# Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies; Draft Guidance for Industry; Availability
**AGENCY:**
Food and Drug Administration, HHS.
**ACTION:**
Notice of availability.
**SUMMARY:**
The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a draft guidance for industry entitled “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies.” This draft guidance describes considerations regarding a comparative clinical study or studies with efficacy endpoints (a comparative efficacy study or CES) intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submitting a marketing application under the Public Health Service Act (PHS Act).
**DATES:**
Submit either electronic or written comments on the draft guidance by January 20, 2026 to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance.
**ADDRESSES:**
You may submit comments on any guidance at any time as follows:
**Electronic Submissions**
Submit electronic comments in the following way:
• *Federal eRulemaking Portal: https://www.regulations.gov* . Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to *https://www.regulations.gov* will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on *https://www.regulations.gov* .
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).
**Written/Paper Submissions**
Submit written/paper submissions as follows:
• *Mail/Hand delivery/Courier (for written/paper submissions):* Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”
*Instructions:* All submissions received must include the Docket No. FDA-2011-D-0605 for “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies.” Received comments will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at *https://www.regulations.gov* or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on *https://www.regulations.gov* . Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: *https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf* .
*Docket:* For access to the docket to read background documents or the electronic and written/paper comments received, go to *https://www.regulations.gov* and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR 10.115(g)(5)).
Submit written requests for single copies of the draft guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10001 New Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. See the *SUPPLEMENTARY INFORMATION* section for electronic access to the draft guidance document.
**FOR FURTHER INFORMATION CONTACT:**
Mustafa Unlu, Center for Drug Evaluation and Research (HF-22), Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 1139, Silver Spring, MD 20993-0001, 301-796-3396, *[email protected]* ; or Philip Kurs, Center for Biologics Evaluation and Research, Food and Drug Administration, 240-402-7911.
**SUPPLEMENTARY INFORMATION:**
**I. Background**
FDA is announcing the availability of a draft guidance for industry entitled “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies.” The final guidance for industry entitled “Scientific Considerations in Demonstrating Biosimilarity to a Reference product” published in April 2015 (Scientific Considerations Guidance) described general considerations for comparative clinical studies intended to support a demonstration that a proposed therapeutic protein product (proposed biosimilar or proposed biosimilar product) is biosimilar to a reference product for the purpose of submitting a marketing application under section 351(k) of the PHS Act (42 U.S.C. 262(k)). Comparative clinical studies typically have been designed to analyze and compare a clinical efficacy outcome or other relevant therapeutic effect between the proposed product and the reference product.
Since publication of the Scientific Considerations Guidance, FDA has gained significant experience in evaluating analytical differences between proposed biosimilar products and their reference products and understanding the impact of those analytical differences on clinical performance. A comparative analytical assessment is generally more sensitive than a CES to detect differences between two products, should any exist, that may preclude a demonstration of biosimilarity. Accordingly, FDA's scientific approach to when a CES may not be necessary to support a demonstration of biosimilarity is evolving. FDA is now issuing this draft guidance to provide an overview of important scientific considerations for determining when a CES may inform a demonstration of biosimilarity. In the future, the Agency intends to consolidate certain recommendations in a new guidance describing scientific considerations in demonstrating biosimilarity to a reference product.
This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
As we develop final guidance on this topic, FDA will consider comments on costs or cost savings the guidance may generate, relevant for Executive Order 14192. We are specifically seeking comments on potential cost savings for biosimilar development programs that use a streamlined approach as described in this draft guidance.
**II. Paperwork Reduction Act of 1995**
While this guidance contains no collection of information, it does refer to previously approved FDA collections of information. The previously approved collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). The collections of information relating to the submission of a biologics license application under section 351(k) of the PHS Act, including the submission of data from comparative analytical assessments and a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed, have been approved under OMB control number 0910-0718. The collections of information relating to formal meetings between sponsors or applicants and FDA have been approved under OMB control number 0910-0001.
**III. Electronic Access**
Persons with access to the internet may obtain the draft guidance at *https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents,* or *https://www.regulations.gov,* or *https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances* .
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.