- Delivery Method:
- VIA UNITED PARCEL SERVICE
Recipient NameJose R. Huerta Rebozo, MD
Recipient TitleCEO, President, Medical Director
- Banco Vida Corp.
239 Arterial Hostos Avenue, Suite 604
Capital Center Building Torre Sur
San Juan 00918
- Issuing Office:
- Office of Biological Product Operations
March 4, 2020
Warning Letter# OBPO 20-597197
Dear Dr. Huerta:
The United States Food and Drug Administration (FDA) conducted an inspection of your firm, Banco Vida Corporation, located at 239 Arterial Hostos Avenue, Suite 604, Capital Center Building, Torre Sur, San Juan, PR 00918, from September 9 - 18, 2019 as well as at your laboratory location, Laboratorio Banco Vida, located at UPR Comprehensive Cancer Center, San Juan, PR 00935, from September 11 - 18, 2019. During the inspections, FDA investigators documented significant deviations from the regulations for Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)1 set forth in 21 CFR 1271, and issued under the authority of Section 361 of the PHS Act of the Public Health Service Act [42 U.S.C. § 264].
The deviations documented on the Form FDA-483, List of Inspectional Observations, were presented and discussed at the conclusion of each inspection. These items of concern include, but are not limited to, the items discussed below. Following our review of your responses dated September 23, 2019, and October 16, 2019 and the documents collected during the inspections, we identified additional concerns that are also included below.
1. Failure to screen a donor of cells or tissues 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)]. Your firm's Medical/Health History Form and Authorization to Collect is used as a relevant medical record to determine donor eligibility. However, the form does not include screening for all conditions and/or behaviors that increase a donor's relevant communicable disease risk. For example, questions for the following risk factors for relevant communicable disease agents and diseases are missing from your screening form:
a. Persons who have lived with (resided in the same dwelling) another person who has hepatitis B or clinically active (symptomatic) hepatitis C infection in the preceding 12 months;
b. Persons who have had a past diagnosis of clinical, symptomatic viral hepatitis after their 11th birthday;
c. Persons who have had a suspicion of West Nile Virus (WNV) infection;
d. Persons who have tested positive or reactive for WNV infection using an FDA-licensed or investigational WNV NAT donor screening test in the preceding 120 days;
e. Persons who have been treated for or had Chlamydia trachomatis or Neisseria gonorrhea infection in the preceding 12 months;
f. Persons who have been diagnosed with variant Creutzfeldt-Jacob disease (vCJD);
g. Persons who have been diagnosed with dementia or any degenerative or demyelinating disease of the central nervous system or other neurological disease of unknown etiology;
h. Persons who have had a medical diagnosis of Zika virus (ZIKV) in the past six months;
i. Persons who resided in, or traveled to, an area with an increased risk for ZIKV transmission within the past six months; and
j. Persons who have had sex within the past 6 months with a person who resided in, or traveled to, an area with an increased risk for ZIKV transmission within the past 6 months.
2. 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, a specimen for communicable disease testing, collected from the donor of umbilical cord blood unit (b)(6), (b)(4), was tested for syphilis using a test kit that was not FDA-licensed, approved, or cleared for donor screening.
3. Failure to adequately control environmental conditions and provide proper conditions for operations, where environmental conditions could reasonably be expected to cause contamination or cross-contamination of HCT/Ps or equipment, or accidental exposure of HCT/Ps to communicable disease agents [21 CFR 1271.195(a)]. Your establishment does not monitor the environment in the biological safety cabinet (BSC) used for processing of umbilical cord blood. Because umbilical cord blood is subject to microbiological contamination, environmental conditions could reasonably be expected to cause contamination or cross-contamination.
4. Failure to validate and approve a process according to established procedures where the results of processing cannot be fully verified by subsequent inspections and tests. The validation activities and results must be documented, including the date and signature of the individual(s) approving the validation [21 CFR 1271.230(a)]. For example, you failed to validate your HPC-C Manufacturing process, which cannot be fully verified, to ensure that your process prevents the introduction, transmission, or spread of communicable disease through the use of the HCT/P.
5. Failure to process each HCT/P in a way that does not cause contamination or cross-contamination during processing, and that prevents the introduction, transmission, or spread of communicable disease through the use of the HCT/P [21 CPR 1271.220(a)]. For example, during the inspection, two personnel were observed processing umbilical cord blood batches, (b)(6), (b)(4) and (b)(6), (b)(4), while alternating the use of the BSC and other equipment. This practice significantly increases the potential risk for cross-contamination.
6. Failure to investigate and document HCT/P deviations and trends of HCT/P deviations relating to core current good tissue practice (CGTP) requirements and make reports if required under §1271.350(b) or other applicable regulations. Each investigation must include a review and evaluation of the HCT/P deviation, the efforts made to determine the cause, and the implementation of corrective action(s) to address the HCT/P deviation and prevent recurrence [21 CPR 1271.160(b)(6)]. For example, umbilical cord blood units (b)(6), (b)(4) and (b)(6), (b)(4) had positive post-processing cultures. You failed to perform an investigation into the source of the microbiological contamination.
7. Failure to establish and maintain procedures for all steps performed in testing, screening, determining donor eligibility, and complying with all other requirements of Subpart C "Donor Eligibility" in 21 CPR 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 CPR 1271.47(a)]. For example, your procedures do not include the requirement to determine as ineligible donors who have a history of travel to or residence in an area with increased risk for ZIKV within the six months prior to donation of HCT/Ps.
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 letters dated September 23, 2019, and October 16, 2019, which provide responses to FDA's inspectional observations. We have reviewed your responses and have the following comments and concerns:
Banco Vida Corporation inspection:
1. In your response to observation 1, you stated that your donors are tested for ZIKV and only those with nonreactive ZIKV test results are accepted as donors. We note that establishments that manufacture umbilical cord blood, which is a HCT/P, must comply with FDA regulations in 21 CPR 1271 including donor screening and testing and compliance with current good tissue practice regulations. As such, umbilical cord blood products are regulated as HCT/Ps. We note that there are currently no available tests for ZIKV that are considered appropriate for preventing transmission of ZIKV through HCT/Ps. As noted in item 1 of this letter, you must screen donors for risk factors for and clinical evidence of ZIKV.
2. We acknowledge the Medical/Health History Form and Authorization to Collect form you submitted with your response to observation 1. However, as noted above in item 1 of the letter, the form does not include screening for all conditions and/or behaviors that increase a donor's relevant communicable disease risk.
3. In response to observation 2, you stated that 21 CFR 1271.65(b)(1) allows for the use of HCT/Ps from an ineligible donor for allogeneic use in a first-degree or second-degree blood relative. We agree that the regulations allow use of HCT/Ps from an ineligible donor in this situation, provided the HCT/P is properly labeled, and you retain documentation indicating the physician using the HCT/P, was notified of the results of testing and screening, in accordance with 21 CFR 1271.65(b). However, we note that your procedures do not require that you determine as ineligible donors who reside in or travel to an area at risk for ZIKV. Since your donors reside in a ZIKV risk area, you must determine them ineligible and label the HCT/Ps from these donors in accordance with 21 CFR 1271.65(b)(2).
Laboratorio Banco Vida Inspection:
1. In response to observation 1, we acknowledge your commitment to revise your procedures to include additional steps for cleaning and environmental monitoring of the BSC. You also state that you intend to acquire (b)(4) and will coordinate processing times to ensure that umbilical cord blood from only one donor is processed at a time. Your updated processes and procedures must ensure that you are implementing effective environmental controls to ensure aseptic processing and prevent contamination or cross-contamination of HCT/Ps during processing.
2. In response to observation 2, you stated that 100% of your products are tested for microbiological contamination. We note that this is an important step in in-process control and testing, however this does not replace the requirement to validate your process to ensure that processing prevents the introduction, transmission, or spread of communicable disease through the use of the HCT/P.
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, Amy Graf, 300 River Place Suite 5900, Detroit, MI 48207 or emailed to email@example.com. If you should have any questions, please contact Amy Graf, Compliance Officer at (313) 393-2034 or via e-mail.
Program Division Director
Office of Biological Products Operations - Division 1
1 This letter applies solely to products manufactured for autologous use or allogeneic use in a first-degree or second-degree blood relative. Accordingly, references in this letter to HCT/Ps do not include other products manufactured by your firm. FDA intends to communicate with Banco Vida Corporation separately regarding these products.