Case 1. FDA, Legal, and EBAA Medical Standards Panel. Case 1. Case 1 6/25/2012. Samuel B. Barone, M.D. Office of Cellular, Tissue, and Gene Therapies

Transcription

1 Case 1 FDA, Legal, and EBAA Medical Standards Panel Samuel B. Barone, M.D. Office of Cellular, Tissue, and Gene Therapies Medical Directors Symposium Eye Bank Association of America Annual Meeting 47 y/o female cornea donor died after three-day hospital admission secondary to complications from end stage liver disease (ETOH related) Date of admit: 1/2; Date of death: 1/5 Hospital course included 2 units PRBC Hemodilution algorithm was acceptable Donor non-reactive for all infectious disease testing (RPR, HBsAg, Hep B Core Ab, HCV Ab, HIV I/II, HTLV I/II, NAT Ultrio-HIV/HCV/HBV) June 23, Case 1 Received PRBCs were donated 12/29 all infectious disease testing: non-reactive PRBCs transfused to the cornea donor 3-days after donation (1/3) One cornea was transplanted Case 1 Approximately 3 ½ months later the eye bank was notified that the PRBC blood donor had tested positive for HIV. Blood donor returned for repeat donation approximately 110 days later, testing then indicated the blood donor to be infected with HIV (HIV I/II repeatedly reactive, HIV-1 confirmatory positive, HIV NAT reactive) 3 4 1

2 Case 1 - Question HIV Testing What is the likelihood that the donor was in the window period and was infected with HIV at the time of the recovery? Case 1 - Question HCT/P Deviation A Biological Product Deviation Report was generated to the FDA as required. Would this case be considered a recall by the FDA, since the eye bank was in compliance with Donor Eligibility requirements at the time tissue was distributed? (1) An event that represents a deviation from applicable regulations... or from applicable standards or established specifications that relate to the prevention of communicable disease transmission or HCT/P contamination (2) An unexpected or unforeseeable event that may relate to the transmission or potential transmission of a communicable disease 7 21 CFR (dd) 8 2

3 Reports of HCT/P Deviations (1) You must investigate all HCT/P deviations related to a distributed HCT/P for which you performed a manufacturing step. Reports of HCT/P Deviations cont. (2) You must report any such HCT/P deviation relating to the core CGTP requirements, if the HCT/P deviation occurred in your facility or in a facility that performed a manufacturing step for you under contract, agreement, or other arrangement. Each report must contain a description of the HCT/P deviation, information relevant to the event and the manufacture of the HCT/P involved, and information on all follow-up actions that have been or will be taken in response to the HCT/P deviation (e.g., recalls). 21 CFR (b) 9 21 CFR (b) 10 Reports of HCT/P Deviations cont. Recall (3) You must report each such HCT/P deviation that relates to a core CGTP requirement on Form FDA within 45 days of the discovery of the event... A firm s removal or correction of a marketed product that the Food and Drug Administration considers to be in violation of the laws it administers and against which the agency would initiate legal action, e.g. seizure. Recall does not include a market withdrawal or a stock recovery. 21 CFR (b) CFR 7.3(g) 12 3

4 Relevant Medical Records Market Withdrawal A collection of documents that includes a current donor medical history interview; a current report of the physical assessment of a cadaveric donor or the physical examination of a living donor; and, if available, the following: (1) Laboratory test results (other than results of testing for relevant communicable disease agents required under this subpart); (2) Medical records; (3) Coroner and autopsy reports; and (4) Records or other information received from any source pertaining to risk factors for relevant communicable disease (e.g., social behavior, clinical signs and symptoms of relevant communicable disease, and treatments related to medical conditions suggestive of risk for relevant communicable disease). A firm's removal or correction of a distributed product which involves a minor violation that would not be subject to legal action by the Food and Drug Administration or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs, etc. 21 CFR (s) CFR 7.3(j) 14 Quality Program: Information Sharing Ensuring that procedures exist for receiving, investigating, evaluating, and documenting information relating to core CGTP requirements, including complaints, and for sharing any information pertaining to the possible contamination of the HCT/P or the potential for transmission of a communicable disease by the HCT/P with the following: (i) Other establishments that are known to have recovered HCT/Ps from the same donor; Quality Program: Information Sharing cont. (ii) Other establishments that are known to have performed manufacturing steps with respect to the same HCT/P; and (iii) Relating to consignees, in the case of such information received after the HCT/P is made available for distribution, shipped to the consignee, or administered to the recipient, procedures must include provisions for assessing risk and appropriate follow-up, and evaluating the effect this information has on the HCT/P and for the notification of all entities to whom the affected HCT/P was distributed, the quarantine and recall of the HCT/P, and/or reporting to FDA, as necessary. 21 CFR (b)(2) CFR (b)(2) 16 4

5 Case 2 Case 2 - Questions Eye bank received a referral of a 37 y/o male who expired from severe trauma following a MVA. Medical/social history is unremarkable except for a history of Bell s palsy. Referral was declined as history of Bell s palsy what was determined to be an identified risk factor for human transmissible spongiform encephalopathy (TSE). Would you rule out a donor due to a history of Bell's palsy? Would you exclude a donor who was in the acute phase with possible active viral infection? Screening for Transmissible Spongiform Encephalopathy You should determine to be ineligible... (20) 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... Eligibility Determination for Donors Of HCT/Ps Sec. IV.E. 19 Facial Nerve (CN VII) Palsy Supranuclear Brain stem (pons) Tumor Vascular Peripheral Bell s palsy Trauma Peripheral cont. Infection HZV/HSV, HIV, Lyme, syphilis Otitis media/externa Sarcoidosis Tumor Acoustic neuroma Meningioma Guillain-Barre Melkersson-Rosenthal 20 5

6 Requirements Case 3 Agent Required for Screening Testing HIV-1 and -2 All X X Hepatitis B All X X Hepatitis C All X X Syphilis All X X TSE All X WNV All X Sepsis All X Vaccinia (recent smallpox vaccination) All HTLV-I and II Viable, Leukocyte-Rich X X CMV Viable, Leukocyte-Rich X Chlamydia trachomatis Reproductive X X Neisseria gonorrhoeae Reproductive X X 21 CFR (r)/.75/.85 X Eye bank received a call from a transplant surgeon who had been informed by one of their patients of the recent death of another patient who contracted Mad Cow Disease from her corneal transplant". The surgeon provided them the recipient's name, but had no further information. Internet search revealed an obituary with the date of death of 5/28/12. Patient died at home with hospice care following hospitalization in the Neurological unit. 22 Case 3 Database revealed patient had a corneal transplant March Donor tissue came from a shared tissue and eye donor. Review of donor record reveals no relevant medical conditions. Travel history was reported but well within the time frames to not pose an elevated risk for CJD or vcjd. Case 3 - Questions How should the eye bank investigate this case? At what point in the investigation should the eye bank notify the FDA and EBAA?

7 Procedures Adverse Reaction You must establish and maintain procedures appropriate to meet core CGTP requirements for all steps that you perform in the manufacture of HCT/Ps. You must design these procedures to prevent circumstances that increase the risk of the introduction, transmission, or spread of communicable diseases through the use of HCT/Ps. A noxious and unintended response to any HCT/P for which there is a reasonable possibility that the HCT/P caused the response 21 CFR (a) CFR (y) 26 Quality Program: Information Sharing Contact Information Guidance for Industry: CGTP and Additional Requirements for Manufacturers of HCT/Ps (December 2011) Section V. E: With Whom Must an Establishment Share Information Pertaining to the Possible Contamination of or Potential for Transmission of Communicable Disease by an HCT/P? CBER or Consumer Affairs Branch (CAB) ocod@fda.hhs.gov Manufacturers Assistance and Technical Training Branch (MATTB) industry.biologics@fda.gov Follow us on Twitter