- Delivery Method:
- VIA UNITED PARCEL SERVICE
Recipient NameOmid A. Khorram, M.D., Ph.D.
Recipient TitleMedical Director
- University Fertility Laboratory, Inc.
23550 Hawthorne Blvd., Suite 210
Torrance, CA 90505
- Issuing Office:
- Division of Biological Products Operations II
Irvine, CA 92612-2506
VIA UNITED PARCEL SERVICE
May 30, 2019
[Warning Letter # OBPO 19-006]
Omid A. Khorram, M.D., Ph.D.
University Fertility Laboratory, Inc.
23550 Hawthorne Blvd., Suite 210
Torrance, CA 90505
Dear Dr. Khorram,
The United States Food and Drug Administration (FDA) conducted an inspection of your firm, University Fertility Laboratory, Inc., located at 23550 Hawthorne Blvd., Suite 210, Torrance, CA 90505
The deviations documented on the Form FDA-483, List of Inspectional Observations, were presented to and discussed with you at the conclusion of the inspection. Additional deviations were noted upon further review of the donor records and procedures collected during the inspection. These items of concern include, but are not limited to, the following:
1. Failure to test a specimen from the donor of cells or tissue for evidence of infection due to relevant communicable disease agents [21 CFR 1271.85(a)]. The Guidance for Industry: “Use of Nucleic Acid Tests to Reduce the Risk of Transmission of West Nile Virus (WNV) from Living Donors of Human Cells, Tissue, and Cellular and Tissue-base Products (HCT/P),” dated September 2016, Corrected May 2017, states that for establishments located within the United States (includes the 50 states and District of Columbia) the FDA recommends performing WNV testing of donors of HCT/Ps recovered from June 1st through October 31st every year. This guidance supplements WNV donor screening recommendations in sections IV. E and IV. F., and supersedes the WNV section of the guidance entitled,“Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps),” dated August 2007. The following oocyte donors were determined to be eligible without WNV Nucleic Acid Testing being performed. For example:
- Anonymous Oocyte donor (b)(6) had oocytes recovered on July 19, 2017 and September 11, 2018.
- Directed Oocyte donor (b)(6) had oocytes recovered on September 23, 2017.
- Anonymous Oocyte donor (b)(6) had oocytes recovered on August 18, 2018.
- Directed Oocyte donor (b)(6) had oocytes recovered on August 20, 2018.
2. Failure to screen a donor of reproductive cells or tissue by reviewing the donor’s relevant medical records for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases [21 CFR 1271.75(a)(1)]. Specifically,
- FDA has identified the Zika virus (ZIKV), as a relevant communicable disease agent or disease under 21 CFR 1271.3(r)(2). Therefore, review of relevant medical records, as defined in 21 CFR 1271.3(s), must indicate that a potential donor is free from risk factors for, or clinical evidence of, ZIKV infection for the purpose of determining donor eligibility. Your procedure, Risk [f]actors for Communicable Diseases or Disease Agents and your Donor Risk Assessment questionnaire (FDA SOP 01/01/2007), failed to assess a donor’s relevant communicable disease risk as it relates to ZIKV transmission. Examples include but are not limited to: Anonymous oocyte donors (b)(6) and (b)(6) and directed oocyte donors (b)(6) and (b)(6).
- Your Donor Risk Assessment questionnaire (FDA SOP 01/01/2007) is used as a relevant medical record to determine donor eligibility. However, this questionnaire does not include all conditions and/or behaviors to assess a donor’s relevant communicable disease risk. For example, the following questions are missing from your questionnaire:
- Question 14 of your updated Donor Eligibility Questionnaire/Exam form states, “Have you been diagnosed with West Nile Virus” should read as, “Have you had a medical diagnosis or suspicion of West Nile Virus (WNV) infections (based on symptoms and/or laboratory results, or confirmed WNV viremia) or have been deferred for 120 days following diagnosis or onset of illness, whichever is later.
- Persons who have been diagnosed with dementia or any degenerative or demyelinating disease of the central nervous system or other neurological disease of unknown etiology.
- Persons who are current or former U.S. military members, civilian military employees, or dependents of a military member or civilian employee who resided at U.S. military bases in Northern Europe (Germany, Belgium, and the Netherlands) for 6 months or more cumulatively from 1980 through 1990, or elsewhere in Europe (Greece, Turkey, Spain, Portugal, and Italy) for 6 months or more cumulatively from 1980 through 1996.
- Questions 21 of your updated Donor Eligibility Questionnaire/Exam form states, “Between 1980 and 1996, did you spend time that adds up to more than 3 months in the UK?” However, it should read as, “Have you spent three months or more cumulatively in the United Kingdom from the beginning of 1980 through the end of 1996?”
- Question 24 of your updated Donor Eligibility Questionnaire/Exam form states, “Have you had a blood or blood component transfusion in the UK or France between 19880 and the present?” We believe that there was a typographical error, however, it should read, “Have you had a blood or blood component transfusion in the UK or France between 1980 and the present?”
- Question 38 of your updated Donor Eligibility Questionnaire/Exam states related to history or symptom of ZIKV infection does not meet the 6-month requirement for donor screening.
- Question 39 of your updated Donor Eligibility Questionnaire/Exam states, “Have you had sexual contact in the past 4 weeks with a person who has been diagnosed with or had symptoms suggestive of ZIKV in 3 months prior to that instance of sexual contact?” However, it should read, “Have you had sex within the past 6 months with risk factors listed in Questions 40 and 41.
It appears you still have oocytes in storage from donors whose screening and/or testing was not completed in accordance with the regulations at 21 CFR Part 1271. For example, donors who were not tested for WNV or other relevant communicable disease agents, donors who were screened using a donor history questionnaire that was missing required screening questions, and donors who were not screened for risk factors for ZIKV. Please note that FDA considers the donor eligibility determinations to be incomplete for these donors. Therefore, as required by 21 CFR 1271.60(a), you must keep these HCT/Ps in quarantine.
Should the need arise in the future to remove any of these HCT/Ps from quarantine, either for use in your own establishment or for transport to another establishment, you must request an exemption or alternative from a requirement in subpart C 21 CFR Part 1271, as specified in 21 CFR 1271.155 (additional information can be found at: http://www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/RegulationofTissues/ExemptionsandAlternativeProcedures/default.htm). Please note that the 21 CFR 1271.155 regulation requires that you provide justification for use of HCT/Ps from these donors, as well as information on how you have mitigated the risk consistent with the goals of protecting the public health and/or preventing the introduction, transmission, or spread of communicable diseases. Before any of these HCT/Ps can be removed from quarantine the request must be granted by FDA.
And lastly, we would like to remind you that in the interest of confidentiality, a distinct identification code to the HCT/P container that relates the HCT/P to the donor and to all records pertaining to the HCT/P must not include an individual’s name, social security number or medical record number except in the case of autologous donations, directed reproductive donations, or donations made by first degree or second-degree blood relatives in accordance with 21 CFR 1271.55(a)(l).
Your response should be sent to the following address: Amy Graf, U.S. Food & Drug Administration, Office of Biological Product Operations – Division 2, 300 River Place Dr., Detroit, MI 48207, or emailed to . If you should have any questions, please contact Amy Graf, Compliance Officer at (313) 393-2034 or via e-mail.
Program Division Director
Office of Biological Products Operations – Division 2