Inspections, Compliance, Enforcement, and Criminal Investigations

Guilin Zizhu Latex Co., Ltd 8/14/15

  

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

Public Health Service
Food and Drug Administration
 10903 New Hampshire Avenue
White Oak Building 66
Silver Spring, MD 20993

 

WARNING LETTER
AUG 14, 2015 
 
VIA UNITED PARCEL SERVICE
 
Tao Ran
General Manager
Guilin Zizhu Latex Co., Ltd.
6 Wushan Road
541001 Guilin
CHINA
 
Dear Mr. Tao:
 
During an inspection of your firm located in Guilin, China, on March 2, 2015, through March 7, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures natural rubber latex condoms.  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.  FDA received a response from your firm, dated March 25, 2015, concerning the investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that 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 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.  Validation was not performed on (b)(4) active condom production (b)(4). Additionally, Performance Qualification (PQ) was not performed for (b)(4)
 
b.  PQ was not performed for the (b)(4) and (b)(4).
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response states that it will train its staff, revise its process validation procedure, and validate (b)(4) by June 2015, and that (b)(4) will be validated between July and November, 2015. However, it is not clear if a retrospective review of other processes was performed to determine if they require validation. Additionally, your firm did not plan a retrospective analysis to ensure that previously manufactured condoms were not nonconforming due to inadequate process validation, and if remedial action may be required.
 
2.    Failure to ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results, as required by 21 CFR 820.72(a). 
 
For example, your firm failed to validate (b)(4) and finished product testing to demonstrate the test equipment is capable of producing valid results.   
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm’s response did not state that it will ensure that the automatic condom (b)(4) capable of producing (b)(4) testing results.
 
3.    Failure to validate computer software for its intended use according to an established protocol when computers or automated data processing systems are used as part of production or the quality system, as required by 21 CFR 820.70(i). 
 
For example, your firm developed "(b)(4) condoms, using the (b)(4) Machines ((b)(4)). However, your firm did not validate the software for its intended use.
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated it intends to train software development engineers on validation, create procedures for validating test equipment software and software maintenance, and perform the software validation for the (b)(4), as well as for other test equipment containing in house developed software. However, a retrospective review was not performed to determine if additional software used in production requires validation. Additionally, your firm did not plan a retrospective analysis to determine whether previously manufactured condoms may be nonconforming due to inadequate software validation, and if remedial action may be required.
 
4.    Failure to establish and maintain procedures to prevent contamination of equipment or product by substances that could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(e). 
 
For example, the investigator observed that a floor mop sponge was being used to remove residual cleaning solution from the condom (b)(4).  Your firm stated that the sponge is changed annually; however, your firm has not evaluated the use of the sponge, including the effectiveness of removing the cleaning solution, and effects of sponge use on the integrity of the latex solution and finished condoms.
 
This violation was not addressed in your firm’s response.
 
5.    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 21 CFR 820.30(a). 
 
For example, in Design & Development Control Procedure, (b)(4), Ver. 2013A, 01/10/13; and Risk Management Procedure, (b)(4), Ver. 2013A, 01/10/13; your firm has not established and implemented the following:
 
a.  Design Plans
b.  Design Inputs
c.  Design Reviews
d.  Design Verification
e.  Design Validation, including risk analysis
f.  Design Transfer
g.  Design History File
 
The adequacy of your firm’s response cannot be determined.  Your firm's response states your firm plans to establish the design control elements listed above. Your firm’s response did not include documentation of the corrective action. Also, your firm’s response states it will conduct a condom shelf-life study and revalidate the manufacturing of all types of condoms. 
 
6.    Failure to establish and maintain adequate procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). 
 
For example, the procedure “Non-Conforming Products Control Procedure,” (b)(4), requires nonconforming product to be identified, segregated, and reviewed.  However, the following product was found without identification, nonconforming status, or disposition:
 
a.  (b)(4) condoms (b)(4), in the non-conforming area of the (b)(4) Area
 
b.  Two cardboard boxes containing finished, boxed condoms in the nonconforming area of the (b)(4).
 
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated it plans to revise its nonconforming product control procedure to require identification of nonconforming status and disposition; create a label to identify nonconforming product; and train affected personnel on the revised procedure. However, your firm did not perform a retrospective analysis to determine if lack of identification of nonconforming product led to the incorrect disposition or distribution of nonconforming product.
 
Given the serious nature of the violations of the Act, the natural rubber latex condoms manufactured by your firm 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 violation(s) described in this letter.  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.
 
Also, 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 actions (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.
 
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 #455114 when replying. If you have any questions about the contents of this letter, please contact: Daniel Walter, Chief, Foreign Enforcement Branch, via telephone at +1(301) 796-5587, or via facsimile at +1(301) 847-8137.
 
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

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