Inspections, Compliance, Enforcement, and Criminal Investigations
Family Beginnings, PC 6/15/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
300 River Place
Detroit, Ml 48207
June 15, 2012
James G. Donahue, MD
Family Beginnings, PC
Family Beginnings, PC
8435 Clearvista Place, Suite 104
Indianapolis, IN 46256
Dear Dr. Donahue:
The Food and Drug Administration (FDA) conducted an inspection of your firm, Family Beginnings, PC, located at 8435 Clearvista Place, Suite 104, Indianapolis, IN, from May 1, 2012 through May 8, 2012. During the inspection, the 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, Part 1271 (21 CFR 1271), and issued under the authority of Section 361 of the Public Health Service Act (42 USC 264).
The deviations documented on the Form FDA-483, Inspectional Observations, were presented to and discussed with you, your Embryologist, Roxanne Williams, and Office Manager, (b)(6) 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 and tissue, whether viable or nonviable, for evidence of infection due to relevant communicable disease agents [21 CFR 1271.85(a)]. For example,
a. Directed semen donor (b)(6) was determined eligible on (b)(6). Semen was collected from donor (b)(6) on (b)(6) and four vials were cryopreserved. Donor (b)(6) was not tested for human immunodeficiency virus, type 1 (HIV-1) and type 2 (HIV-2), hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum.
b. On (b)(6) oocytes were recovered from directed donor (b)(6) and were fertilized with semen from the recipient’s partner. Donor (b)(6) was determined eligible, although the relevant communicable disease testing results, reported on December 31, 2011, did not include testing for HIV-1 and HCV by the nucleic acid test (NAT) method and Treponema pallidum.
2. Failure to test a specimen from an anonymous or directed reproductive donor of viable, leukocyte-rich cells or tissue to adequately and appropriately reduce the risk of transmission of relevant cell-associated communicable diseases including Human T-lymphotropic virus, types I and II (HTLV-I/II) and/or cytomegalovirus (CMV) [21 CFR 1271.85(b)]. For example, directed semen donor (b)(6) was determined eligible on (b)(6). Semen was collected from donor (b)(6) on (b)(6) and four vials were cryopreserved. Donor (b)(6)was not tested for HTLV-I/II and CMV.
3. 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 [21 CFR 1271.85(c)]. For example, (b)(6) oocytes were recovered from anonymous donor (b)(6) on (b)(6), and were fertilized with semen from the recipient’s partner. Donor (b)(6) was determined eligible, although the relevant communicable disease testing results, reported on October 7, 2010, did not include testing for Chlamydia trachomatis and Neisseria gonorrhea.
4. Failure to determine as ineligible, a donor who has risk factors for, or clinical evidence of, relevant communicable disease agents or diseases [21 CFR 1271.75(d)]. For example, directed semen donor (b)(6) provided a history of living in the United Kingdom for more than five years between 1980 and 1996, but was not determined to be ineligible due to risk factors for variant Creutzfeldt-Jakob disease (vCJD). The “Donor Eligibility Determination Form” for donor (b)(6) documented that review of all screening, physical assessments, medical records, and test results were “Not Required.”
5. Failure to screen an anonymous or directed reproductive 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 1271.75(a)]. For example, records for directed semen donor (b)(6) did not include documentation of a physical examination, noted in 21 CFR 1271.3(s) as part of the donor’s relevant medical records.
The above identified violations 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 operations as a whole to assure you are in compliance with all of the FDA regulatory requirements. We acknowledge receipt of your letter dated May 27, 2012, that provides a response to FDA’s inspectional observations.
We have reviewed the corrective actions summarized in your response and we have determined that the response is inadequate to address our concerns, as specified below.
Your response to FDA-483 Observations 1A and 2 discusses your justification for determining as eligible directed semen donor (b)(6) who was not screened or tested as required by 21 CFR 1271.50 and had a risk factor for variant Creutzfeldt-Jakob disease due to having lived in the United Kingdom. Under 21 CFR 1271.50, you must determine whether a donor is eligible based on the results of donor screening in accordance with 1271.75 and donor testing in accordance with 1271.80 and 1271.85. A complete donor screening and donor testing for relevant communicable disease agents are required for both anonymous and directed donors. Under 21 CFR 1271.65(b)(1), an HCT/P from a directed reproductive donor who has been determined ineligible is not prohibited, provided the HCT/P is labeled in accordance with 1271.65(b)(2).
Regarding testing of directed semen donors for relevant communicable diseases, we note that under 21 CFR 1271.80(b), you must collect a donor specimen for testing at the time of recovery of cells or tissue from the donor; or up to seven days before or after recovery. In the Guidance for Industry: Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) (August 27, 2007), FDA clarifies that follow-up testing is not required when semen is donated for directed use. This applies to the requirement for anonymous semen donors to be tested at the time of recovery of cells or tissue and again (follow-up testing) at least six months after donation, during which time the semen donation is under quarantine. This follow-up testing after six-month quarantine is not required for directed semen donors. However, directed donors are required to be tested for all relevant communicable diseases at the time of each donation.
In your response to FDA-483 Observation 1B, regarding the failure to test directed oocyte donor (b)(6) for HIV-1 and HCV by the nucleic acid test (NAT) method and Treponema pallidum, within 30 days of retrieval, your response states that the donor’s “blood tests were on 32 days before the transfer” due to an extended period of ovary stimulation. Under 21 CFR 1271.80(b), you must collect a donor specimen for testing at the time of recovery of cells or tissue from the donor; or up to 30 days before or seven days after recovery for oocyte donors. The results of the testing must be used to determine donor eligibility under 21 CFR 1271.50, prior to the transfer of HCT/Ps to a recipient. It appears the donor specimen for testing was collected (b)(6) within 30 days of oocyte recovery (b)(6). However, you also stated in your response that although it was your intention to have the testing done within the 30 day timeframe, “these tests were negative,” and you provided a copy of the testing results for donor (b)(6) specimen collection date). We note that while all of the reported testing results were negative, the testing did not include HIV-1 and HCV NAT and Treponema pallidum, as required. Your response did not address this missing testing.
In your response to FDA-483 Observation 1C, regarding the failure to test anonymous oocyte donor (b)(6) for Chlamydia trachomatis and Neisseria gonorrhea, we note that you provided a “corrected” donor eligibility determination form for this donor. The form is documented with the following statements: “Not Evaluated for Infectious Substance GC, CT” and “Warning: Advise Patient of Communicable Disease Risks.” Under 21 CFR 1271.50, you must determine whether a donor is eligible based on the results of donor screening in accordance with 1271.75 and donor testing in accordance with 1271.80 and 1271.85. A donor who has not undergone all required testing and screening has an incomplete donor eligibility determination and is not eligible for donation. In addition, donations from an anonymous reproductive donor, who has been determined ineligible, are not allowed under 21 CFR 1271.
While your corrective actions appear to address your plan to ensure that future donors are tested to adequately and appropriately reduce the risk of transmission of relevant communicable diseases, you did not indicate how you plan to address the failure to determine the eligibility of previously accepted donors for whom communicable disease testing was not completed, as required. You stated that, “we are working to get re-testing done” for semen donor (b)(6), but you did not address oocyte donors (b)(6) and (b)(6). In addition, you did not indicate whether you plan to review other donor records to determine the adequacy of testing.
You should take prompt action to correct these deviations and prevent their recurrence. Failure to do so may result in regulatory action being initiated by the Food and Drug Administration without further notice.
We request that you notify this office in writing, within fifteen (15) working days of the receipt of this letter, of the specific steps you have taken to correct the noted deviations and prevent their recurrence. If corrective action cannot be completed within 15 working days, please state the reason for the delay and the time frame within which the corrections will be completed.
Your response should be sent to: CDR Kimberly Martin, Compliance Officer, 101 W. Ohio Street, Suite 500, Indianapolis, IN 46204. If you have any questions about the content of this letter please contact: CDR Martin at (317) 226-6500 ext. 116.
Glenn T. Bass
Detroit District Office