Inspections, Compliance, Enforcement, and Criminal Investigations
Medical Wire & Equipment Co (Bath), Ltd 4/26/07
Department of Health and Human Services
|Public Health Service |
Food and Drug Administration
|2098 Gaither Road |
Rockville MD 20850
APR 26 2007
VIA FEDERAL EXPRESS (AND FACSIMILE)
Mr. Andrew Baggio
Chairman and Managing Director
Medical Wire & Equipment Co (Bath), Ltd.
Corsham, Wiltshire, England SN13 9RT
Dear Mr. Baggio:
During an inspection of your firm located in Corsharn, Wiltshire, England on 11/27/2006 through 11/30/2006, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Transtube and Transwab. 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 responses from [redacted] Operations and Production Manager, dated 12/18/2006, 02/09/2007, and 03/05/2007 concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address these responses below, in relation to each of the noted violations, These violations include, but are not limited to, the following:
1. Failure to validate a process whose results cannot be fully verified by subsequent inspection and test as required by 21 CFR 820.75(a). For example:
a. The filling, capping, packaging, and sealing processes, which utilize semi-automated and automated equipment, are not validated. In addition, the software applications controlling these processes are not validated for their intended uses.
The responses are inadequate because the entire validation of the packing and sealing processes is not complete. The software controlling the capping processes has not been validated and a procedure describing the in-process inspection activities that will now be performed to verify the capping processes has not been provided. In addition, it is not clear for the filling process validation what fluids (i.e. water, media, etc.) were used during the operational and performance qualification of the Dispensers.
b. The sterilization process validation for Transwab transport system failed to evaluate if the radiation dose settings of [redacted] and [redacted] to [redacted] had any adverse affect on product and package performance.
The responses are inadequate because a product and package material evaluation has not been conducted to evaluate the dose settings of [redacted]
c. The sterilization process was not validated at the radiation dose setting of [redacted]
The responses appear adequate because the contract sterilizer, [redacted] will no longer sterilize product with this radiation dose setting [redacted] utilizes the parameters specified by the firm for an appropriate radiation dose.
2. Failure to establish and maintain adequate procedures to analyze appropriate sources of quality data to identify existing and potential causes of nonconforming product or other quality problems as required by 21 CFR 820.100(a)(2). For example:
a. No investigation was conducted under the firm's CAPA system to determine the root cause for spikes in bioburden. Results from routine in-process microbial sampling revealed [redacted] occurrences, from 01/2005 to 11/2006, of media overlay plates being heavily contaminated (i.e. 100%, CFUs) with gram positive rods, gram negative rods, and/or grain positive cocci.
The responses are inadequate because SOP [redacted] does not address the analysis of multiple data inputs from your quality system, the types of information submitted to management for review, and the method for determining verification or validation to ensure the corrective and/or preventive action is effective and does not have an adverse effect on the device. In addition, a [redacted] was not provided.
b. No investigation was conducted wider the firm's CAPA system to determine the root cause of settle plates in the Transtube Dispensing Room failing bioburden testing. Results from settle plate counts revealed multiple occasions from 01/2005 to 10/2006 where the colony counts exceeded the internally accepted limit of [redacted]
The responses appear adequate because an investigation was conducted, according to SOP [redacted] and a root cause was determined for the repeated bioburden testing failures.
c. No investigation was conducted under the firm's CAPA. system to determine the root cause for the process water failing conductivity testing. Conductivity results revealed multiple occasions from 01/2005 to 10/2006 where the conductivity exceeded the internally accepted range of [redacted]
The responses are inadequate because [redacted] a was not provided. Further, the firm has not implemented a correction to address the fact that nonconforming results had occurred repeatedly over an almost 2 year period of time and no one evaluated the nonconformities or took corrective/preventive steps. The firm has not taken steps through training and other means to ensure that other nonconformities are appropriately evaluated, investigated, and handled.
3. Failure to establish and maintain adequate procedures to control environmental conditions as required by 21 CFR 820.70(c). For example:
a. SOP [redacted] does not document the specified limits for settle plate colony counts that will initiate an investigation and if necessary an appropriate corrective action to adequately control the environmental bioburden in the manufacturing area.
The responses are inadequate because SOP [redacted] and Form [redacted] do not address what the specified limits are for the Transwab Dispensing Room. In addition, SOP [redacted] does not clearly define how "daily allowance" and "daily average" correlate to "average plate count" and "max daily allowance" on Form [redacted]
b. SOP [redacted] does not document the specified limits for deionized water conductivity that will initiate an investigation and if necessary an appropriate corrective action to adequately control the water quality.
The responses appear adequate because SOP [redacted] establishes [redacted] as the permitted conductivity range. If the conductivity is outside of this range, then the [redacted] is responsible for investigating and if necessary implementing a corrective action according to the [redacted]
4. Failure to ensure all inspection, measuring, and test equipment, is suitable for its intended purposes and is capable of producing valid results as required by 21 CFR 820.72(a); and failure to document equipment identification, calibration date, the individual performing the calibration, and the next calibration date as required by 21 CFR 820.72(b)(2). For example, there is no documented calibration history for the [redacted] which is used to test the conductivity of the process water.
The responses are inadequate because, although the process water conductivity will now be tested using the [redacted] have not been provided to show the [redacted] from which the conductivity is read have been calibrated. In addition, the firm has not addressed the production and process controls that are now in place to prevent inspection, measuring, and test equipment that can affect product quality from being used prior to being calibrated.
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.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action, which may include detaining your devices without physical examination upon entry into the United States until the corrections are completed. Section 801(a) of the Act (21 U.S.C. § 381(a)). 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. If the documentation is not in English, please provide a translation to facilitate our review.
Your response should be sent to: James Woods, Deputy Director of Patient Safety and Product Quality, Office of In Vitro Diagnostic Device Evaluation and Safety, 2098 Gaither Road, HFZ-440, Rockville, Maryland 20850, If you have any questions about the content of this letter please contact: Tamara Felton at 240-276-0716.
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 I. Gutman, M.D., M.B.A.
Office of In Vitro Diagnostic Device
Evaluation and Safety
Center for Devices and