Devicemakers whose products include a drug component could find GMP compliance especially tricky, due to a 2013 regulation that requires expiration dates like those used for drugs, an industry expert says.

The 2013 cGMP final rule on combination products mirrors the drug GMP focus on expiry dates, but these can be difficult to establish for devices, which typically don’t change over time, according to Linda Mummah-Schendel, senior medical research manager at the NAMSA.

“There’s no easy way to hit all the required testing on both the drug and the device attributes of a combination product,” Mummah-Schendel says. She spoke at a webinar sponsored by the Regulatory Affairs Professionals Society.

Reserve Sample Rules

Under the final rule, labeling for combo products must show the expiration date, and the product must continue to meet the manufacturer’s specs regarding quality of the product. Manufacturers must also establish an in-house definition for “batch” and perform stability, identity and strength testing on at least three sample devices of each size per batch.

Reserve samples of all components of a combination product must be kept for at least a year for future strength testing, says Mummah-Schendel. The FDA requires manufacturers to hold onto at least twice as much of each product as is needed for testing.

Combo product makers also need to ensure the security of container closures and see that any pharma ingredients are properly handled, she says. Drug regulations require a calculation of actual and theoretical yield of the drug component at each stage of manufacturing, processing and packaging, Mummah-Schendel explains.

Mummah-Schendel cautions devicemakers not to overcomplicate their combo product GMPs. For example, a CAPA regulation that requires too many steps may result in actions going undocumented. “If it’s not documented, it’s not done” in the eyes of inspectors, she says.
Mummah-Schendel also stresses that devicemakers must designate one person to be responsible for compliance with combo product GMPs. This information should be included in the company’s organizational chart so that it’s easily available to auditors, she says.

The FDA’s initial attempts to adapt drug GMPs to devices did not work well due to the wide range and complexity of medical technologies, and it was tweaked to allow for a more risk-based approach, à la the quality system regulations, says Mummah-Schendel. Ultimately, though, the 2013 final rule removed much of that flexibility by making some requirements legal mandates, she adds.

With these new cGMP rules, many drug, biologics and device manufacturers remain unclear about how to comply. Make sure you learn all there is to know with The Essential Guide to Combination Products cGMPs.