Could drug product safety improved through post-cured tubing?
A Watson Marlow Fluid Technology Group study shows biopharmaceutical drug efficacy, safety and quality is improved by using post-cured tubing in manufacturing
Watson-Marlow Fluid Technology Group (WMFTG), a provider of single-use components including niche peristaltic pump and associated fluid path technologies, has carried out a study which makes comparisons between the semi-volatile extractables profile of post-cured and non post-cured samples of its own Pumpsil platinum-cured silicone tubing.
The company says the results of the study provides evidence of positive effects of post-curing on the reduction of cyclosiloxane contamination in silicone tubing manufacture.
The company says it offers essential reading for those involved in the manufacture of biopharmaceutical products; many of whom will be concerned about the sources of potential contamination from processing equipment.
According to the report’s author, Sade Mokuolu, Group Product Compliance Manager, WMFTG, the scale of this problem is greater than many may assume: 'It is interesting to note that 15% of the drug recalls reported by the FDA in the last six months have been due to contamination from processing equipment,' she says.,
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 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 in to the final product,' says Dr Mokuolu.
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 may not be carried out by 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 a major safety concern and one that drug manufacturers must be aware of, WMFTG says
The study included in WMFTG’s white paper reveals results that affirm the need for drug manufacturers to adopt post-cured tubing as standard.
The 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 25°C and seven days at 40°C.
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 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.
Dr Mokuolu’s says: 'The drug industry must embrace the arguments for post-cured silicone tubing; and this white paper presents some data to support this position. It offers proof that the post-curing of tubing can significantly reduce the amount of cyclosiloxanes that are present after manufacturing. At a commercial and reputational level, this will help the biopharm and drug industry have greater assurance of the efficacy, safety or quality of their final product.'
The data and analysis are explained in the white paper by WMFTG.
