Inspections, Compliance, Enforcement, and Criminal Investigations
lnnovision A/S 6/4/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|10903 New Hampshire Avenue|
Silver Spring, MD 20993
JUN 4, 2012
VIA UNITED PARCEL SERVICE
Chief Executive Officer
DK-5260 Odense S
Dear Mr. Nielson:
During an inspection of your firm located in Odense, Denmark, on February 13, 2012, through February 16, 2012, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the lnnocor Ergospirometry System, the Cardiopulmonary Exercise Testing Option, and the LCI Option for lnnocor. 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, their 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.
We received responses from Peter Clemensen dated March 9, 2012, and April 30, 2012, concerning our investigator's observations noted on the Form FDA 483 (FDA 483), List of lnspectional Observations, that was issued to your firm. We address these responses below, in relation to each of the noted violations.
Your firm's response to the FDA 483 dated May 15, 2012, was not reviewed because it was not received within fifteen business days of issuance of the FDA 483. The response may be evaluated along with any other written material provided in response to the violations cited in this Warning Letter. These violations include, but are not limited to, the following:
1. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a).
For example· no procedures to control the design of the lnnocor lnnocor Ergospirornetry System (lnnocor) (K051907), cleared March 2, 2006) were developed or used. The original lnnocor was designed for the European Space Agency and it was not designed using the design control requirements of the Quality System Regulation. Also, your firm's management representative stated that your firm does not have design control procedures.
We reviewed your firm's responses and co include that they are not adequate. Your firm's response is to establish and maintain procedures for design control and train relevant personnel. The corrections are to be verified by your firm during the Q2 internal audit. There is no mention of your firm conducting design control activities for the medical devices produced.
2. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a).
For example: during the inspection, your firm's management representative stated that your firm does not have any procedure for implementing a corrective or preventive action (CAPA). Specifically, your firm has no CAPA procedure that includes requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, returns product, and other sources of quality data to identify existing and potential causes of nonconforming product or other quality problems.
We reviewed our firm's responses and conclude that they are not adequate. (b)(4). Employees are to be trained on the revision and confirmation is proposed to be conducted during your firm's 03 internal audit. However, your firm did not provide any indication that it plans to review past quality data to determine if any CAPAs should be initiated. Additionally, your firm did not provide a copy of the proposed CAPA procedures.
3. Failure to adequately review and evaluate all complaints to determine whether an investigation is necessary. When no investigation is made, the manufacturer shall maintain a record that includes the reason no investigation was made, as required by 21 CFR 820.198(b).
For example: complaint record "Non-Conformance #20283" was closed without an investigation. However, the record did not contain information to indicate the reason that no investigation was made. It was only listed as "closed" and included the reference "Covered by 10615." Customer complaint 10615, opened February 28. 2011. is listed as "pending" and does not contain a record of the investigation or a justification for not investigating.
We reviewed your firm's responses and conclude that they are not adequate. Your firm's responses did not address this issue.
4. Failure to adequately maintain complaint files, as required by 21 CFR 820.198(a).
For example: complaint files 20264, 20275, and 20272 are closed. However, these files do not contain an approver's signature or a closed date in the approver and closed-date fields.
We reviewed your firm's responses and conclude that they are not adequate. Your firm explained that complaints 20264, 20275. and 20272 should have been "PENDING" and that closure of the complaints was not approved. Complaints 20264 20275, and 20272 have been subsequently completed with information updated and approval of the complaints received. However, your firm did not provide evidence to indicate that systemic corrective action was considered. Also, your firm provided no evidence to indicate that it reviewed historical complaints to ensure that the complaint files were closed correctly. Lastly, your firm provided no information about how it will prevent such incorrect closings in the future.
5. Failure to establish and maintain adequate instructions and procedures for performing and verifying that the device servicing meets the specified requirements, as required by 21 CFR 820.200(a).
For Example: (b)(4)
The adequacy of your firm's responses cannot be determined at this time. Your firm reviewed the four service reports and updated them with links to the non-conformance reports, identified as complaints. The linked complaints contained investigations as needed (b)(4). Employees are to be trained on the revision and the corrections are to be verified by your firm during the Q2 internal audit. Your firm reviewed all service reports from the last 4 years to determine if any additional complaints need to be raised. Fifty-three additional complaints were found. The adequacy of your firm's responses cannot be determined at this time because evidence of implementation was not provided. The verification of corrections has not been performed yet, and it is unclear how the fifty-three new complaints are being addressed.
6. Failure to establish and maintain adequate procedures to control documentation, as required by 21 CFR 820.40. For example:
a. Procedure QM-001, lss./Rev.: C6. dated 2006-12-12. requires documents, including drawings, to be current, signed , and dated in section (b)(4), Drawing COR-DR-021 0-0000-MOO-IN Issue 1/A 290102 was part of the work instruction package being used by an assembly employee. However. Drawing COR-DR-0210-0000-MOO-IN was not signed and dated.
b. Work instruction COR-PI-SUB-00013. lss. /Rev.: A/4, dated 2009-10-01. contains handwritten changes that were not approved.
c. Procedure (b)(4) Q1-004, lss./Rev/C/1, dated 2005-10-31, requires that the Quality Officer destroy obsolete copies of documents. However, it was observed that an obsolete drawing, COR-DR-0210-0000-MOO-IN, Issue 1/A 290102, was still included in the work instruction package being used by an assembly employee. At the time of the inspection, Drawing COR-DR-0210-0000-MOO-IN. Issue 2/8 250803, was the most current version.
We reviewed your firm's responses and conclude that they are not adequate. Your firm removed the obsolete drawing form the work instructions and planned to update the work instruction for (b)(4) to revision A/5 by April 30, 2012. The document controls section of the Quality Manual will be revised to specify drawing approval requirements. Training is to be performed and documented, and the corrections are to be verified by your firm during the Q2 internal audit. Instruction Q1-009 (Feedback/CAPA) has been updated to Issue/Rev. C/7 to specify requirements for approval, signing, and dating. However, no information was given on a systemic corrective action, i.e., no evidence was provided to indicate that your firm conducted a review of documents to ensure documentation practices were consistent with OS requirements. Also, similar processes were not reviewed to check for other unapproved or obsolete documentation.
7. Failure to adequately maintain device history records (DHRs). The DHR shall include, or refer to the location of the primary identification label and labeling used for each production unit, as required by 21 CFR 820.184.
For example, DHRs 1030269, 1039279, 1024264, and 1111295 do not contain or refer to the primary identification label used for each production unit.
The adequacy of your firm 's responses cannot be determined at this time. Your firm updated the DHRs for production lots 1030269, 1039279, 102464, and 1111295 with the primary identification label, and labels were provided with your response. (b)(4) The corrections are to be verified by your firm during the Q2 internal audit. The adequacy of the responses cannot be determined because it is unclear if employees will be trained on the new procedure and documentation has not been provided from the DHR review.
8. Failure to establish procedures for identifying training needs and ensuring that all personnel are trained to adequately perform their assigned responsibilities, as required by 21 CFR 820.25(b).
For example, your firm's management representative stated that there were no training procedures and no company training plan.
The adequacy of your firm's responses cannot be determined at this time. Your firm performed an overview of training on work instructions. Your firm plans to evaluate other quality system training as needed and update training records accordingly. Q1-020 was updated to include an ongoing formal program for training personnel and to assure that. where relevant, employees will be made aware of device defects that may occur as a result of improper performance of their specific jobs. The corrections are to be verified by your firm during the Q2 internal audit. The adequacy of the responses cannot be determined because your firm has not provided evidence verifying the effectiveness of the corrective action.
Our inspection also revealed that your firm's lnnocor Ergospirometry System, Cardiopulmonary Exercise Testing Option, and LCI Opt ion for lnnocor 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:
Failure to develop, implement, and maintain written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17. For example: your firm's MDR procedures titled, "lnstruktion Feedback I CAPA" Q1-009, lss./Rev.: C/5, Dato 2011-01-10, and "lnstruktion Advisory Not ices & Recall" Q1-041, lss./Rev.: C/3, Dato 2011-01-19, are written primarily in a foreign language. The limited English written information that pertains to 21 CFR Part 803 does not establish a process that meets the requirements of 21 CFR 803.17.
We reviewed your firm's responses and conclude that they are not adequate. Your firm 's revised document titled, (b)(4) Q1-041. lss./Rev.: C/4, Dato 2012-03-01, does not establish internal systems that provide for timely and effective identification, communication. and evaluation of events that may be subject to MDR requirements (b)(4).
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. 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 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 (including any systemic corrective actions) 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.
Your firm's response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Operations Branch, White Oak Building 66, Rm 2609, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case 295417 when replying. If you have any questions about the contents of this letter, please contact Daniel Walter at (301)796-5587 (phone) or (301) 847-8138 (fax)
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 lnspectional 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.
Steven D. Silverman
Office of Compliance
Center for Devices and
The Wood Burditt Group
C/O H. Carl Jenkins
10 E. Scranton Avenue, S201
Lake Bluff, Illinois 60044