|Issuer:||Center for Devices and Radiological Health|
|Issued:||Nov. 29, 2010||Closed:||
Department of Health and Human Services
Public Health Service
Food and Drug Administration
10903 New Hampshire Avenue
NOV 29 2010
VIA United Parcel Service
Mr. Jose M. Bobes Lasa
President and Owner
338 Arturo Soria Street
Dear Mr. Bobes Lasa:
During an inspection of your firm located in Madrid, Spain on May 31, 2010, through June 2, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures tonometers. 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 are intended 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 (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. We received a response from you dated June 24, 2010, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. Your response will not be reviewed at this time for consideration, since the response was received after the 15 day time frame. Your June 24 response will be reviewed at the time we receive your response to this letter. These violations include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures to for the identification, documentation, validation, or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example, there is no design change procedure for the tonometer device.
2. Failure to establish and maintain a device history file (DHF) for each type of device. The DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of 21 CFR 820, as required by 21 CFR 820.30(j). For example, there is no design history file for the Applanation Tonometer Models OP1H and OPIS.
3. Failure to develop, conduct, control, and monitor production processes to ensure that a device conforms to its specifications, specifically, failure to document standards for criteria of workmanship or by means of identified and approved representative samples, as required by 21 CFR 820.70(a)(5). For example, the Work Instruction IT-20-01, Tonometer Verification, includes inconsistent specifications. Section 5.3.1 includes a specification of (b)(4 ) as a tolerance for the tonometer device when the testing is done using a calibration bar. Section 5.3.2 includes (b)(4 as a tolerance when the testing is done using electronic measuring equipment. There is no documented rationale for the discrepancy.
4. Failure to establish and maintain adequate procedures for acceptance of incoming product; to inspect, test or otherwise verify incoming product conforms to specified requirements; and to document acceptance or rejection, as required by 21 CFR 820.80(b). For example:
• Procedure PC-11, Verification of Purchased Product, defines requirements for incoming inspection of materials and components;
• Work Instruction IT-11-01, Quality Control Receipt of Materials and Components, defines the process for the inspection and acceptance of materials and components.
There was no documentation of incoming inspection and acceptance of components and materials used in the production of the tonometer devices.
5. Failure to establish and maintain procedures to control product that does not conform to specified requirements. The procedures shall address the identification, documentation, evaluation, segregation, and disposition of nonconforming product. The evaluation and any investigation shall be documented, as required by 21 CFR 820.90(a). For example:
• Procedure, PC-22, Corrective and Preventative Actions requires that non-conformances be captured in the firm’s corrective and preventative actions system. However, during a walk-through of the manufacturing area, manufacturing components were located on a shelf labeled as non-conforming material. There was no documentation of the non-conformances being documented in the firm’s corrective and preventative action system.
• Procedure PC-21, Non-Conforming Product requires that non-conformances for finished product or components be documented on form RC-21-01. There is no documentation of non-conformances for finished product or components for the tonometer devices.
6. Failure to document equipment identification, calibration dates, the individual performing each calibration, and the next calibration date, as required by 21 CFR 820.72(b)(2). For example, there is no documentation to show that the calipers used for the production of the tonometers are calibrated. There is no documentation of a calibration plan for the calipers used for the production of tonometers as called for by procedure PC-17, Equipment Calibration.
7. Failure to maintain device history records (DHRs) and to establish and maintain procedures to ensure that 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 21 CFR 820 as required by 21 CFR 820.184. For example, the device history records for the tonometer devices lack documentation of the production of the devices, the packaging and labeling of the devices, and release of the devices for distribution.
8. Failure to establish and maintain the quality requirements, that must be met by suppliers, contractors, and consultants. Each manufacturer shall evaluate and select potential suppliers, contractors, and consultants on the basis of their ability to meet specified requirements, including quality requirements. The evaluation shall be documented, as required by 21 CFR 820.50(a)(1). For example, Procedure PC-09, Evaluation of Suppliers, includes requirements for the evaluation of suppliers. There was no documentation to show that suppliers of components and materials used in the tonometer devices were evaluated.
9. Failure to establish and maintain adequate procedures to control all documents and designate an individual(s) to review for adequacy and approve prior to issuance all documents established to meet the requirements of 21 CFR 820, as required by 21 CFR 820.40(a). For example, procedure PC-20, Final Product Inspection, requires the use of form RC-20-02 for the inspection and testing of products prior to release. There is no documentation to show that form RC-20-02 was used to document the inspection and testing of each device. The firm’s records for its devices include the use of a different form for recording the inspection of a batch of devices instead of records for individual devices.
10. Failure to establish 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, there is no documentation to show that internal quality audits were conducted since the last FDA inspection in May 2007.
11. Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of 21 CFR 820 and the manufacturer’s established quality policy and objectives, failure to document the dates and results of the quality system reviews, as required by 21 CFR 820.20(c). For example, Procedure PC-04, Management Review, includes requirements for annual management reviews to be conducted. There is no documentation to show that management reviews were conducted since the last FDA inspection in May 2007.
12. Failure to establish a quality plan which defines the quality practices, resources, and activities relevant to devices that are designed and manufactured, as required by 21 CFR 820.20(d). For example, quality planning activities have not been implemented for the tonometer device.
13. 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 and documented, as required by 21 CFR 820.250(b). For example, Work Instruction IT-11-02, Quality Control Inspection Plans, defines the sampling plans to be used for the incoming inspection and acceptance of materials. However, there is no documentation to show that sampling plans were defined for materials and components used in the tonometer devices.
14. Failure to establish and maintain adequate procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, to include documentation of the training, as required by 21 820.25(b). For example, Procedure PC-05, Training, includes requirements for employee training. However, there is no documentation to show that employees were trained.
A follow up inspection will be required to assure that corrections are adequate. We will contact the appropriate people and request an establishment re-inspection. An FDA trip planner will be in touch with you to arrange a mutually convenient date for this inspection.
Given the serious nature of the violations of the Act, the tonometers 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 may take steps to refuse these products, known as "detention without physical examination," until these violations are corrected. In order to remove the devices from detention, you should provide a written response to this Warning Letter as described below and correct the violations described in this letter. We will notify you if your response is adequate, and we may need to re-inspect your facility to verify that the appropriate corrections have been made.
Also, U.S. federal agencies are advised of the issuance of all 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. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed. Please provide a translation of documentation not in English to facilitate our review.
Your response should be sent to: Ronald L. Swann, Chief, Dental, Ear, Nose, Throat, and Ophthalmic Devices Branch, WO66-3534, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, U.S.A. If you have any questions about the content of this letter please contact: Debra Demeritt at 301-796-5472 or 301-847-8137.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.
Steven D. Silverman
Office of Compliance
Center for Devices and