In 2011, drugmaker BioMarin announced it was buying Pfizer’s Shanbally biologics facility in Cork, Ireland, for $48.5m (€43m) in order to manufacture its then Phase III candidate N-acetylgalactosamine-6-sulfatase (GALNS) enzyme replacement therapy.
The product, since approved in the US and EU in 2014 to treat the rare congenital enzyme disorder Morquio A syndrome, is currently manufactured at the firm’s Novato, California facility and headquarters, but plans to meet commercial demand through the opening up of the secondary Shanbally site are “proceeding very well,” according to management.
“We are going through the process qualification manufacturing campaign now that started in the beginning of January,” said Robert Baffi, EVP of Technical Operations during a call discussing Q4 2015 results yesterday.
“The campaign will end in the June timeframe. We'll then have to write up the documentation and submit it. We'll probably have inspections in the first quarter of 2017 and are anticipating approval in the major regions - US and Europe - by mid-2017.”
He added Californian supplies of the product – which costs patients $380,000 for a year’s supply – will be “more than adequate” to bridge the gap until then, and then BioMarin “will be able to produce product at two different sites for Vimizim, meeting all the commercial demands as required.”
Completing validation and gaining approval at the site will contribute heavily to the firm’s expected $150-175m capital expenditure for the upcoming year, management said.
For 2015, total sales were $890m, up 18.8% year-on-year, driven by the continued global launch of Vimizim. The product itself contributed $228m to the results.
Vimizim Master Cell Bank
At the time of EU approval, the drug’s active substance was being manufactured at Novato with fill/finish – in Europe at least – being conducted by CDMO Vetter in Germany, according to the European Medicine Agency (EMA) assessment report.
The report also described the manufacturing process using BioMarin’s cell banking system derived from a CHO-K1 cell line:
“Following transfection in the host cell line, a stable pool was generated by selection and the pool was limited-dilution cloned for single cell clones producing elosulfase alfa.
“One clone was selected from the stable clones based upon titer and viability, and was selected to use in creation of the master cell bank (MCB). The resistance marker was removed from the culture process prior to preparation of the development bank, and was not utilised during generation of the MCB.”
It added the product is purified in a sequence of chromatography, viral inactivation and filtration, and ultrafiltration/diafiltration steps.