Califf Affirms Recommendations For Efficient Combination Product Reviews
By Jof Enriquez,
Follow me on Twitter @jofenriq
Dr. Robert M. Califf, the official nominee for FDA commissioner and current FDA deputy commissioner for medical products and tobacco, endorsed recently the recommendations of focus groups examining how the agency could conduct more efficient reviews of combination products.
According to the Code of Federal Regulations (CFR), a combination product involves any two or three combinations of a medical device and/or a drug, and/or a biologic. Because the technology behind these products is complex, and because different FDA centers review each component separately, manufacturers experience delay and confusion as they go through the regulatory process.
A 2014 report by the Combination Products Coalition (CPC), an industry group consulted by FDA, states that 70 percent of innovators reported delays as the result of problems during combination product reviews. Moreover, 50-85 percent of respondents stated that when a combination product-related conflict arose with either the Center for Devices and Radiological Health (CDRH) or the Center for Drug Evaluation and Research (CDER), the center would communicate its position without offering scientific and regulatory support for its position.
In response to industry feedback, FDA then held a series of focus groups with staff from two of its centers to identify areas for improvement in inter-center consults. According to RAPS, the study team identified four key problems:
- Different policies, practices and application types
- Separate review and tracking systems between centers
- Unclear communication channels between centers
- Lack of resources to review consults
In order to address these issues, the full report states the following recommendations:
- Establish clear guidance for the review of common combination product types.
- Create new, simplified processes for access to CDER’s Document Archiving, Reporting, and Regulatory Tracking System (DARRTS) and CDRH’s Image 2000 for consulting reviewers; this access should be pre-approved, expedited, and long-lasting.
- Update the Intercenter Consultative/Collaborative Review Process Standard Operating Procedures and Policies (SOPP) Manual and Intercenter Consult Request form, and make them easily accessible on the OCP website.
- Create and maintain a combination-product-specific organizational chart and contact directory, keeping personnel changes current.
- Establish a mechanism for estimating time spent on intercenter consults, so resources can be allocated appropriately to organizational units to assure adequate review performance.
Califf and Jill Hartzler Warner, J.D., FDA’s Associate Commissioner for Special Medical Programs, wrote in an FDAVoice blog post that the agency already has made significant steps to improve the conduct of combination product reviews, using much of the aforementioned feedback as a basis for improvements, but they admit there still is room for improvement.
According to Califf and Warner, improvement steps currently underway at the FDA include:
- Issuing more guidance for review of combination products (e.g., a pending draft guidance document on human factors)
- Enhancing and simplifying data access and sharing for internal staff
- Making it easier for staff to request and monitor inter-center consults
- Updating and maintaining FDA’s internal contact directory for experts to review a combination product
- Improving FDA’s internal standard operating procedures for premarket reviews and compliance activities
In the blog post, Califf and Warner note how the 21st Century Cures Act, currently pending before the Senate, could help bring further clarity to the regulation of combination products, particularly by facilitating the premarket review process. Similar pieces of legislation, in addition to providing continued feedback from stakeholders, would shape FDA's evolving framework on combination product reviews.
"We continue to want to hear your ideas for enhancing how we work with you on combination products. We are listening — and excited to do our part by evaluating innovative combination products and helping to improve the well-being of patients by approving new safe and effective therapies," Califf and Warner wrote in the blog post.