Inspections, Compliance, Enforcement, and Criminal Investigations

Jieying Laboratory Inc 3/9/14

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 10903 New Hampshire Avenue
Silver Spring, MD 20993

 

WARNING LETTER
MAR 9, 2014
 
VIA UNITED PARCEL SERVICE
 
Mr. Ri-Cheng Chian
President and Chief Executive Officer
Jieying Laboratory, Inc.
982 Rue Jean-Neveu
Longueuil, Quebec J4G 2M1
Canada
 
Dear Mr. Chian:
 
During an inspection of your firm located in Longueuil, Quebec, Canada, on October 27, 2014, through October 30, 2014, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Class II assisted reproduction tools. 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 from your firm dated November 17, 2014 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 establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21CFR 820.30(a). For example, your firm has not established design control procedures that outline the requirements for design and development planning; design input; design output; design review; design verification; design validation; design transfer; design changes; and the establishment of a design history file.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm established design control procedures and conducted personnel training on these procedures. However, your firm did not provide these procedures and training records. Additionally, your firm did not evaluate whether the lack of procedures could have led to the release of nonconforming devices.
 
2.    Failure to ensure that when the results of a process cannot be fully verified by subsequent inspection and test that 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:
 
a.    Your firm failed to establish validation procedures for the processes used to manufacture sterile micro-tools used for in-vitro fertility procedures. Your firm failed to validate (b)(4) and (b)(4) machines.
 
b.    The following steps were not performed, as required by your firm’s sterilization process procedure:
 
i.    Yearly bioburden and sterility recovery testing,
 
ii.    Bioburden testing based on a random sampling plan, and
 
iii.    Revalidation of the (b)(4) sterilization process for a change in the material component for the micro-pipettes box.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it plans to update its sterilization validation procedure to address the above deficiencies. However, your firm has not provided the sterilization validation procedure and personnel training records on this procedure.  Additionally, your firm did not conduct a retrospective review of manufacturing processes to ensure that those processes that cannot be verified by subsequent inspection and test are validated.
 
3.    Failure to establish and maintain adequate procedures that define the responsibility for review and the authority for the disposition of nonconforming product, as required by 21 CFR 820.90(b)(1). For example, your firm has not established procedures for review and disposition of nonconforming products.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it has established a procedure for controlling nonconforming products. However, your firm did not provide the updated procedure and personnel training records on this procedure. Additionally, your firm did not evaluate whether the lack of procedure could have led to the release of nonconforming devices.  
 
4.    Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, as required by 21 CFR 820.70(a). For example, your firm’s technical product description and production procedure for micro-tools fail to define the:
 
a.    Current specifications for process parameters and product dimensions;
 
b.    Process controls, such as documented instructions and standard operating procedures for product packaging;
 
c.    Monitoring and control of process parameters, components, and device characteristics; and
 
d.    Approval of processes and process equipment.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it plans to update its technical product description, procedures and forms. However, your firm did not conduct a retrospective review to ensure that production processes are adequately controlled.   
 
5.    Failure to establish and maintain procedures for acceptance activities, to include inspections, tests, or other verification activities, as required by 21 CFR 820.80(a). For example, your firm has not established procedures for acceptance activities for incoming, in-process, and finished device quality control testing. Your firm does not have test records for incoming, in- process, and final quality control testing.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it implemented an acceptance procedure. However, your firm did not provide the acceptance procedure and personnel training records on this procedure. Additionally, your firm did not evaluate whether the lack of procedure for acceptance activities could have led to the release of nonconforming devices.
 
6.    Failure to establish and maintain procedures for changes to a specification, method, process, or procedure, as required by 21 CFR 820.70(b). For example:
 
a.    Your firm has not established procedures to ensure that changes to specifications, methods, processes, and procedures are verified or where appropriate validated, and the changes are documented and approved before implementation.
 
b.    Your firm’s production process procedure was not updated to reflect the use of (b)(4)machines and the use of (b)(4) for the micro-tool pipettes.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response did not address this violation.
 
7.    Failure to establish and maintain adequate procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained, and to include provisions for handling, preservation, and storage of equipment, so that its accuracy and fitness for use are maintained, as required by 21 CFR 820.72(a). For example, calibration records for (b)(4) were not maintained, as required by your firm’s calibration procedure.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it plans to update its calibration procedure, records, and schedules. However, your firm did not provide evidence of implementation of these corrective actions.  
 
8.    Failure to establish and maintain procedures to ensure that sampling methods are adequate for their intended use and to ensure that when changes occur the sampling plans are reviewed, as required by 21 CFR 820.250(b). For example, your firm’s sampling plan for incoming inspections and daily quality control testing for (b)(4) pipettes are not based on a valid statistical rationale.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm plans to establish procedures to ensure that the sampling methods are adequate for their intended uses. However, your firm has not provided evidence of implementation of its corrective actions. Additionally, your firm did not evaluate which production procedures need to be updated as a result of this corrective action.  
 
9.    Failure to establish and maintain procedures to control labeling activities, as required by 21 CFR 820.120. For example, your firm has not established labeling control procedures.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it plans to establish a labeling control procedure. However, your firm’s response did not address whether personnel will be trained on the labeling control procedure. Additionally, your firm did not conduct a retrospective review to determine whether the lack of procedure could have affected the labeling integrity of the released devices.   
 
10.    Failure to maintain device master records (DMRs), as required by 21 CFR 820.181. For example, your firm does not have DMRs for the micro-tool pipettes.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it plans to establish DMRs for micro-tool pipettes. However, your firm did not conduct a retrospective review to ensure that the DMRs are maintained for all devices.
 
11.    Failure to establish and maintain procedures to ensure that device history records (DHRs) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record (DMR) and the requirements of this part, as required by 21 CFR 820.184. For example, your firm has not established DHR procedures. Additionally, your firm has no DHRs.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm indicated that it plans to establish a DHR procedure. However, your firm did not indicate whether relevant personnel will be trained on the DHR procedure.
 
12.    Failure to establish and maintain procedures for quality audits and conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22. For example, your firm’s quality audit procedure does not require auditing of applicable quality system requirements, such as design controls and process validation.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm revised its quality audit procedure. However, your firm did not provide the quality audit procedure and personnel training records on this procedure. Additionally, you firm did not conduct a retrospective review to determine whether previous quality audits failed to cover quality system requirements and if so, whether corrective actions are necessary.
 
13.    Failure to establish procedures for ensuring that all personnel are trained to adequately perform their assigned responsibilities and for identifying training needs were not established, maintained, and documented, as required by 21CFR 820.25(b). For example, your firm has not established training procedures.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm plans to establish training procedures. However, your firm did not conduct an evaluation of personnel training needs.
 
Given the serious nature of the violations of the Act, the devices manufactured by your firm, including assisted reproduction tools, are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated.  As a result, FDA is taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations are corrected.  In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violations described in this letter.  We will notify you regarding the adequacy of your firm’s responses and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
 
U.S. federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. 
 
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 correct 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 and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
 
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Inspections Support Branch, White Oak Building 66, Rm 2622, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case # 445166 when replying. If you have any questions about the contents of this letter, please contact: Mr. Daniel Walter, Branch Chief, Foreign Enforcement Branch, at +1 (301) 796-5587, or fax +1 (301) 847-8139.
 
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. 
 
Sincerely yours,
/S/                                                           
Jan B. Welch, MHS, MT (ASCP) SBB
Acting Director
Office of Compliance
Center for Devices and
      Radiological Health
 
cc:      
Mr. Xiaomin Yu
U.S. Agent
JieYing IVF Labs San Francisco Inc.
1100 S Eliseo Dr, Ste 107
Greenbrae, California 94904

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