- Delivery Method:
- VIA UNITED PARCEL SERVICE
- Reference #:
- OBPO 20-596508
Recipient NameSheila R. Busheri
- R & B Medical Group Inc.
6700 Valjean Ave
Van Nuys, CA 91406-5818
- Issuing Office:
- Division of Biological Products Operations II
January 15, 2020
Warning Letter #OBPO 20-596508
Dear Ms. Busheri:
The United States Food and Drug Administration (FDA) conducted an inspection of your firm, R & B Medical Group Inc., dba Universal Diagnostics Laboratories, located at 6700 Valjean Ave., Van Nuys, California, from September 16 through September 25, 2019. The Food and Drug Administration documented that your firm is a testing laboratory that performs communicable disease testing, under contract, for fertility clinics and medical practices. The results of testing conducted by your firm is used to make final donor eligibility determinations for donors of oocytes, and semen. As such your firm is involved in the manufacture of human cells, tissues or cellular or tissue-based product (HCT/Ps) that are regulated under the purview of FDA.
During the inspection, FDA investigators documented significant deviations from the regulations for human cells, tissues, and cellular and tissue-based products (HCT/Ps) set forth in Title 21, Code of Federal Regulations (CFR) Part 1271 (21 CFR 1271), and issued under the authority of Section 361 of the Public Health Service Act (42 U.S.C. § 264).
The deviations documented on the Form FDA-483, List of Inspectional Observations, were presented to and discussed with your firm’s Medical Director at the conclusion of the inspection. FDA has found additional significant violations upon further review of the documents collected during the inspection. The items of concern include, but are not limited to, the following:
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 diseases [21 CFR 1271.80(c)]. For example:
a. You are not interpreting test results in accordance with the manufacturer’s instructions. Instead of reporting the results of donor screening tests for relevant communicable diseases to your clients, as required under 21 CFR 1271, you are reporting the results after performing confirmatory or additional testing. For example:
i. Your firm performed a screening test on Sample ID 1807100527 for HIV-1/2 Plus O which was determined to be initially reactive on 7/11/2018. Duplicate repeat testing performed by your firm of the sample on 7/12/2018 resulted in sample ID 1807100527 being repeatedly reactive for HIV-1/2 Plus O. You did not report the sample as being reactive on a screening test for HIV-1/2 Plus O to your client. Rather, you reported the sample as being non-reactive for HIV-1/2 Plus O, because the NAT (nucleic acid test) performed by a contract laboratory was negative.
ii. Your firm performed a screening test on Sample ID 1810120654 for HTLV-I/II which was determined to be initially reactive for HTLV-I/II on 10/15/2018. Duplicate repeat testing performed by your firm of the sample on 10/16/2018 resulted in sample ID 1810120654 being repeatedly reactive for HTLV-I/II. You did not report the sample as being reactive on a screening test for HTLV-I/II to your client. Rather, you reported the sample as being non-reactive for HTLV-I/II, because HTLV-I/II Immunoblot testing performed by a contract laboratory was negative.
iii. Your firm performed a screening test on Sample ID 1810010523 for HTLV-I/II which was determined to be initially reactive for HTLV-I/II on 10/2/2018. Duplicate repeat testing performed by your firm of the sample on 10/3/2018 resulted in sample ID 1810010523 being repeatedly reactive for HTLV-I/II. You did not report the sample as being reactive on a screening test for HTLV-I/II to you client. Rather, you reported the sample as being non-reactive for HTLV-I/II, because HTLV-I/II Immunoblot testing performed by a contract laboratory was negative.
b. Your firm performed communicable disease testing using donor specimens that were stored for a time period greater than allowed by the test kit manufacturer’s instructions.
i. Samples from three donors (Sample IDs: 1812290141, 1812310299, and 1809180086) were tested for Hepatitis B core antigen (HBc), Hepatitis B surface antigen (HBsAg), and/or HIV-1/2 Plus O greater than seven days following sample collection. The test kit manufacturer’s instructions state that specimens may be stored at (b)(4)oC for (b)(4) days.
ii. A donor sample (Sample ID: 1904091260) was tested for HTLV-I/II greater than (b)(4) days following sample collection. The test kit manufacturer’s instructions state that specimens may be stored at (b)(4)oC for up to (b)(4) days.
2. Failure to establish and maintain procedures for all steps performed in testing, screening, and determining donor eligibility, and complying with all other requirements of Subpart C “Donor Eligibility” in 21 CFR Part 1271.45 - 1271.90. “Establish and maintain” means define, document, and implement; then follow, review, and as needed, revise on an ongoing basis [21 CFR 1271.47(a)]. For example, your firm has not established and maintained procedures for all steps you perform, including but not limited to, performance of communicable disease testing, documentation of test kit lot numbers, equipment used during testing, incubation times, steps in reporting results to clients, and calibration/maintenance of testing equipment.
3. Failure to establish and maintain procedures for the review, evaluation, and documentation of complaints as defined in 1271.3(aa), relating to core current good tissue practice (CGTP) requirements and the investigation of complaints as appropriate [21 CFR 1271.320].
4. Failure to establish and maintain a quality program that includes investigating and documenting HCT/P deviations relating to core HCT/P deviations and trends of HCT/P deviations relating to core CGTP requirements [21 CFR 1271.160(b)(6)].
5. Failure to maintain records concurrently with the performance of each step required in Subpart C and Subpart D of 21 CFR 1271. All records must be accurate, indelible, and legible. 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 [21 CFR 1271.270(a)]. For example, the FDA investigator documented numerous examples of incomplete records associated with testing for relevant communicable diseases, including missing documentation of the lot number of test kit used, missing documentation of incubation times of individual tests, and missing documentation of the person who performed testing.
The deviations identified above are not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that your establishment is in compliance with all applicable statutory and regulatory requirements. You are responsible for reviewing your operations as a whole to assure you are in compliance with the law.
In addition, the agency is very concerned with your policy of representing the results of screening tests for relevant communicable diseases as negative after performing confirmatory or additional testing. In the preamble to the Final Rule published May 25, 2004, the agency stated that confirmatory tests may not be as sensitive as screening tests in detecting early infection. For example, confirmatory testing for HBV, such as the hepatitis B surface antigen (HBsAg) neutralization assay, is valuable for confirming the presence of HBsAg in specimens found to be reactive by a screening assay and can be helpful for donor counseling. However, the neutralization assay may not always detect all potentially infectious HCT/Ps. Therefore, the agency did not make an exception to the testing requirements that would permit a donor eligibility determination based on HBV confirmatory testing [Federal Register: May 25, 2004 (volume 69, page 29809)].
The regulations at 21 CFR 1271.80(d) specifically require the responsible person who is performing a donor eligibility determination to determine to be ineligible a donor whose specimen tests reactive on a screening test for a communicable disease agent. Your firm has not accurately reported the results of screening tests to your clients, making it impossible for your clients to determine a donor ineligible who tests reactive on a screening test for relevant communicable diseases.
Additionally, in the “Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues and Cellular and Tissue Based Products,”... FDA discusses the use of confirmatory tests and states, “if you perform a confirmatory test, negative or nonreactive results on a confirmatory test would not override a positive or reactive screening test.” (See section VI.A of the HCT/P Donor Eligibility Determination Guidance).
Therefore, we request that you perform a retrospective review of results of all screening tests for relevant communicable diseases and identify those that were repeatedly reactive but were incorrectly reported to your clients as negative based on the results of confirmatory testing, Nucleic Acid Testing, or Immunoblot testing. Upon identifying test results that were not accurately reported to your clients, we request that you notify your clients of the correct test result for the affected donor screening test for relevant communicable disease(s).
You should take prompt action to correct the violations addressed in this letter and prevent their recurrence. Failure to promptly correct these violations may result in regulatory action being initiated by the FDA without further notice.
We request that you respond in writing within fifteen (15) working days from your receipt of this letter, outlining the specific steps you have taken or plan to take to correct the noted violations and prevent their recurrence. Include any documentation necessary to show that correction has been achieved. If you cannot complete all corrections within fifteen (15) working days, please explain the reason for your delay and the time frame within which the remaining corrections will be completed.
Your response should be sent to the following address: Daniel W. Cline, Compliance Officer, U.S. Food and Drug Administration, 19701 Fairchild, Irvine, CA 92612 or emailed to Daniel.Cline@fda.hhs.gov. If you have any questions, please contact Mr. Cline at (949) 608-4433 or via e-mail.
Program Division Director
Office of Biological Products Operations - Division 2