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WARNING LETTER

University of Miami Reproductive and Fertility Center MARCS-CMS 568208 —

Product:
Biologics

Recipient:
Recipient Name
George Attia, MD
Recipient Title
Medical Director
University of Miami Reproductive and Fertility Center

1400 NW 12th Avenue, Suite 5

Miami, FL 33136-1003
United States

Issuing Office:
Center for Biologics Evaluation and Research

United States


WARNING LETTER

VIA UNITED PARCEL SERVICE
SIGNATURE REQUIRED

December 3, 2018 

Warning Letter # OBPO 19-04


George Attia, MD
Medical Director
University of Miami Reproductive and Fertility Center 
1400 NW 12th Avenue, Suite 5
Miami, FL 33136-1003

Dear Dr. Attia: 

The United States Food and Drug Administration (FDA) conducted an inspection of your firm, University of Miami Reproductive and Fertility Center, located at 1400 NW 12th Avenue, Suite 5, Miami, Florida, from July 10, 2018 thru July 12, 2018. 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 United States Code § 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 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) [21 CFR 1271.75 (d)(1)]. From July 29, 2016 to June 2, 2017, Miami-Dade County in Florida was listed as an area at increased risk for Zika virus (ZIKV) transmission. Your establishment is located in Miami-Dade County, therefore, HCT/P donors who traveled to your establishment during this time period were at increased risk for ZIKV transmission and should have been determined ineligible due to ZIKV risk. For example:

a.  Directed oocyte donor (b)(6) was determined eligible on February 24, 2017. Oocytes were recovered on February 28, 2017. 

b.  Semen was recovered on February 28, 2017 from directed semen donor (b)(6). However, the donor’s ZIKV risk was not evaluated.

c.  Oocytes were recovered on March 7, 2017 from directed oocyte donor (b)(6). However, the donor’s ZIKV risk was not evaluated.

2)    Failure to prominently label an HCT/P, for which a donor eligibility determination is not required, with the Biohazard legend shown in 21 CFR 1271.3(h), if the results of any screening or testing performed indicate risk factors for or clinical evidence of communicable disease agents or diseases [21 CFR 1271.90(c)(4)(ii)]. For example, semen donor (b)(6) resided in an area with active ZIKV transmission at the time of donation and also answered “yes” to the question regarding having lived cumulatively for 5 years or more in Europe from 1980 until the present. Semen was recovered from donor (b)(6) on January 5, 2017, for use with a sexually intimate partner. Regardless of the risk factors identified for ZIKV and Creutzfeldt-Jacob disease, the semen was not labeled in accordance with 21 CFR 1271.90(c)(4)(ii). 

3)    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.  Your self-administered Donor Medical History Interview Form fails to include questions to assess a donor’s relevant communicable disease risk for the following:

1. Medical diagnosis of ZIKV in the past 6 months.

2. Residence in, or travel to, an area with an increased risk for ZIKV transmission within the past 6 months.

3. Sex within the past 6 months with a person who has either a medical diagnosis of ZIKV in the past 6 months or has resided in, or traveled to, an area with an increased risk for ZIKV transmission within the past 6 months.

4. Persons who have been treated for or had syphilis within the preceding 12 months.

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

6. Persons who tested positive or reactive for West Nile Virus (WNV) infection using an FDA-licensed or investigational WNV NAT donor screening test in the preceding 120 days.

b.  Question 13 on your Donor Medical History Interview Form regarding a medical diagnosis of WNV infection states, “If the answer is yes to this question defer donation for 28 days from onset of symptoms….” However, persons who have had a medical diagnosis or suspicion of WNV infection should be deferred for 120 days following diagnosis or onset of illness, whichever is later. (See section IV.E of the HCT/P Donor Eligibility Determination Guidance). 

4.    Failure of a responsible person to determine and document the eligibility of a cell or tissue donor [21 CFR 1271.50(a)]. For example, the records for directed oocyte donor (b)(6) did not contain any documentation that the donor was determined “eligible.” Oocytes were recovered from donor (b)(6) on March 7, 2017.

5.    Failure to determine whether a donor is eligible based upon the results of donor screening in accordance with 1271.75 and donor testing in accordance with 1271.80 and 1271.85 [(21 CFR 1271.50(a)]. For example: 

a.  A specimen for communicable disease testing was collected from anonymous oocyte donor (b)(6) on June 14, 2016. The donor was determined eligible the same day, however the test results were not reported until June 15, 2016.

b.  Directed oocyte donor (b)(6) was determined eligible on February 24, 2017. However, there was no documentation of a donor medical history interview and physical examination. In addition, a specimen for communicable disease testing was collected on February 24, 2017; the same day the donor was determined eligible. However, the results were not reported until February 27, 2017.

c.  There was no documentation of a donor medical history interview and physical examination for directed semen donor (b)(6). In addition, a specimen for communicable disease testing was collected on February 24, 2017; the same date the donor eligibility determination was documented. However, the results were not reported until February 27, 2017.

d.  Directed oocyte donor (b)(6) was determined eligible on May 10, 2018. However, the donor medical history interview and physical examination forms were not completed until May 12, 2018.

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 July 27, 2018, which provides a response and corrective actions to FDA’s inspectional observations (FDA-483). We have reviewed your response, and we are providing the following comments:

In response to Observations 1, 2, and 6, you stated that your donor screening forms and procedures were updated to include the 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. However, we note that your response did not include a plan to notify recipients who received HCT/Ps from donors who had an increased risk for ZIKV at the time of donation. 

In response to Observations 3 and 4, you stated that your corrective action was to review and sign the appropriate forms in a timely manner based on the results of donor screening and testing. However, we note that these two observations were also cited during the previous inspection of your establishment conducted from November 19, 2015 to December 2, 2015. Your corrective actions, if any, after the previous inspection were not adequate to prevent recurrence of the same violations, as they were cited again during the current inspection.

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.

Your response should be sent to the following address: U.S. Food and Drug Administration, Cherlita Honeycutt, 6000 Metro Drive, Suite 101, Baltimore, Maryland 21215 or emailed to Cherlita.Honeycutt@fda.hhs.gov. If you should have any questions, please contact Cherlita Honeycutt, Compliance Officer, at (410) 779-5412 or via email. 

Sincerely,

/S/

Elizabeth A. Waltrip
Program Division Director
Office of Biological Products Operations – Division I