Inspections, Compliance, Enforcement, and Criminal Investigations
American Contract Systems 4/21/11
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
April 21, 2011
David G. Thomson, President
American Contract Systems
4801 West 81st Street, Suite 110
Bloomington, Minnesota 55437
Dear Mr. Thomson:
During an inspection of your firm located at 85 Shaffer Park Drive, Tiffin, OH on January 5 through January 14, 2011, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures/repacks and sterilizes custom convenience surgical kits. 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 (CFR), Part 820.
We received a response from Scott Wiest, Vice-President of Operation dated January 20, 2011, 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 ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). For example, your firm’s A-BIO-VAC Ethylene Oxide injection into a bag sterilization method has not been fully validated due to the following deficiencies:
(a) There is no documented evidence that all devices contained within the bag can undergo initial or re-sterilization and that the product integrity and functionality is not compromised. According to your firm, there are approximately 800 various class I/II medical devices (both sterile and non-sterile) that can be placed into these bags, however all devices have not been evaluated to see if they can withstand the sterilization process.
The response dated January 20, 2011, is not adequate. Your firm has not provided an adequate correction and systemic corrective action for demonstrating that all products can undergo re-sterilization and product functionality and that package integrity is not affected. Your firm also did not provide an adequate correction and systemic corrective action demonstrating how you will meet the requirements of the Quality System regulation under 21 CFR 820.75. However, your firm stated that your management has combined industry knowledge of over 100 years of convenience kit assembly and sterilization. Additionally, you state that no novel types of devices are placed into ACS kits. Your firm also stated your management expertise to date has been used to determine if the product can be included in the kit, which according to your firm, is in compliance with the "objectives and uses of AAMI standards and recommended practices" section of the ISO 14397. Additionally, you have developed a Component Evaluation form, FCE-01-1, in order to gather this information from the suppliers and were expected to be completed by April 1, 2011.
(b) Section 220.127.116.11 of your firm’s procedure, QP-02, "Sterilization Plan", Rev 04 dated January 29, 2010, states, “"Residuals shall be tested using the worst case representative product based upon the experience of management". However, there was no documented evidence demonstrating that the products being tested from the kit were worst case scenario.
The response dated January 20, 2011, is not adequate. Your firm has not provided documented evidence demonstrating that products tested during residual tests were worse case scenarios. Your firm stated that you conducted residual testing during all validation activities. Also, you claim that the cited observation (1b) is not a valid statement for the 2 smaller bag sizes because the amount of EO placed into the largest bag size is greater than the highest amount of gas allowed to be placed into the smaller bags. In addition, your firm stated you have performed a 2X sterilization experiment in the past to demonstrate that double the amount of gas allowed nominally still meets the residual limits stated in the FDA recognized standard ANSI/AAMIIISO 10993-7: 2008, Biological evaluation of medical devices-Part 7: Ethylene oxide sterilization residuals. In this manner your firm believes it has validated the residuals which could be present at the upper specification of the EO delivery.
(c) According to procedure #QP-02, "Sterilization Plan", section 12.7.1, the sterilization bags (primary packaging) are considered to be "an integral part of the sterilization process". There is no documented evidence that your firm's acceptable Bag thickness tolerances (b)(4) have been validated.
The adequacy of your firm’s response dated January 20, 2011, cannot be determined at this time. Your firm has not provided documented evidence of the corrective action and system corrective action. Your firm stated due to the identified thickness variability you measured the thickness of all bags used during validations conducted over the last 10 years and they all were within the stated manufacturer's specifications. Also, the data acquired during validations have been analyzed to determine what range of bag thicknesses were used during those validations. It was determined that the range of (b)(4) mils was used during the validations. Your firm stated you believe the data provides a statistically reasonable level of safety to consider variability of the bag thickness as having been fully validated. You also stated your firm will continue to monitor the variability of the bag during validations as well as during routine inspection of every lot of incoming bags. In addition, your firm set an action limit of (b)(4) and above (b)(4) nil thickness (the range so far used during the validations) so that if these limits ever occur during routine processing, you can take action to include using these bags for future validations. In this manner your firm shall validate the outer ranges if these ranges are found to actually occur.
(d) Section 3a of your firm’s procedure, QP-02, "Sterilization Plan", Rev 04 dated January 29, 2010, states, “The expiration date of the kit is equivalent to the earliest expiration date of any component in the kit”. In addition, you claim to create a poly-poly weld seal that is not permeable and is only compromised by assignable events. Finally, the expected life of the kit is less than 3 months; therefore, the company believes the expiration dating policy is adequate.” However there is no documented stability testing demonstrating that products in your firm’s kit containing an expiration date, has been adequately validated according to an established procedure.
Your firm’s response dated January 20, 2011, is not adequate. Your response addresses the future corrective actions, but does not discuss the corrections implemented for the medical device kits that currently contain expiration dates and lacked scientific evidence to support these expiration dates. Your firm has not provided documented evidence of your stated corrective actions to FDA. Your firm stated you are in the process of conducting a formal package shelf life test for the packaging. According to your firm, an audit to qualify a lab to conduct this process, and drafted a protocol was implemented in December of 2010. Additionally, completion of this process is expected to be completed by May 1, 2011. Your firm stated you expect to validate a minimum of a 3 year shelf life and after the completion of this testing an expiration date shall be placed on company products. Your letter also stated that your firm creates a completely intact seal on its packaging that is impervious and does not degrade over time. If there are any devices that the manufacturer states require an expiration date due to degradation, that expiration date is used as the label claim for the entire pack. A package failure is considered event related and the expected life of an ACS convenience kit is approximately 90 days.
(e) Currently, your firm has established an Alert limit of (b)(4) CFUs, and an Action limit of (b)(4) CFUs. Section 10.4.2 of your firm’s procedure #QP-02, "Sterilization Plan", states, “The experience of management shall be initially sufficient to determine worst case products.” However, there is no documented adequate rationale how the Action/Alert Bioburden limits were established.
The response dated January 20, 2011, is not adequate. Your firm has not provided documented evidence of a correction and systemic corrective action demonstrating how you validated the “revised” action and alert limits that was already reset by your firm. You explained that you validated your process to a Sterility Assurance Level (SAL) of 10-6 using spore strips inoculated (b)(4) chose half (b)(4) and a (b)(4) as the alert limit. According to your firm, this is the rationale for choosing these levels believing these to provide a safe level of comfort to maintain the validation. Your firm also stated you have over 10 years of bioburden data in order to continue monitoring this element of the system. Based on this your firm has analyzed this data and determined that the highest bioburden found during the past 10 years was (b)(4) cfu.
2. Failure to establish and maintain procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). For example, there are no procedures describing how your firm is controlling non-conforming product. Your firm has a "NON-CONFORMING PRODUCT REPORT" form, #F-CP-01-2 Rev. 8/09 that documents information such as; what is the non-conformance, a risk assessment (based upon severity, occurrence & detection), cause of the failure & associated failure codes, and product disposition. However, there are no procedures defining activities such as disposition of nonconforming product, rework instructions & review/approvals.
The response dated January 20, 2011, is not adequate. Your firm has not provided to FDA documented systemic corrective action that includes a retrospective review of nonconforming reports. Additionally, your firm did not provide adequate documented evidence of how you will establish (define, document, and implement) and maintain procedures to control product that does not conform to specified requirements. Your firm stated you now have a written procedure, CP-02, Handling NonConforming Product, however there was no documented evidence of this procedure provided to FDA.
3. Failure to establish and maintain procedures for rework, to include retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications, as required by 21 CFR 820.90(b)(2). For example, the following Nonconforming reports (NCRs) involved nonconformances that were reworked, which included re-sterilization, without any procedures that included rework instructions to ensure that the product meet its current approved specifications:
(a) NCR dated September 15, 2010, was opened due a customer unwrapping the pack.
(b) NCR dated November 3, 2011, was opened due to a customer mistakenly opening a kit.
Additionally, other nonconformances were corrected by reworking the tray:
(c) NCR dated December 20, 2010, was opened due to a bug found between the table covers. Investigation surmised that the bug came in with the table covers and was not detected during inspection.
(d) NCR dated September 15, 2010, was opened due to a hole found in the wrap that was “probably by half deep tray during sterilization”.
The response dated January 20, 2011, is not adequate. Your firm did not provide to FDA documented systemic corrective action that includes a retrospective review of nonconforming reports after rework. Your firm stated you now have a written procedure, CP-02, Handling NonConforming Product; however there was no documented evidence of this procedure provided to FDA.
Our inspection (also) revealed that your 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 (MDR) regulation. Significant violations include, but are not limited to, the following:
Failure to develop, maintain, and implement written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17. For example, Section 6.3 of your firm’s "Complaint Handling" procedure, #CH-01 dated September 3, 2009 (note: date on this procedure is typed in error as "1009"), states that complaints shall be reviewed for MDR reporting per 21 CFR 803. However, there are no additional MDR procedures.
The response dated January 20, 2011, is not adequate. Your firm did not provide to FDA adequate documented evidence of a how you would implement the correction. Your firm also did not provide documented evidence of a systemic corrective action for complaints that may be reportable under Medical Device Reporting. Your firm stated you have a written procedure, CH-02, Handling MDR's, which according to your firm specifically addresses MDR related events.
A follow up inspection will be required to assure that corrections and/or corrective actions are adequate.
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 violations 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) business days from the date you receive this letter of the specific steps you have taken to correct the noted violations, as well as an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions you have taken. If your planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of these activities. If corrections and/or corrective actions cannot be completed within 15 business days, state the reason for the delay and the time within which these activities will be completed. Your response should be comprehensive and address all violations included in this WL.
Your response should be sent to: Mr. Stephen J. Rabe, Compliance Officer, Food and Drug Administration, 6751 Steger Drive, Cincinnati, Ohio 45237. Refer to the Unique Identification Number (CIN-11-164433-12) when replying. If you have any questions about the content of this letter please contact: Mr. Rabe at (513) 679-2700 extension 163 or you may forward a facsimile to him at (513) 679-2773.
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 management 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.
Teresa C. Thompson