Wound healing products for which a primary mode of action cannot be elucidated should remain under the jurisdiction of FDA's device center, according to Apligraf manufacturer Organogenesis.

"In the absence of a single mode of action, FDA should defer to the established regulatory paradigm existing under CDRH," Organogenesis contends in a summary statement prepared for a June 24 hearing on combination products containing live cellular components.

The Canton, Massachusetts firm maintains that there is no dominant mode of action in its Apligrafproduct. "In its final form, the level of contribution to the wound healing process by each component cannot be definitely determined," Organogenesis writes.

Supporting Organogenesis' opinion, other commenters suggest that a status quo device framework should remain in place unless there is a clear demonstration that the primary mode of action is biologic.

"Although most of these living constructs produce cytokines and growth factors, it is by no means certain that this represents their mode of action," Vincent Falanga, MD, Boston University, asserts in a statement sent to FDA. "These should be treated as devices until we know more about their mode of action," he recommends.

FDA recently announced that it is considering reassigning primary jurisdiction of certain interactive wound healing products that contain live cellular components to the Center for Biologics Evaluation and Research (¹ Also see "Wound-Healing Product Jurisdiction To Be Challenged At June FDA Hearing" - Medtech Insight, 20 May, 2002., p. 13).

In the notice for the hearing, FDA stated that it is seeking comments on criteria it should use to determine primary mode of action as well as factors the agency should consider when the primary mode of action is unclear.

Industry comments submitted to FDA urge the agency to maintain current device jurisdiction for interactive wound dressings that have already gained approval as devices.

"Currently approved commercial products consisting in combination with a device matrix and intended for wound healing should remain within CDRH," Genzyme Corp. writes in comments prepared for the June 24 hearing.

Other firms like Organogenesis, Ortec and Advanced Tissue Sciences, which all have wound products on the market that contain cellular components, also make clear that they would like the agency to retain its current framework.

For example, ATS points out that it has "built its product portfolio, personnel, systems and marketing apparatus around the expectation that these products would be regulated as devices." Ortec expresses "concern regarding the potential change in jurisdiction."

While Genzyme argues against a switch in jurisdiction for already approved devices, the firm suggests an alternate framework for new products.

"In most cases of products containing living cells, the product should be regulated by CBER in the new Office of Cell, Tissue and Gene Therapy," Genzyme maintains.

"Any scaffold, matrix or biomaterial supporting the cells would in most cases be considered as a delivery system for optimizing or facilitating the effect of the cell being delivered," according to Genzyme. "Such delivery systems should be reviewed by CDRH as a consult to CBER for that component of the final product," the firm maintains.

CBER recently announced that a new office within the biologics center called the Office of Cells, Tissues & Gene Therapy will be established by Oct. 1 (² Also see "CBER Tissue Products Office To Be Established By Oct. 1" - Medtech Insight, 3 June, 2002., p. 6).

The biologics center is striving to create a transparent structure that will make communication with the new office straightforward, according to CBER representatives. In addition, CBER anticipates that the office will collaborate with other FDA centers, including CDRH.

"Could [wound healing products] be changed from PMA products to biological license?" CDRH Director David Feigal recently remarked when asked about their regulatory future at a June AdvaMed device submissions workshop. "Yes, they conceivably could," he confirmed.

Potential shifts in demarcation for combination products are not unique to the United States, the center director emphasized.

"I don't think any of these things are settled anywhere in the world at the moment," Feigal remarked. For example, he pointed out that the European Union is considering legislative changes to pharmaceutical laws that could alter demarcations for certain drug-device combination products.

"My sense is this is going to be an evolving area globally," CBER Director Kathryn Zoon concurred. Internationally, there is "a lot of interest in what the United States is doing," she added.

The announcement of the hearing and potential jurisdictional changes has provoked a flurry of responses and requests to attend from FDA stakeholders. In addition to a number of firms, industry trade associations like AdvaMed and PhRMA have signaled that they will attend and wish to publicly comment.

FDA Science Board member Robert Nerem, PhD, Georgia Institute of Technology, also has submitted a request to speak at the hearing.

Among the items he is planning to discuss is "the unique nature of combination products and the fact that they are not simply combinations." His presentation will address the complexity of combination products and needs of patients and the tissue engineering community.

In addition, Nerem expects to give a summary of the April meeting of the Medical Technology Leadership Forum, which focused on combination products, particularly tissue-engineered products (³ Also see "FDA, Industry Leaders Convene For Combination Products Forum April 21-22" - Medtech Insight, 15 April, 2002., p. 6).

At the meeting, participants sought to create a set of draft principles to help guide the agency in reviewing combination products. However, attendees reported that they were unable to finalize specific recommendations (⁴ Also see "Combination Product Regulation Will Come Under Scrutiny At May 1 Meeting" - Medtech Insight, 29 April, 2002., p. 6).

Potential Jurisdictional Change Draws Protest From Wound Product Firms

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