Posted on November 4, 2022 at 1:26 PM by Jennifer Ahearn
In March 2022, the FDA published guidance on “Certain Ophthalmic Products: Policy Regarding Compliance With 21 CFR Part 4.” This guidance was issued as a result of the court ruling in Genus Medical Technologies LLC v. U.S Food and Drug Administration in April 2021, which focused on the FDA’s previous regulatory authority as it relates to classifying products that meet both the definition of a drug and device as a drug only, at the agency’s discretion. The FDA argued that the device definition was nested within the more universal drug definition, but the court disagreed. The judge found that the medical device definition was narrower, and therefore products that met the definition of a device must be regulated as such even if they also met the definition of a drug. The court ruled that any product that met the statutory definition of a device must be regulated as a device and ordered the FDA to review and reclassify all products that met both definitions as devices (where previously classified at the agency’s discretion).
Understanding The Changes
Before this decision, ophthalmic dispensers packaged together with the associated ophthalmic drug were regulated only as drugs, and not as a combination product as defined in the regulations. These products were therefore not required to meet the requirements in 21 CFR Part 4, which covers the “Regulation of Combination Products.” Though there are multiple definitions for combination products used by the FDA, the one that applies to ophthalmic dispensers would fall under the following: “Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug product.” In theory, ophthalmic dispensers packaged together with the ophthalmic drug with which they were intended to be used have always met the definition of a combination product, but the FDA is now classifying them as such because the dispenser meets the definition of a device constituent part.
At this time, the FDA does not intend to take action on products that have previously not been classified as a combination product until they have fully evaluated the application of 21 CFR Part 820 Quality System Regulations (Devices) on lower risk constituent parts. However, new product applications will be expected to meet the requirements of 21 CFR Part 4. Dr. Jeffrey Shuren, head of the FDA’s Center for Devices and Radiological Health (CDRH), was asked about the impact of the Genus court decision on the FDA’s review of products and the associated reclassification effort during his September 20, 2022 appearance at the Consumer Healthcare Product Association’s Regulatory, Scientific and Quality Conference. He was also asked if manufacturers would have any influence on whether or not their products are reclassified. Dr. Shuren said that Congress is discussing this issue, and he hoped they would address it with legislation changes. He also stated that manufacturers would not have any influence on their product reclassification.
Who Is Impacted
Companies that have developed ophthalmic products under 21 CFR Part 211 Current Good Manufacturing Practice for Finished Pharmaceuticals will now have to incorporate the required elements of 21 CFR Part 820 to be compliant with regulations. This will require modifications to the company’s overall quality management system.
What will this look like? Manufacturers who already meet all the cGMP requirements under 21 CFR Part 211 will now have to include the following elements from 21 CFR 820:
- Section 820.20: Management Responsibility
- Section 820.30: Design Controls
- Section 820.50: Purchasing Controls
- Section 820.100: Corrective and Preventive Action
- Section 820.170: Installation
- Section 820.200: Servicing
Implementation of these new requirements doesn’t have to be overly complex. For example:
- A manufacturer using a streamlined approach following 21 CFR 211 with the required additions of 21 CFR 820 will need to address Management Responsibility. Many drug companies already use the Management Review process, which can be augmented to meet the requirements of Management Responsibility.
- A manufacturer using a streamlined approach following 21 CFR 211 with the required additions of 21 CFR 820 will need to address Purchasing Controls. Supplier Qualification processes can be augmented to add in the necessary provisions for Purchasing Control rather than creating a completely separate SOP.
- A manufacturer using a streamlined approach following 21 CFR 211 with the required additions of 21 CFR 820 will need to address Corrective and Preventive Action (CAPA). Drug investigation processes (21 CFR 211.192) can be augmented to add in the necessary provisions for CAPA rather than creating a completely separate SOP. Keep in mind that CAPAs for medical devices have a different approach than CAPAs for drugs, so create your SOP accordingly.
- Installation and Servicing would not typically need to be addressed for simple device constituent parts such as manual dispensers used with ophthalmic products.
Drug companies may find themselves struggling with design controls and certain usability factors such as the ability of the device to work under the defined drug delivery situation. Design control processes for devices are a significant departure from drug development so drug companies will need to have well-defined Combination Product Development and Combination Product Risk Management procedures.