- MB Industria Cirurgica Ltda
- Issuing Office:
- Center for Devices and Radiological Health
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10903 New Hampshire Avenue
Silver Spring, MD 20993
August 4, 2017
VIA UNITED PARCEL SERVICE
MB Industria Cirurgica Ltda
Rod Br 101 Norte Km 56,7 Sn
Paulista, PE, 53413-000
During an inspection of your firm located in Paulista, Brazil on March 13, 2017, through March 16, 2017, an investigatorfrom the United States Food and Drug Administration (FDA) determined that your firm manufactures wound dressings. 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, its 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. 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, your firm has not validated the following manufacturing processes for the (b)(4) device:
a. The (b)(4) to ensure a homogenous and (b)(4) and (b)(4) operate simultaneously.
b. The (b)(4) to ensure the (b)(4) to ensure the device is (b)(4).
c. The packaging process to ensure a uniform seal of the pouch and ensure the product maintains sterility after sterilization.
2. Failure to ensure where environmental conditions could reasonably be expected to have an adverse effect on product quality, that procedures shall be establish and maintained to adequately control these environmental conditions, as required by 21 CFR 820.70(c). For example:
a. Your firm does not have documentation to show that its cleanroom was installed, tested, and approved in accordance with ISO 14644, as per its “Cleanroom Specifications and Requirements Standard Operating Procedure, MFG.SOP.009.”
b. Your firm does not comply with the cleanroom environmental requirement for the (b)(4) process provided in the Device Master Record. The cleanroom environmental requirement specifies production activities to be performed in a controlled area to comply with ISO 14644 for a Class 100,000 (ISO Class 7) and temperature (b)(4). However, the cleanroom used for the production process (b)(4) is annually certified as only ISO Class 8 cleanroom and the current temperature requirement (b)(4) observed on a sign in the (b)(4) room.
c. Temperature readings documented on 01/05/2017, 01/09/2017, 01/11/2017, 01/12/2017, and 02/02/2017 were higher than the specified temperature limit of (b)(4) in the Device Master Record. Your firm has no documented assessments of these excursions to determine if there was any product impact.
d. A hand-written note observed on the production record of Lot #050916 indicated the (b)(4) on Monday 09/19/2016 for approximately four hours, affecting the (b)(4) room and the cleanroom, (b)(4) during the morning. Your firm does not have procedures established for (b)(4) conditions of the cleanroom after (b)(4) is off for days.
e. Your firm does not have an environmental control program established to adequately monitor the cleanliness and biocontamination level.
3. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, your firm’s procedure for corrective and preventive action titled “Procedimento de Tratamento Das Não Conformidades e Ações Corretivas e Preventivas”, PQ 1-3, Rev. 09, dated 08/01/2016, is not adequate in that:
a. The procedure does not provide requirements to analyze quality data to identify existing and potential or recurring quality problems. An analysis of the complaint data shows that your firm received increase number of complaints (from 36 to 46 from 2015 to 2016) associated with (b)(4), and approximately 50% of those complaints were related to leakage. However, your firm has not evaluated to determine if an action is needed.
b. The procedure does not provide requirements to ensure that information related to quality problems or nonconforming product is disseminated to those directly responsible for assuring the quality of such product or the prevention of such problems; and for submitting relevant information on identified quality problems, as well as corrective and preventive actions, for management review.
4. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example:
a. The complaint handling procedure titled “Procedimento de Atendimento ao Cliente Referente a Informações e Reclamações Sobre Produtos”, PRD 8-1, Rev. 08, dated 08/10/2016, is inadequate in that it does not provide requirements for:
i. All complaints to be processed in a timely manner;
ii. Oral complaints to be documented upon receipt; and
iii. Complaints to be evaluated to determine whether the complaint represents an event which is required to be reported to FDA under part 803, Medical Device Reporting.
b. Your firm has not implemented the complaint handling investigation procedures titled “Procedimento de Atendimento ao Cliente Referente a Informações e Reclamações Sobre Produtos”, PRD 8-1, Rev. 08, dated 08/10/2016, and “Procedimento de Tratamento Das Não Conformidades e Ações Corretivas e Preventivas”, PQ 1-3, Rev. 09, dated 01 Aug 2016, in that the investigation and results of the investigations are not documented, as required by these procedures.
5. Failure to establish and maintain 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:
a. The non-conformance procedure “Procedimento de Tratamento Das Não Conformidades e Ações Corretivas e Preventivas”, PQ 1-3, Rev. 09, dated 08/01/2016, does not provide requirements to determine and document the disposition of nonconforming products and when authorized to use non-conforming products, the justification for use and the signature of the individuals authorizing the use of nonconforming products.
b. Your firm has not implemented the non-conformance procedure “Procedimento de Tratamento Das Não Conformidades e Ações Corretivas e Preventivas”, PQ 1-3, Rev. 09, dated 08/01/2016, in that the quality department stated that non-conforming products encountered in the manufacturing areas are documented in the production record, but are not evaluated and investigated as needed.
6. 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, your firm has not implemented its procedure for release of a lot of (b)(4) for distribution “Procedimento de Liberação do Lote (b)(4), Rev. 03, dated 10/31/2016, Section 5.2 of “Quality Control will send a memorandum with the lot number tested and released to the Production Supervisor.” A review of 11 Device History Records (DHRs) revealed none contained the memorandum. Lots associated with these DHRs have been released for distribution without a review and released by Quality Control.
7. Failure to establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained, as required by 21 CFR 820.72(a). For example, your firm has not implemented its equipment calibration procedure “Procedimento Para Controle Gerenciamento de Equipamentos para Medição e Ensaio de Inspeção e Testes”, PQ 1-11, Rev. 8, dated 09/20/2016, in that the (b)(4) equipment of the (b)(4) has never been calibrated.
8. Failure to establish adequate procedures for identifying training needs and ensure that all personnel are trained to adequately perform its assigned responsibilities, as required by 21 CFR 820.25(b). For example:
a. Your firm’s management representative and quality group indicated that they had no knowledge of the requirements of the Quality System Regulation and stated they were not aware they needed to meet these requirements for the (b)(4) exported to USA.
b. The training procedure titled “Procedimento de Recrutamento, Seleção e Treinamento”, PRH 9-1, Rev. 11, dated 30/09/2016, is not adequate in that training of personnel is not identified, conducted, and documented when procedures are updated for personnel to be adequately trained in the latest revision to ensure they can adequately performed its assigned responsibilities. Two employees utilized an obsolete version of the non-conformance form “Procedimento Para Ações Corretivas e Preventivas”, PQ 1-3, Rev. 02, on 05/19/2016. This form had been revised to revision 3 on 12/15/2015. The management representative, who utilized an incorrect version of this form, stated he was not aware that changes to this non-conformance form.
9. Failure to establish adequate 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 has not implemented its internal quality audit procedure "Procedimento Para Auditoria Interna Da Qualidade", PQ 1-1, Rev. 3, dated 08/01/2016, Section 4.2 of “internal audits should be conducted periodically (at a minimum every 6 months)” and Section 4.3.1 “Areas of firm to be audited – Quality Management, Production, Human Resources, Purchasing, Quality Control, Storage, Sales, Administration Structure, Laboratory, and Sterilization.” Your firm has not conducted internal quality audits at a minimum of every six months to ensure that the quality system is in compliance with the quality system requirements. The last internal quality audit was performed seven months ago on 08/18-19/2016 and previous to that audit it was performed on 12/03-29/2015, also more than six months from the previous audit. In addition, the audit on 12/03-29/2015 did not cover Laboratory.
Our inspection also revealed that your firm’s devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:
10. Failure to develop, maintain, and implement written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17. For example, your firm has not developed procedures to ensure timely and effective identification, communication, and evaluation of events that may be subject to medical device reporting requirements; a standardized review process for determining when an event meets the criteria for reporting; timely transmission of complete medical device reports to US agent; and documentation and recordkeeping requirements.
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 responses 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 3540, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case # 532799 when replying. If you have any questions about the contents of this letter, please contact: Cesar Perez,Branch Chief, at 301-796-5770.
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.
CAPT Sean M. Boyd, MPH, USPHS
Deputy Director for Regulatory Affairs
Office of Compliance
Center for Devices and Radiological Health
Mr. Alan Dishman
310 Arballo Dr. 9L
San Francisco, CA 94132