Excelvision - Fareva(320-26-98)

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

Warning Letter 320-26-98

June 25, 2026

Dear Mr. Fraisse:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Excelvision, FEI 3007058211, at 27 Rue de la Lombardiere, Annonay, from January 12 to 22, 2026.

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).

We reviewed your February 12, 2026, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigators observed specific violations including, but not limited to, the following.

1. 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).

You failed to adequately investigate customer complaints for the various sterile (b)(4) drug products (prescription and over-the-counter) you manufacture. Your investigations were not thorough, did not appropriately expand in scope, and lacked a scientifically supported determination of root causes. You also failed to identify and implement adequate and timely corrective actions and preventive actions (CAPAs).

Your product is intended to maintain sterility of its contents after (b)(4) by the consumer. However, since our previous inspection in November 2024, your firm has received a substantial number of complaints related to the presence of contamination.

Visible evidence of contamination included mold, black specks, and discoloration on the tips and inner caps of containers for your (b)(4) drug product, (b)(4). Several complaint samples subsequently failed sterility testing. Notably, nine such non-sterility events have occurred in the last three years.

You failed to adequately determine which hazards in your manufacturing operation and container-closure systems led to these critical, repeated incidents of contamination in your (b)(4) drug products.

Specifically, you failed to adequately investigate potential container-closure integrity defects that would allow ingress of microbial contamination, which your product is intended to strictly preclude.

You also failed to adequately assess potential sources of contamination from the manufacturing process as you neglected to evaluate relevant environmental and personnel monitoring (EM/PM) data. For example, the microorganism recovered from the failed complaint sample sterility test involving (b)(4) batch (b)(4) was identified as Alternaria alternata. This was the same microorganism recovered in EM/PM samples collected both before and after this batch was manufactured, including in the room where this batch was filled. Your complaint investigation report did not include this critical information.

Similarly, your firm also failed to adequately investigate numerous contamination complaints related to your (b)(4) products.

Instead of conducting a thorough, scientifically supported, and evidence-based root cause analysis, your firm attributed most of the root causes to inadequate handling by customers who used your products and concluded that no further action was necessary.

If contaminated, (b)(4) drug products pose a heightened risk of harm because (b)(4). Microbes introduced directly into (b)(4) can pose a serious risk to consumers. Irreversible damage including (b)(4) can occur, and in some cases, may progress to life-threatening systemic infection. In addition, some components in your (b)(4) drugs, such as (b)(4), could serve as a nutrition source for contaminating microorganisms and promote their growth.

In your response, you state that you will revise the complaint procedure to include a comparison of the microorganisms recovered from complaint samples with those found during environmental monitoring and to describe how to proceed when a complaint sample fails sterility testing. You also acknowledge that the absence of a (b)(4) in a formulation should be factored into your risk analysis when evaluating complaints. You also state that two of the aseptic processing lines will not be used to manufacture additional drug products for the U.S. market and they will be replaced with new processing lines.

Your response is inadequate. It provides no evidence to support the investigation conclusions of inadequate handling by customers. It also provides no explanation for how microorganisms contaminated these drug products if they were sterile when released. We are also very concerned about the suitability of your container-closure system and whether you can effectively assure that every unit released will function as intended throughout its labeled usage period. Finally, although your FDA 483 response includes a letter you sent to the product owner listing specific batches that must be evaluated for recall due to complaint samples with sterility failures, the letter included no decision to recall these batches.

It is essential that these unpreserved formulations and associated presentations afford robust protection in each unit produced in order to prevent potential consumer harm resulting from contamination during use of your (b)(4) products.

In response to this letter, provide:

• A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) 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, quality oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.

• An independent, retrospective review of investigations into all batches with potential microbial contamination or an OOS microbiological result (whether or not later invalidated). The investigations should be updated, wherever necessary, to detail your findings regarding the potential root causes of the contamination.

• An assessment of microbial hazard and patient risk associated with a unit that becomes contaminated in use. Provide your studies on the growth properties (microbial challenge studies) of each formulation in the event of in-use contamination, based on the maximum number of days of permitted use. In addition, in the event the formulation is deemed suitable following these studies, state whether your firm plans to reduce allowable use periods to no longer than 30 days.

• A comprehensive, independent evaluation of the suitability of the container-closure systems used for your (b)(4) drug products that are intended to continuously protect against ingress of microbial contamination throughout the period of use. At minimum, provide an evaluation of the following:
  o Product design considerations
   A general description of each possible failure mode that could potentially permit ingress of microbial contamination over its used period
   Detailed description of all influential variables, on their own or in combination, that may lead to lost integrity (irrespective of whether it may be transient) at any time at point of manufacture, or during consumer use. Regarding the latter, address potential vulnerability to (b)(4) and durability issues. Influential variables should include but not be limited to:
  • internal pressure changes;
  • list of all possible out-of-tolerance characteristics or defects for each container-closure component;
  • each potential mechanical failure mode of (b)(4), etc.);
  • possible assembly errors;
  • potential for a defective (b)(4), or microbial growth in the (b)(4);
  • events leading to leaks or punctures;
  • all other potential variables.
   Compatibility of the product design with the specific container-closure system(s) (e.g., integrity, functionality).
  o Container-closure system capability and suitability of incoming lots
   Detailed container-closure system design and performance specifications that you require of the manufacturer (supplier) who performs the primary container-closure production steps prior to the final filling/closing process performed at your facility.
   Summary of all studies done by your firm to evaluate whether the container-closure system design (and its related performance specifications) is appropriate to maintain the sterility of all marketed units throughout their use period.
   For each lot received from your supplier for the last three years, provide the numbers and types of defects obtained during manufacture of the container-closure system, as well as theoretical and actual yields.
   Whether any incoming container-closure lot was rejected by your firm.
   Process capability (e.g., Cpk, Ppk) of each significant step in the manufacturing assembly process for each of your product container-closure systems. Describe the various nonconformities that can occur, including a list of each defect type and its criticality classification, all in-process tests and limits, and maximum tolerances for each defect type.
   Other quality criteria used by your firm to evaluate suitability of each incoming lot of the pre-assembled product container-closure and its ability to assure backflow prevention (e.g., determining if any significant variances or deviations were associated with the specific lot)
  o Drug product manufacturing and stability
   All functionality tests, their purposes/capabilities, and associated acceptance criteria
   A detailed list of defect types and tolerances, as well as theoretical and actual yields for drug product batches manufactured in the last three years.
   An analysis of when an investigation is triggered, how nonconforming units are removed, how process control is maintained, and how any recurring quality problems are addressed.
   An assessment of whether the process is capable of detecting and removing all nonconforming units and whether nonconformities are appropriately evaluated to determine root cause and appropriate follow-up action to prevent future nonconformities.
   A description of how you assure that every unit released in a batch will have a defect-proof mechanism that always prevents microbial ingress so as to protect consumers from severe infection risk throughout its used period.
  o During use and after opening of sealed units
   Human factors or other studies to determine if your container-closure systems reproducibly yield functionality that always protects products from contamination under repeated and anticipated consumer use, including under conditions of stress throughout the usage period and for the maximum number of (b)(4).
  o CAPAs and mitigations to be implemented based on the above data and independent assessment.

• A list in table format (e.g., spreadsheet) of each complaint for drug product with potential contamination (e.g., foreign matter, discoloration, possible fungi/bacteria) on the container/closure system or in the product from the past three years as of the date of this letter, with the following columns:
  o Product type ((b)(4)), whether it contains (b)(4), batch number, and date of manufacture.
  o Date of complaint awareness, and whether a complaint sample was requested and received. If complaint sample was not initially received, describe how many follow-up attempts were made.
  o Complaint sample analysis results, including sterility test result, microbial identification, and date of analysis.
  o The potential or confirmed root causes.
  o If the product is (b)(4), detail any examination of the complaint samples or a reserve sample that was performed to evaluate proper functioning of the container/closure system.
  o If microorganisms were recovered, detail the number of times the same genus (include species if available) was recovered in EM/PM of your aseptic processing facility within a year (before and after) the date of manufacture.

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 (21 CFR 211.113(b)).

We observed poor aseptic practices during and after the setup of your filling line (b)(4) which is used in the manufacture of (b)(4) drug products.

• Personnel blocked unidirectional airflow to (b)(4) with their gloves during installation of the (b)(4) assembly.

• An operator conducting line clearance after setup leaned their head and torso through (b)(4) into the ISO 5 filling area and failed to disinfect the (b)(4) before (b)(4).

In addition, the (b)(4) equipment on this line was poorly designed. The (b)(4) partially blocked unidirectional airflow over the (b)(4) bowl and fully blocked unidirectional airflow over the (b)(4).

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.

In your response, you state that you will revise your procedures for proper aseptic behavior and retrain personnel. You also state that third-party consultants will observe personnel and provide corrective feedback before commercial production resumes. In addition, you state that the effectiveness of these corrective actions will be evaluated by observing all media fill activities and trending EM/PM results. You also state that the (b)(4) equipment has been modified to prevent the blocking of unidirectional airflow.

Your response is inadequate. It does not include establishing a program to routinely monitor personnel for proper aseptic technique during commercial production, which is especially important considering your previous attempts to correct poor aseptic behavior were unsuccessful. In addition, it does not mention evaluating other aseptic processing line equipment for design deficiencies that are similarly vulnerable to impeded unidirectional airflow.

In response to this letter, provide:

• A remediation plan that better assures ongoing management oversight throughout the manufacturing lifecycle of all drug products. Provide a more data-driven and scientifically sound program that identifies sources of process variability and assures that manufacturing operations meet appropriate parameters and quality standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, ensuring quality of input materials, determining the capability and reliability of each manufacturing process step and its controls, and vigilant ongoing monitoring of process performance and product quality.

• A comprehensive, independent risk assessment of all contamination hazards with respect to all aseptic processes, equipment, and facilities including, but not limited to:
  o all human interactions within the ISO 5 area (e.g., risk reduction or elimination of manual 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)

• 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 this 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, not but limited to, an 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 quality unit (QU) oversight (e.g., audit, ad hoc, daily interactions) of aseptic processing and its support operations
  o adequacy of written procedures
  o the risk assessment should also evaluate how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs

3. Your firm failed to maintain floors, walls, and ceilings of smooth, hard surfaces that are easily cleanable in aseptic processing areas and establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(i) and 211.42(c)(10)(vi)).

Facility Construction and Maintenance

The floors, walls, and ceilings in your aseptic processing area are not constructed of smooth, hard surfaces that can be easily cleaned, or were not adequately maintained. Many ceilings and partitions in the classified areas of your (b)(4) building are made of (b)(4) which you have stated is “not waterproof” and “cannot be decontaminated.” This material is in areas such as filling rooms, compounding rooms, machine part washing rooms, the weighing area, and corridors. This is especially concerning considering the numerous water incursions you have had in the (b)(4) classified areas between January 2024 and January 2026, along with numerous mold recoveries in the routine production data available between January 2024 and March 2025.

Any water leak in cleanrooms of an aseptic processing facility poses an unacceptable risk to environmental control and product sterility.

In addition, our investigators documented damage in the floors, ceilings, and walls in classified areas, including cracks and gaps that exposed the base materials underneath. Our investigators also documented cracked (b)(4) material and apparent rust on the (b)(4) used in some of these areas. Given these multiple water incursions and other issues related to materials of construction, it remains unclear whether your facility infrastructure is suitable for aseptic manufacturing.

Equipment Maintenance

During the inspection, we observed unsuitable conditions in the ISO 5 area of filling line (b)(4) where aseptic processing is conducted. For example:

• A handle above the cap bowl that holds sterile caps during filling was coated with what appeared to be flaking black paint.

• The (b)(4) for the (b)(4), which are adjacent to sterile (b)(4) and open bottles, appeared to be corroded.

In your response to these equipment maintenance deficiencies, you state that these surfaces have been repaired and cleaned, and all other Grade A and B equipment surfaces have been inspected. You also state that procedures for the inspection of the aseptic processing equipment and overhead surfaces in lines (b)(4) have been revised to require routine documented inspections and immediate escalation if issues are found.

Your response is inadequate. It does not sufficiently define routine inspections to determine state of repair of your aseptic processing facility, including but not limited to ensuring these inspections encompass all aseptic processing operations. In addition, it does not address investigating why responsible operations and QU personnel did not recognize and resolve these objectionable conditions when they occurred.

In your response addressing your facility deficiencies, you state that you will replace all (b)(4) with smooth, non-porous, waterproof materials in all classified areas in August 2026. You also state that the damaged areas have been “repaired or temporarily sealed” and that you have created a procedure specifying the need for routine checks into facility conditions, including before resuming production after (b)(4).

Your response is inadequate because it does not state that you will cease manufacturing all (b)(4) drug products (including (b)(4)) for the U.S. market until all comprehensive remediations in the design and maintenance of your facility and equipment have been implemented. In addition, it does not address investigating why your production personnel did not recognize or address the damaged surfaces when they first occurred.

In response to this letter, provide:

• 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, and improved systems for ongoing management review. Your plan should also ensure that appropriate actions are taken throughout the company network.

4. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).

Your aseptic processing operation is inadequately designed to prevent contamination of your sterile (b)(4) drug products.

For example, you do not sterilize critical equipment components, such as bowls, (b)(4) that handle container/closure parts, between batches. Instead, you disinfect the (b)(4) product ISO 5 (Grade A) filling lines (b)(4) using sporicide and (b)(4).

It is critical to assure your firm has a program for cleaning and sterilization of all equipment that comes into contact with sterile product constituents (i.e., parts contacting sterilized formulation, containers, and closures).

In your response, you state that some of these parts cannot be (b)(4) due to machine design, and you plan to start using sporicide between each batch, increase “microbiological sampling” by (b)(4)%, and begin swabbing container/closure contact equipment.

Your response is inadequate. It does not include an impact assessment of this violation on drug product that is currently on the U.S. market, nor a commitment for a CAPA to ensure use of sterilizable equipment in the future. The use of sporicide, increased sampling, and equipment swabbing are not acceptable substitutes for sterilizing your product contact equipment.

In response to this letter, provide:

• A CAPA plan, based on the retrospective assessment of your cleaning and disinfection program, that includes appropriate remediations to your cleaning and disinfection processes and practices, and timelines for completion. Include the following as part of the assessment and CAPA plan:
  o a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning and disinfection
  o a list of improvements, with an explanation how each will enhance cleaning and disinfection effectiveness
  o improved ongoing verification of proper cleaning and disinfection execution for all products and equipment and,
  o any other needed remediations

• Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning and disinfection. Describe improvements to your cleaning and disinfection program, including enhancements to cleaning effectiveness; improved ongoing verification of proper cleaning and disinfection execution for all products and equipment; and all other needed remediations.

• A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:
  o a determination of whether procedures used by your firm are robust and appropriate
  o provisions for QU oversight throughout your operations to evaluate 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

• Describe how top management supports quality assurance and reliable operations, including but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.

Drug Production Ceased and Suspended

We acknowledge your commitment to cease production of (b)(4) drug products on line (b)(4) and suspend production of (b)(4) drug products on lines (b)(4) for the U.S. market until they have been replaced.

If you plan to resume any (b)(4) drug product manufacturing operations regulated under the FD&C Act, notify this office before resuming your (b)(4) drug product manufacturing operations. 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 CAPAs.

Drug Recall

On April 7, 2026, FDA held a teleconference with you recommending you consider removing any batches of (b)(4) drug products currently in distribution from the U.S. market.

Between (b)(4), you issued voluntary recalls of all (b)(4) drug products currently in distribution from the U.S. market due to lack of sterility assurance. The company announcements were posted to the FDA website:

(b)(4)

Repeat Violations at Facility

In a previous warning letter (WL 320-25-70), FDA cited similar severe CGMP violations. The recurrence of these violations demonstrates that your firm’s corrective actions were neither effective nor durable. Notably, your failure to correct these issues led to unacceptable drug product being distributed to the U.S. market.

Ineffective Quality System

Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.

Additional Guidance on Aseptic Processing

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/regulatory-information/search-fda-guidance-documents/sterile-drug-products-produced-aseptic-processing-current-good-manufacturing-practice.

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 audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPA 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

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on April 27, 2026.

Correct any violations promptly. 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 27 Rue de la Lombardiere, 07100 Annonay, Ardeche, France, 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).

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days1. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices and/or submit a request to schedule an FDA inspection. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3007058211 and ATTN: Russell Riley.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research

CC: Mr. Cédric Vandermeiren
General Manager
Excelvision
Email: cvandermeiren.corporate@fareva.com
____________________________

1 Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.