Description
This guidance describes the Agency’s recommendations on the design and evaluation of comparative analytical studies intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product licensed under section 351(a) of the Public Health Service Act (PHS Act). Additionally, this guidance is intended to provide recommendations to sponsors on the scientific and technical information for the chemistry, manufacturing, and controls (CMC) portion of a marketing application for a proposed product submitted under section 351(k) of the PHS Act. This guidance finalizes and replaces the draft guidance of the same title issued on May 22, 2019, and replaces the final guidance “Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product” issued on April 30, 2015.
Scope & Applicability
Product Classes
5Guidance focuses on the development and comparative analytical assessment of these products.
A biosimilar product determined to be interchangeable with the reference product.; may be substituted for the reference product without the intervention of the prescribing health care provider
Biological product shown to be highly similar to an FDA-licensed reference product; Biological product demonstrated to be highly similar to a reference product
single biological product licensed under section 351(a) of the PHS Act; U.S.-licensed reference product used for comparative analytical assessment; analytical studies that demonstrate that the proposed product is highly similar to the reference product
Products produced in microbial cells or cell lines; Complex molecules manufactured in living cells
Stakeholders
1Entity responsible for submitting applications under section 524B
Regulatory Context
Attributes
7Factor for consideration in analytical assessment.
some attributes may be highly critical (e.g., protein sequence) but not amenable to quantitative analysis
The degree of uncertainty can impact the critical quality attribute (CQA) risk ranking
Inherent heterogeneity in protein products
Modifications imparted to the protein product
Nature, location, and levels of sugar chains
Measurement of potency for biological products
Identified Hazards
Hazards
2CMC section provides information on adventitious agent safety
Safety concern regarding viral contamination
Related CFR Sections (2)
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
- 21CFR601.2§ 601.2 Applications for biologics licenses; procedures for filing.
(a) General. To obtain a biologics license under section 351 of the Public Health Service Act for any biological product, the manufacturer shall submit an application to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing aRead full regulation →
See Also (7)
- Questions and Answers on Biosimilar Development and the BPCI Act Guidance for Industry: Guidance for Industry (Status: Final)
- Principles of Premarket Pathways for Combination Products: Guidance for Industry and FDA Staff (Status: Final)
- Sameness Evaluations in an ANDA — Active Ingredients (Status: Draft)
- Potency Assay Considerations for Monoclonal Antibodies and Other Therapeutic Proteins Targeting Viral Pathogens (Status: Draft)
- Nonclinical Safety Assessment of Oligonucleotide-Based Therapeutics (Status: Draft)
- Advanced Manufacturing Technologies Designation Program (Status: Final)
- Cross-Center Master Files: Where to Submit: Draft Guidance for Industry (Status: Draft)