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Regulatory Developments in Ophthalmology: Applying New FDA Guidance, Part One

The global ophthalmic drugs market size was valued at $33.81 billion in 2022 and is expected to grow approximately eight percent from 2023 to 2030[1]. Given this trend, many biopharmaceutical companies are investing in strategies to develop and commercialize new or existing ophthalmic products that address unmet medical needs.

Now, these companies are required to comply with new guidance from the U.S. Food and Drug Administration (FDA) published in March of 2022 pertaining to ophthalmic drugs and devices, titled Certain Ophthalmic Products: Policy Regarding Compliance With 21 CFR Part 4. The FDA has determined that ophthalmic dispensers are now regulated as devices, and the drug and device together are regulated as a combination product.

The new guidance provides detailed information to applicants and manufacturers regarding compliance with the requirements in 21 CFR Part 4 for ophthalmic drugs packaged with eye cups, eye droppers, or other dispensers. Importantly, this guidance applies to all products with pending applications, approved products, and products marketed pursuant to the Federal Food, Drug, and Cosmetic Act (FD&C Act).

At Premier Consulting, our team of pharmaceutical regulatory experts is helping clients understand the changing regulatory landscape related to ophthalmic drugs and devices. Our goal is to help biopharma companies navigate these choppy waters as they strive to comply with evolving federal laws and the new FDA guidance.

Impetus and Rationale for New Regulatory Guidance

In our recent article published in Regulatory Focus titled Update on FDA Regulation of Ophthalmic Combination Products, we highlight and discuss the key legal events that influenced the FDA to issue its new guidance.[2]

On April 16, 2021, the U.S. Court of Appeals for the District of Columbia ruled in Genus Medical Technologies LLC v. United States Food and Drug Administration that the FDA does not possess unfettered discretion to classify a medical product as a drug, where that product falls within the definitions of both a drug and medical device under the FD&C Act. The court’s ruling had important implications for biopharmaceutical companies across the continuum of product development and commercialization, particularly in the area of ophthalmology.

Given the complex regulatory frameworks that apply to drugs and devices under the FD&C Act and the cost of abiding by those frameworks, the court’s decision to rein in the FDA’s discretionary power was significant. The court’s decision had three primary implications for drug and device manufacturers:

  1. The FDA is not granted unfettered discretion in deciding that a product that qualifies as both a medical device and drug should be regulated as a drug. Therefore, the FDA will examine product classifications, especially for those products that have been regulated as drugs even though they may satisfy the device definition.
  1. Companies should pursue early development conversations and advocacy with the FDA in favor of their interpretations of their products’ regulatory identities.
  2. In unclear cases or those with open questions, companies should seek the advice of regulatory experts before engaging the FDA on regulatory pathways.

The FDA Responds with New Guidance

Before the Genus decision, ophthalmic products and their dispensers packaged with the drug with which they were intended to be used were regulated as drugs, not combination products. However, less than a year after the Genus decision, in March of 2022, the agency published new regulatory guidance in compliance with 21 CFR Part 4 for applicants and manufacturers of ophthalmic drugs packaged with eye cups, eye droppers, or other ophthalmic dispensers, where those articles meet the device definition.

The new guidance signaled the FDA’s intention to “regulate these products 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).”2 Importantly, the guidance applies to approved products, those with pending applications, and over-the-counter marketed monograph drugs, so some approved products have been transitioned from drug to combination product status.

In the second of this two-part series, we discuss more about the practical application of the new FDA guidance and what it means for biopharma companies in ophthalmology.

Contact us to learn how we can support you in applying these guidance documents to your development program.


Olu Aloba, PhD
Vice President, CMC Services

Marianthi Karakatsani, PhD
Director, Regulatory Affairs CMC

Laura Kilgore, RAC
Vice President, Regulatory Affairs, CMC

[1] Grand View Research. Ophthalmic drugs market size, share & trends analysis report by drug class, by disease (dry eye, glaucoma), by dosage form, by route of administration, by product type (prescription, OTC), by region, and segment forecasts, 2022-2030. Market Analysis

[2] Aloba O, et al. Update on FDA regulation of ophthalmic combination products. Regulatory Focus. Published online 31 January 2023.