Combo Product Industry Coalition Proposal Elevates Post-Approval Issues

Genzyme, Roche, Guidant are among the firms represented by the Combination Product Coalition to focus on improving post-approval regulatory pathways, such as modifications and cross-labeling for “virtual” combo products.

FDA clarification of labeling for and modifications to combination products tops a list of priorities drafted by a coalition of roughly 20 device, drug and biologic firms.

Formed about a year ago, the Combination Product Coalition (CPC) banded together with the goal of creating cross-sector industry positions on combination product regulatory policy. Indianapolis law firm Baker & Daniels is coordinating the effort, which includes Guidant, Roche Diagnostics and Genzyme.

Following completion of a proposal document, the group met with FDA the week of May 31 to present recommendations.

Besides requesting better guidance on labeling and requirements for firms making changes to approved products, the group is asking FDA to consider clarifying policy regarding adverse incident reporting, quality systems, and roles and functions within FDA's Office of Combination Products.

CPC's attention to regulatory challenges facing firms that already have combination products on the market likely reflects both the maturation of the combo products industry and progress that OCP has made in drafting documents related to the basic premarket assignment and inter-center review processes.

OCP recently issued a formal definition explaining how the agency will assign combo products using the "primary mode of action" mechanism for determining product jurisdiction and also released an appeals guidance.

The combo products office is drafting guidance on adverse event reporting, good manufacturing practices and when to use single versus dual applications.

Those documents could be out in the next several months, according to office reps, who note numerous inquiries into AE and GMP-related issues, as well as stakeholder desire to see FDA policy in writing.

Product modification, however, was not among OCP's initial priorities, according to CPC. This summer, CPC is considering developing a decision chart to aid firms with combo product modifications. The group also is proposing clarifications to labeling policies.

In initial recommendations, CPC advocates that FDA view combo products as falling into three basic categories - integral combination products, where the regulated product is a single unit; kits consisting of separate products packaged together; and "virtual combination products," intended to be used together, but packaged separately.

CPC is particularly keen to see FDA address cross-labeling issues for virtual combination products, such as diagnostics used to determine appropriate patient populations for a given drug therapy.

The group also would like OCP to "take a stronger role in facilitating and monitoring the labeling review process" to ensure that redundant reviews are minimized.

While seeking development of guidance addressing the format and content of labeling, CPC is urging the long-term goal of FDA harmonization of labeling and adverse event reporting with outside U.S. regulatory schemes.

Regarding modifications to approved combination products, CPC suggests creation of a risk-based decision tree flow chart outlining various scenarios.

Such decisions can be especially complex for combination products with device components, CPC notes. Although the device center has guidance on when a 510(k) should be submitted for device modifications, the document does not address combination products.

CPC suggests that the guidance be applied to device components of combo products, with the exception of integrated and virtual combination products handled by the drug center, which should rely on the chart.

The group hopes to meet with FDA again in late summer or fall to discuss the proposed labeling and product modification projects. In the meantime, the coalition, composed of mostly large firms, says it is interested in reaching out to additional industry reps, including small firms and trade associations, such as AdvaMed, BIO and PhRMA.

The Medical Technology Leadership Forum also is drafting recommendations on combination product regulation for presentation to FDA and will hold a July meeting, "Innovative Approaches to Regulation of Combination Products & New Science: Options for Policymakers," in San Diego.

- Cabral Bigman