Biomedical Engineering Reference
In-Depth Information
medical devices. The details of the guidance can be found published in the
Official Journal of the European Union (EMEA, 2004), as well as identified in a
series of International Standards Organization (ISO) guidance documents, ISO
22442-1, -2, and -3 (2007).
Compliance with safe sourcing practices has become a requirement for
companies wishing to commercialize their products. In the US, this is regulated
by a joint review of the product application by the US Department of Agri-
culture (USDA) and Food and Drug Administration (FDA). In Europe, notified
bodies prefer that sponsors obtain European Directorate for Quality in
Medicines and Healthcare (EDQM) approval prior to submission of their
product dossiers for CE mark approval. The EDQM is an organization which
harmonizes and coordinates the guidelines on ensuring a safe supply of
medicines, blood products, and cell- and animal tissue-derived products. They
review a sponsor's submission packet to ensure adherence to the safe sourcing
practices, and will issue a Certificate of Suitability if the submission is approved.
The Certificate is very specific for sponsors using specified suppliers and
documented practices. If a tissue supplier is changed, the Certificate is no longer
valid, and the sponsor must reapply for a new EDQM approval.
While the argument still persists that the absence of detectable disease does
not prove absence of disease, there are several helpful safeguards which every
manufacturer can implement. First, scientific studies done in the United
Kingdom by Gerald Wells and colleagues have shown that BSE takes some time
to develop, even if animals are intentionally inoculated with the infectious agent.
This time is about 32 months, so limiting tissue procurement to animals younger
than 30 months of age is typically done for the heart valve industry. Second, Mr
Wells has studied the pericardium and heart valves (including the aortic and
mitral heart valves) from animals with clinical disease, and he was unable to
demonstrate transmission of infectivity from these tissues (EMEA, 2004). The
lack of infectivity of these tissues, even when taken from animals with known
disease, is another safeguard in mitigating the risk of BSE transmission through
a bioprosthetic heart valve. Owing to the proteinaceous nature of the BSE
infectious agent, it cannot be isolated or destroyed in the tissue without destroy-
ing the tissue itself. Until genetically engineered tissues can be manufactured
with sufficient properties and in adequate supply, safe sourcing is an important
component of an overall risk management strategy to ensure the continued
development and commercialization of products that are safe for human use.
5.7.3 Tissue preservation
It is important to preserve the tissue architecture prior to fixation. If the tissue is
swollen or damaged prior to fixation, fixation can only `lock in' that state, it
cannot reverse any damage that has already been done. While it is traditional to
ship isolated tissues in isotonic saline, this may not be sufficient to prevent tissue
