Combination Products Office Focusing on Consistency, GMP Guidance

The FDA’s Office of Combination Products is reviewing its processes and systems and stepping up staff training in an effort to improve the consistency of product reviews, an OCP official says.

Specific concerns the office is attempting to address include design control issues for legacy products, cross-labeling where a drug and device are meant to be used together but may be made by separate manufacturers, and staff training before inspections that would focus on combination GMPs.

“If the review pathways ask different questions about similar products, that’s a problem,” says John Barlow Weiner, assistant director for policy in OCP, told a Wednesday session of MedCon 2015 in Cincinnati. “We want consistency.”

As part of this effort, OCP is working to finalize guidance on combination product GMPs, Weiner says. The comment period closed in late April, and a preliminary review shows feedback is largely positive. But companies are requesting clarification on certain terms in the guidance, such as the difference between a manufacturer and a sponsor.

Devicemakers also want more information on the role of suppliers in the manufacturing process — for example, whether GMPs would be imposed on makers of components for use in a combination product if they don’t make the finished goods, Weiner says.

Weiner singled out the use of reserve samples to explain how companies might work together, through a trade group, to draft a proposal for an entire device class, with the aim of ensuring guidance is properly addressed.

In 2014, OCP issued 17 product designations after the manufacturer and FDA couldn’t reach agreement on how to review a product. Of those, five were drug-device combinations, one was a drug-biologic and two were innovative drug-device-biologic combinations. The remaining nine products were not considered combination products, OCP Director Thinh Nguyen says. The number of designations has been trending down in recent years, from a high of 44 in 2010, he said.

Still, the number of combination products is trending up, Nguyen says. In fiscal year 2014, 310 combination products were submitted to the FDA. Forty-four of those were reviewed by the FDA’s drugs center, 154 by its biologics center and 112 by CDRH. The largest product classes were drug-coated devices, prefilled syringes and drug pumps.

In addition, OCP was involved in 1,013 intra-FDA consultations on combo products, 650 requests for advice on premarket review and 110 requests to address postmarket issues, Nguyen says. — Elizabeth Orr