Protecting Patients from Prions

With the evolution of science, the world is increasingly benefiting from the amazing lifesaving and life-enhancing medical products developed and commercialized today. As new drugs, biologics, and devices come to market, the regulatory landscape evolves alongside them. Because these products are used on patients, it is critical to ensure they are safe – which can mean a number of different things, all of which should be built into the design of these products well before manufacturing begins. The companies developing these products devote significant care and attention to the products they make, but contamination can occur with any product at any time – even one manufactured under current Good Manufacturing Practice and a robust Quality Management System. Although this statement is true for all pharmaceutical products and medical devices, it is especially true for biologics, human cells, tissues, and cellular and tissue-based products (HCT/Ps) due to their sources and/or the addition of biologic components.

It’s a matter of public record that, a few years ago, the pharmaceutical industry learned this the hard way with an issue involving heparin (a common, animal-derived product). In January 2008, the US health system authorities began to receive isolated reports of hypersensitivity reactions in hemodialysis patients. Symptoms included hypotension, facial inflammation, tachycardia, hives, and nausea. Initially, inquiries were focused on the filters and lines used in dialysis; however, the research carried out by the Centers for Disease Control and Prevention proved that all known cases had in common the use of sodium heparin. In February 2008, the manufacturer withdrew all batches of the product – but there were still reports of allergic reactions, including some fatal cases. After monitoring by the US Food and Drug Administration (FDA), fatalities associated with the use of sodium heparin returned to the usual figures.

The next month, the FDA published the discovery that the heparin – which was highly contaminated – had been purchased from a single supplier, who in turn sourced the heparin from its Chinese factory. They determined that the contaminant was in the heparin material before it reached the supplier – but because the Chinese factory sourced its raw heparin from small suppliers, it could not be fully traced. The deficiency led to extensive revisions of the unfractioned heparin monographs of both the US and European pharmacopeias – and it provided a hard lesson that lead to much stricter control and better understanding of how contamination risks can be mitigated.

Potential human donors of such products bear no lighter a burden. They must be screened to determine their eligibility to donate, and to ensure that the human cells and tissues to be transplanted are free from communicable disease agents. Once a person is deemed eligible to donate, the tissues and cells consented for donation are recovered to be transplanted and processed. If a potential donor is not free from risk factors for – and clinical evidence of – infection with a relevant communicable disease, they may be ineligible to donate their tissues and cells. This is a critical step at the beginning of the lifecycle of the HCT/Ps we use today. Why, then, after this required screening and testing, would you risk introducing one of these communicable diseases back into your tissues and cells? The question may sound absurd; however, the risk is real, especially for prion diseases like bovine spongiform encephalopathy (BSE) and its human variant, Creutzfeldt-Jakob disease (CJD).

In an ideal world, we would eliminate the risk of contamination of human- and animal-derived products by avoiding their use – but that simply isn’t possible; some materials either require, or are cost-prohibitive without, such products. These may include proteins, enzymes, and amino acids; biotechnological products like serums, blood products, and vaccines; or even primary packaging materials like gelatin capsules (which are particularly susceptible to BSE/CJD). Even when a product involves no such materials, there may still be a risk of BSE/CJD contamination if they share equipment or facilities with biologically derived products. It’s important for diagnosticians to bear this risk in mind when dealing with patients experiencing unexplained neurological symptoms – and it’s important for labs that produce such materials to ensure that there’s no risk of contamination when those products are provided to patients.

If the use of animal-derived products is at all avoidable, I suggest that maintaining an animal-origin-free facility is the best way to eliminate the risk of contamination entirely – and to hold suppliers to the same standard. To do otherwise is to welcome the risk of contamination into your laboratory. The pharmaceutical industry is taking precautions to eliminate and mitigate this danger, but academia and other industries have not followed suit. As consumers and patients, we must educate ourselves on the risks associated with these medical products – and, if necessary, we must demand higher standards to ensure our patients’ safety. We must ask questions about the medical products we and our patients use and demand that they be produced safely and with as little risk of contamination as possible. Just think of the alternative if we don’t ask – patients may end up with a degenerative, ultimately fatal brain disorder. The choice is simple.