FDA Issues Draft Guidance on Exclusivity Periods for Biologics

August 2014

The US Food and Drug Administration “the FDA” has issued draft guidance on exclusivity periods for Biological Products.  The guidance is intended to assist sponsors who are developing biological products as well as sponsors of biologics license applications and represents another step towards the first approval of a biosimilar product in the USA.

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) sets out the data/market exclusivity periods for biologics approved by the US Food and Drug Administration “the FDA”.  This legislation mirrors the provisions already provided for small molecule drugs, however, the exclusivity period for a biological product is much more generous.

Biological products approved by the FDA have an exclusivity period of 12 years starting from the date on which the product is first approved by the FDA.  During the exclusivity period, an application for a biosimilar cannot be submitted for the first 4 years (data exclusivity) and a biosimilar cannot be approved until the end of the 12 year exclusivity period (market exclusivity).

The BPCIA sets out various provisions which define what constitutes a new biological product relative to an already approved biological product (the reference product).  This is important because a new biological product will be entitled to its own 12 year exclusivity period whereas minor changes to existing reference product will not.  In particular, the legislation excludes:

  • a subsequent application filed by the same sponsor or manufacturer of the biological product that is the reference product (or a licensor, predecessor in interest, or other related entity) for:

i)  a change (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength; or

ii)   a modification to the structure of the biological product that does not result in a change in safety, purity, or potency.

The FDA has issued draft guidelines clarifying how it  will determine if the applicant is the same or is related to the sponsor or manufacturer and also sets out what information a sponsor will need to provide to demonstrate that a change to the reference product has resulted in a change to the safety, purity or potency of the product.

Related Parties

The draft guidelines make it clear that the FDA intend to construe related parties broadly to ensure that the exclusions cannot be easily avoided.

A “predecessor in interest” includes entities that the sponsor has taken over, merged with or purchased, or has granted the sponsor an exclusive licence to market the product.

The term  “licensor” of a reference product will be construed broadly to include any entity that has granted the sponsor licence to market biological product, even if the license is non-exclusive.

A "related entity” includes entities which own control the other at the directly or through one or more other entities; and entities that are under common ownership or control.  Interestingly FDA may consider two parties to be related if they have engaged in certain collaborations relating to the development of the biological product.

Changes to the Product

To qualify for a new 12 year exclusivity period a sponsor will need to show that the changes made to the reference product results in a change in safety, purity or potency. 

The guidelines set out various examples of what might constitute a “change” to a biologic. These include differences in amino acid sequences, glycosylation patterns, tertiary structure or post-translational changes including for example pegylation.

The use of a modified cell line to manufacture a biologic will not necessarily constitute a change to the product unless the sponsor can show that the product has been structurally modified by the new cell line.

The sponsor will also have to provide data demonstrating that the modified product has resulted in a change in the safety purity or potency of the product compared to the reference product, unless the modified product affects the difference molecular target to the reference product.

An Orange Book for Biologics?

The guidelines suggest that the FDA is considering publishing information on the date of first approval in biologic and the related exclusivity period.


The draft guidelines provide further insight into how the FDA will handle the exclusivity of biological products.  The guidelines are currently in draft form the FDA has opened a 60 day window for comments.  No doubt there will be much debate from interested parties.  This development represents another step towards the first approval of a biosimilar product in the USA.

This update was prepared by Mike Nelson, Partner of our Leeds office.  Tel: +44(0) 113 233 0100

If you would like further advice on this or any other matter, please contact Mike Nelson or your usual HGF representative or visit our Contact Page to get in touch with your nearest HGF office.