This e-alert is part of a series of e-alerts summarizing publicly available FDA enforcement letters (i.e., warning letters and untitled letters) relating to the advertising and promotion of prescription drugs, medical devices, and biologics.
This alert merely summarizes the allegations contained in FDA’s letters. It does not contain any analyses, opinions, characterizations, or conclusions by or of Covington & Burling LLP. As a result, the information presented herein does not necessarily reflect the views of Covington & Burling LLP or any of its clients.
First Quarter Enforcement Letters
During the first quarter of 2025 FDA’s Office of Prescription Drug Promotion (OPDP) posted the following two untitled letters.
- Untitled Letter to Edenbridge Pharmaceuticals, LLC d/b/a Dexcel Ltd. re NDA 211379 HEMADY (Dexamethasone tablets) for oral use (February 3, 2025) (Hemady Untitled Letter).
- Untitled Letter to Taiho Oncology, Inc. re NDA 214801 LYTGOBI® (futibatinib) tablets, for oral use (March 21, 2025) (Lytgobi Untitled Letter).
During the same period the Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) posted the following four warning letters.
FDA’s Advertising and Promotional Labeling Branch (APLB) in the Office of Compliance and Biologics Quality (OCBQ) has not posted any enforcement letters since 2018.
Office of Prescription Drug Promotion (OPDP)
Untitled Letter to Dexcel Ltd. (February 3, 2025)
OPDP’s untitled letter to Edenbridge Pharmaceuticals, LLC d/b/a Dexcel Ltd. (Dexcel) alleges that an exhibit booth panel (exhibit panel) misbrands Hemady by making false or misleading representations about the risks and benefits of Hemady. Hemady is indicated in combination with other anti-myeloma products for the treatment of adults with multiple myeloma (MM).
False or Misleading Risk Presentation
OPDP alleges that the exhibit panel “is misleading because it presents efficacy claims for Hemady but fails to communicate any risk information.” Specifically, OPDP notes the exhibit panel includes the following claims:
- “HEMADY® reduces up to 80% of the number of tablets required for a therapeutic dose of dexamethasone for the treatment of adults with MM.”
- “Hemady® is a unique strength dexamethasone tablet bioequivalent to five 4 mg tablets of dexamethasone.”
OPDP alleges that by omitting the risks associated with Hemady while emphasizing the benefit, “the exhibit panel fails to provide material information about the consequences that may result from the use of Hemady and creates a misleading impression about the drug’s safety.”
False or Misleading Claims About Efficacy
OPDP also takes issue with a table on the exhibit panel titled “REAL-WORLD COMPARISON OF ADHERENCE to Hemady® and generic dexamethasone among patients with MM,” which OPDP alleges “suggest[s] improved patient adherence to Hemedy as compared with generic dexamethasone 4 mg tablets.” OPDP states that “[d]ata on file is cited to support the presentation” but claims that “the referenced study does not support conclusions regarding comparative adherence to Hemady and generic dexamethasone 4 mg in the treatment of patients with MM due to limitations associated with the study design and methodology.” OPDP points to a series of alleged limitations with the referenced study, including that “the patient selection methodology described in the study protocol was not consistent between patients treated with Hemady and generic dexamethasone 4 mg,” “the study protocol did not identify whether Hemady or generic dexamethasone 4 mg was used as monotherapy or as part of combination treatment regimens,” and “the study included a significantly higher number of patients in the generic dexamethasone 4 mg group (n=3,775) compared to the Hemady group (n=43), leading to a notably unbalanced sample size.”
Untitled Letter to Taiho Oncology, Inc. (March 21, 2025)
OPDP’s untitled letter to Taiho Oncology (Taiho) alleges that the “Efficacy Results” webpage on the Lytgobi Healthcare Provider Branded Website misbrands Lytgobi by making false or misleading representations about the benefits of the product. FDA notes that it previously addressed similar concerns about claims in advisory comments provided to Taiho in 2022. Lytgobi is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 gene fusions or other rearrangements. Lytgobi was approved under the accelerated approval pathway.
False or Misleading Benefit Presentation
OPDP alleges that the “Efficacy Results” webpage for Lytgobi includes a series of unsupported efficacy claims related to progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). For example, the webpage includes:
- “A Presentation of a Kaplan-Meier estimate graph of PFS titled, ‘Progression-free survival (PFS),’ showing ‘Progression-free Survival (%)’ on the y-axis and ‘Months’ on the x-axis[.]”
- “Median [PFS], 9.0 mo (95% CI: 6.9, 13.1).”
- “Median follow-up at time of data cutoff was 17.1 months.”
- “A Presentation of a Kaplan-Meier estimate graph of OS titled, ‘Overall survival (OS),’ showing ‘Overall Survival (%)’ on the y-axis and ‘Months’ on the x-axis[.]”
- “Median [OS], 21.7 mo (95% CI: 14.5, Not Reached).”
- “At the time of data cutoff: Median follow-up was 17.1 months; the OS data were not mature; during the study, 40 patients (39%) died following treatment discontinuation with the majority (90%) dying from disease progression.”
- The claim “83% DCR (95% CI: 74, 89)” depicted inside of a pie chart that includes shading to show the 83% DCR.
FDA alleges that these and other claims misbrand Lytgobi because the design of the study Taihocites to support the claims, FOENIX-CCA2, is not capable of supporting the representations or suggestions. FDA alleges that because FOENIX-CCA2 was designed as a single-arm trial the results are not capable of establishing improvement on time-to-event efficacy endpoints such as PFS or OS and, without an appropriate comparator, “it is not possible to determine if the observed effect is attributable to LYTGOBI or to other factor(s), such as the natural history of the disease.” Additionally, FDA states that “[a]n assessment of delay in time to disease progression in patients treated with Lytgobi [] would need to be based on the results of a randomized controlled trial.”
FDA acknowledges that Taiho’s website includes disclaimers, such as “Due to potential variability in the natural history of the disease, a single-arm study may not adequately characterize these time-to-event endpoints and the results may not be interpretable” and “The extended follow-up data were collected after the primary analysis and are descriptive in nature, and results should be interpreted with caution.” However, FDA finds that these disclaimers are inadequate. Specifically, FDA states that “[t]he disclosures of the study’s limitations (noted above) in this promotional communication do not correct or mitigate the misleading representations or suggestions of the presentation.”
CDRH Office of Product Evaluation and Quality (OPEQ) and ORA Office of Medical Device and Radiological Health Operations (OMDRHO)
Warning Letter to Next Science LLC (Issued February 2025, Posted March 2025)
FDA’s warning letter to Next Science LLC (Next Science), issued by OPEQ, arose out of an August 12 – September 5, 2024, inspection of the company and review of its website. FDA alleges that the inspection revealed that Next Science is marketing wound gels (SURGX® and BLASTX®) and wound irrigation solutions (XPERIENCE® and Bactisure®) without 510(k) clearance, and consequently that these products are misbranded.
FDA alleges that:
- the XPERIENCE® product was cleared under K203835 as MIS Solution “indicated for use in cleansing and removal of debris, including microorganisms, from wounds”;
- the BLASTX® product was cleared under K150792 as Next ScienceTM Wound Gel for Over-The-Counter Use “indicated for the management of skin abrasions, lacerations, minor irritations, cuts, exit sites and intact skin”; and
- the SURGX® product was cleared under K163188 as Next Science nonsterile wound gel for Prescription Use and “indicated for the management of wounds such as Stage I-IV pressure ulcers, partial and full thickness wounds, diabetic foot and leg ulcers, post-surgical wounds, first- and second-degree burns, grafted and donor sites.”
However, FDA claims Next Science is marketing these products for additional uses outside of the scopes of clearance issued under K203835, K150792, and K163188, respectively, without obtaining clearance. FDA also states that “some of the claims raise jurisdictional issues, and if [the company] intend[s] to continue making such claims, the product may be regulated by the Center for Drug Evaluation and Research (CDER) and subject to drug requirements.”
Specifically, FDA took issue with a series of claims, including the examples listed below:
- XPERIENCE®
- “XPERIENCE rinses away debris and microorganisms from the surgical wound site.”
- “XPERIENCE does not have cytotoxic effects on osteoblasts. Cell viability and bone growth and healing were shown to be more favorable compared to 10% Betadine.”
- BLASTX®
- “BLASTX® has been shown to suppress inflammation and repair the skin’s barrier function.”
- “BLASTX® inactivates matrix Metalloproteases (MMPs), leading to stopping the cytokine cascade. Also, BLASTX® inactivates proteases production by the bacteria, which prevents tissue destruction and inflammation by the same mechanism.”
- SURGX®
- “SURGX® Sterile Antimicrobial Gel as sterilized by gamma radiation for one time use.”
- “SURGX® is designed to reduce surgical site and post-surgical infections by destroying planktonic and biofilm-encased bacteria within the gel. The proprietary, non-toxic formulation conforms to the postoperative wound to provide proven broad spectrum and sustained effectiveness for up to 5 days.”
FDA also alleges that Next Science is “marketing the XPERIENCE®, BLASTX® and SURGX® products as powered by XBIO® Technology and that the company makes claims that “XBIO® Technology deconstructs biofilm by removing the metal ions holding biofilm together.” For example, FDA highlights the following claims, among others:
- “Since 2012, Next Science has been developing revolutionary material science-based technology that is non-toxic with proven efficacy against bacteria and microorganisms. This technology is called XBIO®.”
- “XBIO™ Technology deconstructs biofilm by removing the metal ions holding it together.”
- “At Next Science, we are leading a paradigm shift with a unique approach to eradicating both biofilm bacteria and planktonic bacteria with our XBIO Technology. XBIO disrupts the biofilm’s extracellular polymeric substance and exposes the bacteria, once protected by the biofilm, leaving it more vulnerable to attack.”
Notwithstanding these claims, FDA alleges that the products “have not been evaluated for safety and effectiveness against biofilm.” FDA also states that it previously communicated these concerns to the company during a regulatory meeting held on May 5, 2022. FDA alleges that in 2022 it explained “the antimicrobial component[s] found in [the] 510(k) cleared products are intended to function as a preservative that inhibits growth of microorganisms in the products and claims of effectiveness against biofilm are outside the clearance of XPERIENCE®, BLASTX® and SURGX®.” FDA also alleges that the company’s claims “go beyond the types of claims appropriate for wound dressings and wound washes categorized under the FRO product code” and that the claims “raise jurisdictional issues” such that the products “may be regulated by CDER and subject to drug requirements.”
Warning Letter to Exer Labs, Inc. (Issued February 10, 2025)
FDA’s warning letter to Exer Labs, Inc. (Exer Labs) arose out of an October 2024 inspection of the company and review of Exer Labs’ website. FDA alleges that the inspection revealed that Exer Labs is marketing the Exer Scan, a measuring exercise equipment device, in a way that exceeds the 510(k) exemption. Specifically, FDA explains that 510(k)-exempt measuring exercise equipment are intended to provide or facilitate exercise rehabilitation and include exercise measurement capabilities. FDA contends that Exer Labs is marketing the Exer Scan for “use of artificial intelligence-based algorithms to screen, diagnose, and treat musculoskeletal and neurological disorders, including Parkinson’s, musculoskeletal tuberculosis, and cerebral palsy,” which are “diagnostic functions that are not limited to measurement of exercises.” FDA points to the following claims on the Exer Labs website, among others:
- “Use Clinical AI to Diagnose and Treat MSK Disorders”
- “AI-Based Screening for MSK Disorders in Neurology – Screen and treat patients with Parkinson’s, TB, Cerebral Palsy and more using AI and computer vision…”
- “The Operating System for Hybrid Orthopedic Care – Automate treatment pathways for operative or conservative care to reduce complications…”
FDA concludes that analyzing patient data “for the screening and diagnosis of specific conditions or disorders represents a new intended use,” meaning the device is not exempt from premarket notification.
Warning Letter to Red Oak Instruments, LLC (Issued February 2025, Posted April 2025)
FDA’s warning letter to Red Oak Instruments, LLC (Red Oak), issued by OPEQ, arose out of a July 15 – 26, 2024, inspection of the company and review of Red Oak’s website. FDA alleges that the inspection revealed that Red Oak is marketing an AC Powered Dynamometer RU-Fit (Model SR-3053) medical device with major changes or modifications to the intended use without submitting a new 510(k) premarket notification to FDA.
According to FDA, AC-powered dynamometer devices classified under 21 CFR 888.1240 are exempt from premarket notification. Such devices are intended “to assess neuromuscular function or degree of neuromuscular blockage by measuring, with a force transducer (a device that translates force into electrical impulses), the grip-strength of a patient's hand.” However, FDA alleges “there is evidence that the RU-FIT (Model SR-3053) is intended for uses that are different from those of legally marketed devices classified under 21 CFR 888.1240 AC-powered dynamometer.” Specifically, FDA alleges “the device is intended to screen for possible mild traumatic brain injury (mTBI), also known as concussion.” FDA points to the following claims, among others, as evidence of this point:
- “This device is intended to screen for possible head injuries in the cases of head impact where there is not any visible blood, other than minor scraps [sic].”
- “The SR-3053 should be used…to compare recognition and choice reaction times of an injured or non-injured individual.”
- “Summary Sheet For Concussive Impact”
- “Since denial is a strong symptom of mTBI subjects, the necessary compliance is not always achievable. A better technology is needed. RedOak Instruments provides the needed technology.”
- “RedOak Instruments, LLC is a USA based biomechanical and software-based company which provides objective physiological measurements to screen for injuries, ailments and to monitor recovery. The test will document the reduction or improvement of factors related to head injury including fine motor control, coordination and reaction time.”
FDA also claims that because the RU-FIT (Model SR-3053) was previously cleared under K012492 for specific indications, which do not include mTBI, promoting the device to screen for possible mTBI “would constitute a major change or modification to its intended use, for which [Red Oak] lacks clearance or approval.”
Warning Letter to Rex Implants Inc. (Issued March 12, 2025)
FDA’s warning letter to Rex Implants Inc. (Rex Implants) arose out of a December 2023 inspection of the company and review of Rex Implants’ website. FDA alleges that the inspection revealed that Rex Implants is marketing the PiezoImplant REX BL 2.9 implant system, a tissue level blade form endosseous dental implant body and associated dental implant abutments, for uses that exceed or otherwise differ from the 510(k) clearance. FDA alleges that while the cleared instructions state that the implant body should be removed if it is mobile at placement, the Instructions for Use instead advise that the surgeon may place the implant body deeper if there is mobility at placement. FDA claims that this change in surgical procedure represents a “significantly modified risk,” requiring a new 510(k). Additionally, the cleared labeling states that the minimum buccolingual ridge the system can be used in is 3.5mm, but the Instructions for Use state that the BL implant bodies are meant to be placed in ridges measuring 3mm or more. FDA alleges that this constitutes a major change or modification to its intended use that requires a new 510(k) clearance.
Additionally, FDA alleges that Rex Implants is marketing titanium bases designed for the REX Piezoimplant TL system that are intended to be used with a patient-specific top half. However, the 510(k) submission for the system included only abutments that are not designed for use with a patient-specific top half. Therefore, the titanium bases “introduce new biocompatibility concern” compared to the cleared devices.
Second Quarter Enforcement Letters
During the second quarter of 2025 FDA’s Office of Prescription Drug Promotion (OPDP) posted one untitled letter and one warning letter.
- Untitled Letter to Mayne Pharma, LLC re NDA 214154 NEXTSTELLIS (drospirenone and estetrol tablets), for oral use (April 28, 2025) (Nextstellis Untitled Letter).
- Warning Letter to Sprout Pharmaceuticals, Inc. re NDA 022526 ADDYI (flibanserin) tablets, for oral use (June 10, 2025) (Addyi Warning Letter).
During the same period, the Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) posted three warning letters relating to the advertising and promotion of medical devices.
The Office of Medical Device and Radiological Health Operations (OMDRHO) in the Office of Regulatory Affairs (ORA) did not post any warning letters relating to the advertising and promotion of medical devices during this period. FDA’s Advertising and Promotional Labeling Branch (APLB) in the Office of Compliance and Biologics Quality (OCBQ) has not posted any enforcement letters since 2018.
Office of Prescription Drug Promotion (OPDP)
Untitled Letter to Mayne Pharma, LLC (Issued April 28, 2025)
OPDP’s Untitled Letter to Mayne Pharma(Mayne) alleges that a professional “presentation for NEXTSTELLIS promotional programs with speaker notes” (“speaker deck”) makes false or misleading claims and presentations about the risks of Nextstellis. Nextstellis is indicated for use by females of reproductive potential to prevent pregnancy.
False or Misleading Claims and Presentations about Risk
OPDP claims the speaker deck misleadingly suggests that Nextstellis is safer than other forms of CHC (Combined Hormonal Contraception), because its active estrogen ingredient is estetrol. OPDP alleges these claims “suggest that estetrol is different from—and lower risk than—other estrogens because of purported native characteristics and a ‘unique pharmacologic profile’ that ‘results in tissue selective actions’ and a ‘low impact.’” Moreover, OPDP alleges the speaker deck misleadingly suggests that estetrol “has differential selectivity in tissues that distinguishes it functionally from other estrogens, when this has not been demonstrated.” OPDP highlights a series of claims, including:
Warning Letter to Sprout Pharmaceuticals, Inc. (Issued May 29, 2025, Posted June 10, 2025)
OPDP’s warning letter to Sprout Pharmaceuticals, Inc. (Sprout) alleges that a social media post by Sprout’s Chief Executive Officer for Addyi is false or misleading “in that it makes representations about the benefits of Addyi but fails to include any risk information about the drug and omits material information regarding the full indication, including the limitations of its use.” OPDP notes that it sent Sprout a warning letter in August 2020 addressing “presentation of Addyi with certain similarities to the post addressed in this letter” and that “OPDP is concerned that, despite receiving this previous Warning Letter, Sprout continues to promote Addyi in a similarly misleading manner.”
Addyi is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to a co-existing medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance. Addyi is not indicated for the treatment of HSDD in postmenopausal women or in men and is not indicated to enhance sexual performance.
False or Misleading Risk Presentation
OPDP alleges “[t]he post is misleading because it includes representations about the benefits of Addyi but fails to communicate any risk information,” thereby creating a misleading impression about the drug’s safety. OPDP suggests “[t]his omission is especially problematic from a public health perspective given the serious risks associated with the drug.” OPDP references the specific claims:
- “The first articles on @addyi a decade ago questioned the women struggling, told them it was normal, debated how many more satisfying sexual events were enough for them to deserve a pill…”
- “…Addyi, the Sex Pill for Women…”
- “Addyi is the first FDA-approved treatment for women’s sexual dysfunction.”
Omission of Material Facts
OPDP also alleges that by “failing to disclose the full indication and limitations of use associated with Addyi, the post creates a misleading suggestion about the FDA-approved indication and use for Addyi.” OPDP states that “[t]his broad claim suggests that Addyi is indicated, among other things, to enhance sexual performance, which is particularly concerning given the limitations of use and serious risks of this product.”
Failure to Submit Under Form FDA-2253
OPDP also alleges that Sprout failed to submit the FDA transmittal form (Form FDA-2253) and a copy of the post at the time of initial dissemination or publication as required by FDA regulations at 21 CFR 314.81(b)(3)(i).
Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH)
Warning Letter to DRG Instruments GmbH (Issued March 31, 2025, Posted May 27, 2025)
OPEQ’s warning letter to DRG Instruments GmbH (DRG), regarding the company’s in vitro diagnostic devices, including the Salivary Cortisol ELISA RUO test, arose out of an inspection of the company November 4 through 7, 2024, and a review of DRG’s website.
OPEQ alleges that the Salivary Cortisol ELISA RUO is misbranded because the test is intended for clinical diagnostic use and lacks 510(k) clearance, notwithstanding the product’s labeling for research use only. OPEQ alleges that the evidence obtained during the inspection and DRG’s website are inconsistent with the company’s assertion that the test is intended for research use only. For example, OPEQ alleges that DRG’s website describes the test as having advantages for “clinical applications such as: Diagnosis of systemic/local conditions,” that the test instructions describe how to collect samples from individuals (e.g., “Eating, drinking, chewing gums or brushing teeth should be avoided for 30 minutes before sampling.”), and that customer records demonstrate the company shipped the test to companies in the business of performing clinical analysis that do not perform research. OPEQ notes DRG’s website compares the Salivary Cortisol ELISA RUO to a reference test and “states it provides ‘Industry Leading Accuracy with Kit Components Calibrated to Mass Spectrometry,’” thereby implying the Salivary Cortisol ELISA RUO is intended for clinical diagnostic use. In addition to concerns with marketing claims, OPEQ alleges that “during the inspection, [DRG] provided to the FDA investigator copies of certification letters from certain customers of the Salivary Cortisol ELISA RUO as evidence that these customers were aware that they were only supposed to use these products for research purposes. However, . . . a review of these customers’ websites strongly suggests that these customers are engaged in clinical diagnostic testing.”
Separately, OPEQ alleges the DRG’s website includes a tab called “FDA Cleared Tests” and lists several devices, such as a Thyroid Stimulating Hormone (TSH) assay for in vitro diagnostic use, for which there is no record of a 510(k) clearance held by DRG. Additionally, OPEQ claims the DRG’s website includes misleading language indicating that a class I 510(k) exempt product, the DRG Hybrid XL, has been reviewed and approved by FDA. Specifically, the claim states it is “Now FDA Approved.”
Warning Letter to Reset Technology Corporation (Issued June 9, 2025)
FDA’s warning letter to Reset Technology Corporation (Reset Technology) arose out of an October-December 2024 inspection of the company and review of Reset Technology’s website. FDA alleges that Reset Technology is marketing the ResetSmile Impression Kit for new uses that lack 510(k) clearance or approval.
FDA alleges that the 510(k) summary for the impression material states that it is “intended for use with all crowns, bridges, and orthodontic impression techniques to reproduce the structure of a patient’s teeth and gums” and is for prescription use only. However, ResetSmile’s “impression material is intended to be used by customers to take their own impression without the supervision of a dentist.” FDA asserts that the change from prescription to over-the-counter use could significantly affect the safety or effectiveness of the device, stating that consumers who take their own impressions may take improper impressions, leading to ill‑fitting dentures that can cause irritation, sores, bone loss, or temporomandibular joint (TMJ) complications. Therefore, FDA asserts that this use is not within the cleared indication for use, and a new 510(k) clearance is required.
Warning Letter to Mectronic Medicale S.R.L. (Issued June 27, 2025)
FDA’s warning letter to Mectronic Medicale S.R.L. (Mectronic Medicale) arose out of a February 2025 inspection of the company. FDA alleges that Mectronic Medicale is marketing Doctor Tecar, Doctor Tecar Smart, and Doctor Tecar Plus devices for uses outside of their 510(k) clearances. FDA alleges that the devices have been cleared for topical heating intended to raise tissue temperature to treat pain, muscle spasms, and increase in local circulation, but Mectronic Medicale is marketing the devices for the following uses:
- “Doctor Tecar Therapy is an innovative, high-performance therapy in the treatment of Carpal Tunnel Syndrome.”
- “Doctor Tecar Therapy not only provides rapid pain relief, but also accelerates the healing process, significantly reducing recovery time and improving the effectiveness of treatments.”
- “Accelerated Healing: Boosts cellular metabolism for faster and more effective rehabilitation.”
FDA contends that these statements were not reviewed as part of the 510(k) submission and are outside of the scope of the clearances. FDA explains that these devices “use energy to generate heat within layers of the skin and require performance testing for specific indications for use that presume a specific clinical outcome,” that the new intended uses raise different effectiveness concerns than those normally associated with the cleared uses of the devices, and that FDA is “currently unaware of any evidence that could support” the above intended uses. Therefore, a new 510(k) clearance or approval is required for these uses.
FDA also alleges that Mectronic Medicale’s CHELT, iLux Plus, iLux Smart, and Ixyon XP devices exceed the limitations of 510(k) exempt classifications for infrared heating lamps, under which the devices were listed with FDA. FDA contends that 510(k)-exempt infrared lamps are intended “to provide topical heating and are intended for medical purposes including, but not limited to, temporary increase in local blood circulation and temporary relief of: muscle spasms, minor joint pain and stiffness, minor muscle pain and stiffness, and minor arthritis pain,” but Mectronic Medicale’s devices are being marketed for different specific intended uses, namely “for the treatment of pathologies of the musculoskeletal system such as lumbago, cervicalgia, epicondylitis, medial epicondylitis, . . . as well as contractures . . .” FDA states that it “is currently unaware of any clinical evidence that could support these intended uses,” which increase the risk of injury due to “deeper tissue penetration, and potentially higher energy and temperature delivery.” Therefore, the devices do not fall within the 510(k) exemption and require 510(k) clearance or approval.
Third Quarter Enforcement Letters
During the third quarter of 2025, the Center for Drug Evaluation and Research (CDER) issued more than 50 Warning Letters and more than 50 Untitled Letters to pharmaceutical companies for drug advertisements.
During the same period, the Center for Biologics Evaluation and Research (CBER) sent one Untitled Letter to AstraZeneca Pharmaceuticals LP regarding FluMist (September 9, 2025) (AstraZeneca Untitled Letter). Prior to this letter, CBER’s Advertising and Promotional Labeling Branch (APLB) had not posted any enforcement letters since 2018.
Additionally, the Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) posted four Warning Letters relating to the advertising and promotion of medical devices.
The Office of Medical Device and Radiological Health Operations (OMDRHO) in the Office of Regulatory Affairs (ORA) did not post any Warning Letters relating to the advertising and promotion of medical devices during this period.
CDER and CBER Advertising Warning and Untitled Letters
The majority of the Warning and Untitled Letters were issued following a September 9, 2025, presidential memorandum setting forth the Administration’s desire to enhance transparency in direct-to-consumer (DTC) advertising. Along with this presidential memorandum, FDA issued a press release announcing a crackdown on deceptive drug advertising. The press release states that “FDA is sending thousands of letters warning pharmaceutical companies to remove misleading ads and issuing approximately 100 cease-and-desist letters to companies with deceptive ads.” Presumably, the Warning and Untitled letters are the “cease-and-desist letters” mentioned in the press release.
The 50+ Untitled Letters primarily address DTC broadcast advertisements. However, some of the letters cite other forms of advertising and promotion, including healthcare professional webpages, healthcare professional visual aids, and DTC print advertisements.
Many of the letters assert that the advertisement or promotional labeling at issue is false or misleading “in violation of the Federal Food, Drug, and Cosmetic Act.” However, the letters do not generally cite specific provisions of the FDCA or FDA regulations. For most of the letters, the grounds cited for why the advertisement or promotional piece is allegedly misleading fall into one of the categories listed below:
- Overstatement of efficacy based on implied claims of improvement in patients’ lives or functioning based on suggestive imagery and/or language, including before-and-after depictions of patients.
- Misleading presentation of risk in the major statement due to “attention-grabbing visuals,” failing to present adequate information in the voiceover and in text (dual modality) or other presentational elements of the major statement.
- Misleading presentation of risk in the major statement due to particular risks or aspects of a risk being omitted.
- Overstatement of efficacy based on implied claims of ease of use or dosing.
- Overstatement of efficacy based on data that is exploratory, such as an extended analysis of a study.
- Presentation of data for oncology products on stable disease, progression-free survival (PFS), overall survival (OS), or other time-to-event endpoints based on a single-arm trial. CDER asserts that the presentations are misleading even with disclaimers about the limitations of the data and the lack of overt claims.
The 50+ Warning Letters seem to have been reserved primarily for obesity products, including both FDA-approved prescription drug products and compounded products, and largely take issue with website content. Some warning letters were also issued for the marketing of compounded methylphenidate, amphetamine, sildenafil, tadalafil, and immune globulin products. The Warning Letters sent to FDA-approved prescription drug manufacturers focus primarily on allegations of false and misleading presentation of risk information and/or the omission of material facts. The Warning Letters sent to entities marketing compounded products tend to challenge claims that “imply that [] products are the same as an FDA-approved product when they are not” (e.g., statements that the compounded products are “generic” versions of the FDA-approved product or that they have the “same active ingredient”). They also challenge claims suggesting that the compounded products have been shown in clinical trials to be safe and effective (e.g., “proven effectiveness” or “clinically proven”).
These Warning and Untitled Letters differ from prior Warning and Untitled Letters to pharmaceutical companies in content and form. For example, the letters generally state that the determinations are those of FDA, as opposed to those of the Office of Prescription Drug Promotion (OPDP) or APLB, and they are signed by the CDER or CBER Director, rather than an OPDP or APLB official. Additionally, the letters state that “FDA requests [Company] take immediate action to address any violations (including, for example, ceasing and desisting promotional communications that are misleading as described above.” This language is somewhat different from prior letters, which stated, in the case of OPDP, that “OPDP requests that [Company] cease any violations of the FD&C Act” and did not include language on “immediate action.”
Warning Letter to Insightra Medical Inc. (Issued June 3, 2025, Posted July 8, 2025)
OPEQ’s Warning Letter to Insightra Medical Inc.(Insightra Medical), regarding the firm’s Double Pump and Ultra Intra Aortic Balloon Pump (IABP) Catheter Kits, arose out of an inspection of the firm in January 2025.
OPEQ alleges that the Double Pump and Ultra Intra Aortic Balloon Pump (IABP) Catheter Kit is misbranded because the firm made major changes or modifications to the intended use without submitting a new premarket notification to FDA. Specifically, the firm’s labeling, including promotional materials and information on its website, state that the device is compatible with the Cardiosave IABP Hybrid and the AutoCat 3 despite the fact that the premarket notification under which the device was 510(k) cleared recommended the device only for use with the Datascope System 97, System 98, System 98XT, CS100 and CS300 devices and the Arrow ACAT, AutoCat, AutoCat 2, AutoCat 2 Wave, and KAAT II devices. OPEQ states that listing Cardiosave IABP Hybrid and the AutoCat 3 in the labeling as compatible pump consoles constitutes a significant change or modification to the device’s intended use that requires a new 510(k) clearance. OPEQ explains “[t]he more critical the other device, component, or accessory is to overall system function, the more likely a labeling change regarding compatibility or interoperability could significantly affect safety or effectiveness.” OPEQ concludes that “the pump console is required for the operation of [the] device and therefore has substantial impact on the safety and effectiveness of [the] device. A change to a different pump console that may have different performance characteristics could impact the safety and effectiveness of an IABP catheter.”
Warning Letter to Spectra Therapy, LLC (Issued July 22, 2025)
FDA’s warning letter to Spectra Therapy, LLC (Spectra Therapy) arose out of a September 2024 inspection of the company and a review of its website. FDA alleges that Spectra Therapy is marketing the LASERwrap system for uses that exceed the scope of the 510(k) exemption for infrared lamp devices and marketing the Spectra Therapy Spectra A1000 Laser Device for uses that exceed the 510(k)-cleared indications.
510(k) exempt infrared lamps are intended to provide surface level heating for medical purposes such as temporary increase in local blood circulation and temporary relief of minor muscle and joint pain and stiffness. However, FDA alleges Spectra Therapy is marketing the LASERwrap system for different intended uses, including “treatment of diseases or conditions such as irritable bowel syndrome, wounds, and urinary tract infections, and cure of ‘inflammatory issues’ such as tendonitis, bursitis, and plantar fasciitis.” FDA points to the following claims, among others:
“The Physiological Effects of [Low-level laser therapy] LLLT are:”
- “Bio-stimulation”
- “Improved metabolism”
- “Increase of cell metabolism”
- “Stimulation of wound healing…”
- “How has LLLT worked for others?”
- “Increases . . . tensile strength of tissue repair”
- “Develops collagen ...”
- “Promotes faster wound healing and clot formation ...”
- “Abdominal & Back LASERwrap® Treatments ...”
- “Reduce IBS [Irritable Bowel Syndrome] & UTI [Urinary Tract Infection]”
In addition, the Spectra Therapy website included testimonials for “Wounds,” “Chronic Pain,” and “Fibromyalgia.” For example, one testimonial stated:
LASERwrap® eliminated PAIN from 7 patients in less than a week to 10 days, that had been fighting neuropathy & plantar fasciitis conditions from 6 MONTHS to 2 YEARS. Good news for lower extremity diabetic patients with wounds on the bottom of their feet, LASERwrap® healed decubitus wounds in 2 weeks versus 4-5 months using conventional debriefing methods.
FDA also states that the Spectra Therapy Spectra A1000 Laser Device was previously cleared to provide topical heating “for the temporary relief of minor muscle and joint pain, arthritis and muscle spasm, relieving stiffness, promoting relaxation of muscle tissue, and to temporarily increase local blood circulation.” FDA asserts that the device was promoted for new uses that were not cleared, including for “irritable bowel syndrome, wounds, and urinary tract infections, and to cure ‘inflammatory issues.’” FDA asserts that the company “provided no evidence to FDA supporting” these claims and that the lack of supporting data “raises public health concerns, including the risk of a delay in definitive treatment” if the device is used for wound care, neuropathy or the other advertised conditions. Therefore, these claims constitute a major change or modification to the intended use of the device, which requires a new 510(k) clearance or approval.
Warning Letter to Les Encres LLC (Issued July 30, 2025)
FDA’s warning letter to Les Encres LLC (Les Encres) arose out of a March-April 2025 inspection of the company and review of its website. FDA alleges that Les Encres is marketing Les Encres absorbable polydioxanone (PDO) surgical suture devices (“Les Encres threads”) for uses outside of the 510(k)-cleared indications for use.
According to FDA, Les Encres threads were cleared “for use in soft tissue approximation where use of absorbable suture is appropriate.” However, FDA alleges that there is evidence that “the devices are intended for specific cosmetic uses, which would constitute a major change or modification to their intended use.” FDA points to the following claims:
- “Using Les Encres Threads, we can lift, tighten and add volume where needed, all in the time it takes you to eat lunch.”
- “Ideal for Light cheek lift, Jawline lift, Neck lift, Brow lift and Lower Face treatments.”
FDA states that the agency raised these concerns with Les Encres in 2024. At the time, FDA “strongly recommended that [Les Encres] conduct the performance testing appropriate for barbed sutures and submit a new 510(k) notification, including identifying a suitable predicate device to the Agency.” In the warning letter, FDA adds that “for any cosmetic use related to sutures, the Agency has required comprehensive performance testing, including clinical evidence, to establish substantial equivalence to a legally marketed predicate device. This information must be submitted as part of a new 510(k) submission.”
Warning Letter to SeniorLife Technologies, Inc. (Issued August 21, 2025, Posted September 16, 2025)
FDA’s Warning Letter to SeniorLife Technologies, Inc. (Senior Life) regarding the firm’s SeniorLife.AI mobile application arose out of an inspection of the firm on March 24 through March 26, 2025.
OPEQ alleges that the SeniorLife.AI mobile application is misbranded because the claims on the website for the device indicate it is for intended uses that exceed the scope of the 510(k)-exempt classification for Measuring Exercise Equipment, 21 CFR 890.5360, under which the device was marketed. Specifically, “[m]easuring exercise equipment consist of manual devices intended for medical purposes, such as to redevelop muscles or restore motion to joints or for use as an adjunct treatment for obesity,” but OPEQ alleges SeniorLife is “distributing SeniorLife.AI for a different intended use, namely the use of artificial intelligence-based algorithms to screen and ‘pre-diagnose’ mobility and cognitive health conditions.” OPEQ cited website claims such as “[p]roactively identifies fall risk, recommends interventions, and continuously tracks patient mobility over time” and “[c]onducts a 5-minute gaze-based test on an iPad to detect early signs of Alzheimer’s.” OPEQ notes these functions are not the same as measurement of exercises and that “[b]ecause there is evidence that SeniorLife.AI is intended for uses that are different from those of legally marketed devices classified under 21 CFR 890.5360, it does not fall within the scope of that regulation and requires a premarket submission prior to marketing.”
Fourth Quarter Enforcement Letters
During the fourth quarter of 2025 FDA’s Office of Prescription Drug Promotion (OPDP) posted four untitled letters and no warning letters.
- Untitled Letter to Daiichi Sankyo, Inc. re NDA 211810 TURALIO® (pexidartinib) capsules, for oral use (November 24, 2025) (Turalio Untitled Letter)
- Untitled Letter to Karuna Therapeutics, Inc., a Bristol Myers Squibb Co. re NDA 216158 COBENFY™ (xanomeline and trospium chloride) capsules, for oral use (December 15, 2025) (Cobenfy Untitled Letter)
- Untitled Letter to BeOne Medicines USA, Inc. re BLA 761232 TEVIMBRA® (tislelizumab-jsgr) injection, for intravenous use (December 17, 2025) (Tevimbra Untitled Letter)
- Untitled Letter to Esperion Therapeutics, Inc. re NDA 211617 NEXLIZET® (bempedoic acid and ezetimibe) tablets, for oral use (December 19, 2025) (Nexlizet Untitled Letter)
During the same period, the Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) posted one warning letter relating to the advertising and promotion of medical devices.
- Technological Medical Advancements LLC re Diowave 250 WLS and Diowave 100 WLS laser system (September 26, 2025) (TMA Warning Letter)
The Office of Medical Device and Radiological Health Operations (OMDRHO) in the Office of Regulatory Affairs (ORA) did not post any warning letters relating to the advertising and promotion of medical devices during this period. FDA’s Advertising and Promotional Labeling Branch (APLB) in the Office of Compliance and Biologics Quality (OCBQ) did not post any warning letters relating to the advertising and promotion of biologics during this period.
Office of Prescription Drug Promotion (OPDP)
Untitled Letter to Daiichi Sankyo, Inc. (Issued November 24, 2025)
OPDP’s letter to Daiichi Sankyo, Inc. (Daiichi Sankyo) alleges that a direct-to-consumer (DTC) video for Turalio is false and misleading. Specifically, OPDP alleges that before-and-after images in the video of a patient gardening “suggest[s] that all patients with [tenosynovial giant cell tumor (TGCT)] treated with Turalio will experience a complete resolution of disease and will be able to return to daily activities (e.g., gardening), without limitations from TGCT stopping them.” However, OPDP states that according to the clinical studies the overall response rate “does not adequately support the suggestion that all patients would be able to live as they did prior to their TGCT diagnosis.”
Furthermore, OPDP states that the totality of the claims and presentations misleadingly suggest that treatment with Turalio will improve patients’ emotional and physical functioning and may allow them to return to their original selves “when this has not been demonstrated.” OPDP acknowledges the video includes a disclaimer that “[o]utcomes may vary and are dependent on each patient’s clinical profile and history.” However, it concludes that “inclusion of this statement in this promotional communication does not correct or mitigate the misleading suggestions regarding Turalio treatment.”
Untitled Letter to Karuna Therapeutics, Inc. (Issued December 15, 2025)
OPDP’s letter to Karuna Therapeutics, Inc. (Karuna) alleges that a TV ad for Cobenfy is false or misleading because the “claims and presentations create a misleading representation that treatment with Cobenfy will improve both the positive and negative symptoms of schizophrenia” despite the fact that “the pivotal trials supporting the schizophrenia indication for Cobenfy were not designed to capture changes in positive or negative symptoms as distinct groups.”
Specifically, OPDP refers to a voiceover stating that “Cobenfy showed overall improvement across a range of schizophrenia symptoms . . .” made in conjunction with on-screen text that it offers “improvement ACROSS A RANGE OF SYMPTOMS” and an image of overlapping circles with the text “POSITIVE SYMPTOMS” and “NEGATIVE SYMPTOMS.” OPDP explains that the primary efficacy measure was a “change from baseline in the Positive and Negative Syndrome Scale” and that the “pivotal trials for Cobenfy were not designed to evaluate the efficacy of the drug in treating negative symptoms because the patients in the studies were experiencing acute exacerbations of schizophrenia, which can confound the assessment of improvements in negative symptoms.”
Additionally, OPDP states the ad creates a misleading impression about the indication for Cobenfy due to the inclusion of a voiceover stating, “[i]f you still have symptoms, be bold and ask your healthcare provider about Cobenfy . . . .” OPDP explains this claim “misleadingly suggests that Cobenfy has efficacy in treatment-refractory cases of schizophrenia, when this has not been demonstrated.” Further, OPDP claims the ad misclassifies Cobenfy by stating it is “not an antipsychotic” even though Cobenfy is considered a member of the antipsychotic drug class based of its therapeutic indication for treating schizophrenia and its effects on psychotic symptoms, not its mechanism of action.
Untitled Letter to BeOne Medicines USA, Inc. (Issued December 17, 2025)
OPDP’s letter to BeOne Medicines USA, Inc. (BeOne) alleges that two “Teams Backgrounds” promotional communications for Tevimbra are false or misleading because they make representations about the indication of Tevimbra for the treatment of upper GI cancers, but fail to include risk information and material information regarding Tevimbra’s full FDA-approved indication.
OPDP alleges that the backgrounds include representations about the use of Tevimbra with the claim “BRINGING MORE TO THE TABLE IN UPPER GI CANCERS” in direct conjunction with a visual of a long, curving dinner table similar to the upper digestive tract and the claim “APPROVED IN CERTAIN UPPER GI CANCERS.” However, the backgrounds do not include any risk information about Tevimbra. OPDP states that by “omitting the major side effects associated with Tevimbra, the branded backgrounds 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.”
Additionally, OPDP alleges the branded backgrounds fail to provide material information regarding Tevimbra’s full FDA-approved indication, thereby presenting a misleading impression about the drug’s FDA-approved indication. The indications and usage section of Tevimbra’s FDA-approved prescribing information states:
“TEVIMBRA in combination with platinum-containing chemotherapy, is indicated for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1).”; “TEVIMBRA, as a single agent, is indicated for the treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.”; “TEVIMBRA, in combination with platinum and fluoropyrimidine-based chemotherapy, is indicated for the first-line treatment of adults with unresectable or metastatic HER2- negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ) whose tumors express PD-L1 (≥1).”
OPDP states that the branded backgrounds suggest that Tevimbra can be used for the treatment of upper GI cancers, but they do not include the full indication, as set forth above.
Untitled Letter to Esperion Therapeutics, Inc. (Issued December 19, 2025)
OPDP’s letter to Esperion Therapeutics, Inc. (Esperion) alleges that a DTC connected TV (CTV) broadcast ad for Nexlizet is false or misleading for two reasons.
First, OPDP alleges that the ad includes claims and presentations that misleadingly suggest that bempedoic acid, a component of Nexlizet, is the only nonstatin “FDA approved to lower bad cholesterol and reduce the risk of heart attack in statin intolerant patients” and “proven to reduce the risk of heart attack in patients who are unable to take recommended statin treatment” (i.e., “NEXLIZET may help. It contains the only nonstatin FDA approved ...,” “The bempedoic acid ingredient of NEXLIZET is the only nonstatin proven to reduce the risk of heart attack ... ,” and “Can't take a statin? Make NEXLIZET happen.”). OPDP alleges that because certain PCSK9 inhibitors are also approved to lower LDL cholesterol and reduce the risk of major adverse cardiovascular events such as heart attack in patients who are statin intolerant, the ad is misleading.
Second, OPDP claims the ad is misleading because “the compelling and attention-grabbing visuals” interfere with the comprehension of the major statement. FDA specifically refers to “cartoon-like ‘lipid lurkers’ entering and exiting the various scenes in an artery while swimming around and towards the viewer, diving, doing flips, collecting and sticking to arterial walls, and talking to one another in the ‘arterial environment’ where blood is constantly flowing.”
Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH)
Technological Medical Advancements LLC (Issued September 26, 2025)
OPEQ’s warning letter to Technological Medical Advancements LLC (TMA), regarding the company’s Diowave 250 WLS and Diowave 100 WLS laser systems, arose out of an April 2025 inspection of the company and a review of TMA’s website, along with a number of product brochures and operating manuals. OPEQ alleges the inspection revealed that TMA is marketing Diowave 250 WLS and Diowave 100 WLS laser systems for uses that exceed the scope of the 510(k) exemption for infrared lamps without submitting a required 510(k) premarket notification to FDA.
According to OPEQ, infrared lamps classified under 21 CFR 890.5500 are exempt from premarket notification. Such devices are “intended for medical purposes that emits energy at infrared frequencies to provide topical heating.” However, FDA alleges “there is evidence that the Diowave 250 WLS and Diowave 100 WLS operate using a different fundamental scientific technology than that generic type of device.” Specifically, OPEQ explains “the Diowave 100 WLS and Diowave 250 WLS laser systems appear to utilize stealth micro-pulse laser technology, which does not provide topical heating.” OPEQ points to the following claims as evidence of this point:
- “All heat during a stealth treatment is inhibited, allowing for deep penetration as there is no heat during treatment.”
- “Diowave is pleased to reveal the Stealth Micro-Pulsed Laser System™. SMPLT allows you to hold a hand piece static over a focal pathology without heating tissue.”
- “Our Stealth Micro-Pulse Technology allows care providers to treat various pathologies by Micro-Pulsing at appropriate power levels without introducing heat.”
- “The Doctor can remove all heat from the laser beam allowing him to hold the laser directly over the injury for an indefinite amount of time.”
Additionally, OPEQ alleges the Diowave 250 WLS and Diowave 100 WLS laser systems are intended for uses that are different from those of legally marketed devices classified under 21 CFR 890.550. Infrared lamps classified under 21 CFR 890.550 “emit energy at infrared frequencies (approximately 700 to 50,000 nanometers) to provide topical heating and are intended for medical purposes including, but not limited to, temporary increase in local blood circulation and temporary relief of: muscle spasms, minor joint pain and stiffness, minor muscle pain and stiffness, and minor arthritis pain.” OPEQ alleges “there is evidence that the Diowave 250 WLS and Diowave 100 WLS are intended for uses that are different from the intended use of the type of devices classified under 21 CFR 890.5500 Infrared Lamp.” OPEQ points to the following claims, among others, as evidence of this point:
- “[A] painless, non-surgical, and side-effective way to treat conditions previously refractive to traditional medical care”
- “[T]reatment of various pathologies, including those refractive to traditional therapy”
- “Because laser therapy is the only treatment in medicine that actually heals living tissue, most conditions respond favorably to repeated laser therapy treatments. It has been proven to deliver results when all other forms of insurance-based medicine have failed.”
- “[R]esults come from the laser’s ability to stimulate tissue growth and repair…results in accelerated wound healing with a dramatic decrease in…inflammation, and scar tissue formation.”
OPEQ also notes that TMA has an existing clearance (K121363) under 21 CFR 890.5500, but that “promotion of the device provides evidence that the device is intended for conditions beyond the indications for which it was cleared” and that this “constitutes a major change or modification in the intended use.” Further, OPEQ alleges the claims demonstrate that TMA “made a technological change to the device that could significantly affect the safety or effectiveness of the device” which constitutes “a significant change or modification for which a new premarket notification is required.”
If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drugs, and Devices practice.
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