- Prodimed SAS
- Issuing Office:
- Center for Devices and Radiological Health
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| ||10903 New Hampshire Avenue|
Silver Spring, MD 20993
NOV 2, 2015
VIA UNITED PARCEL SERVICE
Chief Executive Officer
Zi 4 Avenue de L'Europe
60530 Neuilly En Theile
Dear Mr. Chicheportiche:
During an inspection of your firm located in Neuilly En Theile, France, on June 29, 2015, through July 2, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures endometrial sampling devices, embryo transfer sets, insemination cannulas, and oocyte puncture 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 a response from your firm, dated July 21, 2015, concerning our investigator's observations noted on the Form FDA 483 (FDA 483), List of lnspectional 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 for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d). For example:
a. Your firm's endotoxin testing procedure, "Dosage des Endotoxines Bacteriennes par le Test LAL," (b)(4), requires testing on at least (b)(4) lot every (b)(4) months in each sterilization family. However, for the sterilization family 3a, which includes the Oocyte Puncture System, LAL testing was not conducted between February and October in 2014. Over (b)(4) devices were distributed from sterilization family 3a during this period.
b. The sampling plan for pyrogen testing of the Oocyte Puncture System requires sampling LAL in at least (b)(4) lot every (b)(4) months for each sterilization family, regardless of the number of lots manufactured during the (b)(4) month period. However, your firm has not established a statistical rationale for sampling (b)(4) lot every (b)(4) months.
The adequacy of your firm's response cannot be determined. Your firm's response includes plans to review the sampling performed for the batch release tests and to update the batch release procedure and associated forms in order to comply with ANSI/AAMI/ST-72 Standard requirements. Your firm's response states it plans to revise its SOP (b)(4) "Dosage des Endotoxines Bacteriennes par le Test LAL" to comply with the ANSI/AAMI/ST-72 Standard. Your firm's response states it plans to perform the LAL test on all lots destined for distribution in the US. Also, your firm's response states it plans to perform endotoxin dosage testing on all batches already distributed in the US. Your firm's response did not include documentation of completion of these activities.
2. Failure to establish and maintain procedures to ensure that where 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 procedures, as required by 21 CFR 820.75(a). For example, Work Instruction (b)(4) requires the (b)(4) for the tube and fitting to be conducted at a (b)(4) of (b)(4) and a pressure of (b)(4). However, your firm did not perform validation of the (b)(4).
We reviewed your firm's response and conclude that it is not adequate. Your firm's response states that it plans to qualify the (b)(4) and validate the (b)(4). Additionally, your firm's response states that additional tests will be performed to control the safety and effectiveness of the products concerned by this process, such as the (b)(4) on the puncture needle. Also, your firm's response states it will review the other processes which were not validated. However, your firm's response did not include a risk assessment to determine if distributed devices were nonconforming. Your firm's response did not include documentation of completion of the activities listed here.
3. Failure to establish and maintain procedures to adequately control environmental conditions, where environmental conditions could reasonably be expected to have an adverse effect on product quality, as required by 21 CFR 820.70(c). For example, your firm did not adequately establish procedures for control of temperature and biocontamination in the (b)(4) where Oocyte Puncture Systems are assembled. For example:
a. The Instruction "Maitrise de L'Environment des ZAC," (b)(4), references (b)(4), but does not specify the frequency and method of monitoring, including the (b)(4).
b. The "Releve de Temperature Salle" Form, (b)(4), requires the temperature in (b)(4) be (b)(4) °C ± (b)(4) °C. However, during production on (b)(4), 2015, the (b)(4). Further, (b)(4).
c. The work instruction, "(b)(4), requires the Microbiology Manager to establish sampling for biocontamination testing for the hands of (b)(4) assemblers. However, the frequency and selection of operators for sampling was not defined.
We reviewed your firm's response and conclude that it is not adequate. Your firm's response states it plans to review and revise procedure (b)(4), and associated form (b)(4), to require recording the (b)(4). Your firm's response states that its SOP (b)(4) “Frequence des prelevements” (Sampling Frequency) was reviewed to clarify the selection of operators and the frequency of operators for sampling. However, your firm's response did not assess the risk associated with the lack of sufficient (b)(4), or how it plans to mitigate the risks as they relate to previously distributed product.
Additionally, your firm's response states it has retrained operators on hygiene rules and required the employees to sign a commitment relative to the hygiene rules. Your firm's response did not include documentation of completion of these activities.
4. Failure to establish and maintain procedures for implementing corrective and preventive action (CAPA), as required by 21 CFR 820.100(a). For example, your firm did not demonstrate verification/validation of effectiveness of the corrective action. Specifically:
a. CAPA 14/015 was initiated as a result of incorrect expiration dates on labeling. The "Verification de l'efficacite des Actions" states that a new form is in place; however, the CAPA does not state that the form is effective in preventing the recurrence of the mislabeling.
b. CAPA 14/062 was opened as a result of nonconformities in bioburden in Oocyte Puncture Systems manufactured in the (b)(4). A corrective action required increasing the frequency of hand sanitation to every 30 minutes, issued via a Note de Service on September 26, 2014. However, your firm's production employees in the (b)(4) did not perform hand sanitation during 1 hour of observation.
The adequacy of your firm's response cannot be determined. Your firm's response stated that it has initiated Non-Conformity NC 15/190 to verify the effectiveness of the corrective action in CAPA 14/015. Also, your firm's response states it has conducted a review of internal nonconformities and customer complaints since implementation of the labeling form, and determined mislabeling did not recur. Your firm's response states that the CAPA procedure was determined to be ineffective. Please describe your firm's plan to retrospectively review previous CAPAs to determine whether they were executed effectively, and perform remediation where ineffective. Your firm's response includes plans to audit the CAPA process twice a year for 2 years. Your firm's response did not include documentation of completion of these activities.
Given the serious nature of the violations of the Act, all devices 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.
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 3523, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #481475 when replying. If you have any questions about the contents of this letter, please contact: L T David Dar, Acting Chief, Foreign Enforcement Branch, at firstname.lastname@example.org (email) or +1 (240) 402-4020 (phone).
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 lnspectional 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.
CAPT Sean M. Boyd, MPH, USPHS
Office of Compliance
Center for Devices and Radiological Health