- Delivery Method:
- VIA UNITED PARCEL SERVICE
Recipient NameMichele R. Birsinger
Recipient TitleAssistant Vice President
- Family Fertility Center
6651 Main St. Ste E350
Houston, TX 77030-2352
- Issuing Office:
- Division of Biological Products Operations II
Irvine, CA 92612-2506
September 30, 2019
Warning Letter #OBPO 19-11
Dear Ms. Birsinger
The United States Food and Drug Administration (FDA) conducted an inspection of your firm, Family Fertility Center, located at 6651 Main Street, Ste. E350, Houston, TX, from June 18, 2019 to June 26, 2019. 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, lnspectional 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 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)]. For example:
a. There is no evidence that donor screening included an assessment of communicable disease risk factors for six of (b)(4) directed or anonymous donors. For example:
i. Directed oocyte donor (b)(6) who was determined to be eligible on (b)(6)
ii. Anonymous oocyte donor (b)(6) who was determined to be eligible on (b)(6).
b. FDA has identified that Zika virus (ZIKV) is 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 of HCT/Ps is free from risk factors for, or clinical evidence of, ZIKV infection for the purpose of determining donor eligibility. You failed to screen your donors for the following risk factors for ZIKV:
i. Medical diagnosis of ZIKV infection in the past six months
ii. Residence in, or travel to, an area with active ZIKV transmission within the past six months
iii. Sex within the past six months with a person who is known to have either of the risk factors listed in the above two bullets.
2) 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 [1271.50(a)]. The responsible person did not determine and document the eligibility of two anonymous oocyte donors based on a review of their health risk assessments, donor physical examinations, and donor testing results. For example:
a. Anonymous Oocyte Donor (b)(6) EDS (oocytes recovered on (b)(6))
b. Anonymous Oocyte Donor (b)(6) (oocytes recovered on (b)(6)).
3) Failure to determine as ineligible a donor who is identified as having a risk factor for, or clinical evidence of, any of the relevant communicable disease agents or diseases for which screening is required under 21 CFR 1271.75(a)(1), (b), or (c) [1271.75(d)]. For example, anonymous oocyte donor (b)(6) who traveled to Aruba, a ZIKV transmission risk area in (b)(6), was determined eligible on (b)(6).
4) Failure to establish and maintain procedures for all steps performed in testing, screening, and determining of donor eligibility, and complying with all other requirements of subpart C "Donor Eligibility" in 21 CFR Part 1271.45-1271.90. "Establish and maintain" mean define, document, and implement; then follow, review, and as needed, revise on an ongoing basis [21 CFR 1271.47(a)]. For example:
a. You have not established a written procedure that includes screening for risk factors related to ZIKV and how to evaluate donors with identified risk factors for ZIKV.
b. Your procedure, Reproductive Donor Eligibility Determination (FFC.REI.FDA.SOP.200A, version date: April 01, 2015) states that donor eligibility is documented on the "Donor Eligibility-Summary of Records" form. However, at least nine anonymous oocyte donors did not have a donor eligibility determination documented in accordance with 21 CFR 1271.50(a).
c. Though you test donors for these viruses, your procedure, Reproductive Donor Communicable Disease Testing (FFC.REI.FDA.SOP.200B, version date: April 01, 2015) does not include Hepatitis B virus (HBV) NAT and West Nile virus (WNV) NAT as required donor screening tests to adequately and appropriately reduce the transmission of relevant communicable diseases.
We acknowledge receipt of your response dated July 16, 2019, to the Form FDA 483. We have reviewed your response, and we are providing the following comments:
In your response to observations 1, 2, and 3, you stated that your donor screening forms and procedures were updated to include donor eligibility determination, ZIKV screening questions and other missing screening and testing requirements. These documents will be reviewed during the next inspection of your establishment to confirm that they are in compliance with 21 CFR 1271.
We also note that Attachment 5, as referenced in item 4c of this letter, does not include HBV NAT and West Nile Virus NAT as required donor screening tests, though you do test donors for these viruses. In addition, Attachment 7, Donor Eligibility-Summary of Records (FCC.RELFDA.FORM 200D, version date: April 01, 2015) does not include HBV NAT and West Nile Virus NAT, nor does it include the donor type (i.e., anonymous or directed donor).
In your response to observation 4, you stated your procedure, Reproductive Donor Eligibility Determination (FFC.REI.FDA.SOP.200A, updated June 27, 2019) reflects that donor eligibility screening is to be completed for each donor and reviewed/signed by the medical director or other responsible person. These documents will be reviewed during the next inspection of your establishment to confirm they are in compliance with 21 CFR 1271. Finally, we note that you have not updated your donor screening procedure to include the requirement to screen donors for risks of ZIKV.
If you still have oocytes or semen in storage from donors who were not screened for risk factors for relevant communicable diseases or disease agents in accordance with the regulations in 21 CFR Part 1271, 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 oocytes or semen 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.
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).
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 ensure that you are in full compliance with all FDA regulatory requirements.
You should take prompt action to correct these deviations. 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 of receipt of this letter outlining the specific steps you have taken to correct the noted violations, including an explanation of your plan to prevent these violations or similar violations from occurring again. Include any documentation necessary to show that correction has been achieved. If you cannot complete all corrective actions within fifteen (15) working days, please explain the reason for your delay and the timeframe within which the remaining corrections will be completed.
Your response should be sent to the following address: Michele L. Forster, PhD, compliance officer, U.S. Food & Drug Administration, Office of Biological Product Operations - Division 2, 678 Front Ave. NW, Suite 225, Grand Rapids, Ml 49504 or emailed to Michele.Forster@fda.hhs.gov. If you should have any questions, please contact Michele Forster at (616) 233-9311 (ext. 1017) or via e-mail.
Karlton T. Watson
Program Division Director
Office of Biological Products Operations - Division 2