Reclassification of Ophthalmic Drugs, Part 2: The Rules Have Evolved?
Top Food and Drug Agency Regulatory Cases
By: Cheryl L. Rowe-Rendleman, PhD
The FDA adheres to the Federal Drug & Cosmetics (FD&C) act to decide whether a product should be regulated as a drug or device. There have been variances in a few cases and sponsors in turn have accepted the FDA interpretations and the differing regulatory strategies for these products. A recent court case, Genus Medical Technologies vs FDA has challenged FDA conventions. As a result, FDA will investigate and reclassify certain ophthalmic drugs as drug-led combination products composed of a drug constituent part that provides the primary mode of action and a device constituent part (an ophthalmic dispenser). The implications to ophthalmology and the recent FDA Policy update are discussed in parts 2 and 3 of this 3-part series.
Part 2.
Obsolete Language about Ophthalmic Products in the Code of Federal Regulations
Ophthalmic drug development has been a special case. The Code of Federal Regulations for ophthalmic products states that “Eye cups, eye droppers, and other dispensers intended for ophthalmic use should be sterile and may be regarded as falling below their professed standard of purity or quality if they are not sterile. These articles, which are regulated as drugs if packaged with the drugs with which they are to be used, should be packaged so as to maintain sterility until the package is opened and be labeled, on or within the retail package, so as to afford adequate directions and necessary warnings to minimize the hazard of injury resulting from contamination during use.
As a result of the Genus Medical Technologies case—this language is now obsolete because “eye cups, eye droppers, and other dispensers” when packaged together with the drugs they are to be used, shall be considered as devices. This change will be implemented immediately and impacts products subject to pending applications, approved products, and OTC monograph drugs.
In the past few months several ophthalmic companies have received complete response letters (upon denial) or product classifications (upon approval) that are consistent with the FDA’s new view that “These articles, are now regulated as devices if packaged with the drugs with which they are to be used.
Eye Drops Reclassified as Drug-led Combination Devices
For example, Eyenovia received a complete response letter from the FDA that its fixed microdose formulation of tropicamide and phenylephrine for pupil dilation could not be approved because it had been reclassified from drug to device. Consequently, the company needs to develop the appropriate device files to support the eyedropper that delivers the microdose.
Recently there have been approvals of NDAs for ophthalmic drugs as drug-led combination products, including:
- VITUITY (pilocarpine hydrochloride ophthalmic solution), 1.25%
- TYRVAYA (varenicline solution) nasal spray, 0.6 mg/mL
Upon NDA approval these companies have to agree to adhere to certain postmarketing safety rules for combination devices. Some of these additional responsibilities include reports related to changes in device (drug bottle) design, design history, malfunctions, and adverse events as described in 21 CFR 4, Subpart B (Postmarketing Safety Reporting for Combination Products).
In its current Policy Update issued March 22, 2022, the FDA states it “does not intend to take action with respect to noncompliance with part 820 [(21 CFR part 820; Quality system Regulation for Devices] with respect to ophthalmic product for a period of 12 months following the issuance of the guidance.”
Reference: Certain Ophthalmic Products: Policy regarding compliance with 21 CFR part 4. US Department Health and Human Services. March 2022.
Author: Cheryl L. Rowe-Rendleman, PhD is a clinical and regulatory development expert and founder of Omar Consulting Group, LLC.
Omar Consulting Group, LLC helps drug developers and investigators create successful clinical and regulatory strategies.