Reducing cyclosiloxanes contaminates in biopharmaceutical products
Drug manufacturers are increasingly concerned about the sources of potential contamination from processing equipment. To give a sense of the scale of this problem, 15% of the drug recalls reported by the FDA in the last six months have been due to contamination from processing equipment.
A primary area of concern is the direct contact of plastic processing materials that comprise single-use components with the drug product. It is widely known that this can result in the presence of compounds which may affect the efficacy, safety or quality of the final drug. For manufacturers working on multi-million dollar drug trials and treatments, the implications of this from a product development and brand integrity perspective, are significant.
Focus must therefore be given to the process used to manufacture equipment and ancillaries. Specifically, the manner in which platinum-cured silicone tubing is manufactured must be given attention: the process used to manufacture this tubing has the potential to affect the types of leachables which may migrate into the final product.
Here in, Watson-Marlow Fluid Technology Group (WMFTG), fluid path solutions provider of peristaltic pumps and single-use component, outlines the results of a study which makes comparisons between the semi volatiles extractables profile of post-cured and non post-cured samples of its Pumpsil platinum-cured silicone tubing.
At WMFTG, as part of the manufacturing of the Pumpsil silicone tubing, there is an additional post-curing step to the tubing production process. This additional step ensures more cross linking that not only makes the tubing mechanically stronger, but reduces the semi volatile compounds. This extra processing step is not carried out by most other manufacturers of platinum-cured silicone tubing, which means there is a very real risk of cyclosiloxanes migrating into fluids that come into contact with the tubing. This is of course a safety concern and one that drug manufacturers must be aware of.
Focus and outcome of this study
The study reveals noteworthy results that affirm the need for drug manufacturers to adopt post-cured tubing as standard. This paper details that samples of WMFTG Pumpsil tubing (post-cured and non post-cured) were extracted with a 50% ethanol: 50% water solution for 30 minutes at 25C and seven days at 40C.
For the purposes of this paper, the extractables studied were the cyclosiloxanes (mixtures of cyclosiloxanes have been of particular interest due to concerns about their potential toxicity).
The extracts were analysed by Gas Chromatography – Mass Spectrometry (GCMS). The study demonstrated the presence of cyclosiloxanes was reduced by a minimum of 25% in the post-cured extracts, as compared with non post-cured extracts over a seven day extraction period and by 50% over a 30 minute time point.
Tubing has been a part of biopharmaceutical manufacturing processes for many years. Even in the early days of the biopharmaceutical industry, tubing was used for fluid transfer, peristaltic pumping and filling operations.
The advent of single-use technologies has increased the usage of tubing from being a minor player within the manufacturing process, to become a major part of single-use biopharmaceutical manufacturing assemblies, used to link the different technologies such as filters, connectors and biocontainers together. Silicone tubing comprises of polydimethylsiloxanes (PDMS) polymers. Silicone tubing can be divided into two cross-linking types, those manufactured by addition (platinum) and free radical (peroxide) curing systems.
The peroxide-cured silicone tubing has fallen out of favour in recent years due to concerns about the presence of 2-4 dichlorobenzoyl acid as a by-product which has the potential to leach into contacting fluids. Addition cure has no by-products, and as a result the biopharmaceutical industry has transitioned to mostly using platinum-cured tubing.