FDA 就无菌眼药向乐敦制药发出警告信，涉及数据造假与未批准新药标签

Delivery Method:

VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTED

Reference #:

320-27-06

Product:

Drugs
Over-the-Counter Drugs

Recipient:

Recipient Name

Mr. Kunio Yamada

Recipient Title

Chairman and Representative Director

Rohto Pharmaceutical Co., Ltd.

1-8-1 Tatsuminishi
Ikuno-Ku, Osaka
544-8666
Japan

(b)(4)

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

October 14, 2026

WARNING LETTER
Reference number: 320-27-06

To Mr. Kunio Yamada:

This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) inspection of your facility. Promptly address the violations described herein without delay, including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory action without further notice.

FDA Inspection

Violations were observed and documented during an inspection of your drug manufacturing facility, Rohto-Mentholatum (Vietnam) Co., Ltd., FDA Establishment Identifier (FEI) 3008808745, at No. 16 VSIP Street No. 5, Vietnam - Singapore Industrial Park, Thuan Giao Ward, Ho Chi Minh, Vietnam, from April 6 to 14, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

In addition, violations were identified and documented during a review of your product labeling and website at the internet address https://rohtoeyedrops.com/ and your Instagram account at https://www.instagram.com/rohtoeyedrops/ in August 2026. Based on our review, your “ROHTO® Cooling Eye Drops COOL RELIEF,” “ROHTO® Cooling Eye Drops ALL-IN-ONE,” “ROHTO® Cooling Eye Drops MAX STRENGTH,” “ROHTO® Cooling Eye Drops DIGI EYE,” “ROHTO® Cooling Eye Drops OPTIC GLOW,” “ROHTO® Cooling Eye Drops DRY AID,” and “ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF” are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a). In addition, these products are misbranded under sections 502(a) and 502(ee) of the FD&C Act, 21 U.S.C. 352(a) and 352(ee). As explained further below, introducing or delivering these products for introduction into interstate commerce is prohibited under sections 301(d) and (a) of the FD&C Act, 21 U.S.C. 331(d) and (a).

We reviewed your May 1, 2026, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

Violations of the Federal Food, Drug, and Cosmetic Act

CGMP Violations

The following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.

1. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards. Your firm also failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.194(a) and 21 CFR 211.67(a)).

Your firm manufactures over-the-counter (OTC) topical ophthalmic drug products using aseptic processing.

Our inspection revealed systemic data falsification. Notably, we observed critical data integrity breaches in your environmental monitoring (EM), personnel monitoring (PM), and cleaning records.

Falsified Environmental Monitoring Records

Our inspection identified critical discrepancies in your surface monitoring records. Your standard operating procedure (SOP) required post-batch surface sampling at (b)(4) locations. Your firm acknowledged repeatedly submitting unexposed plates to the laboratory and confirmed that you did not perform the actual sampling. In other instances, only partial sampling was performed.

Similarly, personnel monitoring samples were not collected for production and engineering personnel who worked in the aseptic processing room. Instead, unexposed plates were submitted to the laboratory and the associated records reflected that personnel sampling had been performed.

Further, in a separate instance, active air samples for a batch were collected at incorrect locations but falsely documented as having been collected at the required locations.

These falsification practices fundamentally undermine any confidence in your microbiology data. Notably, you lacked reliable data indicating that environmental control existed in your aseptic processing operations and to support release of batches to the U.S. market. During this period, you reported 0 colony-forming unit findings across all EM and PM sampling with the exception of a single deviation following a water leakage event. In stark contrast, following discussion of deficiencies with firm management, actual plate readings conducted during the inspection (April 10 to 14, 2026) yielded numerous EM and PM samples with microbial growth, including approximately 25 ISO 5 excursions.

Falsified Cleaning Records

Your SOP required cleaning ISO 5 surfaces (b)(4) decontamination of the room. Although cleaning records documented that these activities were completed on January 23, January 30, March 10, and March 21, 2026, our inspection found no evidence that the cleaning activities were performed. Your management confirmed that the documented cleaning activities were not performed and that the records reported false information.

The profound data integrity breaches at your firm critically undermined assurance of sterility for U.S.-distributed drug products.

In your response, you state that you suspended drug production for the U.S. market and notified your U.S. distributor of the need to halt distribution. You acknowledge that EM, PM, and cleaning records were falsified. You note several root causes, including a lack of independent oversight by quality assurance personnel and insufficient real-time supervision of cleaning execution. You state that you suspended all personnel involved and engaged an independent third-party to assess the scope of the data integrity issues. Notably, throughout your response, you reference your historical viable EM data, citing the absence of adverse trends, as a key “quality indicator data” source to support your initial product impact assessment.

Your response is inadequate. Falsified EM data cannot be used for trending analysis. Therefore, your initial product impact assessment is not supportable as it relies on EM data confirmed to be unreliable. Furthermore, you have not sufficiently acknowledged the potential scope of the systemic data integrity breaches, which extended well beyond procedural gaps or individual misconduct. Widespread falsification across many staff members, multiple record types, and over an extended period of time went unchecked, reflecting a systemic quality failure and demonstrating a general failure of senior managers in your company to exercise their responsibility to ensure integrity of manufacturing and laboratory records.

In response to this letter, provide:

• A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, supervisory oversight, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.
• A comprehensive, independent assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm’s documentation practices to ensure you retain contemporaneous, attributable, legible, complete, original, and accurate records throughout your operation.
• A comprehensive CAPA, overseen by a qualified consultant, for handling microbiological sampling media to ensure robust and reliable data. Establish a system that ensures uncompromised and uninterrupted custody, with full reconciliation of all microbiological samples including, but not limited to, the following:
  o Unique labeling of each sample
  o Signatures of all staff who handle the sample
  o Complete tracking of uncompromised sample integrity and custody
  o Date and time of each activity (e.g., sample collection, transport, delivery, incubation, removal from incubator)
  o Digital time-stamped photos of all plates
  o Laboratory tools and methods to optimize visibility and detectability of colonies on plates
  o Signatures of personnel performing reading of microbial counts
  o Provisions for verifications and routine quality assurance oversight
• An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program whenever needed, ensures final quality unit (QU) decision authority, and is fully supported by executive management.
• An independent review of your antimicrobial effectiveness testing (AET) program, including assuring that all (b)(4) products are evaluated using sound AET study protocols and that each formulation is suitable throughout its use period.
• A comprehensive assessment and CAPA, overseen by a qualified consultant, for your cleaning and disinfection program. Establish a system that ensures robust cleaning and disinfection and full verification and reconciliation of all related activities, including, but not limited to, provisions for meaningful independent verifications of cleaning and disinfection execution (using appropriate methods at required locations and frequencies) and effective routine quality assurance oversight.

2. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes. Your firm also failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.113(b) and 21 CFR 211.63).

Your firm failed to adequately design, control, and supervise your aseptic processing line.

Poor Aseptic Practices and Cleanroom Behavior

We observed numerous poor aseptic practices across multiple batches, operators, and dates during the manufacture of U.S.-marketed ophthalmic drug products including, but not limited to, the following:

• A gowned operator stood inside the ISO 5 area near the (b)(4), picking up exposed open sterile bottles with (b)(4) and reintroducing them into the bottle supply rather than rejecting them.
• Operators repeatedly used (b)(4) directly above and in contact with open bottles and critical surfaces during undocumented interventions without rejecting the exposed containers.
• Operators removed partially used open sterile (b)(4) packaging component bags from the ISO 5 area following batch manufacture, stored in the ISO 7 area for up to (b)(4), and reintroduced to future batches without following appropriate practices to ensure the contents remained sterile.

These interventions were not documented in the batch record. Many interventions occurred in the (b)(4) area where equipment, including the (b)(4) and conveyer, directly contacted sterile open bottles. Despite the frequency of (b)(4) interventions in this area, you only performed infrequent decontamination (e.g., (b)(4)) of the sterile (b)(4) area of the aseptic processing line.

In addition, we observed multiple deficiencies in aseptic processing operator gowning.

These and other inspectional findings indicated a lack of adequate supervisory oversight of your aseptic processing operations.

Inadequate Equipment Design

We also noted equipment design deficiencies and a lack of unidirectional airflow. For example, the position of the (b)(4) obstructed unidirectional airflow to the sterile (b)(4) in the (b)(4), leading to inadequate ISO 5 protection of sterile (b)(4) packaging components.

Your aseptic manufacturing processes should be designed, and operations executed, to prevent contamination hazards to your sterile product. Flaws in the design of cleanrooms and aseptic processing lines, or improper execution of aseptic operations, can promote influx of contamination into the critical processing area.

These significant deviations in aseptic processes and disinfection are a further indication of insufficient control of aseptic processing operations to assure drug product sterility.

In your response, you state that operator practices did not consistently align with your procedures, and that you will be remediating your qualification program for both operators and direct supervisors. You also acknowledge deficiencies in your smoke studies. To help address these deficiencies, you commit to engaging independent third-party experts to assess your operation, including aseptic practices. You also commit to conducting all future smoke studies using a qualified, neutrally buoyant smoke agent and to implementing corrective actions, including potential design modifications, based on the outcome of airflow evaluation. Your response also commits to working with the vendor to ensure the entire ISO 5 (grade A) zone for the sterile product can be decontaminated (b)(4).

Your response is inadequate because it does not adequately address the scope and root cause of the poor aseptic practices observed.

See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.

In response to this letter, provide:

• A comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to, the following:
  o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of (b)(4) interventions wherever possible)
  o Equipment suitability (e.g., reliability, capability, ergonomics, placement) and sufficient cleanroom space
  o Air quality in the ISO 5 area and surrounding room including, but not limited to, air volume and flow
  o Facility layout
  o Personnel flow and material flow (movement throughout all rooms used to conduct and support sterile operations, and all material transfers)
  o Disinfection practices and procedures
  o Specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessment
• A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible improvements to be made to aseptic processing operation design and control at your facility and explain how CAPA plan will robustly remediate your deficient sterile manufacturing operations. Include comprehensive changes to the design of both your aseptic processing lines and cleanrooms. Also, describe your plans for qualification and validation of your extensively remediated operations.
• Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures, including but not limited to an independent assessment of the following with accompanying CAPA:
  o Suitability of actual practices based on extensive retrospective review and prospective observation of aseptic processing operations
  o Deficiencies in production management oversight and identification of specific improvements to ensure effective and routine supervisory oversight for all batches
  o Frequency and depth of QU oversight (e.g., audit, ad hoc, daily interactions) of aseptic processing and its support operations
  o Adequacy of written procedures and operational ergonomics
  o The assessment should also evaluate how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs.
• Perform a critical evaluation of airflow unidirectionality in your aseptic process with the assistance of a qualified consultant. Ensure smoke studies are conducted under dynamic conditions with thorough and complete evaluations of aseptic processing line airflow unidirectionality, including the impact of dynamic interactions and aseptic interventions. These thorough smoke studies should be performed after you remediate your aseptic operation and conducted using proper practices, including neutrally buoyant media, to appropriately visualize airflow.
• Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, enhanced production floor supervision, and improved systems for ongoing management review.
• A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function, that includes, but is not limited to, the following:
  o A determination of whether procedures used by your firm are robust and appropriate
  o Provisions for QU oversight throughout your operations to ensure satisfactory procedures and adherence to appropriate practices
  o A complete and final review of each batch and its related information before the QU disposition decision
  o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products
  o Also, describe how executive management will support robust quality assurance at your firm, including but not limited to timely provision of resources that enable proactive detection and resolution of emerging manufacturing/quality issues to assure a continuing state of control.

3. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Your firm failed to adequately investigate out-of-limit 100% visual inspection findings for two batches of sterile ophthalmic drug products that exceeded the (b)(4)% total reject limit. Rather than conducting a full 100% re-inspection, only (b)(4) units per batch were re-inspected, and the investigations did not characterize the nature, composition, or source of the particles. Both batches were released and shipped to the U.S. market without determining whether the particles were intrinsic, extrinsic, or inherent.

Ophthalmic products operations should be designed to prevent particle contamination and to protect consumers from the risk of instilling potentially harmful particles into the eye. In addition, when categorizing any visible particles, extrinsic or foreign matter should receive special attention, as it may indicate possible microbial contamination. Microbes introduced directly into the eye can pose a serious risk to consumers. Irreversible damage, including partial vision loss or blindness, can occur and, in some cases, may progress to life-threatening systemic infection.

In your response, you acknowledge that your investigations were inadequate and that samples sent to an external laboratory for Fourier-Transform Infrared spectroscopic analysis could not conclusively determine the composition or source of the particles. While you identified a statistical correlation between high reject rates lots and a specific (b)(4) container supplier, the particle source(s) was not confirmed through analytical testing.

Your response is inadequate. The identification of particles and their sources remained inconclusive and incomplete at the time of your initial response. Your response also did not address your decision to release batches despite your significant adverse quality defect trends.

A substantial number of consumer complaints have been received since 2019, including reports of leakage, burning and stinging sensation, worsening eye redness, blurry vision, and reports of foreign matter or “floating matter.” Your firm recorded "no need" or “NA” for corrective action for those customer complaints.

In response to this letter, provide:

• A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, out-of-limit results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.
• A comprehensive, independent assessment and remediation plan for your visual inspection program to ensure compliance with CGMP. The assessment and remediation should include, but not be limited to, the following:
  o Implementing enhancements to your 100% visible inspection program, including defining critical, major, and minor defects and the individual defect limits for drug products.
  o Ensuring adequate methods, equipment, and personnel qualifications to reproducibly detect visible particulates, including particulates historically found in your operation.
  o Conducting rigorous qualification studies to ensure your (b)(4) visible particulate inspection systems consistently and reproducibly detect the variety of visible particulates encountered in your drug products.
  o Implementing destructive testing and other advanced technologies (e.g., (b)(4)) as appropriate, with statistically significant sample sizes, for drug products that are difficult to inspect (e.g., (b)(4) containers).
  o Incorporating product-specific knowledge, process experience, deviation investigation analysis, recall/complaint data, and quality risk management to improve the visual inspection program.
  o Remediating your visual inspection program, including establishing new written procedures, equipment, and methods. Include a summary of the review and recommendations made by your independent consultant.

The following are violations identified during our review. As a reminder, this is not an all-inclusive list of violations that may exist in connection with your products or operations.

Unapproved New Drug Violations

Based on a review of the product labeling, “ROHTO® Cooling Eye Drops COOL RELIEF,” “ROHTO® Cooling Eye Drops ALL-IN-ONE,” “ROHTO® Cooling Eye Drops MAX STRENGTH,” “ROHTO® Cooling Eye Drops DIGI EYE,” “ROHTO® Cooling Eye Drops OPTIC GLOW,” “ROHTO® Cooling Eye Drops DRY AID,” and “ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF” (collectively, “ROHTO® Cooling Eye Drops products”) are drugs under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or intended to affect the structure or any function of the body. Examples from your product labeling, including your website and social media, that provide evidence of the intended uses (as defined in 21 CFR 201.128) of these products as drugs include, but may not be limited to, the following:

All ROHTO® Cooling Eye Drops products

““Our cooling eye drops additionally strengthen eye’s lipid film, promoting better stability of the tear film…” [from your “About” webpage, https://rohtoeyedrops.com/pages/about]

“ROHTO® Cooling Eye Drops COOL RELIEF”

“ROHTO® Cooling Eye Drops COOL RELIEF . . . Drug Facts . . . Purpose…Redness reliever…Lubricant . . . soothes up to 8 hrs. with CoolSense™ Technology . . . Proprietary formula cools…eyes….” [from product label]

“ROHTO® Cooling Eye Drops ALL-IN-ONE”

“ROHTO® Cooling Eye Drops ALL-IN-ONE . . . Drug Facts . . . Purpose…Lubricant…Redness Reliever…Astringent . . . soothes up to 8 hrs. with CoolSense™ Technology . . . Proprietary formula cools…eyes…” [from product label]

“ROHTO® Cooling Eye Drops MAX STRENGTH”

“ROHTO® Cooling Eye Drops MAX STRENGTH . . . Drug Facts . . . Purpose…Redness reliever…Lubricant . . . soothes up to 8 hrs. with CoolSense™ Technology . . . Proprietary formula cools…eyes…” [from product label]

“ROHTO® Cooling Eye Drops DIGI EYE”

“ROHTO® Cooling Eye Drops DIGI EYE . . . Drug Facts . . Purpose…Lubricant…Redness reliever . . . soothes up to 8 hrs. . . . Proprietary formula cools…eyes. . . . Soothes Redness and Dryness due to Digital Eye Strain…” [from product label]
“…specially designed to provide eye strain relief from the symptoms of Digital Eye Strain.” [from product webpage, https://rohtoeyedrops.com/products/rohto-digi-eye-digital-eye-strain-eye-drops]

“ROHTO® Cooling Eye Drops OPTIC GLOW”

“ROHTO® Cooling Eye Drops OPTIC GLOW . . . Drug Facts . . . Purpose…Redness reliever…Lubricant . . . Soothes up to 8 hrs. . . . Proprietary formula cools…eyes…” [from product label]

“Helps improve the health of the corneal surface….” [from product webpage, https://rohtoeyedrops.com/products/rohto-eye-drops-optic-glow-eye-whitening-drops]

“ROHTO® Cooling Eye Drops DRY AID”

“ROHTO® Cooling Eye Drops DRY AID . . . Drug Facts . . . Purpose…Lubricant . . . Soothes up to 12 hrs. Long-Lasting . . . Repairs Natural Tear Film . . . Proprietary formula cools…eyes. . . . Repairs All Layers Of The Tear Film…” [from product label]

“Rohto® Dry Aid® Eye Drops For Dry Eyes with Liquid Shield™ Technology . . . repairs the natural tear film over time . . . Unlike most over-the-counter eye drops that only work on one layer of the tear film, Rohto® Dry Aid® with Liquid Shield™ Technology works in a unique way to restore moisture to the tear film by working on all layers to mimic a stable, natural tear.” [from product webpage, https://rohtoeyedrops.com/products/rohto-dry-aid-eye-drops-for-dry-eyes]

“ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF”

“ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF . . . Drug Facts . . . Purpose…Lubricant . . . Our eye drops…relieve symptoms of digital eye strain . . . protect your corneal cells from UV and Blue Light damage . . . HydroCorneal™ Protection Technology” [from product webpage, https://rohtoeyedrops.com/products/rohto-dual-light-relief-hydrating-eye-drops]

“ROHTO® Dual Light Relief . . . It employs HydroCorneal™ protection technology to protect corneal cells from UV damage.” [from your @rohtoeyedrops Instagram post, https://www.instagram.com/p/DQb_GmTAD7c/]

Based on the above labeling evidence, “ROHTO® Cooling Eye Drops COOL RELIEF,” “ROHTO® Cooling Eye Drops ALL-IN-ONE,” “ROHTO® Cooling Eye Drops MAX STRENGTH,” “ROHTO® Cooling Eye Drops DIGI EYE,” “ROHTO® Cooling Eye Drops OPTIC GLOW,” “ROHTO® Cooling Eye Drops DRY AID,” and “ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF” are intended for use as ophthalmic drug products. As described below, these drug products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).

A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these drug products identified above.

Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "OTC monograph drugs"—may be legally marketed if they meet applicable requirements. With respect to nonprescription ophthalmic drug products, such as your ROHTO® Cooling Eye Drops products, in order to be GRASE and not new drugs the products must, among other things, conform to the conditions in the applicable OTC monograph, here Over-the-Counter (OTC) Monograph M018: Ophthalmic Drug Products for Over-the-Counter Human Use (henceforth “M018”).¹ However, your nonprescription ROHTO® Cooling Eye Drops ophthalmic drug products do not conform to the conditions specified in M018 for the reasons described below.

Claims on the product labeling for your ROHTO® Cooling Eye Drops products include intended uses that are not permitted in M018 for ophthalmic drug products. Specifically, the names of all of your ROHTO® Cooling Eye Drops products contain the term “Cooling.” Also, the “About” webpage of your website states that your ROHTO® Cooling Eye Drops products “strengthen eye’s lipid film, promoting better stability of the tear film.” In addition, your “ROHTO® Cooling Eye Drops COOL RELIEF,” “ROHTO® Cooling Eye Drops ALL-IN-ONE,” “ROHTO® Cooling Eye Drops MAX STRENGTH,” “ROHTO® Cooling Eye Drops OPTIC GLOW,” and “ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF” product labels state that the product “cools eyes” and reference, “CoolSense™ Technology.” Such claims go beyond the allowed general intended uses for OTC ophthalmic drug products and do not conform to M018.

Furthermore, your products “ROHTO® Cooling Eye Drops DIGI EYE,” “ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF,” and “ROHTO® Cooling Eye Drops OPTIC GLOW” include additional intended uses that are not permitted in M018. For example, your product label for “ROHTO® Cooling Eye Drops DIGI EYE” states, “Soothes Redness and Dryness due to Digital Eye Strain,” and your website states that this product is “designed to provide eye strain relief from the symptoms of Digital Eye Strain.” Additionally, your website states that the product “ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF” is intended to “…relieve symptoms of digital eye strain,” and “protect your corneal cells from UV and Blue Light damage.” Moreover, a post on your @rohtoeyedrops Instagram page states that this product “employs HydroCorneal™ protection technology to protect corneal cells from UV damage. In addition, your website states that the product, “ROHTO® Cooling Eye Drops OPTIC GLOW” “helps improve the health of the corneal surface….” Such claims go beyond the allowed general intended uses for ophthalmic drug products and do not conform to M018.

The product labels for “ROHTO® Cooling Eye Drops COOL RELIEF,” “ROHTO® Cooling Eye Drops ALL-IN-ONE,” “ROHTO® Cooling Eye Drops MAX STRENGTH,” “ROHTO® Cooling Eye Drops DIGI EYE,” and “ROHTO® Cooling Eye Drops OPTIC GLOW” claim that these products “soothes up to 8 hrs.” and your product label for “ROHTO® Cooling Eye Drops DRY AID” claims that it “Soothes up to 12 hrs.” Time-specific extended efficacy claims such as these do not conform to M018.

Thus, your “ROHTO® Cooling Eye Drops COOL RELIEF,” “ROHTO® Cooling Eye Drops ALL-IN-ONE,” “ROHTO® Cooling Eye Drops MAX STRENGTH,” “ROHTO® Cooling Eye Drops DIGI EYE,” “ROHTO® Cooling Eye Drops OPTIC GLOW,” “ROHTO® Cooling Eye Drops DRY AID,” and “ROHTO® Cooling Eye Drops DUAL LIGHT RELIEF” products do not comply with the applicable conditions specified in M018 and have not otherwise been found to be GRASE.² Accordingly, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there are no applications in effect for these products, these products are unapproved new drugs.

The introduction or delivery for introduction of these unapproved new drug products into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).

Misbranded Drug Violations

Your ROHTO® Cooling Eye Drops products are misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), because the product labeling include statements that misleadingly suggest that the drug products are endorsed by FDA and are cGMP compliant. Specifically, on your “About” webpage, you display the acronym “FDA,” in a form that is similar to the FDA logo. Your use of the acronym FDA in a form that is similar to the FDA logo on your website misleadingly suggests that the drug products are approved or endorsed by FDA in some way. Your ROHTO® Cooling Eye Drops products are not the subject of an FDA-approved application. Additionally, on your website you claim, “Our manufacturing practices are US FDA GMP Compliant…,” and “GMP Compliance guarantees our eye drops are 100% sterile, 100% free from contamination, and meet rigorous quality standards….” Generally, current good manufacturing practice (CGMP) compliance cannot be implied or explicitly indicated on product labeling. Based solely on a determination of CGMP compliance at one point in time it would be unreasonable to assure permanent CGMP compliance, or to guarantee that products are 100% sterile or free from contamination at any given time. Moreover, when even a single aspect of a firm’s operations deviates from CGMP during the course of manufacturing a product, regardless of the significance of the deficiency, the product is deemed adulterated under section 501(a)(2)(B) of the FD&C Act. Your firm cannot reliably guarantee that a product is sterile, free from contamination, or meets rigorous quality standards when it manufactures that product under conditions that fail to meet CGMP requirements, as described above. Such representation can mislead consumers into believing the product is safe despite the existence of serious manufacturing risks. Therefore, these products are misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), because your labeling representation suggesting that your products are FDA-approved and CGMP compliant is false or misleading.

Additionally, your ROHTO® Cooling Eye Drops products are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.

The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).

Data Integrity Remediation

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance with Drug CGMP: Questions and Answers for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.

We strongly recommend that you retain an independent, qualified third-party consultant to assist in your remediation. In response to this letter, provide:

• A comprehensive investigation into the extent of the inaccuracies and inconsistencies in data, records, and reporting. Your investigation should include:
  o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.
  o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.
  o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity deficiencies.
  o A comprehensive retrospective evaluation of the nature of the testing/manufacturing/other data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all occurrences.
• A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a data integrity event and analyses of the risks posed by ongoing operations.
• A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:
  o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all data, including analytical data, manufacturing records, and all data submitted to FDA.
  o A comprehensive description of the root causes of each data integrity deviation, including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for the data integrity breaches remain able to influence CGMP-related or drug application data at your firm.
  o Interim measures describing the actions you have taken or will take to ensure the quality of your drugs and protect patients, such as notifying your customers, recalling product(s), conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.
  o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.
  o A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness after you have executed your data integrity remediation protocol.
  o Inform FDA if you will be hiring a chief integrity officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by an independent quality assurance function, along with expertise from outside entities whenever needed).
  o A status report for any of the above activities already underway or completed.

Drug Recall

On July 7, 2026, FDA held a teleconference with you recommending you recall all drug batches from the U.S. market. On July 8, 2026, you agreed to voluntary recall all drugs in current distribution in the United States.

On July 14, 2026, you initiated a voluntary recall of all lots of Rohto Cool Relief, Rohto All-In-One, Rohto Max Strength, Rohto Digi-Eye, Rohto Optic Glow, and Rohto Dry Aid, due to lack of sterility assurance. The recalls were posted to the FDA’s Enforcement Report website at:

https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221557
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221558
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221559
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221560
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221561
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221562
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221563
https://www.accessdata.fda.gov/scripts/ires/index.cfm?Product=221564

Drug Production Suspended

We acknowledge your commitment to suspend production of all drugs at this facility for the U.S. market. In response to this letter, clarify whether you intend to resume manufacturing drugs for the U.S. market at this facility in the future.

If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic
flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).

CGMP Consultant

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. The qualified consultant should also perform a comprehensive six-system audit³ of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

Conclusion

You are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.

FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on August 13, 2026.

FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.

Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Rohto-Mentholatum (Vietnam) Co., Ltd., FEI 3008808745, at No. 16 VSIP Street No. 5, Vietnam - Singapore Industrial Park, Thuan Giao Ward, Ho Chi Minh, Vietnam into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

Send your written response to [email protected] within fifteen (15) business days of receipt of this letter. Identify your written response with FEI 3008808745 and ATTN: Compliance officer Emily Wu in the subject line of the email.

If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.

FDA posts warning letters to www.FDA.gov.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

/S/

Tina Smith
Captain, U.S. Public Health Service
Director
Office of Unapproved Drugs & Labeling Compliance
Office of Compliance
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

cc:
(b)(4)

Mr. Shiramatsu Hirofumi
General Director
Rohto-Mentholatum (Vietnam) Co., Ltd.,
(b)(4)

Ms. Meryl Reis
VP of US R&D, Regulatory Affairs, QA/QC
The Mentholatum Company
(b)(4)

__________________

1 M018 reflects the conditions set forth in the relevant final order established and in effect under section 505G; see Order ID OTC000023, available at FDA’s website OTC Monographs@FDA, https://www.accessdata.fda.gov/scripts/cder/omuf/.

2 FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that your ROHTO® Cooling Eye Drops products are GRASE for use under the conditions prescribed, recommended, or suggested in their labeling, nor has FDA determined these drug products to be GRASE pursuant to an order issued under section 505G(b).

3 i.e. Quality System, Facilities & Equipment System, Materials System, Production System, Packaging & Labeling System, and Laboratory Control System per FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations.