Canada: Health Canada Seeks Comment On Revised SEB Guidance Document: New Requirements For SEB Sponsors

On Dec. 7, 2015, Health Canada released a revised Guidance Document for sponsors of Subsequent Entry Biologics (SEB).1 The proposed revisions introduce a number of changes regarding the eligibility, submission and evaluation, and marketing requirements for SEBs from the current Guidance Document, in force since 2010.

Interested parties have until Feb. 15, 2016 to submit comments to the Biologics and Genetic Therapy Directorate (BGTD) of Health Canada on the revised Guidance Document.2

Below is an overview of some of the possible consequences for pharmaceutical stakeholders involved in SEBs, followed by a detailed explanation of the proposed changes.

Possible Consequences

If adopted, increased eligibility for SEB designation may be possible because under the proposed revisions, SEB sponsors will be permitted to refer to clinical studies from more than one biologic drug, so long as each version is similar at the level of quality.

The process for preparing and evaluating SEB regulatory submissions may also become easier. Under the proposed revisions, SEB submissions must be filed in common international formats, while SEB sponsors will be able to obtain early guidance from Health Canada for their regulatory submission.4

However, if adopted, SEB manufacturers will also be subject to new submission, evaluation, as well as pre- and post-marketing requirements that are more extensive and onerous than those that currently exist.

As examples, clinical data submitted must be customized for each SEB so as to detect differences in responses between the SEB and reference drug.5 SEB sponsors seeking to gain approval for additional indications based on extrapolation from clinical data of the reference drug must also now consider additional SEB specific factors.6 

If adopted, SEBs will also be classified as "new drugs".7 Thus SEB sponsors will be subject to all the associated regulatory requirements as new drugs, including the obligation to evaluate and report on post-notice of compliance changes, and, where appropriate, submit periodic benefit risk evaluations reports.8

Proposed Changes

The specific proposed changes include the following:

New Policy:9 Three new principles are included in the proposed revisions. 

First, it is now explicit that an SEB is eligible to apply for both the indications and conditions of use as authorized by the Canadian reference drug.  

Second, an SEB designation does not amount to a declaration of bioequivalence, in addition to pharmaceutical and therapeutic non-equivalence. 

Third, an SEB becomes a "new drug" upon receipt of its NOC, and subject to all associated regulatory requirements. 

Criteria for Reference Drugs:10 Two new criteria are imposed on reference drugs. 

First, SEB sponsors can now refer to more than one reference drug in a submission. 

Second, when referring to a non-Canadian reference drug, new conditions will apply. These conditions include the non-Canadian reference drug must be the same medicinal ingredient, dosage form, and route of administration as the Canadian reference biological.  The drug must also be from a jurisdiction that has an established relationship with Health Canada, is widely marketed and uses ICH guidelines, and has regulatory standards and principles that are similar to Canada.

SEB Drug Submission Format:11 All drug submissions should be filed in the Common Technical Document format established by the ICH. Specific requirements will also apply to the preparation of data for assessment of similarity.

Determining Similarity:12  Under the proposed revisions, determining similarity will no longer be based on the weight of analytical and biological testing.  Instead, the analytical and biological data will be used to inform the scope of clinical and non-clinical data to be gathered and submitted, and should address the potential areas of residual uncertainty.

Requirements for Submitting and Referring to Clinical and Non-Clinical Information:

At least three new requirements are included for submission of clinical data, non clinical data, and extrapolation from clinical data of the reference drug.

In submitting clinical data for an SEB, the sponsor is now required to customize its clinical trials. In particular, sponsors must consider the sensitive population in clinical trial design, and use both clinically relevant and sensitive endpoints.  Sponsors will also be required to justify to Health Canada its clinical trial strategy to evaluate immunogenicity using methods with sensitivity sufficient to detect (i) differences between reference drug and SEB, and (ii) potential impact on safety and efficacy.13

For non clinical data, where similarity is well established by analytical, biological, and in vitro testing, then a single arm non clinical studies in a relevant species can replace comparative non-clinical studies prior to the first human study.14

For SEBs seeking approval for additional indications based on "extrapolation" from comparative clinical data of the reference drug, additional and considerations now apply. Those considerations include (i) characteristics of study population and clinical trials, (ii) risk and impact of immunogenicity, and (iii) impact of concurrent therapies.15

Labelling Requirements:16 SEB sponsors are subject to new requirements to disclose additional information in their product monograph that includes the following:

  • Data generated by the SEB sponsor
  • Information on the basis for which each indication is authorized
  • For all indications, safety information including warnings, precautions, adverse drug reactions or effects, and key post market safety information

Post- Marketing Requirements:17 As part of the designation of SEBs as "new drugs", SEBs will now be subject to all the associated "new drug regulatory requirements. This includes obligations to report post-notice of compliance changes affecting the safety, efficacy, and quality. 

Consultation with BGTD:18 The BGTD is launching a three year pilot that would allow for regulatory review to occur alongside SEB development. As part of this pilot program SEB sponsors will be able to request a Scientific Advice Meeting from BGTD for advice on the preparation of their comparability package.


The draft guidance document can be found here.

The current guidance document can be found here.

More information on Health Canada's consultation currently underway can be found here.


1 Draft-Revised Guidance Document: Information and Submission Requirements for Subsequent Entry Biologics (SEBs), Issued by Health Canada [Draft Guidance]

2 Health Canada Consultation on the Draft Guidance

3 Draft Guidance, Reference Biologic Drug, s 2.1.3

4 Draft Guidance, Organization of data, s 2.3.1, and Consultation with BGTD, section 3

5 Draft Guidance, Clinical Studies, s, and Non Clinical Studies, s

6 Draft Guidance, Extrapolation, s

7 Draft Guidance, Policy Statements, s 1.3.7

8 Draft Guidance, Post Marketing Requirements, s 2.4

9 Draft Guidance, Policy Statements, ss 1.3.5; 1.3.5; 1.3.7

10 Draft Guidance, Reference Biologic Drug, s, 2.1.3, and Considerations for the use of a non-Canadian Reference Biologic Drug, s

11 Draft Guidance, Information requirements for new drug submissions, s 2.3, and Organization of data, s 2.3.1

12 Draft Guidance, Determination of Similarity, s, compare with Guidance For Sponsors: Information and Submission Requirements for Subsequent Entry Biologics (SEBs), issued by Health Canada March 5, 2010 s,

13 Draft Guidance, Clinical Studies, s

14 Draft Guidance, Non Clinical Studies, s

15 Draft Guidance, Extrapolation, s

16 Draft Guidance, Labeling requirements- Product monograph, s 2.3.4

17 Draft Guidance, Post Marketing Requirements, s 2.4

18 Draft Guidance, Consultation with the Biologics and Genetic Therapies Directorate (BGTD), s 3

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

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

Similar Articles
Relevancy Powered by MondaqAI
In association with
Related Topics
Similar Articles
Relevancy Powered by MondaqAI
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 (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

To Use 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