On April 6, 2021, the CPC filed a comment letter on FDA’s draft guidance “Human Gene Therapy for Neurodegenerative Diseases.” The CPC appreciates FDA’s efforts to provide additional guidance for delivery devices used with human gene therapy products, but offers certain recommendations regarding the delivery device-related expectations described in the draft guidance. Overall, these comments suggest that FDA pursue a more flexible approach with regard to sponsors’ use of delivery devices.
On December 14, 2020, the CPC submitted comments on FDA’s Draft Guidance “Select Updates for Biocompatibility of Certain Devices in Contact with Intact Skin” (the “Draft Guidance”). The CPC generally agrees with the concepts proposed in the Draft Guidance, and appreciates FDA’s recognition of the low risk posed by various common device materials that contact intact skin, but has identified areas of the document that would benefit from additional clarity. The CPC also recommends inclusion of combination products within the scope of the Draft Guidance.
On September 28, 2020, CPC submitted comments on FDA’s “New Drugs Regulatory Program Modernization: Implementation of the Integrated Assessment of Marketing Applications and Integrated Review Documentation.” While CPC supports the integrated review template and acknowledges the value of implementing a system that effectively communicates the basis for new drug approvals, we are concerned that the proposed integrated review template will lack the level of detail currently provided in the discipline-specific review memos, which our members regularly reference. As such, we strongly recommend that, as FDA implements the integrated review document, the discipline-specific review memos remain publicly available to ensure full transparency and understanding of the Agency’s current thinking with respect to combination product requirements.
The CPC has provided this document to inform potential guidance on cross-labeled combination products and “combined use,” noting that this has not been agreed to by FDA, but we hope can facilitate future discussions on the topic. Contents include background on the topic, impact on industry, request for guidance and considerations (defining cross-labeled combination products, regulatory requirements for such products, and defining “combined use”), and examples of cross-labeling and combined use.
On June 22, 2020, the CPC filed comments on FDA’s “Technical Considerations for Demonstrating Reliability of Emergency-Use Injectors Submitted under a BLA, NDA or ANDA: Draft Guidance for Industry and FDA Staff.” While we appreciate FDA’s efforts in providing needed guidance on this topic, we believe many of the recommendations in the Draft Guidance will create inherent regulatory uncertainty (if requirements are strictly imposed in FDA NDA/BLA review correspondence late in development), and some recommendations do not appear to be practical. The comment letter offers 11 major comments, including requests for FDA to resolve uncertainty around (among other areas) the parameters to which the 99.999% reliability specification applies, the point at which the specified reliability must be met, and the devices that fall within the scope of the Draft Guidance.
On May 18, 2020, CPC filed comments on FDA’s “Restricted Delivery Systems: Flow Restrictors for Oral Liquid Drug Products Guidance for Industry.” In addition to certain specific comments, CPC asked that FDA further clarify the designation of restricted delivery systems, including whether they are considered as medical devices, as part of the drug container closure system/package or combination products. In addition, we noted that the Draft Guidance should lay out considerations and recommendations for use of restricted delivery systems, but should not outline requirements for their use. As such, we asked that the Draft Guidance be updated to provide considerations for manufacturers to address during their risk-based development activities and revise the sections which appear to be defining requirements.
On February 24, 2020, CPC submitted comments on FDA’s draft guidance “Requesting Food and Drug Administration Feedback on Combination Products.” CPC appreciates FDA’s efforts to enhance clarity and transparency of regulatory considerations for combination products through the publication of the Draft Guidance outlining the feedback mechanisms available to sponsors. However, CPC has identified the following overall concerns and suggestions:
• FDA should revise the Draft Guidance to describe the parameters for CPAM interactions, including when a CPAM would be appropriate over an application-based mechanism along with examples.
• CPC recommends that FDA include opportunities for iteration of proposals, which are linked back to the earlier discussion to allow for sponsors to receive FDA feedback, revise proposals and discuss with FDA until ‘agreement is reached,’ which is common to other types of formal meetings.
• CPC recommends that FDA provide more detailed timelines for the CPAM submissions and responses.
• The guidance should focus on the new or distinct information related to combination product meetings through the application-based and CPAM mechanisms and remove the content that is duplicated from other guidance.
On February 14, 2020, CPC filed comments on FDA’s “Bridging for Drug-Device and Biologic-Device Combination Products Guidance for Industry” (which was issued on December 18, 2019). CPC believes the development of a step-wise process approach and framework to conduct a gap analysis and for identifying (and closing) these information gaps is a valuable element of the Draft Guidance, and is consistent with and builds upon key ICH guidance documents (Q5e comparability, Q9 QRM) on comparability analysis and risk assessments. CPC further appreciates the ample references and broad allowances for leveraging prior experience throughout the Draft Guidance, demonstrating the willingness of FDA to consider prior knowledge of drug attributes and device platforms. Unfortunately, CPC found the format FDA chose to use in the Draft Guidance to convey study recommendations to be confusing and limiting in the ability to provide useful guidance on the needed bridging information.
On January 29, 2020, the CPC submitted comments on FDA’s “Identification of Manufacturing Establishments in Applications Submitted to CBER and CDER Questions and Answers Guidance for Industry,” which was issued on October 22, 2019. While the CPC appreciates the value of this Guidance in providing FDA’s expectations for identification of manufacturing establishments to facilitate FDA’s review and inspection activities, the CPC has some concerns and suggestions for improvement. For example, we recommend that FDA: (1) limit the scope of sites listed on FDA Form 356h and in Module 3 to those involved in the disposition of commercial product; (2) limit inclusion of FEI number, name and title of onsite contact person, contact details, and confirmation of inspection readiness to Form 356h in accordance with least burdensome approach; and (3) clarify that facilities manufacturing device components/sub-assemblies which are separately provided to combination product manufacturers for further modification/assembly/packaging with the drug constituent part are considered device component manufacturing facilities and should not be listed on Form 356h or in Module 3.
On December 26, 2019, the CPC provided comments on FDA’s “Type V DMFs for CDER-Led Combination Products Using Device Constituent Parts With Electronics or Software Guidance for Industry.” The CPC believes regulatory efficiency and consistency can be improved by the approach proposed by the Agency, which can lead to timely access to new combination products for patients. To ensure utilization of this approach, however, the CPC strongly recommends that the Draft Guidance better clarify how the rapid, iterative nature of software updates are considered in the process, submissions and amendments for Type V DMFs that contain electronics or software. In addition, the CPC believes that the Draft Guidance should clarify that the proposed Type V DMF submission approach should be available to all types of platform device constituent parts, not just those containing electronics or software.
