- Delivery Method:
- VIA UNITED PARCEL SERVICE
- Medical Devices
Recipient NameOlof Nord
- M Dialysis AB
Hammarby Fabriksvag 43
120 33 Stockholms Lan
- Issuing Office:
- Center for Devices and Radiological Health
10903 New Hampshire Avenue
Silver Spring, MD 20993
June 6, 2018
Dear Mr. Nord:
During an inspection of your firm located in Stockholm, Sweden on November 6 through November 9, 2017, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the ISCUS Flex system. 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 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 requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
We received a response from you dated December 1, 2017, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. 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 requirements, including quality agreements, that must be met by suppliers, as required by 21 CFR 820.50(a). For example:
a. Your firm has not evaluated supplier (b)(4) annually as required by Supplier (b)(4). The last supplier evaluation was made in April 2016, and the last full evaluation was made in January 2014. Additionally, there is no signed supplier agreement with (b)(4). Your firm has rejected lots of lactate and pyruvate reagents in the past for not meeting specifications.
b. Your firm does not have documentation of the process validation for the sterilization or agreement for the sterilization of (b)(4) supplied by supplier (b)(4).
We reviewed your firm’s response and concluded it is not adequate. You indicated that you would evaluate the supplier (b)(4) and conduct an on-site audit, gather sterilization reports from (b)(4), update the quality agreement with (b)(4) to include requirements for sterilization, and update supplier control procedure. However, your firm did not provide the updated procedures or any evidence of the planned corrective actions nor a plan for a systemic corrective action. For example, you did not conduct a review of other suppliers to ensure they have been adequately evaluated. Furthermore, you did not address training to the new procedures to ensure the same problems do not reoccur. In addition, your firm did not conduct an evaluation of the perfusion fluid to make sure it met sterility specifications.
2. Failure to establish and maintain adequate procedures for acceptance of incoming product, as required by 21 CFR 820.80(b). For example: the incoming inspection and testing of the finished Pyruvate Reagent and Buffer/Lot T25901 received from the supplier, did not meet the acceptance testing for Linearity and Stability. Additionally, the receipt from (b)(4) did not include a Certification of Analysis as required. [Repeat FDA 483 Observation from inspection dated March 13, 2014]
We reviewed your firm’s response and concluded it is not adequate. You indicated you plan to gather a Certificate of Analysis for batch T25901 from the supplier, document rational for releasing the lot, and update the procedure. However, you did not provide the updated procedures or any evidence of the planned corrective actions, nor a plan for a systemic corrective action. For example, you did not conduct a review of other quality records related to other products to ensure all products received were within specification. Furthermore, your firm did not address training to the new procedures to ensure the same problems do not reoccur.
3. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example: document ISCUS Quality Issues and Possibilities describes test failures for measurement cells and issues with reagents; however, your firm did not issue a CAPA as required by procedure (b)(4) Handling of Nonconforming Product.
We reviewed your firm’s response and concluded it is not adequate. You indicated you plan to document the nonconformance, update the CAPA procedure, and conduct training to the updated procedures. However, you did not provide the updated procedures or evidence of the planned corrective actions for review. Additionally, you did not have a plan for taking systemic corrective actions. For example, you did not review other records to ensure they did not rise to a CAPA.
4. 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: Lot T25187 of Lactate reagent was scrapped on November 5, 2016 due to concerns about the sensitivity and stability. At this time your firm had (b)(4) of the reagent remaining. However, you did not have documentation of the disposition of the non-conforming product.
We reviewed your firm’s response and concluded it is not adequate. You indicated you plan to document the disposition and update procedures (b)(4) and (b)(4); however, you did not provide the updated procedures for review or provide a plan for systemic corrective action. For example, plan to review other non-conformances to make sure they were adequately handled and conduct training in the updated procedures to ensure the issue does not reoccur.
Given the serious nature of the violations of the Act, ISCUS Flex system manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations are corrected. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and correct the violation(s) described in this letter. We will notify you regarding the adequacy of your firm’s response(s) and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
Also, U.S. federal agencies may be advised of the issuance of 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.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review.
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Inspections Support Branch, White Oak Building 66, Rm 3540, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #554169 when replying. If you have any questions about the contents of this letter, please contact: Matthew Krueger at 301-796-5585.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems.
Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.
CAPT Sean M. Boyd, MPH, USPHS
Deputy Director for Regulatory Affairs
Office of Compliance
Center for Devices and Radiological Health