on which it believes the sponsor could reasonably assert an infringement claim, and shall give, for each patent on either list, either a claim-by-claim statement of the factual and legal basis for its opinion that the patent is invalid, unenforceable or will not be infringed, or a statement that it does not intend to begin commercial marketing before the patent expires. It shall also respond to the sponsor's licensing offers (262(l)(3)(B))².
4. Sponsor's replyNot later than 60 days after that, the sponsor shall give a claim-by-claim statement of why the patent will be infringed, with a response on validity and enforceability (262(l)(3)(C))².
5. Negotiation, then suitThe parties shall negotiate in good faith on which patents will be the subject of an infringement action. If they fail to agree within 15 days, they exchange lists under paragraph (5). The sponsor shall then sue within 30 days of the agreement or of the exchange of lists (262(l)(4) to (6))².
6. Notice before launchThe applicant shall give the sponsor notice not later than 180 days before the first commercial marketing of the licensed product. After that notice the sponsor may seek a preliminary injunction on certain patents (262(l)(8))².

See Orange Book for the drug side and Patent cliff for how both kinds of loss of exclusivity are discussed.