Inspections, Compliance, Enforcement, and Criminal Investigations
Haemonetics Corporation 04-Dec-08
Department of Health and Human Services
Public Health Service
December 4, 2008
RETURN RECEIPT REQUESTED
President and CFO
400 Wood Road
Braintree MA. 02184
Dear Mr. Nutter:
During an inspection of your firm located in Niles, Illinois on June 26, 27, 30 and July 1, 3, 2008, investigator(s) from the United States Food and Drug Administration (FDA) determined that your firm manufactures thromboelastograph devices and accessories. 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, 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 (CFR), Part 20. We received a response from Mr. Norman Brunner, Site Director, dated July 22, 2008, concerning our investigator's observations noted on the Form FDA483, 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 establish and maintain procedures for implementing corrective and preventive action, including verifying or validating the corrective and preventive action (CAPA) 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:
a. Supplier Corrective Action (SCA), SC# 0027, was opened on 12/05/07 due to the rejection of four lots of the Level II QC control (R0831207-5, R100907-2, R110607-1, R112007-3) received from (b)(4) and customer complaints of out-of-range results when using approved lots RX02307-3 and R101607-1. SC# 0027 documents the root cause as being due to the "variability associated with characteristics of this abnormal control." The corrective action was to tighten the acceptable internal ranges. The corrective action was determined to be adequate and implemented on 01/14/08 and the CAPA was closed on 01/15/08. The box labeled "evidence exists that demonstrates the effectiveness of the supplier corrective action" was not checked and no documentation of the verification or validation of the CAPA was provided. After the CAPA was closed, Product Review Requests 741, 742, 749, 754, 774, and 781 were initiated due to nonconformances of the level II control. The PRRs indicate that the root cause and corrective action is documented in SC#0027.
We have reviewed your response and have concluded that it is inadequate because you have not provided evidence of implementation of your correction and your corrective actions do comply with the requirements in 21 CFR 820.100(a)(4). You state that a new SCA has been opened (SC# 0032) to address the continuing Level II QC control problems but that the verification or validation work has not been completed. You did not provide a validation protocol or validation schedule. Under 21 CFR 820,100(a)(4), you shall, as part of CAPAs, verify or validate the CAPA to ensure that it is effective and does not adversely affect the finished device.
Your response further indicates that the SCA procedure (SP1026) will be revised to require "verification data from suppliers for process changes potentially affecting process quality." This is inadequate because 21 CFR 820.75(c) requires manufactures to review and evaluate validated processes when any change or process deviation occurs and perform revalidation where appropriate.
b. Supplier Corrective Action., SC# 0028, was opened on 1/08/08 due high scrap rates because of loose caps and customer complaints of low water levels in vials manufactured by (b)(4) SC#0028 documents the root cause as being due to the "caps not properly secured to vials." The corrective action was to inform all personnel involved in the capping process and instruct them to "fasten caps until each cap meets full resistance with the tubes." The CAPA remains open. The corrective action was implemented on 02/08/08 and approved on 02/11/08 but no evidence of verification or validation of the CAPA was provided.
We have reviewed your response and have concluded that it is inadequate because you have not provided evidence of implementation of your correction and your corrective actions do not fully comply with the requirements in 21 CFR 820.100(a)(4). You state that SC# 0028 was to remain open until July 31, 2008, in order to gather data on the loose caps for review and determination of the effectiveness of the corrective action. You have not demonstrated how you will verify or validate the corrective action to ensure that it is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). This required verification and/or validation ensures that the root cause determination and corrective action are appropriate. Additionally, any specification for the appropriate cap torque should be documented in the device master record and included in the work instructions for the capping process. 21 CFR 820.181(a)&(b).
2. Failure to establish and maintain procedures for implementing corrective and preventive action, including identifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 CFR 820.100(a)(3). For example, a CAPA, CA38I, was opened on 6/05/08 for nonconformance, "Level II normal ranges were not fully updated when the new lot was implemented." CA381 indicates that corrective actions will be implemented to update certain internal procedures. CA381 does not indicate that manufacturing procedure MP 04-013, which utilizes Level I and II controls for verification testing of the "TEG instrument, will be revised to ensure that personnel performing the testing verify that test criteria are current and appropriate.
We have reviewed your response and are unable to determine its adequacy at this time because you have not provided sufficient detail or evidence of implementation. Your correction apparently includes revising MP04-013 and "other associated documents." You should submit these documents for review, as well as evidence of their implementation. Please also identify any and all additional corrective and preventive actions you have taken.
3. Failure to establish and maintain procedures for identifying valid statistical techniques required for establishing, controlling, and verifying the acceptability of process capability and product characteristics, as required by 21 CFR 820.250(a). For example, Form RDOb2, "Normal Ranges for New Lot of Level II control," dated February 25, 2008, indicates that a new lot of Level II control was received and tested to determine the new Level II control ranges for test parameters R, K, Angle, and Ma. The ranges are included in the product package insert and used by the user to verify the TEG analyzer is working properly. The new ranges were based on 32 sampled vials tested in duplicate (64 total data points) from five batches. No documentation was provided that included statistical justification of the Level II control ranges.
We have reviewed your response and are unable to determine its adequacy at this time because you have not provided sufficient detail or evidence of implementation. Please provide a copy of the procedure you indicated in your response would be developed and in use by October 1, 2008. Your procedure should specifically identify methods, based on valid statistical techniques, for determining normal ranges for level I and level II controls, taking into account clinical risk.
4. Failure to establish and maintain the requirements, including quality requirements, that must be met by suppliers, contractors, and consultants, as required by 21 CFR 820.50(a).
a. Document SP1016, rev 6, "Supplier Selection, Evaluation, and Qualification," dated 04/29/08, section 5.3.4, page 4 states, "Written agreements are for Level I suppliers unless justification is provided on QR1008 for not requiring a written agreement" The section also indicates that a purchase order cannot replace a written agreement because "ALL contract manufactures and contract test labs MUST have a written agreement completed." Documents FR1008 and QR1008, "Request for New Supplier/Supplier Qualification," dated 12/12/05, 05/19/06, 05/16/07, and 05/26/08, document that (b)(4) is a Level I supplier, that a written agreement is required, and that the firm was "Qualified with CONDITIONS" because no written agreement was in place. No justification is given for not requiring a written agreement.
b. Document SP1003, rev 4, "Quality Audits," dated 04/26/07 states, "This procedure applies to quality audits performed at Haemoscope facilities with all Haemoscope design activities, manufacturing operations, and product lines. This procedure may also be used as a guide for audits that Haemoscope performs at Haemoscope suppliers." A letter dated June 10, 2008 addressed to (b)(4) outlining the findings of Haemoscopes supplier audit of the firm on May 30th states, "CAPA Program -The corrective and preventive action process is well defined. All essential elements are covered under the current CAPA program." The letter did not address the ongoing nonconformance related to the Level I control related to SC# 0027 (Observation 1) and no documentation was provided to show that the nonconformance was addressed in the audit.
We have reviewed your response and are unable to determine its adequacy at this time because you have not provided sufficient detail or evidence of implementation. Please submit to us the written supplier agreement you have developed, or will be developing, with Nu-Millennium, as well as documentation and results of your review of all critical supplier files, which you indicated in your response would be complete by September 1, 2008.
5 . Failure to establish and maintain procedures for acceptance of incoming product. Incoming product shall be inspected, tested, or otherwise verified as conforming to specified requirements,as required by 21 CFR 820.80(a). For example, report (b)(4) dated 02/13/07 was used to assess the precision of a new master lot of Level II controls (1125-0702). There are no documented acceptance criteria for precision testing. There are no criteria for magnitude of the parameter response. There is no procedure in place for determining what levels are acceptable and what testing is done to ensure that the new batch falls within the acceptable range.
We have reviewed your response and are unable to determine its adequacy at this time because you have not provided sufficient detail or evidence of implementation. Please submit for our review the procedure you indicated in your response would be developed and in use by October 1, 2008. Moreover, it does not appear that this procedure fully addresses the requirement in 21 CFR 820.80(b) that you define acceptance/rejection criteria for inspection, testing, or verification of incoming product.
You should take prompt action to correct the violation(s) addressed in this letter. Failure to promptly correct these violation(s) may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, 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.
We are requesting that you submit to this office on the schedule below, certification by an outside expert consultant that he/she has conducted an audit of your establishment's manufacturing and quality assurance systems relative to the requirements of the device QS regulation (21 CFR, Part 820). You should also submit a copy of the consultant's report, and certification by your establishment's Chief Executive Officer (if other than yourself) that he or she has reviewed the consultant's report and that your establishment has initiated or completed all corrections called for in the report. The initial certifications of audit and corrections and subsequent certifications of updated audits and corrections should be submitted to this office by the following dates:
- Initial certifications by consultant and establishment -received in this office before or by June 1, 2009.
- Subsequent certifications -received in this office before or by June 1, 2010.
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 violation(s), or similar violation(s), from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur overtime, 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 send your reply to the Food and Drug Administration: Matthew J. Sienko Compliance Officer at the above address. If you have any questions about the content of this letter, please contact Mr. Sienko: at (312) 596-4213 or Fax (312) 596-4195.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violation(s) at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violation(s) noted in this letter and in the Inspectional Observations, Form FDA483 (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 violation(s), and take prompt actions to correct the violation(s) and to bring your products into compliance.
Scott J. MacIntire