- New Hope Fertility Center
- Issuing Office:
- New York District Office
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
New York District
158-15 Liberty Avenue
Jamaica, NY 11433
November 20, 2014
WARNING LETTER NYK 2015-7
VIA UNITED PARCEL SERVICE
Dr. John Zhang, Medical Director & Tissue Bank Director
New Hope Fertility Center
4 Columbus Circle, Floors 3 & 4
New York, NY 10019-1100
Dear Dr. Zhang:
The United States Food and Drug Administration (FDA) conducted an inspection of your firm, New Hope Fertility Center, located at 4 Columbus Circle, Floors 3 & 4, New York, NY, from August 26, 2014 through September 15, 2014. 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, 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, List of Inspectional Observations, were presented to and discussed with you at the conclusion of 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 in order to adequately and appropriately reduce the risk of transmission of relevant communicable diseases [21 CFR 1271.85(a)]. For example, the donor specimen collected from anonymous oocyte donor (b)(4) on March 27, 2014 was not tested for the antibody to Hepatitis B core antigen and human immunodeficiency virus, type 1 (HIV-1) and hepatitis C virus (HCV) by the nucleic acid test (NAT) method. Despite the missing test results, the donor was determined eligible and oocytes were recovered on April 20, 2014.
2. 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), (b), or (c) [21 CFR 1271.75(d)(1)]. For example:
a. Anonymous oocyte donor (b)(4) tested positive for Chlamydia trachomatis on August 15, 2013. The donor returned on October 11, 2013 and was retested for Chlamydia trachomatis and the results were negative. A note in the donor’s record documented that the donor was treated with antibiotics. Donor (b)(4) was subsequently determined eligible and oocytes were recovered on November 20, 2013.
b. On a Donor Medical History Interview Questionnaire date July 28, 2014, anonymous oocyte donor (b)(4) answered “yes” to the health history questions, “Since 1980, have you ever lived in or traveled to Europe?” and “Since 1980 have you spent time that adds up to 5 years or more in Europe (including time spent in the U.K. between 1980 and 1996)?” A note on the donor’s record indicated that the donor came to the U.S. from Europe in August 2013. Despite the donor’s risk factor for human transmissible spongiform encephalopathy, including variant Creutzfeldt-Jakob disease (vCJD), donor (b)(4) was determined eligible and oocytes were recovered on July 30, 2014.
3. Failure to collect donor specimens for testing for relevant communicable diseases at the time of recovery of the cells or tissue from the donor; or for oocyte donors, within 30 days prior to oocyte recovery or up to seven days after recovery [21 CFR 1271.80(b)]. For example:
a. The specimen from anonymous oocyte donor (b)(4) was collected on October 22, 2012; however oocytes were recovered from donor (b)(4) on December 18, 2012.
b. The specimen from anonymous oocyte donor (b)(4) was collected on August 16, 2013; however oocytes were recovered from donor (b)(4) on September 24, 2013.
4. Failure to maintain documentation of the results and interpretation of all donor screening for communicable diseases in compliance with 21 CFR 1271.75 [21 CFR 1271.55(d)(1)(ii)]. For example, the documentation of the physical examination for at least six donors was incomplete, in that documentation of the screening of the donor for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases was missing.
5. Failure to maintain documentation of the donor-eligibility determination, including the name of the responsible person who made the determination and the date of the determination. All records must be accurate, indelible, and legible [21 CFR 1271.55(d)(1)(iii) and (d)(2)]. The records for the following donors contained either an Initial Donor Eligibility Determination form or Repeat Donor Eligibility Determination form; however one or more of the following items was missing from the forms: 1) documentation that the donor was determined “eligible;” 2) the name of the responsible person who made the determination; and 3) the date of the determination. For example:
a. Donor (b)(4) (oocyte recovery dates: 1/27/13; 5/24/13; 12/23/13; 4/29/14 )
b. Donor (b)(4) (oocyte recovery date: 4/26/14)
c. Donor (b)(4) (oocyte recovery date: 7/30/14)
d. Donor (b)(4) (oocyte recovery dates: 8/28/13; 4/28/14)
e. Donor (b)(4) (oocyte recovery date: 7/20/14)
6. Failure to establish and maintain procedures for all steps performed in the testing, screening, 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)]. Specifically, your procedure, H.1. Modalities for the Rejection of Anonymous Donors, is not in compliance with the requirements of 21 CFR 1271. For example:
a. The section entitled “Laboratory Tests, 3. Hepatitis Profile” states, “For a donor to remain in the program, both the HBcAb and the HBsAg must be found to be negative. Donors testing HBsAb(+), HBcAb(+), HBsAg(-) have had prior exposure to the virus and are not infectious. It is perfectly safe to use these donors.” Under 21 CFR 1271.80(d), you must determine to be ineligible a donor whose specimen tests reactive on a screening test for a communicable disease agent in accordance with Sec. 1271.85. This includes a reactive screening test for the antibody to Hepatitis B core antigen (HBcAb).
b. The section entitled “Laboratory Tests, 3. Hepatitis Profile” states, “A donor will be excluded from the program if HBcAb is positive in conjunction with a negative HBsAg and negative HBsAb. They may be in the window of seroconversion and should not be used and should be retested in 1 to 2 months.” Under 21 CFR 1271.80(d), you must determine to be ineligible a donor whose specimen tests reactive on a screening test for a communicable disease agent in accordance with Sec. 1271.85. This includes a reactive screening test for the antibody to Hepatitis B core antigen (HBcAb).
c. The section entitled “Laboratory Tests, 4. HIV Tests” states, “A seropositive test with a confirmatory Western Blot test will permanently exclude an individual from becoming a donor.” Under 21 CFR 1271.80(d), you must determine to be ineligible a donor whose specimen tests reactive on a screening test for a communicable disease agent in accordance with Sec. 1271.85. This includes a reactive screening test for the antibodies to human immunodeficiency virus, types 1 and 2 (anti-HIV-1/2).
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 all of the FDA regulatory requirements.
We acknowledge receipt of your letter dated October 3, 2014, which provides a response to FDA’s inspectional observations. We have reviewed the corrective actions outlined in the response and we have determined that the response is inadequate to address our concerns. The response outlines changes to your donor testing and screening procedures, including implementation of revised forms. However, your response addresses only prospective changes to your practices and does not address the inadequacy of donor screening and relevant communicable disease testing for previous HCT/P donors. You did not discuss plans to review previous donor records to determine whether additional violations exist.
In addition, you did not address the increased risk of communicable disease transmission for HCT/Ps remaining in storage at your Establishment. Regarding donors whose eligibility determination was not performed according to the requirements of 21 CFR 1271.50, the use of HCT/Ps from these donors is not in compliance with 21 CFR 1271. In order to utilize such HCT/Ps, you must submit to FDA a request for an exemption from a requirement in 21 CFR 1271, Subpart C including supporting documentation to show how you will mitigate the risks of communicable disease transmission to the recipient(s), in accordance with 21 CFR 1271.155.
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, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. 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.
Please send your written response to the Food and Drug Administration; Attention:
LCDR Frank Verni, R.Ph.
U. S. Food and Drug Administration
158-15 Liberty Avenue, Room 4050
Jamaica, NY 11433
If you have any questions about the content of this letter please contact: LCDR Verni at (718) 662-5702.
Ronald M. Pace
New York District
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