Sept 29, 2022 Open Letter to RPP

Sep 29

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September 29, 2022

VIA FEDEX EXPRESS AND EMAIL

C. Randall Harrell MD, Chairman & CEO
Regenerative Processing Plant LLC
34176 US Hwy 19 N
Palm Harbor, FL 34684

OPEN LETTER TO REGENERATIVE PROCESSING PLANT LLC
What is in Regener-Eyes Ophthalmic Solution? Is it a biologic?

Dear Dr. Harrell:

The Dry Eye Foundation is a 501(c)(3) nonprofit organization serving the ocular surface disease and ocular surface pain patient communities. We provide platforms for mutual education, support and encouragement across the international community of sufferers, and we advocate for patient-centered research into effective treatment for the multi-factorial conditions collectively referred to as dry eye disease.

Chronic ocular surface pain, often but not always associated with “dry eye”, causes profound suffering. Eye pain affects all of our basic daily activities such as working, driving, sleeping, even just taking a walk. It feels relentless and inescapable. It can have a devastating impact on our quality of life. Too often, it spills over into our mental health. Depression, anxiety and suicidal ideation are serious problems in our community(1). And the number of people affected is constantly growing, including in younger populations.

The lived experiences of people with ocular surface pain have transformed dry eye disease from an obscure syndrome associated with auto-immune conditions to today’s five billion dollar global industry. When the first dry eye drug received FDA approval in 2003, its unexpected blockbuster success prompted badly needed new investments in research and development. But it also attracted companies more interested in profit than verified medical advances. The notorious readiness of severely symptomatic dry eye patients to try anything and pay anything continues to be a magnet for profiteers. We are vulnerable to promises of relief. Sometimes, we overlook warning signals and abandon safety in favor of hope.

Biologic eye drops(2) are a relatively recent innovation, introduced to our dry eye community by the Regenerative Medicine industry. They promise well: they are said to be natural; they are said to help our body heal itself; and they are certainly more convenient to procure and to store than the eye drops manufactured from our own blood which so many of us now use.

As you are probably aware, the Dry Eye Foundation has been running an educational campaign about biologic eye drops on a website dedicated to this purpose(3). We first became concerned about the safety of biologic eye drops upon discovering that they are packaged in an unsafe bottle which offers no protection against bacterial contamination(4). We opened a dialogue with the Food and Drug Administration. As our research progressed, more safety red flags emerged, ranging from demonstrably false claims about regulatory compliance status to reports we have received from our community of adverse events. Our worries have been augmented by reading the detailed findings in recent FDA Warning Letters sent to two noncompliant manufacturers of two biologic eye drops(7,8).

For Regener-Eyes, our first safety concern is very simple: we don’t know what it is.

What is in Regener-Eyes?

There is no Ingredient List on the Regener-Eyes bottle, package, insert (Attachments 1,2,3) or website(9).

Regener-Eyes LLC sales representatives refuse to answer questions about ingredients, even when asked by patients who are concerned because they have ingredient allergies or sensitivities(10).

DailyMed (National Library of Medicine) is the recognized drug label database where the ingredients of prescription and over-the-counter medications may be found. According to DailyMed(11,12), Regener-Eyes’ active ingredient is glycerin (0.4% for Lite and 0.5% for Pro), and it has two inactive ingredients: “Tonicity Solution™” and sterile water.

In our organization’s interactions with patients and providers, no one has seemed aware that Regener-Eyes might contain glycerin (common enough in OTC eye drops) let alone that it might be the active ingredient.

Tonicity Solution™ does not have a Unique Product Identifier (UNII) or any references. We cannot determine what it is without your cooperation.

Is Regener-Eyes “biologic”?

Patients pay $75 to $175 or more for a single 3 mL vial of Regener-Eyes because they believe it to be an all-natural biologic eye drop.

Regener-Eyes has always been known as a biologic. Its marketing tagline, until quite recently, was “The power of a biologic in the ease of an eyedrop”(13). Key Opinion Leaders in optometry and ophthalmology uniformly describe Regener-Eyes as a biologic in trade journals(14,15,16,17,18,19). A White Paper sponsored by Regener-Eyes LLC and published in the July 2021 issue of Eyeworld describes Regener-Eyes as a biological product(Attachment 4).

In August 2022, Regener-Eyes LLC stopped describing Regener-Eyes as biologic. All obvious references to biologic substances have been removed from regenereyes.com and from the social media accounts of Regener-Eyes LLC and its employees. Regener-Eyes LLC’s product brochure(Attachment 5), distributed to visitors at a recent national trade show, contradicts the White Paper about what Regener-Eyes is and what it does(20).

In the meantime, doctors continue to recommend Regener-Eyes as a biologic, often quoting content originating from regenereyes.com before it was scrubbed of biologic references(21,22,23,24), and distributors continue to advertise Regener-Eyes to physicians(25) and consumers(26) as a biologic.

If Regener-Eyes is biologic, what is its tissue or fluid of origin?

Your website, which currently states that Regener-Eyes’ ingredients are “proprietary”, previously stated that it was derived from placenta.(27) The White Paper states that Regener-Eyes is derived from placental biomaterials (Attachment 4).

According to DailyMed archives, from October 2021 to August 2022, Regener-Eyes was stated to contain the active ingredient glycerin and the inactive ingredients “d-MAPPS” and 0.9% Sodium Chloride USP(28,29). “d-MAPPS” does not have a Unique Ingredient Identifier (UNII) and cannot be found in any ingredient database. According to your 2022 study in Analytical Cellular Pathology(30), d-MAPPS is a biological substance; its origin is not specified. Your 2019 study in Current Stem Cell Research & Therapy(31) reports that d-MAPPS is derived from amniotic fluid. A 2018 publication in Clinical Ophthalmology(32) reports that Regener-Eyes is made from amniotic fluid.

We patients need to know what we’re putting in our eyes.

Drug ingredients are basic information. There is no legitimate reason to conceal ingredients. The Federal Code of Regulations requires this information to be provided for all prescription and over-the-counter medications(33).

The Dry Eye Foundation eagerly anticipates a definitive resolution to the question of what is in Regener-Eyes.

Sincerely,

Rebecca Petris

President

NOTES

ATTACHMENTS

Regener-Eyes bottle (photographs)
Regener-Eyes package (photographs)
Regener-Eyes package insert (photograph)
Therapeutic Potential of Regener-Eyes Ophthalmic Solution (Eyeworld supplement, June 2021)
Regener-Eyes product brochure (Vision Expo West, September 2022)

COPIES TO:

1. Food and Drug Administration

CDER / Office of Unapproved Drugs and Labeling Compliance
CBER / Director (Peter Marks, MD, PhD)
CBER / Office of Regulatory Operations (Christopher Joneckis, PhD)
CBER / Office of Compliance and Biologics Quality (Melissa Mendoza, JD)
CBER / Office of Biological Products Operations, Division 2 (Karlton Watson)
CBER / Office of Biological Products Operations, Division 1 (Elizabeth Waltrip)
CBER / Office of Product Jurisdiction (Sheryl Lard-Whiteford, PhD)

2. Clinical Advisory Board of Regener-Eyes LLC

3. Scientific Advisory Board of Regener-Eyes LLC

4. Additional organizations:

Sjogrens Foundation
Prevent Blindness
Scleral Lens Education Society

5. Dry Eye Foundation Board of Directors

Regenereyescorrespondence