November 7, 2024 Open Letter to Key Opinion Leaders

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OPEN LETTER TO KEY OPINION LEADERS

Partnering with the FDA for Patient Safety

Dear Key Opinion Leaders:

Approximately 25 million Americans use over-the-counter (OTC) lubricant eye drops.(1)

In 2022 and 2023, 4 people died and 18 lost their sight because of an OTC lubricant eye drop which was produced at a facility in India that did not follow sterile manufacturing practices.(2) This eye drop was sold by a US-based company that lacked the expertise and motivation to take responsibility for product safety.(3)

Since then, the Dry Eye Foundation has identified hundreds of eye drops with similar and additional risk factors, including “compare with” generics, scams, clones and counterfeits. We have reported these products to the Food & Drug Administration (FDA).

The entities that market these eye drops are attracted by consumer demand for low-cost products and ‘natural’, ‘organic’ or ‘regenerative’ remedies; unrestricted access to the American market through e-commerce; and lack of effective policing by major e-commerce platforms.

Limitations of Food & Drug Administration response to misbranded or adulterated OTC eye drops

The FDA took several steps in response to the tragic events in 2022 and 2023. First, it expedited the inspections of foreign and domestic manufacturing facilities that produced multiple OTC eye drops for the US market. Second, it increased its enforcement actions and public warnings. Third, it increased its internet surveillance for certain classes of eye drops which contained ingredients and/or made therapeutic claims which are not allowed by law for OTC ophthalmic preparations (called misbranding).

However, the FDA lacks both the authority and the resources to remove all high-risk ophthalmic products from the market. Contrary to popular perception, drug recalls are initiated by manufacturers or distributors, not the FDA. Several eye drop companies are openly defying FDA enforcement efforts by continuing to sell their products without correcting marketing and manufacturing violations. [Appendix A]

The principal distributor of an OTC drug (called the packager), and manufacturers who are also distributors, are required to list their products on DailyMed(4), the National Library of Medicine’s drug database. The FDA neither reviews nor approves OTC listings.(5) This creates an unfortunate path to pseudo-legality for unscrupulous companies. An eye drop may be listed on DailyMed and have a National Drug Code (NDC) number, yet violate numerous regulations related to OTC eye drop formulation, sterile manufacturing, and marketing. The Dry Eye Foundation has identified a number of these products. [Appendix B]

The FDA currently does not have the authority to require that an OTC drug manufacturing facility undergo inspection before its products enter the US market. Eye drops produced in uninspected facilities have been contaminated with bacteria and fungus(6), and manufactured with raw ingredients that have not been tested for contaminants.(7) 

The role of Key Opinion Leaders in prescription drug marketing

Prescription drug companies use KOLs extensively for a simple reason: KOLs are effective in persuading colleagues to change their prescribing patterns in favor of new prescription eye drops. Eye care providers typically trust their KOL colleagues and accept their public statements about the treatment of specific diseases – such as dry eye disease – as factual and unbiased, even when a financial conflict of interest is disclosed. 

Typical KOL marketing channels include authoring articles and providing interviews that are published in trade journals; speaking at industry-sponsored symposia; discussing an eye drop favorably from the podium in a non-sponsored meeting session; making scheduled appearances at exhibitor booths during national meetings; and quotations or testimonials in social media outlets.

Prescription drugs are highly regulated throughout development, manufacturing and marketing. The FDA inspects the manufacturing facility as part of the pre-approval process for a new prescription drug. Distributors are keenly aware of the FDA’s enforcement actions against off-label promotion.

A KOL promoting a prescription eye drop is very unlikely to mislead their colleagues about approved drug product claims or manufacturing quality.

Key Opinion Leaders in the 21st century: Partnering with the FDA for patient safety

Key Opinion Leaders are expert clinicians, not regulatory experts. 

Nonetheless, KOLs have an ethical responsibility to their colleagues – and by extension to the patients of colleagues – to determine the regulatory compliance of an unusual or unique eye drop before engaging in multi-channel marketing on behalf of the product’s distributor. The most effective way to fulfill this responsibility is to enlist the help of the FDA.

Any clinician may contact the FDA CDER Division of Drug Information to discuss any drug.(8) If the drug is not listed on DailyMed, it is by definition an illegal drug. Marketing or selling this drug to US consumers – including sale at the office retail level – is an illegal activity.

If the eye drop is listed as an OTC product on DailyMed, the FDA staff can determine whether it contains ingredients, and/or makes product claims, which are not allowed for OTC ophthalmic preparations. The FDA considers statements on the product’s web site, in written documents, and in social media content created by the distributor when assessing product claims. Marketing or selling an eye drop that does not comply with all the requirements for OTC ophthalmic product ingredients and claims is an illegal activity.

Often, the primary distributor is not the manufacturer. Even when operated by the same individuals, the distributor and manufacturer are usually distinct business entities. A KOL who is invited to promote an eye drop from a little-known distributor – whether domestic or foreign – should request the manufacturer’s FDA Establishment Identifier (FEI) and physical address. Knowing the FEI, FDA staff can assist KOLs with the slightly technical process of locating and interpreting the facility inspections. Distributor reluctance or refusal to provide this information is a red flag. 

Pharmaceutical distributors are required to document, investigate and report to the FDA all complaints received from patients or health care providers regarding their products (known as adverse event reporting). Each drug distributor should have a policy that spells out the steps for adverse event reporting. A KOL who is invited to promote an eye drop from a small or little-known distributor should ask for a copy of the company’s adverse event reporting policy. Reluctance, delay or refusal to provide this policy are red flags.

As recent events have shown, KOLs may unwittingly promote an eye drop that is deceptively marketed; contains ingredients that require FDA prescription drug approval; is mis-formulated; is contaminated; or all of the above. 

Conclusion

Eye care providers respond favorably to KOL drug promotion for several reasons. First, the KOL has subspecialty expertise. Second, the KOL is assumed to be acting altruistically and speaking honestly, even if a financial conflict of interest exists. Third, until very recently, no drug company has attempted – and succeeded – in misleading KOLs to the extent that those KOLs persuaded their colleagues to recommend and/or sell unapproved prescription eye drops to their patients. 

Every ECP who has recommended or sold these products faces the possibility of malpractice risk, disciplinary action by their State licensing board, action by their State Office of Consumer Protection, damage to specific patient-physician relationships, and general harm to their professional reputation.

Key Opinion Leaders in the 21st century have a duty to their colleagues to ensure that they are promoting drugs which fully comply with the Federal Food, Drug & Cosmetic Act by independently confirming the regulatory compliance of the drug. This duty is readily fulfilled by contacting the FDA.(8)(9)

Additional Resources

The Foundation has created extensive free resources on eye drop safety for patients and ECPs. [Appendix C] Please share these resources with your patients.

Sincerely,

Sandra Brown MD, Board Member, Medical Advisor

Rebecca Petris, President

Aidan Moore, Executive Director