WARNING LETTER

The Fertility Partnership LLC MARCS-CMS 553045 — May 24, 2018

Recipient:: Recipient Name

David E Simckes, MD; The Fertility Partnership LLC; 5401 Veterans Memorial Pkwy
St Peters, MO 63376
United States

Issuing Office:: Chicago District Office; United States

Chicago District Office
550 W. Jackson Blvd., 15th Floor
Chicago, IL 60661
Telephone: (312) 353-5863
Fax: (312) 596-4187

WARNING LETTER

VIA UNITED PARCEL SERVICE

SIGNATURE REQUIRED

May 24, 2018
[Warning Letter #OBPO 18-04]

David E Simckes, MD, Medical Director

The Fertility Partnership LLC

5401 Veterans Memorial Pkwy

Saint Peters, MO 63376

Dear Dr. Simckes:

The United States Food and Drug Administration (FDA) conducted an inspection of your firm, The Fertility Partnership LLC, located at 5401 Veterans Memorial Pkwy, Saint Peters, Missouri, from February 21 through March 5, 2018. During the inspection, an FDA Investigator documented deviations from the regulations governing human cells, tissues, and cellular and tissue-based products (HCT/Ps) set forth in Title 21, Code of Federal Regulations, Part 1271 (2 1 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, 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 test a specimen from an anonymous or directed donor of reproductive cells or tissue, whether viable or non-viable, for evidence of infection due to relevant communicable disease agents [21 CFR 1271.85(a)]. For example:

a. The donor specimen collected from anonymous oocyte donor (b)(6) on (b)(6), 2017 was not tested for human immunodeficiency virus, type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV) and West Nile Virus (WNV) by the nucleic acid test (NAT) method.

b. The donor specimen collected from anonymous oocyte donor (b)(6) on (b)(6), 2017 was not tested for HIV-1/HCV/HBV NAT and Hepatitis B Surface Antigen (HBsAg). Donor (b)(6) was determined eligible on (b)(6), 2017.

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 donor testing [21 CFR 1271.50(a)]. For example:

a. The eligibility determination was made for directed oocyte donor (b)(6) without a review of the results of donor testing. The specimen for communicable disease testing for HIV-1 /HCV/HBV NAT was collected on (b)(6), 2016. The donor was determined to be eligible on (b)(6), 2016, but the results were not reported untiI (b)(6), 2016.

b. The "Donor Eligibility Determination Form" for anonymous oocyte donor (b)(6) oocyte recovery: (b)(6), 2017) was not signed by a responsible person.

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)]. For example, FDA has identified Zika virus (ZIKV) as a relevant communicable disease agent or disease (RCDAD) 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 is free from risk factors for, or clinical evidence of, ZIKV infection for the purpose of determining donor eligibility. Your "Donor Medical History Interview Form" does not adequately assess a donor's residence in, or travel to, areas with active ZIKV transmission, according to the Centers for Disease Control and Prevention. The following donors were not adequately screened for ZIKV at the time of donation:

a. Directed oocyte donor (b)(6) [donor questionnaire dated (b)(6), 2016]
b. Anonymous oocyte donor (b)(6) [donor questionnaire dated (b)(6), 2017]
c. Anonymous oocyte donor (b)(6) [donor questionnaires dated (b)(6), 2017 and (b)(6), 2017]
d. Anonymous oocyte donor (b)(6) [donor questionnaire dated (b)(6), 2017]

4. Failure to test using appropriate FDA-licensed, approved or cleared donor screening tests, in accordance with the manufacturer's instructions, to adequately and appropriately reduce the risk of transmission of relevant communicable disease agents or diseases [21 CFR 1271.80(c)]. For example,the specimen for communicable disease testing, collected from anonymous oocyte donor (b)(6) on (b)(6), 2017, was tested for HCV NAT using a test kit that was not FDA-licensed, approved, or cleared for donor screening.

5. Failure to maintain records that are accurate, indelible, and legible (21 CFR 1271.55(d)(2)]. For example, the "Donor Eligibility Determination Form" for donor (b)(6) donor eligibility determination: (b)(6), 2017) did not include a distinct identification code in order to relate the record to a specific donor.

6. Failure to establish and maintain procedures for all steps performed in testing, screening, and 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, documents, and implement; then follow, review, and as needed, revise on an ongoing basis [21 CFR 1271.47(a)]. For example, your procedures do not include the requirement to screen donors for ZIKV and test donors for WNV and Hepatitis B by NAT to adequately and appropriately reduce the risk of transmission of relevant communicable diseases.

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 response dated March 18, 2018, which provides a response to FDA 's inspectional observations. We have reviewed the corrective actions outlined in the response and we have detennined that they are inadequate to address our concerns.

We have specific comments regarding your response, as follows:

In response to Observations 1 and 4, you acknowledge that donor testing was performed using test kits that were not FDA-licensed, approved, or cleared donor screening tests as required by 21 CFR 1271.80(c) and stated, "Our team erroneously assumed that by requesting NAT from (b)(4) labs on the requisition that it would be performed." 21 CFR 1271.150(c)(iii) requires that before entering into a contract, agreement or other arrangement with another establishment to perform any step in manufacture for you (which includes donor testing), you must ensure that the establishment complies with applicable CGTP requirements.

It is your responsibility to confirm that the testing lab you are using is registered with FDA, is CLIA certified, and is using FDA-licensed, approved, or cleared donor screening tests. You must also ensure that your establishment is requesting the appropriate HCT/P donor screening tests for your donors. Our review of the donor testing records collected during your recent inspection noted that there appears to be additional examples of donor testing for relevant communicable diseases that was performed using test kits that are not FDA-licensed, approved, or cleared for donor screening and/or donors who were missing requ ired donor screening tests.

For example, donor (b)(6) (specimen collection date: (b)(6), 2017 does not appear to have been tested for Hepatitis B Surface Antigen at the time of donation. Donor (b)(6) (specimen collection date: (b)(6), 2017) may have been tested for anti-HIV- 1/2 using a test kit that was not FDA-licensed, approved, or cleared for HCT/P donor screening. Please note that these are not the only examples we identified. You should review your donor records to identify which of your donors were not tested in accordance with 21 CFR 1271.80 and 1271.85.

FDA considers the donor eligibility determination to be incomplete for donors who were not tested with test kits that are licensed, approved, or cleared for testing of HCT/P donors and for those who are missing required donor screening tests. Accordingly, you must follow the quarantine requirements in 21 CFR 1271.60 for HCT/Ps for such donors.

We are concerned about your ability to correct the violations noted above and prevent their recurrence. We acknowledge the voluntary suspension of your establishment's operations on multiple occasions to correct similar violations noted during inspections. However, deviations have recurred despite your attempts to correct them during these vo luntary suspensions. In addition, your response indicated that you recently had a "significant turnover in staffing" and we continue to be concerned about your ability to effect corrective actions after expanding your operations.

You should take prompt action to correct the violations described 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 and prevent their recurrence. 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: Samuel Labinjo, Compliance Officer, Food & Drug Administration, Office of Biological Product Operations - Division 2, 550 W. Jackson Chicago, IL 60661 or emailed to Samuel.Labinjo@fda.hhs.gov. If you should have any questions, please contact Sam Labinjo, Compliance Officer at 312-596-4254 or via e-mail.

Sincerely,

/S/

Karlton Watson

Program Division Director

Office of Biological Products Operations – Division 2