FDA Tackles Antibiotic Cements and Implants With Growth Factors

In 2016, the FDA issued a final rule on postmarket reporting for combination drugs.

Orthopedic combination products include implants with growth factors and antibiotic loaded bone cements.

The rule seemed to create more questions and concerns than answers, so on July 22, 2019, the agency issued a 44-page final guidance explaining how to comply with the 2016 final rule.

For instance, AdvaMed, had requested detailed tables outlining the requirements and illustrating various scenarios and expectations.

The Guidance titled: Postmarketing Safety Reporting for Combination Products can be accessed here.

Defining Combo Product

The FDA defines a combination product as: “A combination product is a product composed of any combination of a drug, a device, and a biological product. Each drug, device, and biological product included in a combination product is referred to as a “constituent part” of the combination product.”

According to a report from Transparency Market Research, the drug device combination products market, (Drug Eluting Stents, Infusion Pumps, Photosensitizers, Orthopedic Combination Products, Wound Care Combination Products, Inhalers, Transdermal Patches, Intraocular Implants and Drug Eluting Beads), is expected to reach an estimated value of $115.1 billion by 2019.

Guidance Outline

MedtechDive reports the guidance outlines how to submit reports and avoid duplication. It also explains recordkeeping requirements, with examples for both drug and device-led products, including detailed charts showing which content is required in reports under the rule and when they are due to FDA.

It also spells out which products are subject to the final rule and provides hypothetical scenarios illustrating how to comply with various requirements, including reporting triggers and timeframes.

According to the FDA, combination product will be assigned to an agency center that will have primary jurisdiction for that combination product’s regulation. Assignment of the combination product to a lead Center is based on a determination of which constituent part provides the primary mode of action (PMOA) of the combination product.

“If, for example, the PMOA of a device-biological product combination product is attributable to the biological product constituent part, the center responsible for premarket review of such a biological product would have primary jurisdiction for the regulation of the combination product.”

FDA Principal Deputy Commissioner Amy Abernethy said, “Today, the FDA is taking another step to help applicants better comply with important product postmarketing safety reporting requirements and provide us timely, comprehensive safety information about combination products at established intervals.

The FDA will begin to enforce the additional constituent part-based requirements in July 2020 for most combination products and January 2021 for vaccine combination products.