While many of us may think of medical devices as complex combinations of metals, plastics, and electronics, many medical devices also contain animal-derived materials. Examples include bovine materials used to make heart valves, sutures, tear duct plugs, and dental implants. These animal-derived materials are not without risk. They may carry transmissible spongiform encephalopathies (TSEs) – including Mad Cow Disease – when improperly collected, stored, or manufactured. The risks are compounded by the fact that currently, there are no treatments for TSE diseases and no way of screening for them in a live person or animal.
To address the risks of TSEs, FDA recently released a draft guidance entitled “Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices).” This guidance is meant to replace an earlier 1998 guidance that focused on the risk of transmitting bovine spongiform encephalopathy (BSE), commonly known as Mad Cow Disease. While BSE is still included, FDA’s latest guidance also contains the risks of other forms of TSEs, such as scrapie (found in sheep), chronic waste disease (found in deer), and Creutzfeldt-Jakob Disease (found in humans). The guidance is applicable to all medical devices that contain or are exposed to animal-derived materials (e.g., bovine, ovine, porcine, avian materials), with the exception of in vitro diagnostic devices.
FDA recommends that companies using any material derived from an animal with potential to carry TSE infection (e.g., cattle, sheep, goats, and cervids such as deer and elk) document the following:
- Animal species
- Specific tissue used (if multiple tissues are used, identify all tissues used)
- Animal’s country of origin and country of residence (or a more specific geographic information when appropriate)
- Methods for actively monitoring the health of herd and the health of specific animals from which tissues are collected
- Information concerning the long-term health of the herd (e.g., documented breeding history, animal traceability, absence of TSE disease, and standard vaccinations such as live modified viruses that could co-purify in the desired tissue)
- The frequency and type of veterinarian inspections
- Animal feed composition (e.g., animal feed history records, including recordation of co-mingling of feeds, and labeling of animal feed composition at distribution locations)
- USDA status of the abattoir
- Animal age at sacrifice
- Animal sacrifice methods that reduce the risk of cross contaminating non-TSE tissues with material from tissues that could contain TSE
- Specifics of the pre- and/or post-mortem inspections (e.g., gross visual inspection, specific organs and anomalies exams, lab tests such as PrP testing)
- Tests performed (and release criteria) for permitting tissue to be further processed and/or combined with other tissues and device components (e.g., a Certificate of Analysis)
FDA further recommends that companies maintain test results for each lot of material at the manufacturing facility. Methods for maintaining the records as well as a description of the tests performed should be provided in regulatory submissions. Moreover, companies should analyze the source of their animal-derived materials, as non-TSE-transmitting animals may be slaughtered in facilities that also process TSE-transmitting animals.
Although FDA’s most recent guidance is a draft, companies using animal-derived material should take note of FDA’s expanded view of not only which animal materials contain risk (i.e., no longer limited to bovine material), but also which steps are appropriate to ensure the safety of those materials. Moreover, companies should remain vigilant about future developments. To date, no test exists that can reliably identify TSE-containing materials. However, should one be developed, “FDA will consider revisiting this guidance as appropriate and recommending that such a test be introduced into the standard operating procedures for bovine tissue collection and processing.”