Cooper Institute

The United States Food and Drug Administration (FDA) conducted an inspection of your firm, Cooper Institute for Advanced Reproductive Medicine, located at 7500 Beechnut Street, Suite #308, Houston, TX, from July 8, 2021 through July 19, 2021. During the inspection, an FDA Investigator 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 you at the conclusion of the inspection. The items of concern include, but are not limited to, the following:

1. Failure to test a specimen from an anonymous or directed reproductive donor of cells or tissue, whether viable or non-viable, for evidence of infection due to relevant communicable disease agents [21 CFR 1271.85(a)]. For example: a. Living HCT/P donors should be tested for West Nile Virus (WNV) using an FDA-licensed Nucleic Acid Test (NAT) donor screening test for HCT/Ps recovered between June 1st and October 31st every year. Two anonymous oocyte donors ((b)(6)) were not tested for WNV during that time period.

b. The donor specimen collected from anonymous oocyte donor (b)(6) on July 8, 2020, was not tested for human immunodeficiency virus, types 1 and 2 (HIV-1/2), hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum at the time of recovery on July 14, 2020.

2. Failure to test a specimen from an anonymous or directed reproductive donor of cells or tissue, to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents of the genitourinary tract. The reproductive cells or tissue were not recovered by a method that ensured freedom from contamination of the cells or tissue by infectious disease organisms that may be present in the genitourinary tract [21 CFR 1271.85(c)]. For example, there is no record that anonymous oocyte donor (b)(6) was tested for Chlamydia trachomatis and Neisseria gonorrhea at the time of oocyte recovery.

3. Failure of a responsible person to determine and document the eligibility of a donor of reproductive cells or tissue based on the results of donor screening and testing [21 CFR 1271.50(a)]. For example, the records for the following anonymous oocyte donors did not contain documentation of the donor eligibility determination, including the name of the responsible person who made the determination, the date of the determination, and documentation that the donor was determined “eligible:”

a. Oocytes were recovered from anonymous donor (b)(6) on June 28, 2021. b. Oocytes were recovered from anonymous donor (b)(6) on April 19, 2021. c. Oocytes were recovered from anonymous donor (b)(6) on February 6, 2021. d. Oocytes were recovered from anonymous donor (b)(6) on November 28, 2020. e. Oocytes were recovered from anonymous donor (b)(6) on July 14, 2020. f. Oocytes were recovered from anonymous donor (b)(6) on March 18, 2020.

4. 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)]. Under 21 CFR 1271.75(a), you must screen a donor of 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 1271.3(s) defines the term “relevant medical records” to include a current donor medical history interview and a current report of the physical examination of a living donor. For example: a. Your Donor/Surrogate Eligibility Questionnaire is a relevant medical record used to determine donor eligibility. However, your questionnaire does not include screening for all conditions and/or behaviors that increase a donor’s relevant communicable disease risk. For example, questions for the following risk factors for relevant communicable disease agents and diseases are missing from your screening forms:

i. Persons who have had a medical diagnosis of Zika Virus (ZIKV) in the past 6 months

ii. Persons who resided in, or travelled to, an area with an increased risk for ZIKV transmission within the past 6 months.

iii. Persons who have had sex within the past 6 months with a person who has either of the risk factors listed in items i or ii, above.

iv. 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.

v. Persons who are at increased risk for CJD if they have received a non-synthetic dura mater transplant.

vi. Persons who received any transfusion of blood or blood components in the France between 1980 and the present.

vii. Persons who spent 5 years or more cumulatively in Europe from 1980 until the present (note this criterion includes time spent in the U.K. from 1980 through 1996). Your questionnaire only asks, “Have you lived cumulatively in Europe for 5 years or more from 1980 through 1996?”

b. The records for anonymous oocyte donor (b)(6) lack documentation of a current report of the physical examination of the donor. Oocytes were recovered from donor (b)(6) on June 28, 2021.

5. Failure to establish and maintain procedures for all steps performed in testing, screening, and determining 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 (in writing or electronically), and implement; then follow, review, and as needed, revise on an ongoing basis [21 CFR 1271.47(a)]. Your firm does not have procedures for all steps that you perform in donor testing, screening, and determining donor eligibility of semen and oocyte donors.

To date, we have not received a response to the observations on the FDA-483 provided to you at the close of the inspection; therefore, we are unable to evaluate what, if any, corrective actions you have implemented, or plan to implement and whether they are adequate to address our concerns. We acknowledge the corrections your firm made during the inspection to the “Donor/Surrogate Eligibility Questionnaire” to include the screening for ZIKV. In addition, you stated at the close of the inspection on July 19, 2021 that you have committed to ensuring donors are tested for West Nile Virus using an FDA-licensed NAT donor screening test for HCT/Ps recovered between June 1st and October 31st every year. Please note these are requirements per 21 CFR 1271.75(a)(1) and 21 CFR 1271.85(a), and therefore all donors should be evaluated using your revised questionnaire and tested accordingly. These will be verified during the next inspection of your facility.

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 requirements of the federal regulations. You are responsible for reviewing your firm’s operations as a whole to assure that you are in compliance with the law.

Please note that if you still have oocytes and/or semen in storage from donors whose screening and/or testing was not completed in accordance with 21 CFR Part 1271, FDA considers the donor eligibility determinations to be incomplete for these donors. For example, donors who were screened using a donor history questionnaire that was missing required screening questions, and donors who are missing a required donor history questionnaire, physical examination, and/or testing for relevant communicable disease agents and diseases. 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 oocytes or semen from quarantine, either for use in your own establishment or for transport to another establishment, you may 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: https://www.fda.gov/vaccines-blood-biologics/tissue-tissue-products/exemptions-and-alternatives). Please note that 21 CFR 1271.155 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.

If you still have embryos in storage for which the donor eligibility requirements under Part 1271, Subpart C are not met, 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 may release these HCT/Ps from quarantine (21 CFR 1271.90(b)) provided they are labeled in accordance with the applicable regulations at 21 CFR 1271.90(c).

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.

Your response should be sent to the following address: Young Mi Yoon, Compliance Officer, U.S. Food & Drug Administration, Office of Biological Product Operations – Division 2, 222 W. 7th Avenue, #25, Room 122, Anchorage, AK 99513 or emailed to YoungMi.Yoon@fda.hhs.gov. If you should have any questions, please contact Young Mi Yoon, Compliance Officer at (907) 271-1242 x 104 or via e-mail.