AAOS Bulletin - June, 2005

FDA: Report adverse reactions with tissue

By Donna Toohey

The Food and Drug Administration (FDA) is encouraging physicians who use implantable human tissue products to voluntarily report adverse reactions observed with their use. Reports should be directed to both the source facility/manufacturer and the FDA. Physicians are also encouraged to report certain product problems such as unreadable labels, appearance of contamination or inadequate packaging to the tissue manufacturer.

New regulations

In recent years, there has been a heightened awareness of adverse reactions associated with the implantation of contaminated tissues. These concerns have prompted the FDA to develop new regulations that require tissue manufacturers to report certain adverse reactions and product deviations. These regulations became effective May 25, 2005.

In addition, the FDA has formed a Tissue Safety Team to monitor and coordinate investigative response activities to adverse reactions with implanted tissues. Formally categorized as “human cells, tissues, and cellular- and tissue-based products” (HCT/Ps) under the FDA regulatory paradigm, bone, cartilage, fascia, ligament, skin, tendon, vascular grafts and heart valves are covered under this initiative.

Under the new regulations, an adverse reaction is defined as “a noxious and unintended response to any HCT/P for which there is a reasonable possibility that the HCT/P caused the response.” Physicians are not required to report adverse reactions with tissues to either the source facility/manufacturer or to the FDA; physician reporting to both sources is voluntary.

Manufacturers of tissue products, however, are required under current regulations to report certain adverse reactions to the FDA. The establishment or manufacturer that distributed the HCT/P must investigate any adverse reaction involving a communicable disease related to its HCT/P products. Furthermore, adverse reactions with HCT/Ps involving communicable diseases must be reported to the FDA by the source facility/manufacturer if the adverse reaction:

• Is fatal

• Is life-threatening

• Results in permanent impairment of a body function or permanent damage to body structure

• Necessitates medical or surgical intervention, including hospitalization

Tissue manufacturers must investigate all reports of adverse reactions they receive to determine whether the adverse reaction meets the criteria mandating a report to the FDA. The primary source for manufacturers’ information on adverse events with HCT/Ps remains physician and hospital users. Physician vigilance in reporting known or suspected adverse reactions will assist in investigating and identifying possible epidemiological or manufacturing concerns that affect the safety of the tissue supply.

The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) recently approved standards for the storage and issuance of tissue that require prompt reporting of post-transplant infections to the source facility or tissue manufacturer (see accompanying article).

The physician’s role

There are several points along the continuum, from tissue receipt through implantation, where physicians can assist tissue manufacturers and the FDA in monitoring the safety of the U.S. tissue supply. In particular:

Physician users should return requested information on the tissue’s use to the manufacturer.

Physician users are encouraged to voluntarily report to the source facility/manufacturer if an HCT/P has transmitted or may have transmitted a communicable disease or any other complication relating to the potential for disease transmission, such as the failure to comply with good tissue practices (e.g., compromised packaging).

Physician users are also encouraged by the FDA to voluntarily report to the FDA any adverse reactions with HCT/Ps through the Med Watch on-line reporting system. Patients are also able to report suspected problems with tissue products through the FDA Med Watch system.

The AAOS reminds orthopaedic surgeons and patients that the overall quality of HCT/Ps in the United States is considered to be very high, and the incidence of infection in tissue remains low. The public can have confidence that these products are safe for human use. The AAOS encourages its members to report adverse reactions to both the manufacturer and the FDA.

To report adverse reactions to the FDA, AAOS members can complete and submit Form 3500A for Voluntary Reporting, available at: http://www.fda.gov/medwatch/report/hcp.htm. More information on the new FDA regulations can be found at http://www.fda.gov/cber/tiss.htm.

Donna Toohey, regulatory analyst, department of research and scientific affairs, is the staff liaison to the AAOS Biological Implants Committee, which monitors areas of biologic concern with regard to the practice of orthopaedics. She can be reached at toohey@aaos.org.

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