- Delivery Method:
- Via Email
- Medical Devices
Recipient NameMr. Tsz Kin Kent Yim
Recipient TitleQuality Director
- Ming Fai Industrial Co LTD
Ming Fai Industrial Estate, Bainikeng, Pinghu
Guangdong Sheng, 518111
- Issuing Office:
- Center for Devices and Radiological Health
June 1, 2023
Dear Mr. Yim:
During an inspection of your firm, located in Shenzhen, China, on March 06, 2023, through March 10, 2023, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures ultrasound gel and probe cover products. 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 a response dated March 23, 2023, 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 this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). For example, your firm did not maintain documentation of validation for the following processes:
a. Ethylene Oxide (EO) sterilization of the probe cover kit containing the sterile gel pouch
- Your firm’s EO sterilization validation was conducted for a kit containing another device, C-Arm Drape, that is also packaged in a Tyvek pouch.
However, the C-Arm Drape kit differs from the ultrasound gel probe cover kit, as the probe cover kit contains a sterile gel pouch. Your firm did not maintain documentation with justification that the EO validation conducted on the C-Arm Drapes packaged in a Tyvek pouch is representative for the probe cover kit.
b. Formulation calculation software for mixing of the ultrasound gel
- Your firm did not maintain validation records for the software used to calculate the amounts for the (b)(4) ingredients to be mixed for the ultrasound gel formulation.
c. Cleaning of the mixing tank equipment used for ultrasound gel manufacture
- Your firm did not maintain documentation of cleaning validation conducted for the mixing tank equipment used for manufacturing ultrasound gel.
We reviewed your firm’s response and concluded that it is not adequate. Your firm provided four updates corresponding to the listed examples regarding process validation.
a. Your firm provided a new procedure, (b)(4) Procedure for Irradiation Sterilization Dose, to document the irradiation validation dose similar to the validation report in Exhibit 22. However, this document does not address the concern of your firm not being able to provide adequate records of the gel lots used during the sterilization validation. Additionally, there is no evidence of procedure effectiveness and documentation of training on the new procedure.
b. Your firm provided a procedure for “Evaluate the Medical Device Family for EO sterilization” under procedure (b)(4). The purpose of this procedure is for your firm to evaluate the sterilization methods and parameters of devices to determine how to select a representative model for sterilization of a device family. However, the evaluation has not been completed by your firm and only the procedure to evaluate the representative device has been provided. The response is inadequate because your firm has not provided documentation on training and effectiveness of the new procedure. Therefore, the Agency cannot determine if your firm’s corrections adequately address the requirements of the regulation.
c. Your firm established a procedure “Software Validation for formulation” (b)(4) for the “validation of formulation systems.” The procedure documents how an Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) should be performed. However, the response is inadequate because of the following:
- There is no specific documentation of the IQ/OQ/PQ protocol and report related to the formulation of the ultrasound gel that include acceptance criteria.
- No CAPA to track and evaluate effectiveness of corrective actions
- No documentation of training on the new procedure
d. Your firm states that their cleaning validation incorrectly did not list the mixing tank used in the manufacture of ultrasound gel. In your response, your firm provided an equipment list that only lists the mixing tank used for the ultrasound gel manufacturing process. Your firm states that the assigned QA engineer is responsible to review and check the mixer code for each validation report. However, the response is inadequate because of the following:
- There is no documentation of the investigation and evidence to show that the mixing tank was incorrectly listed on the report information.
- No documentation of any updated procedure that instructs the responsible QA engineer to review and check mixer code for each validation report.
- No documentation of training on new procedure.
2. Failure to identify by suitable means the acceptance status of the product, to indicate the conformance or nonconformance of product with acceptance criteria, as required by 21 CFR 820.86. For example, your firm had several pallets of in-process product held next to finished products in an area designated for finished sterile product ready for release. Additionally, the sterility status of product was not identified (e.g., stickers affixed directly to finished product). Only a single loose paper with the lot number and one sterile color identifier ((b)(4)) was taped to the pallet.
We reviewed your firm’s response and concluded that it is not adequate. Your firm provided an updated warehouse layout where you proposed storage of sterilized semi-finished products and stated that “labeling on the rack is corrected immediately”. Additionally, your firm has provided a revised procedure for “Finished Device Acceptance, (b)(4)”. However, the response is inadequate because of the following:
a. No evidence of the labeling on the rack was provided.
b. No documentation was provided demonstrating personnel were trained on the updated layout and procedure.
c. No documentation of a review or evaluation on the effectiveness of the layout change and revised Finished Device Acceptance procedure.
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.
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 #660075 when replying. If you have any questions about the contents of this letter, please contact: Yanna Kang, Ph.D. at +1(301)796-6704.
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 the violations, and take prompt actions to correct the violations and bring the products into compliance.
Robert Ochs, Ph.D.
OHT8: Office of Radiological Health
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
144 Research Drive
Hampton, Virginia 23666