Inspections, Compliance, Enforcement, and Criminal Investigations
Z-Medica, LLC 12/3/09
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
|New England District
One Montvale Avenue
Stoneham, Massachusetts 02180
VIA FEDERAL EXPRESS
December 3, 2009
Mr. Brian Herrman
Chief Executive Officer
4 Fairfield Blvd
Wallingford, CT 06492
Dear Mr. Herrman:
During an inspection of your firm located in Wallingford, Connecticut on October 26-28, 2009 and November 3, 2009, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures medical devices such as haemostatic agents including QuikClot Combat GauzeTM. 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. These violations include, but are not limited to, the following:
1. Failure to fully validate and approve according to established procedures as required by 21 CFR 820.75 (a).
Specifically, the sterilization validation procedure identifies the sterility validation for the product was done according to ISO 11137-2:2006 Part 2. ISO 11137-2:2006 Part 2 requires that (b)(4) separate lots of product to be used in the validation of the product manufactured on a frequency of more than one lot per quarter. Your firm's procedure labeled as "Initial Sterilization Validation" identifies one lot of product consisting of (b)(4) units is to be used in the validation of the product. In addition, the protocol does not require and your firm does not place dosimeters or biological indicators in routine production runs sent to (b)(4) for gamma sterilization.
We acknowledge your written response dated November 20, 2009 which provided your proposed corrective actions for this deficiency. Your response appears inadequate. Your response to this deviation states in part "To meet the requirement the revised Sterilization Validation procedure we will re-validate the sterilization of Combat Gauze using three lots. This will be completed by December 31, 2009."Please provide us with a copy of the sterilization re-validated data for our review.
2. Failure to establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met as required by 21 CFR 820.75 (b).
For example, your firm's procedure for process validation of your sealing machine (b)(4) lacks documentation of monitoring of periodic burst testing of in process or finished product during periodic manufacturing. Your firm used a burst strength finished specification of (b)(4) as a baseline test marker for the finished product specification, while the validation protocol testing met the validation requirements there is no formal program to monitor (e.g. annually, weekly, daily) daily production to assure the (b)(4) sealer meets the finished product specification for the seal integrity. In 2008, your firm changed the testing for seal integrity from burst testing to a peel test performed for you by (b)(4) a contract vendor. Your management stated the recommendation for changing from the burst test to the peel test was based on a recommendation from the contract vendor, however, there is no formal approved protocol changing the test procedure from the burst test to the peel test documenting the validation of the sealer for the Combat Gauze and identifying the frequency of testing to assure the sealer maintains the finished product peel test parameter.
We received your firm's written response dated November 20, 2009 in which you provided your proposed corrective action to this deviation. Your response appears to be inadequate. Your response to this deviation states in part "We have drafted procedure (b)(4) to formally require a sampling plan for package integrity testing, and to require the results to be part of DHR. All effected employees will be trained on the procedure and the procedure will be fully implemented on or before Dec. 4, 2009." Please provide us for our review a copy of the approved procedure (b)(4) and evidence that all employees have been trained on this procedure.
3. Failure to review, evaluate, and investigate a complaint involving the possible failure of a device, labeling or packaging to meet any of its specification as required per 21 CFR 820.198 (c).
Specifically, three complaints received by your firm concerning the vacuum packaging of the finished product were investigated by placing the returned products in (b)(4) with unknown time/temperature and observing them for package shrink around the product. Your conclusion on all three investigations was that the packaging did shrink and the final conclusion was that the vacuum packaging was adequate.The (b)(4) test is not a formally approved test procedure for any of your products and is not validated or documented as equivalent to your finished product test procedure for finished product packaging. In addition review of complaint (b)(4) noted 15 samples were returned to Z-Medica for what was termed a "'loose" condition of packaging (indicating loss of vacuum). The investigation consisted of a visual inspection of the packages by the investigating individual who indicated the term" loose" was subjective and the seals were not tested by either the burst or peel methodology used by your firm to assure packaging meets the finished product specification validated in the process validation procedure.
We acknowledge your written response dated November 20, 2009 which provided your proposed corrective actions for this deficiency. Your response for this deviation appears to be inadequate. Your response in part states "By November 27, 2009, we will revise the complaint handling procedure, train our personnel, and implement the revised procedure. In addition, for the complaints on packaging cited by investigator, we will perform peel and leak tests on the packaging to provide objective supporting data toward complaint resolution. " Please provide us for our review a copy of the revised approved complaint handling procedure, and evidence that your employees have been trained on this revised document.
4. Failure to conduct management reviews at defined intervals as required by 21 CFR 820.20 (c).
For example, your Product Development Review Meetings that are routinely conducted by the company do not fully satisfy your Management Review Policy identified as (b)(4). When your management was asked if the firm had conducted a documented formal Management Review at any time in the past, management responded that they had not.
Your written response dated November 20, 2009 provided your proposed corrective action for this deficiency. Your response appears adequate. We will assess the full adequacy of this corrective action during our next inspection of your firm.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations 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.
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.
Your response should be sent to: Maren Forsyth,Food & Drug Administration, One Montvale Avenue, Fourth Floor, Stoneham, Massachusetts 02180. If you have any questions about the content of this letter please contact Ms. Forsyth at (781) 596-7769.
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.
John R. Marzilli
New England District