Inspections, Compliance, Enforcement, and Criminal Investigations
Reproductive Medicine Associates of Michigan 1/06/09
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
300 River Place
Detroit, MI 48207
RETURN RECEIPT REQUESTED
January 6, 2009
Bradley T. Miller, M.D.
Reproductive Medicine Associates of Michigan
130 Town Center Drive, Suite 106
Troy, Michigan 48084-1744
Dear Dr. Miller:
The Food and Drug Administration (FDA) conducted an inspection of your firm, Reproductive Medicine Associates of Michigan, located at 130 Town Center Drive, Suite 106, Troy, Michigan, from September 8, 2008 through September 15, 2008. During this inspection, the FDA investigators documented significant deviations from the regulations for human cells, tissues, and cellular and tissue-based products (HCT/P's) 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 were presented to, and discussed with, you and your partner, Dr. Lynda Wolf, 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 nonviable, for evidence of infection due to relevant communicable disease agents [21 CFR 1271.85(a)]. Specifically, your establishment failed to adequately and appropriately test for human immunodeficiency virus, type 1 and hepatitis C virus by the nucleic acid test (NAT) method for the following anonymous oocyte donors:a. Oocytes were recovered from donor #797 on December 1, 2007. Two resulting embryos were transferred to a recipient on December 6, 2007. Six resulting embryos were cryopreserved for future use.
b. Oocytes were recovered from donor #964 on October 2, 2007. Two resulting embryos were transferred to a recipient on October 7, 2007. Two resulting embryos were cryopreserved for future use.
c. Oocytes were recovered from donor 41132 on November 25, 2007. Two resulting embryos were transferred to a recipient on November 30, 2007. Three resulting embryos were cryopreserved for future use.
d. Oocytes were recovered from donor #830 on September 12, 2007. Two resulting embryos were transferred to a recipient on September 15, 2007.
e. Oocytes were recovered from donor #1060 on October 6, 2007. Two resulting embryos were transferred to a recipient on October 11, 2007. One resulting embryo was cryopreserved for future use.
2. Failure to collect a donor specimen for testing for relevant communicable diseases within 30 days prior to oocyte recovery or up to 7 days after oocyte recovery or up to 7 days before or after recovery for semen donors [21 CFR 1271.80(b)]. Specifically, records indicate that a donor specimen was not collected within the required timeframe for directed oocyte donor A.B. The viral marker testing for donor A.B. occurred on April 11, 2008; however oocyte recovery was performed on July 24, 2008. Three resulting embryos were transferred to a recipient on July 29, 2008.
3. 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). and 21 CFR 1271.75(e)]. Specifically, records for the following donors did not include documentation of a donor medical history interview, as defined in 21 CFR 1271.3(n), and/or physical examination of a living donor (both required as relevant medical records under 21 CFR 1271.3(s)). As a result, there was no documentation related to risk factors for the relevant communicable disease agents listed in 21 CFR 1271.3(r).
a. Oocytes were recovered from anonymous donor # 1132 on May 12, 2008 and resulting embryos were transferred to a recipient. The last documented physical examination was performed June 29, 2007.
b. Oocytes were recovered from anonymous donor #1469 on December 12, 2007 and July 18, 2008 and resulting embryos were transferred to two recipients. Records for donor #1469, a repeat donor, did not include documentation of a complete donor screening or abbreviated donor screening. The last documented physical examination was performed September 24, 2007.
c. Oocytes were recovered from anonymous donor #919 on May 17, 2008 and July 27, 2008 and resulting embryos were transferred to two recipients. Records for donor #919, a repeat donor, did not include documentation of a complete donor screening. The last documented complete donor screening and physical examinations were performed May 30, 2007.
d. Oocytes were recovered from anonymous oocyte donor #10 14 on January 16, 2008 and resulting embryos were transferred to a recipient. Records for donor #1014, a repeat donor, did not include documentation of a complete donor screening or abbreviated donor screening. The last documented complete donor screening and physical examinations were performed July 19, 2007.
4. Failure of a responsible person to determine and document the eligibility of an anonymous or directed donor of reproductive cells or tissue [21 CFR 1271.50(a)]. Specifically, no documentation was found during the review of anonymous oocyte donor records for #1061, #830, #797 and #1643 to substantiate that a responsible person from your firm had determined these donors to be eligible to donate. Oocytes were recovered from these four donors and resulting embryos were transferred to recipients.
5. Failure to keep an HCT/P in quarantine until completion of the donor-eligibility determination required by 21 CFR 1271.50 [21 CFR 1271.60(a)]. Specifically, oocytes were recovered from anonymous donor # 1132 on November 25, 2007. The embryology worksheet for donor 1132 documents that the oocytes were placed inside incubator #5; however, incubator #10 was the designated quarantine incubator.
6. Failure to establish and maintain procedures for all steps that you perform in testing, screening, determining donor eligibility, and complying with all other requirements of 21 CFR Part 1271, Subpart C - Donor Eligibility. "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 firm's standard operating procedures do not address all steps required for donor screening and determining donor eligibility, including, but not limited to: (1) donor screening for risk factors for, or clinical evidence of relevant communicable disease agents and diseases; and (2) the criteria used to determine donor eligibility and ineligibility.
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 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 October 10, 2008 that 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 procedures, including implementation of revised forms and the implementation of a new protocol. While these corrective actions may address communicable disease testing and donor eligibility of future donors, you did not indicate how you plan to address the failure to determine the eligibility of previously accepted donors for whom communicable disease testing and donor eligibility determinations were not completed prior to transfer of resulting embryos. Please explain what corrective action you will take in regard to completing eligibility determinations and communicable disease testing for these donors.
You should take prompt action to correct these deviations and to prevent their recurrence. Failure to do so may result in further regulatory action. For example, FDA may issue an order to cease manufacturing of HCT/P's.
We request that you notify this office in writing, within fifteen (15) working days of receipt of this letter, with further details of the specific steps you have taken to correct the noted deviations, including an explanation of each step being taken to prevent the recurrence of similar deviations. 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 reply should be sent to the Sandra Williams, Compliance Officer, Food and Drug Administration, 300 River Place, Suite 5900, Detroit, Michigan 48207. If you have any questions, please feel free to contact Ms. Williams at (313) 393-8118.
Joann M. Givens
Individual copy sent via certified mail to firm address to: Lynda Wolf, M.D., Partner