Sunrise Medical Laboratories, Inc received warning letter in violation to 21 CFR Part 1271

• Date: May 26, 2011
• Source: Editor

On Feb 23 2011 Sunrise Medical Laboratories, Inc a clinical and anatomical pathology laboratory received warning letter from FDA in relation to violation of not providing adequate protections against the risks of communicable disease transmission through the use of the HCT/Ps for which the company performs testing for relevant communicable diseases. The agency has also determined that there are reasonable grounds to believe this violative HCT/Ps pose a danger to health. Hence the agency has issued an order to Order to Cease Manufacturing effective with immediate notice. This Order to Cease Manufacturing relates to conduct occurring on or after May 25, 2005, the effective date of the applicable regulations. FDA retains authority to pursue other actions and remedies.

The warning letter states “Because of your failure to provide adequate protections against the risks of communicable disease transmission, pursuant to 21 CFR 1271.440(a)(3), Sunrise Medical Laboratories must immediately cease all manufacturing of HCT/Ps until compliance with the regulations in 21 CFR 1271 has been achieved and you have been provided written authorization from FDA to resume operations. Under 21 CFR 1271.3(e) manufacture means, but is not limited to, any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any HCT/P, and the screening or testing of the HCT/P donor.

Additionally, this is to advise you that FDA will notify, by copy of this Order, the client reproductive facilities for whom you performed donor testing since January 2008.”

FDA’s inspection and record review noted significant noncompliance with the federal regulations including, but not limited to, the following:

A. Donor Testing

1. Failure to test using appropriate FDA-licensed, approved, or cleared donor screening tests, in accordance with the manufacturer’s instructions, to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents or disease [21 CFR 1271.80(c)]
2. The manufacturer’s instructions for the hepatitis B core (HBc) assay state the absorbance value for the substrate blank must be greater than or equal to ---(b)(4)--- and less than or equal to ---(b)(4)--. The instructions further state that these criteria must be met in order for a plate (test run) to be considered valid. For 76 assays performed between January 2008 and October 2010, the blank absorbance value was greater than -(b)(4)-. The assays were not considered invalid and the results were reported to clients despite being obtained from an invalid test run.
3. The manufacturers of the test kits used for HIV-1/2, HBc, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV), require the use of a multichannel aspirator-washer capable of dispensing and aspirating 300µL to 800µL of wash solution per microplate well. In addition, the manufacturer’s instructions caution that strict adherence to the specified wash procedure is critical to ensure optimum assay performance. The instructions provide very specific steps to follow for washing the microplates. However, your firm’s procedure involves using a hand-held irrigation bottle to wash the wells, then inverting the microplates over a laboratory waste container to discard the wash solution. This method has been standard practice at Sunrise Medical Laboratories since January 2008, and was observed by the investigator during the inspection and documented in an affidavit signed by Mr. Paul Doherty, Laboratory Manager, on November 18, 2010.
4. The incubation and washing steps for the HBc, HBsAg, HCV, and HIV-1/2 assays are not always performed for the required time specified in the manufacturer’s instructions. During the inspection, on October 28, 2010, the investigator observed that incubation times for specific steps in the assays were not documented or verified.
5. The manufacturer’s instructions for the HBc assay require re-testing of donor specimens with an absorbance reading of less than -(b)(4)-. On 6/17/10, the absorbance reading for donor ----(b)(6)--- was -0.034. The donor specimen was not re-tested and the result of testing of this HCT/P donor was reported as negative.

B.Records

Failure to maintain records concurrently with the performance of each step required in subpart D and subpart C of Part 1271. 21 CFR 1271.270(a) states that any requirement in Part 1271 that an action be documented involves the creation of a record, which is subject to the requirements of this section. In addition, this section requires that all records must be accurate, indelible, and legible and that the records must identify the person performing the work and the dates of the various entries, and must be as detailed as necessary to provide a complete history of the work performed and to relate the records to the particular HCT/P involved. For example:

1. From January 2008 to October 2010, you did not document incubation temperatures and times; solution preparation and usage times; and stop solution addition times for HBc, HBsAg, HCV, syphilis, and HIV-1/2 assays.
2. The identification of the individual performing HBc, HBsAg, HIV-1/2, and syphilis assays was not documented on 180 out of -(b)(4)- worksheets/plate reader printouts.
3. Donor specimen numbers were not documented on 40 out of -(b)(4)- data sheets/plate reader printouts for HBc assays performed in 2008.
4. The calculation of the average value of the negative controls was not documented for three HCV assays and four HBsAg assays performed in 2008 and 2009

FDA further says that the testing was not performed in accordance with manufacturer’s instructions. Specifically: improper washing of microplates; failure to monitor the time and temperature of each step performed in testing; failure to invalidate test runs which did not meet manufacturer’s acceptance criteria and misinterpretation of test results based on use of an incorrect cutoff value.

FDA instructs the company to inform its’ client reproductive facilities and FDA of each donor test result that was affected by non-compliance with the manufacturer’s instructions in order that the client can make an informed decision regarding the status of the donor and /or any affected HCT/Ps that may remain in their inventory.

Source:

For more details of this warning letter http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/TissueSafety/ucm244563.htm