WARNING LETTER
Randox Laboratories Limited
MARCS-CMS 696569 —
December 06, 2024
Delivery Method:
VIA Electronic Mail
Product:
Medical Devices
Recipient:
Recipient Name
Steven Peter FitzGerald
Recipient Title
Founder and Managing Director
Randox Laboratories Limited
30 Randalstown Road
Antrim
BT41 4FL
United Kingdom
peter.fitzgerald@randox.com
Issuing Office:
Center for Devices and Radiological Health
United States
WARNING LETTER
December 6, 2024
Dear Mr. Steven Peter FitzGerald:
During an inspection of your firm located in Antrim, United Kingdom on August 5, 2024 through August 8, 2024, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the RX series test systems, including the RX daytona, the RX daytona + (plus), and the RX imola test systems. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21,
Code of Federal Regulations
(CFR), Part 820.
We received responses from Linda A Magee, Chief Operating Officer dated August 29. 2024, and Oisin Quinn, Quality Improvement Manager dated November 8, 2024 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address these responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to adequately establish and maintain procedures for validating device design, including appropriate risk analysis, as required by 21 CFR 820.30(g). For example, your firm has initiated five Class II Recalls, beginning in 2018 (Event IDs 81746, 86236, 91097, 92650, 93775), related to assay reagents from the previously used assays carrying over to the subsequent assay test, which caused erroneous results of the subsequent assay conducted on your RX series analyzers, including RX daytona and RX imola. Your firm’s procedure, Risk Management, RQA-1707, Revision O, drafted on June 6, 2023, section 5.1.3.4 Post Market surveillance, states “The Risk Management Report must be updated with any new hazards or hazardous situations identified and or any additional control measures that are required”. Additionally, section 5.2.4 Risk Control requires that control measures should be implemented using “
(b)(4)
,” in that order of priority. However, your firm has not conducted adequate risk analysis nor identified adequate control measures to address the risks of reagents from the precedent assays carrying over to the subsequent assay conducted on the RX series analyzers to ensure the devices (i.e., manufactured assays tested on RX series analyzers) meet their intended use.
We reviewed your firm’s responses and conclude that they are not adequate. Your firm has identified that the root cause is related to ambiguity in your risk analysis procedures, lack of clear responsibility for the activities, and that maintenance of the risk management files and not been effective. Your firm states that you have reviewed and updated the risk management files for the recalled products, however, copies of those files were not provided for review because they are currently under review by specified teams at your firm. An estimated date of completion was not provided.
Your firm also provided Risk Management Report for RX Series Analyzers – Automated RX modena, RX daytona+, RX daytona, RX imola, RX monaco, dated September 30, 2024 and Risk Analysis for RX Series Analyzers – Automated, revision number 4, approved on September 30, 2024. A carryover and contamination category was added to analyzer risk analysis. The risk evaluation before
(b)(4)
.” However, no information was provided to support
(b)(4)
as required by RQA-1707.
Your firm provided a revised job description for the Device Documentation Specialist (JD1402), who is within the
(b)(4)
of RQA-1707, revision Q, drafted September 20, 2024. The procedure has been revised to require the Quality Assurance department to review
(b)(4)
. Post Market Surveillance, RQA-1664, revision M, drafted September 20, 2024 was revised to, among other things, define that the Quality Assurance Department is responsible
(b)(4)
. Control of Non-Conforming Product or Process, RGP-2032, revision U, drafted November 7, 2024 was revised to include responsibility for Quality Assurance Department for
(b)(4)
. However, RQA-1707, RQA-1664, and RGP-2032 do not reference the Device Documentation Specialist. Therefore, it is unclear how the revised job description will prevent similar failures in the future. Your firm stated retraining on RQA-1707, RQA-1664, and RGP-2032 was completed and provided examples for how a completion of training event was documented. However, information on the verification or validation of the retraining (a corrective action) to ensure that the action is effective was not provided. Your firm plans to
(b)(4)
. However, evidence that appropriate control measures will be applied has not been provided. Your firm should provide an update on this review and any remediation efforts needed. You firm also stated that RGP-1002 has been updated but FDA was unable to open this file to review and therefore the Agency unable is unable to determine whether this action is effective.
2. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, CAPA NCP INC612, was initiated on October 16, 2023, due to a customer complaint related to issues when running Copper assay on a RX daytona + analyzer. Your firm confirmed the testing of total protein carried over to the subsequent copper assay, causing falsely elevated Copper results. The root cause description states, “Carryover from both cuvettes and pipettes,” but fails to identify the underlying cause of why the reagent from the previously used assay carried over to the subsequent assay. The CAPA was closed on May 20, 2024, with the correction, “Technical bulletin RXTB-0121 to be updated with as a result of the testing recommending that Copper and Total protein on the same machine.” Since December 2018, your firm has initiated five US market Class II Recalls (Event IDs 81746, 86236, 91097, 92650, 93775) due to erroneous results caused by reagent carryover and, in each your firm has issued an updated Technical Bulletin for carryover avoidance (RXTB-0083, issued February 16, 2018 and RXTB-0098, issued November 20, 2018; RXTB-0121, issued July 31, 2020; RXTB-0136, issued September 22, 2022; RXTB-0148, issued June 6, 2023; RXTB-0148, issued November 22, 2023). The bulletin currently includes a list of over 50 combinations of assays to avoid running in sequence. CAPA #NCP INC612 fails to identify the action(s) needed to correct and prevent recurrence of carryover of assays run on the RX series analyzers. Additionally, activities to ensure the effectiveness of the corrective actions were not identified. Your firm states “Confirm no further complaints since bulletin” but fails to verify or validate the corrective and preventive action to ensure that such action is effective.
We reviewed your firm’s responses and conclude that they are not adequate. Your firm has identified the root cause is related to inadequate procedure and absence of dedicated training resources on root cause analysis for the staff to perform root cause analysis adequately and effectively. Your firm determined the actual root cause for the carryover event from CAPA #NCP INC612 is because of inadequate cleaning of the pipette/cuvette after programmed cleaning on the automated analyzer so the remaining residue of the reagents from Total Protein assay, which contains copper, impacted the subsequent Copper assay. Your firm has not identified corrective and prevention actions for CAPA #NCP INC612 and has not provided information on how you will verify or validate the corrective and preventive action is effective.
Your firm has updated the CAPA procedure “Control of Non-Conforming Product or Process, RGP-2032, revision U, drafted November 7, 2024” to include reference to root cause analysis training material and created training slides “QAT 2.17.pptx” for performing root-cause analysis. Your firm stated training on RGP-2032 and QAT 2.17 was completed and provided an example for how the completion of training event documented. However, information on the verification or validation of the retraining (a corrective action) to ensure that the action is effective was not provided.
Your firm proposed
(b)(4)
. Your firm should provide an update on this review and any remediation efforts needed.
Your firm initiated a CAPA (qNCP 1394) dated August 29, 2024 to determine
(b)(4)
. Your firm has yet identified the root cause for causing the inadequate cleaning which your firm stated in an email dated November 8, 2024, is the common root cause of all the initiated recalls related to carryover on the RX series instruments. Your firm has yet to define actions to prevent recurrence.
Your firm plans to review CAPAs and root cause
(b)(4)
. Your firm should provide an update on this review and any remediation efforts needed.
Other federal agencies may take your compliance with the FD&C Act and its implementation regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed.
Additionally, based on information provided to the investigator during and following the inspection, it appears that your establishment registrations and device listings are incorrect and should be further clarified. During teleconferences following the inspection with the investigator on September 5 and 11, 2024, you promised to evaluate
(b)(4)
. However, as of the date of this letter your registration and listing data remains unchanged.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective action (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm’s response(s) and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.
Your firm’s response should be sent via email to CDRHWarningLetterResponses@fda.hhs.gov.
Refer to CMS case #696569 when replying
. If you have any questions about the contents of this letter, please contact: I-Lin Wu at i-lin.wu@fda.hhs.gov.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.
Sincerely yours,
/S/
Courtney H. Lias, Ph.D.
Director
OHT7: Office of In Vitro Diagnostic Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
CC:
Cheryl OHagan
US Agent
Content current as of:
01/14/2025
Regulated Product(s)
Medical Devices