In 2013, Shire bought rare disease frim ViroPharma for $4.2bn (€3.8bn) and added the half billion dollars-a-year product Cinryze (complement C1 esterase inhibitor) to its product portfolio.
The protease inhibitor is derived from human plasma and is made by Amsterdam, Netherlands-based contract manufacturing organisation (CMO) Sanquin Blood Supply using a series of precipitation, filtration and chromatography steps.
Speaking with this publication in 2015, Shire said it was unlikely to bring Cinryze manufacturing in house as the nature of making a blood plasma product in the firm’s then cell culture network could have led to potential cross contamination issues.
But on a call this week, CEO Flemming Ornskov told investors it is now looking to produce approximately 30% of its Cinryze supply from its own manufacturing facilities.
Sanquin warning letter
100% of Cinryze supply is currently being produced by Sanquin, Shire spokeswoman Kirsty Langton told Biopharma-Reporter this morning.
But having just one manufacturing source leaves the supply chain at risk. When Shire bought ViroPharma, Sanquin’s facility was subject to a US Food and Drug Administration (FDA) warning letter – lifted last September – which caused significant constraints on Cinryze production.
“The combination of demand increases coupled with our focus on addressing the warning letter caused us a challenge with supply of Cinryze last year, however this impact was minimised over the last 12 months through a focussed and ongoing collaboration between Shire and Sanquin,” Langton said.
“We did our best to minimise the impact to our patients through close collaboration with our supply chain and our external stakeholders including our regulatory agencies. Sanquin & [its manufacturing subsidiary] CAF had follow-on inspections late in 2014 that resulted in the majority of the warning letter findings being resolved. The remaining few findings were resolved during 2015.”
The decision to use other suppliers was more part of Shire’s continued strategy “to optimise its independent supply network,” and not directly triggered by Sanquin’s regulatory issues, Langton said.
But the U-turn to take production in house was supported by the combination of Baxalta – acquired for $32bn last year – and its plasma fractionation capabilities, and she told us technology transfer from Sanquin has begun.
“Sanquin has provided Shire access to its manufacturing technology for CIinryze. We are now starting to build supply capability for the product in our plants in Vienna [Austria], Reiti [Italy] and Los Angeles [US],” she told us.
“The equipment to manufacture Cinryze is mostly in place. There may be some modest investment into additional equipment as required. However, the capacity will become available once the manufacturing process is qualified and approved.” This is expected to be in 2018, rather than this year.
First quarter Cinryze sales clocked in $226m, up 30% year-on-year due to an increase in the number of patients on the therapy and the impact of stocking following an improvement in supply levels.