United States: FDA Releases Biosimilar Guidance For Industry

Last Updated: January 10 2017
Article by Jacob D. Moore

On December 29, 2016, the FDA issued guidance to assist applicants seeking FDA approval of a proposed biosimilar product under the Biologics Price Competition and Innovation Act of 2009 (BPCIA). To obtain such approval, an applicant must demonstrate that the proposed product is "biosimilar" to a reference biological product already approved by the FDA. The new biosimilar guidance provides information on how such a showing can be made.

Biosimilar By The Totality Of The Data And Information

Consistent with previous biosimilar guidance, the December 2016 guidance highlights the importance of a holistic evaluation of biosimilarity based on analytical data (e.g., structural and functional comparisons between the biological product and the reference product), animal studies, and clinical studies. According to the guidance, analytical data revealing differences between the proposed and reference products may not per se disqualify the proposed product from being approved as a biosimilar, but obtaining approval of such a product likely will require additional studies—e.g., animal or clinical studies—explaining or addressing those differences in a clinical context. On the other hand, the guidance indicates that if the proposed and reference products show a high level of analytic similarity (e.g., products with so-called "fingerprint-like analytical similarity"), approval may be obtained via a "more targeted and selective approach to conducting animal and/or clinical studies [to] resolve residual uncertainty and . . . support a demonstration of biosimilarity."

Complementing the FDA's emphasis on a holistic "totality of the data and information" approach, the guidance advocates adopting a step-wise approach to data collection. For example, the guidance proposes that analytical studies be conducted before animal or clinical trials are even designed. That way, the results of initial analytical experiments can illuminate the course of subsequent animal or clinical trials. Subsequent studies can be designed—with feedback from the FDA—to specifically address any differences/uncertainties observed in the earlier studies.

The "Critical" Role Of Clinical Pharmacology Studies

The guidance provides specific recommendations regarding the "critical" role of clinical pharmacology studies to a biosimilar evaluation. Particularly relevant are pharmacokinetic (PK) and pharmacodynamics (PD) data, which should provide exposure (e.g., C¬max, Ctrough ss and AUC data) and exposure-response (e.g., data showing the relationship between drug exposure and the pharmacological or toxicological effect) information for both the proposed and reference products.

While both PK and PD data are preferred by the FDA, the agency recognizes that the "complex molecular structure" of biological products may pose challenges in obtaining this data. For example, the guidance acknowledges that "conventional" bioanalytical methods for evaluating PK and PD might not be suitable. The guidance therefore points to the "particular importance" of specific bioanalytical methods, such as ligand binding assays, concentration and activity assays, and/or PD assays (e.g., using biomarkers as discussed below), that can be used to support a biosimilar application.

Collecting informative PD response data can be especially challenging in the context of demonstrating biosimilarity between proposed and reference biological products. With this in mind, the guidance stresses that a PD response can be evaluated by monitoring a biomarker or a panel of biomarkers that "effectively demonstrate the characteristics of the product's target effects." In assessing target biomarker(s) that might be useful for this purpose, the guidance highlights the importance of the following five characteristics:

  • The time of onset of change in the PD biomarker relative to dosing and its return to baseline with discontinuation of dosing
  • The dynamic range of the PD biomarker over the exposure range to the biological product
  • The sensitivity of the PD biomarker to differences between the proposed biosimilar product and the reference product
  • The relevance of the PD biomarker to the mechanism of action of the drug (to the extent that the mechanism of action is known for the reference product)
  • The analytical validity of the PD biomarker.

Conducting pharmacological experiments that account for the above characteristics will facilitate the FDA evaluation of whether the proposed product is sufficiently biosimilar to the reference product to support approval.

Communication With FDA Is Key

The guidance stresses the importance of maintaining an open dialogue with the FDA regarding a proposed clinical pharmacology development plan. Such communication will ensure that clinical trials are designed to resolve lingering uncertainty (and address FDA concerns) regarding biosimilarity. With this in mind, the guidance sets forth several "critical topics" that should be discussed with the FDA "in the early stages of the biosimilar product development plan." These topics include

  • study design
  • the reference product used in the studies
  • the study population,
  • dose selection,
  • route of administration
  • the PK measurements to be obtained
  • the PD measurements to be obtained
  • the time profile for PD measurements and
  • the appropriate statistical analysis to apply when evaluating the clinical data.

Biosimilar Applicants Should Welcome The Detailed Guidance

Applicants seeking a license for a biosimilar product likely will welcome the new guidance. Especially helpful may be the detailed recommendations regarding PK and PD experiments. Indeed, such recommendations set forth with greater clarity a path by which an applicant can obtain FDA approval for their biosimilar product.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Similar Articles
Relevancy Powered by MondaqAI
Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
In association with
Related Topics
Similar Articles
Relevancy Powered by MondaqAI
Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions