We Provide a Wide Variety of Single Use Products that are ADC Free
While there is much debate as to whether the Hippocratic Oath contains the verbiage, “First, do no harm”, there is no question that this principle not only applies to doctors, but the bioprocess industry as well. It is incumbent upon all drug manufacturers, particularly those of parenteral drugs, that the manufacturing process does no harm to the end user. As is often the case, this responsibility has been distributed throughout the supply chain. While initially of little concern in the days of all stainless process equipment, the topic of animal derived component free products has quickly become a hot button issue in the rapidly maturing single use product market. While initially plastic extractables and leachables were of key concerns, there has been a growing emphasis on bioprocessors to use materials made exclusively of animal derived component free materials. This blog post will address what animal components are used in the production of single use bioprocessing equipment, why it is important that animal derived components (ADC) are avoided where possible, and what products are currently offered in ADC free versions.
The single use and disposable bioprocess equipment market is a rapidly maturing part of our industry. Disposable processing products include flexible tubing, sanitary fittings, cylindrical tanks, carboys, bags, and capsule filters. Most commonly, these components are made from polyethylene and polypropylene. Polyethylene, polypropylene, as well as thermoplastic elastomers are all manufactured from petroleum feedstock which often use animal derived components during processing. Long chain fatty acids, such as stearic acid give products lubricity and prevent the polymers from sticking to metal surfaces during extrusion or mold release. They are often referred to as “slip” agents. Stearic and other long chain fatty acids are rendered from tallow, or beef fat. Beef comes from cattle, which are a member of the biological subfamily of Bovinae. These bovine derived additives have become an integral part of polymer processing because they’re cheap and work well.
So if they’re economical and effective, then what’s the big deal? Well, in the 1990’s cattle in in Europe, specifically the UK, started getting sick. Cattle are herbivores and are generally fed either with corn (USA) or grass (UK). As any corn-fed, beef-loving Wisconsinite will tell you, the grass fed hamburgers in England just don’t taste the same (it has to do with the pH in the stomachs of the cattle- corn requires more stomach acid to break down and digest which alters cattle’s fat composition and leads to a fuller flavored filet, but that’s a topic for another post). To supplement their cows and get them to slaughter weight faster, English farmers began to supplement their livestock feed with stocks produced from meat and bone meal made from ground and cooked leftovers of the slaughtering process. Worldwide, soybean meal is the primary protein supplement fed to cattle, however soybeans do not grow well in Europe. It is believed that the ingestion of nerve tissue is what allowed prion disease to first take hold in cattle herds.
While European commissions dismissed that the idea that these feeds were solely responsible for the sick cows, it became clear that an outbreak of bovine spongiform encephalopathy (BSE or mad cow disease) was a serious problem. BSE is caused by mutated proteins, known as prions, which cause a group of diseases including BSE, scrapie (sheep), chronic wasting disease (deer and elk), and Creutzfeldt-Jakob disease (humans). These prions are extremely small (smaller than a virus) and are unique in that they lack DNA or RNA, making them tough to stop from replicating (i.e. kill). Prions are also unique in that they are 100% fatal. The breakouts of BSE led to mass culling of cattle in Europe.
Prions soon made the leap to humans and while there have been very few cases of Creutzfeld-Jakob disease, just YouTube “Fatal Familial Insomnia”, another genetic prion disease, to see the affect these mutated proteins have on humans.
The fear among bioprocessors is that “sick” animals may be used in the production of stearic acid and other polymer additives. Why is this such a big deal if the product is going into a highly filtered, highly sterilize process? As mentioned previously, the rogue proteins are extremely small. They can escape viral filtration, are resistant to the high heats and pressures of autoclaves and steam, and are unaffected by acid washes. In response to the unpredictability of BSE and CJD, many bioprocessors, especially in Europe, now request fluid handling products that are free of materials of animal origin. Animal-free materials eliminate unnecessary risk as well as the need to trace materials of construction back to raw materials.
The hardest part of manufacturing animal free polymers is not cost, but sourcing and supply. The products that drug manufacturers produce are so valuable (with campaigns and batches being worth millions of dollars) that cost is often irrelevant. The polymer resin industry that the processing components come from, however, is much more price sensitive. Polymer resins are the prototypic commodity product. About 60 million tons of polyethylene are produced each year. This forces manufacturers to put in a tremendous amount of work to identify and carefully select the few base resins that are ADC free.
All Saint Gobain C-Flex Tubing Formulations are now ADC Free
As the burden shifts to suppliers to produce equipment that is ADC free, Holland has been able to work with business partners like Saint Gobain to offer a variety of products that are free of any animal products. This includes products such as C-Flex 082 and 074. Other components, such as PureFit SIB connectors and Colder fittings are also manufactured with virgin polypropylene resins that our biopharmaceutical customers prefer. Holland is able to provide complete validation guides for many products that include ADC free certificates. While the FDA does not currently prohibit AD components, the straight forward certification of ADC-free is much simpler for highly validated process systems than reinventing the wheel each time a new component is introduced.
Hopefully this post serves a primer on the dangerous effects of prion disease and the steps bioprocessors are taking to minimize risk to end users. For more information about ADC free product offerings, contact Holland today.