Dispatches from the Biological Production Forum, Dublin
Sartorius: QbD for single-use systems could help assure quality
During a full first day at the 13th Annual Biological Production Forum in Dublin, Ireland, Sartorius Stedim Biotech said that whilst the benefits of single use systems have been well documented, problems still persist for suppliers of such containers – including the quality of bags, extractables and leachables and integrity testing – to ensure lot-to-lot consistency for the end user.
Luke Coxon, FMT Application Specialist at Sartorius used the example of bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP), a leachable compound used in the construction of single-use bioprocess containers and discovered by Amgen to be detrimental to cell growth in a PDA Journal article last year.
“What was found was during the gamma sterilization process there was a degradation compound that led to an impact on cell growth,” Coxon said. “This was very high profile, very high key and something we single-use suppliers and the industry as a whole weren’t really expecting.”
In order to ensure Sartorius’ films were not degraded in this way, the firm took proactive action to develop a design space for the output and temperature extrusion parameters, he continued.
This assurance has been further enhanced by Sartorius taking a quality by design (QbD) approach to the manufacture of its containers. Coxon spoke of developing key quality attributes by “looking at customers application use and ultimately wanting to ensure there is no adverse interaction with the product, the product is robust and it’s not going to lead to leaks and – sitting above all of that – wanting to ensure the product is going to be consistently supplied.”
Whilst a single-use bag’s barrier properties and the quality of the film is essential (though Coxon did speak of the trade off between flexibility and stiffness of the film), there are a number of processes in the manufacture of the systems done both internally and by external partners and Coxon said it was essential for a producer to keep full control of these.
“This leads to a high level of quality assurance, ensuring you have got consistently high quality product data, assurance of supply even in disaster scenarios, and also effective change control process” to limit impact of any changes.
Sartorius use third parties for resin cracking, film extrusion and gamma sterilization whilst the making of the bags, components and the single use assembly are done in-house, Coxon said.