Inspections, Compliance, Enforcement, and Criminal Investigations
Smiths Group Plc. 24-May-06
Department of Health and Human Services
Public Health Service
2098 Gaither Road
May 24, 2006
VIA FEDERAL EXPRESS
Mr. Keith Butler- Wheelhouse
Chief Executive Officer
Smiths Group Plc.
765 Finchley Road
London NW 11 8DS UK
Dear Mr. Butler-Wheelhouse:
During an inspection of your firm located in Watford, Hertshire, UK on December 1, 2005 through December 6, 2005, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures infusion pumps. These products are devices within the meaning of section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 321(h)).
This inspection revealed that these devices appear to be 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 (CFR), Part 820. Significant violations include, but are not limited to, the following:
1. Failure to adequately investigate the cause of nonconformities relating to product, processes, and the quality system, as required by 21 CFR 820.100(a)(2). For example, during an investigation of at least ten complaints for the MS 16A and MS26 syringe pumps, several of which involved over-delivery of medication, your firm determined that the pumps failed the cam switch or cam alignment tests. One investigation stated that "it is possible but not conclusive that over-delivery could have occurred because of the error in the cam switch alignment." The only corrective action taken was to realign the cam switches for these specific pumps; however, the underlying cause of the nonconformities was not investigated.
2. Failure to identify the actions needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 CFR 820.100(a)(3). For example, your firm received ten complaints for the MS 16A and MS26 syringe pumps claiming the pumps had over-delivered medication. Through testing of the pumps, your firm determined that the pumps failed the cam switch or cam alignment tests. The cam switches were realigned for those ten pumps in question. Your firm did not adequately identify if other pumps currently in distribution could potentially have mis-aligned cam switches and what actions should be taken to correct those pumps.
3. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, which include requirements for verifying or validating the corrective action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). For example, your firm's corrective and preventive action procedure, SOP [redacted], does not include requirements to verify or validate corrective or preventive actions to ensure the action does not adversely affect the finished device prior to implementation.
In addition, the investigator noted during a review of Customer Issue Forms (CIF) that at least six were not signed off as having been reviewed. We are concerned that these CIFs may not have been properly analyzed as part of your CAPA system. Please include a detailed explanation in your response to this letter.
Additionally, the above stated inspection revealed that your 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 any material or information required by or under section 519 of the Act, 21 U.S.C. 360i, respecting the device and 21 CFR Part 803 - Medical Device Reporting (MDR) regulation. Significant violations include, but are not limited to, the following:
1. Failure to submit an MDR within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1). For example, your firm failed to submit the following MDR reports involving death and serious injury to the FDA within the 30 day timeframe: 9612511-2004-00001, 9612511-2004-00003, 9612511-2004-00015, and 9612511-2005-0004. Also, MDR report number 9612511-2005-0004 was incorrectly identified as a malfunction when it actually represents a serious injury.
2. Failure to submit an MDR within 30 days of receiving or otherwise becoming aware of information that reasonably suggests that a marketed device has malfunctioned and such device or similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur, as required by 21 CFR 803.50(a)(2). For example, your firm failed to submit the following MDR reports involving malfunctions to the FDA within the 30 day timeframe: 9612511-2004-00004 and 9612511-2005-00002.
This letter is not intended to be an all-inclusive list of 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.
Given the serious nature of these violations of the Act, infusion pumps manufactured by your firm imported or offered for import 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 "detained 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. In addition, 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 government contracts.
We received a response from, [redacted], Director, RA/QA, Smiths Medical International Ltd. dated December 19, 2005, concerning our investigator's observations noted on the FDA 483. We have reviewed the response and have concluded that it is inadequate because the corrective actions are not complete. When the actions stated in Mr. Demarest's response are completed, please forward adequate documentation for our review.
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 all documentation of the corrective action you have taken. If you plan to make any corrections in the future, include those plans with your response to this letter as well. If the documentation is not in English, please provide a translation to facilitate our review.
Your response should be sent to the Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Division of Enforcement A, General Hospital Devices Branch, 2094 Gaither Road, Rockville, Maryland 20850 USA, to the attention of Carolyn Niebauer, Chief, General Hospital Devices Branch.
If you need help in understanding the contents of this letter, please contact Carolyn Niebauer at the above address or at (240) 276-0115 or FAX (240) 276-0114.
Timothy A. Ulatowski
Office of Compliance
Center for Devices and Radiological Health