cber tissue safety team
DESCRIPTION
CBER Tissue Safety Team. Ruth Solomon, M.D. Director Division of Human Tissues OCTGT/CBER/FDA Blood Products Advisory Committee May 1, 2008. Outline. Background What are HCT/Ps? How are they regulated? What is an Adverse Reaction? Which Adverse Reactions must be reported? - PowerPoint PPT PresentationTRANSCRIPT
CBER Tissue Safety Team
Ruth Solomon, M.D.Director
Division of Human TissuesOCTGT/CBER/FDA
Blood Products Advisory CommitteeMay 1, 2008
Outline
Background What are HCT/Ps? How are they regulated? What is an Adverse Reaction? Which Adverse Reactions must be reported?
Tissue Safety Team Challenges Summary Data on Reports
WHAT ARE HCT/Ps?
What are HCT/Ps? Human cells, tissues or cellular or tissue
based products (HCT/Ps) means articles containing or consisting of
human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient
21 CFR 1271.3(d)
Examples of HCT/Ps Musculoskeletal tissues Skin Dura mater Cardiovascular tissues Ocular tissues
Reproductive tissues Hematopoietic stem/progenitor cells derived
from peripheral and cord blood Other cellular therapies
Not HCT/Ps Vascularized human organs Whole blood or blood components or
blood derivative products Secreted or extracted human products s.a.
milk, collagen, cell factors Minimally manipulated bone marrow for
homologous use and not combined with another article
Not HCT/Ps, cont. Ancillary products used in manufacture of
HCT/Ps Cells, tissues, and organs derived from
animals other than humans In vitro diagnostic products Blood vessels recovered with an organ,
intended for use in organ transplantation and labeled “For use in organ transplantation only”
HOW ARE HCT/Ps REGULATED BY FDA?
HCT/P Regulations(all effective 5/25/05)
21 CFR Part 1271 Establishment Registration and Product
Listing Donor Eligibility Current Good Tissue Practice—contains
requirements for adverse reaction reporting Legal Authority: Section 361 of Public
Health Service (PHS) Act—prevent the introduction, transmission, or spread of communicable disease
Regulatory Pathways “361” HCT/Ps
No pre-market review; follow Part 1271 only Compliance with regulations determined on inspection
Biological Products Follow Part 1271 and other applicable regulations Pre-market review and approval (BLA)—must show
safety, purity, potency Medical Devices
Follow Part 1271 and other applicable regulations Pre-market review and clearance/approval (510(k),
PMA)—must show safety and efficacy
ADVERSE REACTIONS
What is an Adverse Reaction?
Adverse reaction [1271.3(y)] (for “361” HCT/Ps) means a noxious and unintended response to any HCT/P for which there is a reasonable possibility that the HCT/P caused the response
Adverse experience [600.80(a)] (for biological products) means any adverse event associated with the use of a biological product in humans, whether or not product related…
What Adverse Reactions Must Manufacturers Investigate?
Manufacturers must investigate Any adverse reaction involving a
communicable disease related to an HCT/P they made available for distribution
21 CFR 1271.350(a)(1)
Manufacturers are not required to investigate (but are encouraged to do so) Adverse reactions that do not involve a
communicable disease (e.g., product defects)
What Adverse Reactions Must Manufacturers Report?
Manufacturers must report to FDA any adverse reaction involving a communicable disease, if it: Is fatal Is life-threatening Results in permanent impairment or damage Necessitates medical or surgical intervention
21 CFR 1271.350(a)(1)
ExamplesReporting Required Bacterial infection
in HCT/P recipient Graft failure
surgeon believes is secondary to infection
Viral seroconversion of recipient suspected to be allograft related
Reporting not Required*
Package labeled incorrectly
Mechanical failure of graft
Allergic reaction Product damage Donor-transmitted
malignancy* Reports may be submitted, even if not required
How are Adverse Reactions Reported to FDA?
For Manufacturers: Use Form FDA 3500A (MedWatch) Report w/in 15 days of receipt of
information Via fax/mail21 CFR 1271.350(a)(2)
How are Adverse Reactions Reported to FDA?
For Voluntary Reporters: Use Form FDA 3500 (MedWatch) Via online, fax, mail, telephone Recommend prompt reporting to HCT/P
establishments (CBER does not forward consumer reports to manufacturer)
Sources of Reports
Reports received from various sources
Tissue Establishment
Consumer/Healthcare Professional
CBERMedSun
CDC, Other
MedWatch Office
CDRH
MedWatch Website
http://www.fda.gov/medwatch Provides information on the MedWatch
reporting program, reporting forms
CBER TISSUE SAFETY TEAM
Tissue Safety Team (TST) First CBER Safety Team First meeting in May 2004 Purpose:
Provide a coordinated, efficient approach to the receipt, routing, investigation, evaluation, documentation and trending of reported adverse reactions involving HCT/Ps across 5 Offices in CBER and beyond the Center
FDA’s Tissue Safety Team Includes multiple offices at CBER Reviews all MedWatch reports received Conducts follow-up on infectious adverse
reactions related to HCT/Ps Seeks additional information from clinician and
manufacturer as needed Evaluates cases at Tissue Safety Team
meetings SOPP 8508 describes procedures for handling
AR reportswww.fda.gov/cber/regsopp/8508.htm
FDA’s Tissue Safety Team
OBEOffice of Biostatistics and
Epidemiology
OCTGTOffice of Cellular, Tissue and Gene
Therapies
OCBQOffice of
Compliance and Biologics Quality
OCTMAOffice of Communication,
Training, and Manufacturer Assistance
ODOffice of the
Director
TST Points of Contact Outside of CBER
Outside of CBER, within FDA Center for Devices and Radiological Health Office of Regulatory Affairs Office of Crisis Management
Outside of FDA CDC
CDC Epidemic Intelligence Service (EIS) Officer at FDA HRSA CMS
Special government employee consulted on unusual cases
Tracking and Routing Reports Reports received by OBE—determine if
“361” HCT/P Enter into database If an infectious adverse reaction,
determine if High Priority (criteria) and immediately notify TST Working Group and begin follow-up
For other reports, determine if follow-up is needed (criteria)
High Priority Cases Fatality; infection with Clostridium sp., or
group A Streptococcus Serious viral disease or seroconversion (e.g.,
HIV, HBV, HCV); or CJD Two or more recipients of tissues or organs
from a single donor develop infections with the same organism
Same unusual organism cultured from recipient as was found in one or more recovery, pre-processing or post-processing cultures (on tissues) or environmental cultures
Clinical Follow-up: OBE Specific name/type of product/lot
number/ manufacturer Time interval from implantation to onset
of symptoms Culture results (e.g., transport fluid, pre-
implant, wound, explanted graft) Patient—immunosuppressed? Infection
prior to graft implant? Anything unusual about the surgery?
Clinical Information (cont.)
Medical or surgical interventions e.g., debridement, explant, antibiotics started or
changed Special handling or preparation of allograft
prior to implantation Devices implanted along with tissue? General impression/indicators that adverse
reaction was related to the allograft Results of hospital infection control
investigation, if any
Manufacturing Information: OCBQ
Processor’s investigation—conclusion? Donor medical records reviewed Processing methods reviewed—any
deviations? Environmental monitoring reviewed Pre- and post- processing culture results
—do any match recipient’s culture results?
Whether there are other complaints related to same donor—if so, same organism?
Challenges in HCT/P Adverse Reaction Surveillance
Limitations of passive surveillance (under-reporting, biases, etc.)
Distinguishing graft-attributable infections vs. common post-operative wound infections
Labor intensive follow-up activities Case closed when investigation complete and
based on the available information, further TST action is not indicated. Usually no conclusion that adverse reaction was due to graft
SUMMARY DATA ON HCT/P REPORTS
Reported Adverse Reactionsby Tissue Type
Reported Adverse Reactionsby Outcome
Reported Adverse Reactionsby Reporter
Further Information Tissue Home Page
http://www.fda.gov/cber/tiss.htm Tissue-Related Documents/Publications
http://www.fda.gov/cber/tissue/docs.htm For general questions contact Office of
Communication, Training and Manufacturers Assistance (OCTMA) at: [email protected] 301-827-1800
Questions?