Labeling for Biosimilar Products

The guidance document "Labeling for Biosimilar Products," published by the U.S. Department of Health and Human Services Food and Drug Administration (FDA) in July 2018, is designed to help industry applicants create preliminary labeling for proposed biosimilar products, with a focus on section 351(k) of the Public Health Service Act.

According to FDA regulations, the labeling of prescription drugs must contain sufficient information to help healthcare providers use the drug safely and as intended. The approved prescribing information provides a summary of crucial scientific details necessary for healthcare providers to use the drug safely and effectively.

The FDA recommends including clinical study information in a biosimilar's label only if it supports safe usage. Typically, such labels avoid details from similarity studies, which don't independently ensure safety or efficacy. Emphasizing similarity to the original product, the guidance suggests incorporating relevant data from its label, adjusting as necessary, and offers guidance on structuring the label accordingly.

?Specific recommendations on content of Biosimilar Product labeling:

1.??? Approaches to Product Identification:

• ?The labeling of a biosimilar product should use its specific name or proprietary name if available, especially in sections specific to the biosimilar product like indications, dosage, description, and safety information. When giving directives or discussing the drug substance, the proper name of the biosimilar should be used. For instance, in sections like warnings, precautions, contraindications, and drug interactions, the proprietary name or proper name should be applied accordingly.
• In biosimilar product labeling, when discussing clinical studies or data from the reference product, the proper name of the reference product should be used. This applies to sections like adverse reactions and clinical studies within the labeling.
• The risk-benefit profile of the reference product is important for the biosimilar product, even if certain risks haven't been reported with the biosimilar yet. This applies to labeling sections where risks are relevant to both the biosimilar and reference products.
• Different approaches to product identification may be necessary for accuracy, even if based on the reference product's labeling. All labeling text should be carefully reviewed for the most suitable product identification method. For instance, multiple approaches like using the biosimilar product name and its proper name may be required, especially when conveying specific information such as adverse effects and monitoring recommendations.

?2.??? Approaches to Content Presentation:

The biosimilar product's labeling should be specific to its intended use, such as indications and dosing, and should match the language approved for the reference product in those uses. If the biosimilar is approved for fewer uses than the reference product, certain information from the reference product's labeling not relevant to the biosimilar may be omitted. However, in some cases, including information not directly related to the biosimilar's approved uses may be necessary for safety reasons, but it must be written carefully to avoid implying additional approvals. This affects sections like warnings, precautions, adverse reactions, drug interactions, and use in specific populations.

3.??? Approaches to Specific Sections of Biosimilar Product Labeling

• The "Highlights of Prescribing Information" section for a biosimilar product includes the initial U.S. approval year and a statement confirming its biosimilarity to the reference product. The statement should be placed below the approval year and include the proprietary names of both products, followed by an asterisk footnote explaining biosimilarity.
• The "Indications and Usage" section should align with licensed indications and include relevant limitations of use.
• The "Adverse Reactions" section should include a statement about immunogenicity and factors affecting antibody detection, preceding immunogenicity data.

For biosimilar product labeling, applicants must comply with existing regulations for Medication Guides if required. If the reference product's patient labeling includes Patient Information or Instructions for Use (IFU), applicants should create similar materials for the biosimilar, incorporating relevant information from the reference product's labeling with necessary adjustments. Any proposed changes beyond accuracy should be discussed with the FDA, especially if human factors studies are planned, and the final labeling review will occur during the application process.

?During a biological product's lifecycle, changes in labeling may be required to provide updated safety and usage information. The application holder must comply with adverse experience review and reporting regulations. If new information makes labeling inaccurate or misleading, changes must be made accordingly. This includes updating labeling to ensure accuracy, adequate directions for use, and warnings. Additionally, if seeking licensure for additional conditions of use, the application holder can submit a prior approval supplement to the original application with necessary data and revised labeling. Guidance on this process is available on the FDA's website.

?New Biologics License Applications (BLAs) and supplement submissions for biosimilar product labeling should contain the following components:

- An unaltered copy of the reference product labeling, which was utilized in developing the biosimilar product labeling.

- A version of the proposed biosimilar product labeling with tracked changes and annotations, detailing deviations from the reference product labeling.

- A finalized, unmarked version of the proposed biosimilar product labeling.

?Therefore, this guidance serves as a valuable resource for industry stakeholders involved in the development and approval of biosimilar products, offering clear and detailed recommendations to ensure regulatory compliance and patient safety.

Reference:

Research, Center for Drug Evaluation and. “Labeling for Biosimilar Products Guidance for Industry.” Www.fda.gov, 24 Apr. 2020, www.fda.gov/regulatory-information/search-fda-guidance-documents/labeling-biosimilar-products-guidance-industry.