USFDA Draft Guidance: Biosimilar and Interchangeable Biosimilar Products – Considerations for Container Closure Systems and Device Constituent Parts

As biosimilar development continues to advance, regulatory expectations extend well beyond demonstrating analytical similarity and clinical performance. Product presentation—including the container closure system (CCS) and device constituent parts—has become an important aspect of ensuring product quality, usability, and patient safety throughout the product lifecycle.

The U.S. Food and Drug Administration (FDA) has published the draft guidance Biosimilar and Interchangeable Biosimilar Products: Considerations for Container Closure Systems and Device Constituent Parts to provide recommendations for sponsors developing therapeutic protein biosimilars and interchangeable biosimilars. The guidance outlines scientific and regulatory considerations for evaluating product presentations, user interfaces, and device design while supporting successful demonstrations of biosimilarity and interchangeability.

Why This Guidance Is Important

As more biologics are delivered using prefilled syringes, autoinjectors, pens, and other combination products, ensuring consistency between a biosimilar and its reference product extends beyond the drug substance itself. Differences in packaging, delivery devices, or user interfaces can influence product use, patient safety, and regulatory approval.

This guidance provides a structured framework for evaluating container closure systems and device constituent parts while helping sponsors develop biosimilar and interchangeable products that meet FDA's scientific and regulatory expectations.

Container Closure Systems and Product Quality

FDA emphasizes that quality expectations for container closure systems and device constituent parts are generally consistent with those for originator biologics.

Sponsors should provide comprehensive Chemistry, Manufacturing, and Controls (CMC) information describing the complete product presentation, including the container closure system and associated device components. Appropriate studies should demonstrate compatibility between the biologic formulation and the delivery device through stability evaluations, extractable and leachable studies, performance testing, and other supporting quality assessments.

User Interface and Device Design

Because many biologics are administered by patients, caregivers, or healthcare professionals, the user interface plays an important role in ensuring safe and effective product administration.

FDA recommends systematic comparative analyses between the proposed biosimilar and the reference product to identify any design differences. These evaluations should assess physical device characteristics, user tasks, product labeling, and instructions for use to determine whether any differences could affect critical tasks performed during product administration.

The guidance also recommends classifying identified differences based on their potential impact on user performance and patient safety.

Human Factors and Comparative Assessment

When design differences are identified, sponsors should evaluate whether they could increase the likelihood of use errors or affect the successful completion of critical administration tasks.

Minor design differences that do not impact critical tasks may require only comparative analyses. However, more significant design differences may require additional supporting evidence, including use-related risk assessments, human factors validation studies, comparative use studies, or other scientific data demonstrating that the differences do not affect biosimilarity or interchangeability.

FDA also encourages early communication during product development to discuss proposed presentations and obtain regulatory feedback before marketing application submission.

Interchangeable Biosimilars and Lifecycle Management

For interchangeable biosimilars, additional considerations apply because these products may be substituted for the reference product without intervention from the prescribing healthcare provider.

Where meaningful differences exist between the proposed product and the reference product, sponsors may need additional scientific evidence to demonstrate that these differences do not impact safe and effective product use or the standards required for interchangeability.

The guidance also highlights the importance of incorporating presentation-related considerations into lifecycle management strategies, particularly when future presentation changes or interchangeability applications are planned.

As biosimilar innovation continues to expand, thoughtful evaluation of container closure systems, delivery devices, and user interfaces will help sponsors generate robust scientific evidence, reduce regulatory risk, and support successful biosimilar and interchangeable biosimilar approvals.

References

• Draft Guidance for Industry:  Biosimilar and Interchangeable Biosimilar Products: Considerations for Container Closure Systems and Device Constituent Parts (July 2026).