2015-10063. Guidance for Industry on Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product.” This guidance is intended to provide sponsors with an overview of analytical factors that are relevant to assessing whether a proposed product and the reference product are highly similar for the purpose of submitting a marketing application through an abbreviated licensure pathway. This guidance finalizes the draft guidance issued in February 2012.

DATES:

Submit either electronic or written comments on Agency guidances at any time.

ADDRESSES:

Submit written requests for single copies of this guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 2201, Silver Spring, MD 20993-0002 or the Office of Communication, Outreach and Development (HFM-40), Center for Biologics Evaluation and Research (CBER), Food and Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, 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 guidance document.

Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Sandra Benton, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6340, Silver Spring, MD 20993-0002, 301-796-1042, or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry entitled “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product.” This guidance is intended to provide sponsors with an overview of analytical factors that are relevant to assessing whether a proposed product and the reference product are highly similar for the purpose of submitting a marketing application through the abbreviated licensure pathway under section 351(k) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(k)). Although the 351(k) pathway applies generally to biological products, this guidance focuses on therapeutic protein products.

The Biologics Price Competition and Innovation Act of 2009 was enacted as part of the Patient Protection and Affordable Care Act (Pub. L. 111-148) on March 23, 2010, created an abbreviated licensure pathway under section 351(k) of the PHS Act for biological products demonstrated to be biosimilar to or interchangeable with a reference product. Under this abbreviated licensure pathway, FDA will license a proposed biological product submitted under section 351(k) of the PHS Act if FDA “determines that the information submitted in the application . . . is sufficient to show that the biological product . . . is biosimilar to the reference product . . .” and the 351(k) applicant (or other appropriate person) consents to an inspection of the facility that is the subject of the application (i.e., a facility in which the proposed biological product is manufactured, processed, packed, or held).^[1]

All product applications should contain a complete and thorough chemistry, manufacturing, and controls section that provides the necessary and appropriate information, including, but not limited to, characterization, adventitious agent safety, process controls, and specifications, for the product to be adequately reviewed.^[2] This guidance describes important factors for consideration when assessing whether a proposed product and the reference product are highly similar, including:

• Expression System
• Manufacturing Process
• Assessment of Physiochemical Properties
• Functional Activities
• Receptor Binding and Immunochemical Properties
• Impurities
• Reference Product and Reference Standards
• Finished Drug Product
• Stability

In the Federal Register of February 15, 2012 (77 FR 8884), FDA announced the availability of the draft guidance entitled “Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product” dated February 2012. FDA received a number of comments on the draft guidance. In response to these comments, this guidance provides further clarification on general principles on topics including, but not limited to, the use of comparative analytical data to provide the foundation for a biosimilar development program, the timing of submission of analytical similarity data, the appropriate number of lots needed, and the type of bridging data needed when sponsors use a non-U.S.-licensed comparator product in certain studies. The guidance provides additional clarification on the factors for consideration in assessing whether a proposed product is highly similar to the reference product. This guidance finalizes the draft guidance issued in February 2012.

This guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidance represents the Agency's current thinking on quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

II. Comments

Interested persons may submit either electronic comments regarding this document to http://www.regulations.gov or written comments to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments with the docket number found in brackets in the heading of this document. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

III. The Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of information found in FDA regulations, which are not expected to change as a result of the guidance. These 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. 3501-3520). The collections of information related to the submission of: (1) An investigational new drug application, which is covered under 21 CFR part 312 and approved under OMB control number 0910-0014; (2) a new drug application, which is covered under 21 CFR 314.50 and approved under OMB control number 0910-0001; (3) a biologics license application (BLA) under section 351(a) of the PHS Act, which is covered under part 601 (21 CFR part 601) and approved under OMB control number 0910-0338; and (4) a BLA under section 351(k), which is covered under part 601 and approved under OMB control number 0910-0719.

IV. Electronic Access

Persons with access to the Internet may obtain the document at either http://www.fda.gov/​Drugs/​GuidanceComplianceRegulatoryInformation/​Guidances/​default.htm,, http://www.fda.gov/​BiologicsBloodVaccines/​GuidanceComplianceRegulatoryInformation/​default.htm,, or http://www.regulations.gov.

Dated: April 24, 2015.

Peter Lurie,

Associate Commissioner for Public Health Strategy and Analysis.

Footnotes

1.  Section 7002(a)(2) of the Affordable Care Act, adding section 351(k)(3) of the PHS Act (citing section 351(a)(2)(C) of the PHS Act).

2.  For CMC requirements for submission of a marketing application, applicants should consult current regulations, the guidance for industry for the “Submission of Chemistry, Manufacturing, and Controls Information for a Therapeutic Recombinant DNA-Derived Product or a Monoclonal Antibody Product for In-Vivo Use,” and other applicable FDA guidance documents.