|Issuer:||New England District Office|
|Issued:||Sept. 25, 2008||Closed:||
Department of Health and Human Services
Public Health Service
New England District
VIA CERTIFIED MAIL
September 25, 2008
Mr. Walter M. Rosebrough
President and CEO
5960 Heisley Road
Mentor, OH 44060
Dear Mr. Rosebrough:
During an inspection of your firm, Steris Isomedix Inc., located at 8 Industrial Drive, Coventry RI, on June 4 through June 17, 2008, an investigator from the United States Food and Drug Administration (FDA) determined that your firm sterilizes medical devices. 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) regulations found at Title 21, Code of Federal Regulations (C.F.R.), Part 820. We received a response from Frank Yacino, Plant Manager, dated July 16, 2008, concerning our investigator's observations noted on the Form FDA-483, List of Inspectional Observations, that was issued to this facility on June 17, 2008, (copy attached). 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 adequate procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). For example, two ethylene oxide loads were released for shipment to the customer with deviations.
a. Load 1031, processed in Lot R060119-03, did not meet the specified requirements for the load. The minimum duration for steam injection should be [redacted] minutes, however the load only received [redacted] minutes of steam injection. In addition, the maximum aeration temperature should be [redacted]F, however this temperature was exceeded by seven degrees for a total of [redacted] minutes. The load was shipped to the customer on 2/2/06.
b. Load 39189, processed in Lot R070321-10, did not meet the specified requirements for the load. The maximum time for ethylene oxide injection phase should be [redacted] minutes; however the maximum time was exceeded by [redacted] minutes. The load was shipped to the customer on 3/26/07.
We have reviewed your response dated July 16, 2008, and have concluded that it is inadequate because while you have opened a Correction and Preventative Action (CAPA) to address this issue, your corrective actions did not address any product that was processed prior to the initiation of this CAPA.
2. Failure to establish and maintain adequate procedures to identify all the actions needed to correct and prevent the recurrence of nonconforming product and other quality problems as required by 21 CFR 820.100(a)(3). For example, on 2/15/07, load R070215-07 was processed using revision 10 of the cycle; however, revision 9 was the currently approved version. Your firm was notified by the customer that the load was processed incorrectly. You subsequently opened a CAPA to address this issue and later identified the root cause of the problem as the [redacted] server migration of unapproved cycles into the [redacted] software. However, at the time, you did not initiate any preventative actions to ensure that this problem does not recur.
Your response cannot be evaluated at this time because while you have opened a CAPA to address the [redacted] server migration of unapproved cycles into the [redacted] software and have provided a copy of this CAPA, you have not provided any evidence that demonstrates that the process controller replacements will adequately address the migration of unapproved ethylene oxide sterilization cycles. Therefore, the adequacy of the CAPA cannot be evaluated until this information is submitted for our review.
3. Failure to establish and maintain adequate procedures for finished device acceptance to ensure that each production run, lot or batch of finished devices meets acceptance criteria and finished devices shall not be released for distribution until: (1) the activities required in the Device Master Record (DMR) are completed;(2) the associated data and documentation is reviewed; (3) the release is authorized by the signature of a designated individual(s); and (4) the authorization is dated, as required by 21 CFR 820.80(d). For example:
a. On 12/19/06, an operator removed an incorrect pallet from aeration without properly identifying the product. Pallet #20 of load #1186 was subsequently shipped to a customer instead of Pallet #20 from load #1187.
b. On 3/6/07, an operator removed load #1221 from aeration 19 hours before scheduled completion time. The load was subsequently shipped to the customer.
c. On 8/31/07, one pallet consisting of four boxes was incorrectly removed from the load and therefore 36 boxes were processed instead of 40.
We acknowledge that this particular deficiency was not addressed during the inspection. We have also reviewed your response dated July 16, 2008, and have concluded that it is inadequate because while you have opened a CAPA to address the issue of operators not verifying load paperwork, your corrective actions did not address any released product to ensure that they conformed to specified requirements.
4. Failure to establish and maintain adequate acceptance procedures to ensure that specified requirements for in-process product are met; as required by 21 CFR 820.80(c). For example:
a. On 1/9/07, 2 pallets in load R070109-07 were processed in chamber 2; however, chamber 2 was not an approved sterilizer for the loads.
b. On 5/4/08, one pallet consisting of 11 boxes was processed using the wrong cycle in load R080503-03.
We acknowledge that this particular deficiency was not addressed during the inspection. We have also reviewed your response dated July 16, 2008, and have concluded that it is inadequate because while you have opened a CAPA to address the issue of operators not verifying load paperwork, your corrective actions did not address any product that was processed prior to the initiation of this CAPA.
5. Failure to adequately validate computer software used as part of production, as required by 21 CFR 820.70(i). For example, your [redacted] software, used for the sterilization chambers, was not adequately validated in that unapproved ETO sterilization cycle revisions are migrated from the [redacted] server into the software and are not identified as unapproved cycles. The ETO chamber operators can access these unapproved cycles and run the non validated sterilization cycles without the customers consent.
Your response cannot be evaluated at this time because while you have opened a CAPA to address the migration of unapproved ethylene oxide sterilization cycles and have provided a copy of this CAPA, you have not provided any evidence that demonstrates that the process controller replacements will adequately address this Issue and that they have been adequately validated. Therefore, the adequacy of the CAPA cannot be evaluated until this information is submitted for our review.
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations. The specific violations noted in this letter and in the Form FDA-483 issued at the conclusion of the inspection may be symptomatic of serious underlying problems in your establishment's quality system. 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.
You should know that these serious violations of the law may result in FDA taking regulatory action without further notice to you. These actions include; but are not limited to, seizing your product inventory, obtaining a court injunction against further marketing of the product, or assessing civil money penalties.
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, no premarket submissions for Class III devices to which the Quality System/Current Good Manufacturing Practice deficiencies are reasonably related will be cleared or approved until the violations have been corrected. Also, no requests for Certificates to Foreign Governments will be approved until the violations related to the subject devices have been corrected.
We acknowledge the receipt of your letter dated July 16, 2008 which responded to the Form FDA-483 that was issued to your facility on June 17, 2008. We also acknowledge our previous letter to you dated August 5, 2008 that indicated the Form FDA-483 response was adequate. Please note that upon further review, we realized that the deficiencies discussed above warranted this Warning Letter to bring these violations to your attention.
Please let this office know in writing what steps you have taken to correct the noted problems within fifteen (15) working days from the date you received this letter. We also ask that you explain how you plan to prevent these problems from happening again. If you need more time, let us,know why and when you expect to complete your correction. Please direct your response or any questions you may have to Karen Archdeacon, Compliance officer, Food and Drug Administration, One Montvale Avenue, 4th Floor, Stoneham, Massachusetts, 02180. Her telephone number is (781) 596-7707; FAX No. 781-596-7899.
John R. Marzilli
Acting District Director
New England District