Inspections, Compliance, Enforcement, and Criminal Investigations
Inditherm Medical 6/10/2009
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
|Center for Devices and Radiological Health
9200 Corporate Blvd
Rockville, MD 20850
JUN 10, 2009
VIA FEDERAL EXPRESS
Mr. Nick Bettles
Roundhill Park, Bolton Road
Rotherham, S63 7LG
Dear Mr. Bettles:
During an inspection of your firm located in Rotherham, United Kingdom, on (b)(4), an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures (b)(4). 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 Andy Curtis dated January 5, 2009, concerning our investigator's observations noted on the Form FDA 483, List of Inspectional Observations, that was issued to you. 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 adequately establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 C.F.R. § 820.30(i) (Design Changes). For example:
a. A design change is documented in Design Change Record (b)(4) for approximately (b)(4) controller modules for (b)(4) in the United States. This design change record lacks the required date and signature for approval, pursuant to your firm's (b)(4).
b. A design change to the (b)(4) and software changes to the (b)(4) are documented in Design Change Record (b)(4). This design change record indicates that both changes were implemented on January 11, 2006. However, Design Change Record (b)(4) was not approved, signed, and dated until May 26, 2006.
c. A design change was made to the original (b)(4) for the (b)(4), and there was no record of approval for this design change before the implementation of new versions (b)(4).
d. A design change to the (b)(4) to prevent elevated temperatures from contacting the patient in the event of a rail break is indicated in the drawing (b)(4).There is no record of approval of this design change before its implementation.
We have reviewed your response and have concluded it is inadequate because you have not provided any preventive action to ensure that design changes will be identified, documented, validated or where appropriate verified, reviewed, and approved before they are implemented.
2. Failure to adequately 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 C.F.R. § 820.22 (Quality Audit). For example, you did not follow your firm's (b)(4), which requires than an audit be conducted every twelve months and that the results be reviewed at the Management Review meeting. The required audits for 2007 and 2008 were not documented.
We have reviewed your response and have concluded it is inadequate because you did not complete the internal audit, as promised, by 2009. You provided a 2009 audit schedule as support for your response. Please provide evidence of completion of your yearly internal audits program.
3. Failure to adequately establish and maintain procedures to ensure that Device History Records (DHR) for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the Device Master Record (DMR), as required by 21 C.F.R. § 820.184 (Device History Record). For example:
a. Approximately (b)(4) controller modules for (b)(4), which required field modifications, have manufacturing records (DHRs) that are missing documentation of the field correction, as required by your firm's (b)(4).
b. Manufacturing Record (b)(4) is missing its final QC test graph as required by your firm's (b)(4).
We have reviewed your response and have concluded it is inadequate because you provide a correction to the DHRs, but you do not propose a preventive action. Please submit a revised procedure with regard to DHRs that ensures that the device is manufactured in accordance with the DMR, and provide evidence that the relevant staff have been trained to the revised procedure.
4. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 C.F.R. § 820.100 (Corrective and Preventive Action). For example, your firm's (b)(4) states that (b)(4) are required for nonconformances, complaints, and preventive and (b)(4) suggestions. Not all (b)(4) were reviewed and signed off, as required. This deviation was not noted on the Inspectional Observations, Form FDA 483 (FDA 483), that was issued to you following FDA's inspection.
5. Failure to adequately establish and maintain procedures to control all required documents, as required by 21 C.F.R. § 820.40 (Document Controls). For example:
a. The following drawings: (b)(4) and (b)(4) lack an approval signature, as required by your firm's (b)(4).
b. Design Change Record (b)(4) lacks an approval signature or date, as required by your firm's (b)(4).
c. Drawing (b)(4) is labeled incorrectly. It should be labeled as being (b)(4).
We have reviewed your response and have concluded it is inadequate because you have not provided a response which ensures that design changes will be identified, documented, validated or where appropriate verified, reviewed, and approved before they are implemented.
Our inspection also revealed that your (b)(4) and (b)(4) 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 C.F.R. Part 803 - Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:
6. Failure to develop, maintain, and implement written MDR procedures, as required by 21 C.F.R. § 803.17. Your firm's MDR (b)(4), does not meet all the requirements of21 C.F.R. § 803.17. For example:
a. There are no internal systems described that provide for:
1. Timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements;
11. A standardized review process or procedure for determining when an event meets the criteria for MDR reportability; and,
111. The timely transmission of complete medical device reports on FDA Form 3500A.
b. No description is included for documentation and recordkeeping requirements for:
1. Information that was evaluated to determine if an event is reportable;
11. All medical device reports and information submitted to FDA; and,
111. Systems that ensure access to information that facilitates timely follow up and inspection by FDA.
We have reviewed your response and have concluded that it is inadequate because you have not provided a revised procedure which meets all of the MDR requirements.
7. Failure to meet other requirements under 21 C.F.R. Part 803 (Medical Device Reporting).
a. Your firm lacks procedures for investigation and evaluation of each potential reportable event, as required by 21 C.F.R. § 803.50(b)(3);
b. Your firm lacks instructions for establishing and maintaining MDR event files or records, as required by 21 C.F.R. § 803.18; and
c. Your firm lacks instructions for obtaining and documenting information missing from reports from user facilities or other initial reporters, as required by 21 C.F.R. § 803.50(b)(2).
These deviations were not noted on the PDA 483 that was issued to you following FDA's inspection.
8. Failure to report to FDA no later than 30 calendar days after the day that a manufacturer receive or otherwise become aware of information, from any source, that reasonably (b)(4) suggests that a device that they market may have caused or contributed to a reportable death or serious injury, as required by 21 C.F.R. § 80J.50(a)(1). For example, your firm failed to file a serious injury MDR (b)(4).The injuries included to the patient that required medical intervention. This observation was not part of the FDA 483 that was issued following FDA's inspection.
Our inspection also revealed that your (b)(4) and (b)(4) 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 C.F.R. Part 806 - Reports of Corrections and Removals regulation. Significant deviations include, but are not limited to, the following:
9. Failure to provide justification for not reporting a correction or removal action to FDA, as required by 21 C.F.R. § 806.20 (b)(4). For example, (b)(4) notes a field correction to the (b)(4) that was not reported to FDA. A justification for not reporting the correction or removal action to FDA was not documented in your (b)(4), which shall contain conclusions and any follow-ups, and be reviewed and evaluated by a designated person.
We have reviewed your response and have concluded that it is inadequate because it is unclear, according to your procedure, when to report a correction and removal and to require a written justification should the event not be reportable. The revised procedure, includes a reference to the FDA website. However, it is unclear who is designated to access the internet to check FDA requirements such that Corrections and Removals are identified and carried out adequately.
During our inspection, you indicated to our investigator that your firm plans to introduce the (b)(4) to oncologists for the use of (b)(4) for better exposure of patient veins during the injection of chemotherapy drugs. When intended for this use, FDA believes that your device, classified as a (b)(4), 21 C.F.R. § 890.5740, exceeds the limitations of exemptions from section 510(k) of the Act, 21 C.F.R. § 890.9(a), in that it introduces a new indication for use for a (b)(4). Accordingly, you must submit a 5l0(k) premarket notification to FDA at least 90 days before you propose to begin the introduction or delivery for introduction of this device into interstate commerce. 21 C.F.R. § 807.81 (a)(3)(ii).
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 80l(a) of the Act, 21 U.S.CO § 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 fifteen (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: Anastacia Bilek, PhD; Chief, Orthopedic and Physical Medicine Devices Branch; Division of Enforcement B; Office of Compliance; Center for Devices and Radiological Health; U.S. Food and Drug Administration; 9200 Corporate Boulevard; Rockville, Maryland 20850. If you have any questions about the content of this letter please contact: Amy Skrzypchak at (301) 796-5613.
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 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.
Timothy A. Ulatowski
Office of Compliance
Center for Devices and Radiological Health