Inspections, Compliance, Enforcement, and Criminal Investigations
Tri-State Hospital Supply Corporation 02-Jun-06
Department of Health and Human Services
Public Health Service
RETURN RECEIPT REQUESTED
June 2, 2006
Thomas A. Archipley, Il .
Co-Chief Executive Officer
Tri-State Hospital Supply Corporation
301 Catrell Drive
Howell, MI 48843
Dear Mr. Archipley:
During a Food and Drug Administration (FDA) inspection of your establishment located in Howell, Michigan, on January 18 - February 3, 2006, our Investigators determined that your firm manufactures circumcision clamps and reprocesses circumcision clamps and "floor grade" surgical instruments, such as hemobstats, forceps, scissors, and needle holders.[Redacted] circumcision clamps and floor grade surgical instruments are devices as defined by section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h).
The above-stated inspection revealed that your devices are adulterated under 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 conformance with the Current Good Manufacturing Practice (CGMP) requirements for medical devices which are set forth in the Quality System Regulations, as specified in Title 21, Code of Federal Regulations (CFR), Part 820. At the close of the inspection, you were issued a form FDA 483 which identified a number of significant deviations including; but not limited to, the following:
1. Failure to adequately validate a process whose results cannot be fully verified by subsequent inspection and test, and failure to document the validation activities and results, as required by 21 CFR 820.75(a). For example:
a) You lack documentation showing that your firm has adequately validated the processes involved in reprocessing the [redacted] circumcision clamp, a Class II medical device. Specifically, there is no documentation of cleaning validation, [redacted] process validation, or sterilization validation for this device.
b) You reprocess disposable, single use devices described as "floor grade" instruments (versus operating room grade), including hemostats, forceps, scissors and needle holders. There is no documentation of a cleaning validation to demoristrate that all possible, cleaning/sanitization compound residues, foreign materials, and organic substances have been adequately removed.
c) Your validation protocol entitled, "Validation Protocol for the Processes Involved in the Refurbishing of [redacted] Disposable Floor Grade Instruments", date stamped May 20, 1996, does not fully document all process parameters and acceptance criteria. For example,
i. Step 4 of the protocol states that the containers (containing the instruments) are to be subjected to an industrial EtO sterilization process before further handling, but does not specify the EtO sterilization parameters.
ii. Step 5 of the protocol states that instruments are to be pre-soaked in [redacted] but does not specify how much of the detergent compound is required or how many instruments can be soaked at one time. This step also states that after the instruments pre-soak, they are to be cleaned in a [redacted]. There are no documented parameters that define the maximum number of instruments that can be cleaned at this step. In addition, the acceptance criteria for "clean" are not defined.
Your firm responded to the inspectional observations documented in form FDA 483 by letter dated February 15, 2006, which was signed by Mr. Matt Price, Director of Quality Assurance and Regulatory Affairs. With regard to the deviations described above, which are noted in Observation 1 of the FDA 483, Mr. Price's response indicates that your firm is in the process of updating its validation activities to correct these deviations. However, this response is inadequate because it fails to outline the specific steps your firm will take to correct these violations and prevent their reoccurrence. Please submit a copy of your, validation protocol for the [redacted] circumcision clamp and your revised validation protocol for the reprocessed floor grade instruments. In addition, if available, please submit any new validation data based on these protocols. Additionally, FDA will verify the adequacy of the corrective actions taken by your firm during the next inspection.
2. Failure to review and evaluate the process and perform revalidation where appropriate when changes or process deviations occur, and failure .to document such activities, as required by 21 CFR 820.75(c). Your firm did not have documentation of the revalidation of a process conducted in response to changes or process deviations.
a) Specifically, Step 5 of the validation protocol entitled, "Validation Protocol for the Processes Involved in the Refurbishing of [redacted] Disposable Floor Grade Instruments", date stamped May 20, 1996, states that instruments are to be "cleaned" in a [redacted] using the detergent [redacted] and [redacted]. Your Director of Quality Assurance and Regulatory Affairs wrote a memorandum to file, dated October 08, 2004, which documents that your firm no longer uses [redacted] during this step, but instead uses [redacted] an [redacted] and is designed with [redacted] to improve surface as well as provide a deep shine. [Redacted] is an [redacted] with an operating [redacted] and has burnishing and bleaching properties. There was no documented evidence that your firm validated this change.
Additionally, procedure QSR-38, "Instrument Refurbishing Procedure", provides work instructions for the instrument reprocessing-process. A review of this procedure's revision history revealed that revision number eight (8), dated July 09, 2001, documents the change [redacted] in the [redacted] step.
In his February 15 response to these deviations (FDA 483 Observation 2), Mr. Price states that changes to the instrument reprocessing program since the initial validation were being reviewed and assessed for revalidation requirements. This response is inadequate because there are no specific steps outlined to correct the violation and prevent its reoccurrence. Please submit documentation showing your analysis of which changes to the instrument reprocessing program will require revalidation, including the change in cleaning compound. In addition, you should submit a schedule outlining the dates on which you plan to perform revalidation for those changes for which revalidation is determined to be necessary. Additionally, FDA will verify the adequacy of the corrective actions taken by your firm during the next inspection.
3. Failure to establish and maintain process control procedures that describe all process controls necessary to ensure conformance to specifications, as required by 21 CFR 820.70(a). For example:
a) Procedure QSR 38, "Instrument Refurbishing Procedure" (revision 13), provides work instructions for the steps included in the instrument reprocessing process.
i. Step IV of this procedure states that instruments are to pre-soak in [redacted] but does not specify the length of time required for the pre-soak, nor does it specify the maximum number of instruments that can be soaked at a single time.
ii. Step V of this procedure states that the instruments are to be rotary finished, but does not specify the length of time the instruments are to undergo this process. Step V also states that the instruments are to be transferred to a second chamber for drying, but does not specify the required drying time and the number of instruments that can be dried in a single load.
b) Procedure-QSR-56, entitled [redacted] (revision 7), provides instruments for operating the vibratory finishing machine for reprocessing instruments.
i. Step B of this procedure states, "rinse the media with water". However, Step B does not specify the type of water required nor the amount required to adequately rinse the media [redacted].
ii. Step G of this procedure states "place the instruments to be processed into the inner chamber of the machine. Process the instruments until the machine operator determines they are ready for the drying chamber." Step G does not provide parameters to include the number of instruments that can be processed [redacted] at one time and does not specify the processing time requirements for this step.
iii. Step H of this procedure states that when the instruments are sufficiently cleaned, they are to be transferred to the drying chamber until dry. Step H does not provide parameters for determining when the instruments are "sufficiently clean" or the length of time required for this drying step.
Mr. Price's response to these deviations (FDA 483 Observation 3) is that all,process control procedures at your firm are being evaluated, to determine whether greater definition of process parameters is needed. Mr. Price also states that process control procedures will likely be revised by March 1, 2006 to reflect any necessary changes.
This response is inadequate because you failed to outline the specific steps you will take to correct the violations and prevent their recurrence. Please submit copies of your revised process control procedures, including the process control procedures discussed in FDA 483 Observation 3. We request that you highlight the changes you make to these procedures so that FDA can readily identify the revised text. FDA will review the revised process control procedures you submit to determine their adequacy.
4. Failure to monitor and control process parameters during production as required by CFR 820.70(a) (2). For example, your firm does not perform routine [redacted] specifically focused on reprocessed devices (floor grade instruments and circumcision clamps).
Mr. Price's response to this deviation (FDA 483 Observation 4) indicated that [redacted] performed on a routine basis for all instruments as part of the firm's annual finished kit package requalification procedure, QSR-122, 'Bioburden Parameters and Sample Collection Procedure." While reprocessed devices may be covered by the procedure, the procedure does not specifically state that reprocessed instruments are included in this analysis as a "family" of their own. Mr. Price indicated that this procedure is being revised to include a specific callout for reprocessed instruments. Also he indicated that in addition to this annual testing [redacted] of reprocessed instruments pending use in kits is conducted on a random basis. This response is inadequate because a copy of the revised procedure (QSR-122) which formalizes this as a routine practice was not submitted for our review.
5 . Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198 (a) For example,
a) Procedure QSR-127, "Product Complaint Procedure" (revision 6), states that complaints are entered into the Electronic Complaint Log (Excel database). The Log's data fields include documentation of kit, lot and component (device) numbers. Reprocessed devices are identified by the component number followed by the letter "K". A review of approximately [redacted] complaints received between January 2003 and January 2006 revealed that the firm does not always document the correct component number when a complaint involves a reprocessed device. For example, the following complaints document/identify (in the Complaint Log data fields) that the complaint involves a "new" device, but a review of the complaint investigation revealed that the complaint actually involved a reprocessed device:
Complaint Log (data field)
Complaint Investigation Component #(s) Documented
Complaint #3006 describes a complaint regarding instances where the circumcision clamp fell apart during use and caused excessive bleeding during the procedure. The component documented in the data field is [redacted]. A review of the complaint investigation revealed that the circumcision clamps involved in the complaint were reprocessed.
Your firm's response to these deviations (FDA 485 Observation 5) indicates that your firm's Product Complaint Procedure (QSR-127) will be revised. This response is inadequate because a copy of the revised procedure was not submitted for our review. Please submit a copy of your revised "Product Complaint Procedure" (QSR-127) .
6. Failure to establish and maintain procedures for management review as required by 21 CFR 820.20(c).
a) For example, policy QM-18, "Management Responsibility and Commitment - Management Representative" (revision 7, printed January 17, 2006), describes your firm's management review process. This quality policy states that a report of performance with the quality system shall be presented (annually) at a meeting attended by at least one owner of your firm, production facility managers, and quality managers. A review of your firm's attendance records for the annual Quality System Meeting revealed that the Production Facility Managers for [redacted] were not present at the 2003 meeting held on August 07, 2003 and the 2004 meeting held on October 12, 2004.
In response to these deviations (FDA 483 Observation 6), Mr. Price states that the Management Responsibility and Commitment policy (QM-02) would be revised to address alternative methods of participation when physical attendance of required attendees is not feasible. This response is inadequate because no revised procedure was submitted to the FDA for review.
7. Failure to establish and maintain procedures for implementing corrective and preventive action which include requirements for investigating the cause of nonconformities relating to product, processes, and the quality system, as required by 21'CFR820.100(a)(2). For example, the following complaint investigations are incomplete for the following reasons:
a) Complaint #2988 was submitted November 29, 2004 regarding the [redacted]. The complaint description states that the physician complained of "slippage" during the procedure, "thus not creating good enough hemostasis, causing more bleeding to the infant". The complaint investigation is incomplete in that the failure was determined to be related to the procedure and not the product, but there was no documentation to support this conclusion. In addition, two bases and two inserts were returned and analyzed, but there is no documentation describing the method of analysis.
b) Complaint #2893 was submitted March 15, 2004 regarding the [redacted].The complaint description documents that "doctors are complaining of bleeders" after using the circumcision clamp and that the opening on the top of the base makes it difficult to get a clean cut. The complaint investigation is incomplete in that there is no documentation describing the analysis/examination of the sixteen (16) clamps that were returned by the complainant.
c) Complaint #2826 was submitted October 17, 2003 regarding the [redacted]. The complaint description documents that the circumcision clamp fell off without unscrewing it. The complaint investigation is incomplete in that it was determined that it was not a product failure, but there is no documentation to support this conclusion. In addition, the circumcision clamp was returned by the complainant for analysis, but there is no documentation describing the analysis.
d) Complaint #2698 was submitted January 13, 2003 regarding the [redacted]. The complaint description documents that several users have complained about skin "shearing off, during the circumcision procedure. This complain investigation is incomplete in that: there is no documentation demonstrating that efforts were made to retrieve the clamp in question for analysis; no documentation of an attempt to identify the lot in which it was manufactured; and the investigation does not document actions taken to prevent recurrence.
Your firm's response to these deviations (FDA 483 Observation 7) states that the Product Complaint Procedure (QSR-127) will be revised to require the inclusion of what you describe as supplementary information (e.g., test data, analytical reports, phone logs) with the completed complaint investigation reports. This response is not adequate because no revised procedure was submitted to the FDA for our review. As stated above, please submit a copy of your revised "Product Complaint Procedure" (QSR-127)
Additionally, we acknowledge receipt of your detailed response, dated May 12, 2006, to the FDA 483, and received on May 22, 2006. We have not yet had an opportunity to review the information contained in your May 12 response and recognize that it may contain information requested in this letter.
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that your firm is in compliance with all applicable requirements of the. Act and regulations. The specific violations noted in this letter and in the FDA 483 issued at the close of the inspection may be symptomatic of serious underlying problems in your firm's manufacturing and quality assurance systems. You are responsible for investigating and determining the causes of the violations identified by the FDA. You also must promptly initiate permanent corrective and `preventive action on your Quality System.
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, FDA will not approve an application for premarket approval for Class III devices to which the Quality System regulation deficiencies are reasonably related until the violations have been corrected. Also, no requests for Certificates to Foreign Governments will be granted until the violations related to the subject devices have been corrected.
You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction,. and/or civil money penalties.
Please notify, this office in writing within fifteen (15) working days of receipt of this letter, of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to prevent the recurrence of similar violations. 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. Your written reply should be directed to Paige E. Wilson, Compliance Officer, at the above address.
Joann M. Givens