CBER Presentation
FDA Adverse Reaction Reporting System for Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps)
AATB Annual Meeting
September 2006
Laura M. St. Martin, M.D., M.P.H.
Division of Human Tissues
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research (CBER), FDA
FDA's Reporting Requirement: 21 CFR Part 1271.350-Effective May 25, 2005
- Manufacturers must investigate:
- Any adverse reaction involving a communicable disease related to an HCT/P that they made available for distribution.
- Manufacturers must report to FDA
- An adverse reaction involving a communicable disease if it:
- Is fatal
- Is life-threatening
- Results in permanent impairment of function or permanent damage to body structure; or
- Necessitates medical or surgical intervention, including hospitalization
FDA's Reporting Requirements
- Adverse reaction means a noxious and unintended response to any HCT/P for which there is a reasonable possibility that the HCT/P caused the response
- To report adverse reactions, manufacturers must submit a MedWatch 3500A to FDA within 15 days of receipt of information
- And submit follow-up MedWatch report within 15 days of receipt of new information from the investigation
How are Adverse Reactions Reported to FDA?
- For Manufacturers:
- Use Form FDA 3500A (MedWatch)
- Report w/in 15 days of receipt of information
- For Voluntary reporters:
- Use Form FDA 3500 (MedWatch)
- Also promptly report to HCT/P establishments
- FDA MedWatch reporting system
What Information to Include on MedWatch Report
- Specific name and type of product used
- Recipient outcomes (symptoms, medical or surgical interventions, recovery, morbidity, death)
- Indicators that adverse reaction was related to a communicable disease
- Relevant dates
- Results of cultures and other relevant studies
- Devices implanted
- Special handling/prep of product at implanting facility
- Confirmation that donor met eligibility requirements and HCT/P met release criteria
- Recipient risk factors for infection
- If other recipients of donor tissue had adverse reactions (review of complaint file)
- Impression of likelihood that adverse reaction was related to product (reasonable possibility)
Other Information to Review in Investigation and Make Available to FDA if Requested
- Donor screening records
- Did any deviations from facility's SOP occur in donor tissue processing
- Copies of pre- and post-processing cultures of donor tissue
- Copies of relevant recipient culture, serology, pathology and imaging results, clinic and operative notes
- Copies of culture results from other recipients of donor's tissue
- Results of hospital infection control investigation, if applicable
Common Problems with MedWatch Reports
- Manufacturer reporting on voluntary form (3500) instead of mandatory form (3500A)
- Reporting of device information in product section (and the reverse)
- Insufficient information about the adverse reaction
- Reporting of product problems when product was not implanted
- Failure to submit a follow-up report
CONTACT INFORMATION
Laura M. St. Martin, M.D., M.P.H.
Medical Officer
Division of Human Tissues, OCTGT
CBER/FDA
1401 Rockville Pike (HFM 775)
Rockville, MD 20852-1448
Laura.St.Martin@fda.hhs.gov
301-827-6039