WARNING LETTER
Imprimis Rx LLC
MARCS-CMS 627802 —
June 30, 2022
Delivery Method:
VIA UPS
Product:
Drugs
Recipient:
Recipient Name
John Saharek
Recipient Title
President
Imprimis Rx LLC
1000 Aviara Parkway, Suite 220
Carlsbad
,
CA
92011
United States
Issuing Office:
Division of Pharmaceutical Quality Operations IV
United States
WARNING LETTER
June 30, 2022
John Saharek, President
Imprimis Rx LLC
1000 Aviara Parkway, Suite 220
Carlsbad, CA 92011
Dear Mr. Saharek:
This is to advise your firm that the U.S. Food and Drug Administration has reviewed promotional materials sponsored by Imprimis Rx LLC (ImprimisRx), including ImprimisRx-sponsored content in the professional periodicals
Glaucoma Physician
(March 2021) and “The Ophthalmic ASC” by
Ophthalmology Management
(February 2021).
1
The promotional materials, titled “
Pred-Moxi-Brom: The Whole Is Greater Than The Sum Of Its Parts
” and “
Compounding Pharmacies: It Pays To Know Your As And Bs
,” discuss your firm’s compounded drug product, Pred-Moxi-Brom (PMB) (prednisolone acetate 1%, moxifloxacin 0.5%, and bromfenac 0.075%) available in 5mL and 8mL bottles.
The claims made in these promotional materials establish that this product is a drug under section 201(g)(1) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), 21 U.S.C. 321(g)(1), because it is intended for use in the cure, mitigation, treatment or prevention of disease. As explained further below, these promotional materials make false or misleading claims regarding Pred-Moxi-Brom, a compounded drug product. Thus, the promotional materials misbrand your Pred-Moxi-Brom drug product within the meaning of the FD&C Act and make its distribution violative. 21 U.S.C. 352(bb); 321(n); and 331(a).
These violations are concerning from a public health perspective because they create a false or misleading impression about the safety and effectiveness of this drug product. This is especially concerning in light of the many known risks associated with the active ingredients in this drug product, as reflected in ImprimisRx’s own Product Information website and the prescribing information for FDA-approved drug products containing the same active ingredients, as well as potential safety risks of using these drug products together.
Prior Communication
The FDA has expressed concerns regarding promotional materials for compounded drug products from Imprimis Pharmaceuticals Inc.
2
in a previous letter. On December 21, 2017, the FDA sent Imprimis Pharmaceuticals Inc. a Warning Letter based on a firm website and social media posts that misbranded the firm’s “Dropless,” “LessDrops,” “Simple Drops,” and “Klarity C-Drops” products by omitting important risk information and otherwise making false or misleading claims regarding the safety and efficacy of these products. We are concerned that ImprimisRx is continuing to promote its products in a manner that similarly fails to adequately and truthfully convey risk and efficacy information about the products, despite concerns previously expressed by the FDA.
False or Misleading Claims Regarding FDA Approval
The following claim appears in “
Pred-Moxi-Brom: The Whole Is Greater Than The Sum Of Its Parts
”:
“As a compounded eye drop comprising medications already approved by the FDA, PMB also costs less than the same ingredients purchased separately.”
Furthermore, the following claim appears in “
Compounding Pharmacies: It Pays To Know Your As And Bs
”:
“Unlike off-the-shelf prescription medications made by the major drug manufacturers, compounded prescription drugs are specifically created and ‘made to order’ from two or more existing medications already approved by the U.S. Food and Drug Administration (FDA) for safety and efficacy.”
These claims in your promotional materials suggest that components of your compounded “Pred-Moxi-Brom” drug product are FDA-approved. Specifically, these statements suggest that you use individual FDA-approved drug products, which have undergone premarket review for safety, effectiveness, and quality, to compound your Pred-Moxi-Brom drug product. While there are individual FDA-approved ophthalmic drug products containing prednisolone acetate
3
, moxifloxacin hydrochloride
4
, and bromfenac
5
, it is our understanding that you use bulk drug substances - not approved drug products - in compounding Pred-Moxi-Brom. Because Pred-Moxi-Brom is compounded using bulk drug substances, which are not FDA-approved, rather than FDA-approved drug products, your promotional materials suggesting otherwise are false or misleading.
Unsubstantiated Superiority Claims
Promotional materials misbrand a drug product if they contain false or misleading comparisons that represent or suggest that a drug product is safer or more effective than another drug product when this has not been demonstrated.
The following claims appear in “
Pred-Moxi-Brom: The Whole Is Greater Than The Sum Of Its Parts
”:
“Pred-Moxi-Brom is also a prednisolone acetate suspension medication; these suspensions are preferred by ophthalmologists, owing to better corneal penetration and higher overall anti-inflammatory effects than prednisolone sodium phosphate solutions.
6
”
“By its ability to improve quality of care and the patient experience, PMB maximizes patient compliance and reduces pharmacy callbacks for generic substitutions.”
“The bottom line: Pred-Moxi-Brom doesn’t just represent a win-win for physicians and patients; it represents a new and higher standard in the treatment of postsurgical pain and inflammation.”
“It’s worth noting that a compounded medication like PMB demonstrated quality that is equal to, if not higher than, drugs produced by the major pharmaceutical companies.”
This presentation misleadingly suggests that Pred-Moxi-Brom is superior to multiple individual FDA-approved drug products, but it does not provide support for these claims. The first statement listed above implies that Pred-Moxi-Brom is preferred over prednisolone sodium phosphate solutions. This statement purports to rely for support on a study by Kupferman and Leibowitz; however, this study did not ask for ophthalmologists’ preferences and is therefore insufficient to support this claim. Moreover, because the study was performed in 1975, it did not include several of the topical ophthalmic corticosteroids approved and marketed today. Without additional context, this statement - based solely on an outdated study - creates the misleading impression that Pred-Moxi-Brom is preferred over more recently approved ophthalmic corticosteroid drug products. The FDA is not aware of any data to support such a conclusion.
The additional claims listed above imply that Pred-Moxi-Brom improves patient compliance and treatment outcomes with quality that equals or surpasses that of “drugs produced by the major pharmaceutical companies,” but it provides no support for these statements. The FDA is not aware of any data to support the suggestions that Pred-Moxi-Brom increases patient compliance, improves treatment outcomes, or is of higher quality compared to other drug products. If you have data to support these suggestions, please submit them to the FDA for review.
False or Misleading Risk Presentation
Promotional materials misbrand a drug product if they are false or misleading with respect to risk. The determination of whether promotional materials are misleading includes, among other things, not only representations made or suggested in promotional materials, but also failure to reveal facts material in light of the representations made or with respect to consequences that may result from the use of the drug product as recommended or suggested in the materials.
The following claims appear in “
Pred-Moxi-Brom: The Whole Is Greater Than The Sum Of Its Parts
”:
• “Although generic medications are available, they can potentially cause unknown adverse effects. Pred-Moxi-Brom virtually eliminates all these challenges with just one drop.”
• “Pred-Moxi-Brom’s tolerability is also high.”
• “In our clinic’s experience, few patients have had to discontinue treatment because of allergies, burning sensation, or other adverse events.”
The FDA is unaware of any evidence that supports the safety claims for your compounded Pred-Moxi-Brom drug product. Additionally, while the promotional materials include claims and/or representations about the safety of Pred-Moxi-Brom, they fail to communicate any risk information associated with the product. This is particularly concerning in light of the many known risks associated with the active ingredients in these drug products according to your firm’s own website
7
, which provides “Possible Adverse Effects” and “Potential Contraindications/Precautions” associated with each component, as well as the product labeling of drugs approved by the FDA that contain these active ingredients. Finally, we note that Pred-Moxi-Brom is likely to be associated with additional safety risks because it contains both a corticosteroid and a non-steroidal anti-inflammatory ingredient, each of which may slow healing.
By omitting the risks associated with Pred-Moxi-Brom, the promotional materials fail to provide material information about the consequences that may result from the use of the drug and create a misleading impression about the drug’s safety. Specifically, the omission of risk information suggests that Pred-Moxi-Brom is not associated with the risks that are known to be associated with its active ingredients. This is particularly concerning from a public health perspective because the promotional materials do not enable healthcare providers to make informed decisions about whether the benefits of your drug product outweigh the risks for their patients or to inform patients of appropriate monitoring that could minimize consequences of potential adverse events.
Conclusion
For the reasons discussed above, the promotional materials sponsored by your firm in the professional periodicals
Glaucoma Physician
and “The Ophthalmic ASC” by
Ophthalmology Management
misbrand Pred-Moxi-Brom within the meaning of the FD&C Act and make its distribution violative. 21 U.S.C. 352(bb); 321(n); and 331(a).
This letter notifies you of our concerns and provides you an opportunity to address them. We request that ImprimisRx cease any violations of the FD&C Act. Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of any violations, as well as copies of related documentation. Such documentation should include a listing of all other promotional communications for Pred-Moxi-Brom that contain representations such as those described above and an explanation of any plan for discontinuing such communications, or for ceasing distribution of Pred-Moxi-Brom.
Failure to adequately address this matter may lead to regulatory action. If you believe that your drug product is not in violation of the FD&C Act, please include in your submission to us your reasoning and any supporting information for our consideration within 15 working days from the date of receipt of this letter. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will do so.
The concerns discussed in this letter do not necessarily constitute an exhaustive list of potential violations. It is your responsibility to ensure compliance with each applicable requirement of the FD&C Act and FDA implementing regulations.
Please direct your electronic reply to ORAPHARM4_Responses@FDA.HHS.GOV or mail your reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
U.S. Food & Drug Administration
19701 Fairchild Road
Irvine, California 92612-2506
Please identify your responses with the unique identifier:
CMS 627802
.
If you have questions regarding the contents of this letter, please contact Andrew Haack, Compliance Officer via email at, Andrew.Haack@fda.hhs.gov by telephone at 206-340-8212.
Sincerely,
/S/
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
Cc:
Mark L. Baum, CEO
Harrow Health Inc.
102 Woodmont Blvd., Suite 610
Nashville, TN 37205
______________________________
1
See
Vance Thompson, MD, Brian Shafer, MD,
Pred-Moxi-Brom: The Whole is Greater Than the Sum of Its Parts: ImprimisRx’s Compounded Medication Takes Postsurgical Pain and Inflammation Treatment to a Whole New Level; William Wiley, MD, Compounding Pharmacies: It Pays to Know Your As and Bs
(attached as Exhibit 1).
2
Imprimis Pharmaceuticals Inc. has since been renamed Harrow Health, Inc. According to its website, https://www.imprimisrx.com/, “ImprimisRx is a wholly owned subsidiary of Harrow Health, Inc.”
3
See, e.g., PRED FORTE® (prednisolone acetate ophthalmic suspension, USP) 1% sterile Prescribing Information,
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017011s047lbl.pdf
4
See, e.g., VIGAMOX® (moxifloxacin hydrochloride ophthalmic solution) 0.5% as base, sterile topical ophthalmic solution Prescribing Information,
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021598s017lbl.pdf
5
See, e.g., BROMSITE (bromfenac ophthalmic solution) 0.075%, for topical ophthalmic administration Prescribing Information,
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206911s000lbl.pdf
6
Kupferman A, Leibowitz, HM. Anti-inflammatory effectiveness of topically administered corticosteroids in the cornea without epithelium. Investigative Ophthalmology & Visual Science. 1975; 14:252-255.
7
See Product Information, Pred-Moxi-Brom (Prednisolone Acetate, Moxifloxacin, Bromfenac) – Potential Ingredient Risks at https://www.imprimisrx.com/productinformation/
Content current as of:
07/19/2022
Regulated Product(s)
Drugs