In January 2013, the US Food and Drug Administration (FDA) approved Protein Sciences Corporation’s trivalent influenza vaccine Flublok, made using the firm’s Baculovirus Expression Vector System (BEVS) rather than the influenza virus itself or eggs, as in other flu vaccines.
Up-scaling to commercial production was therefore needed, VP of Manufacturing Operations Mireli Fino said at last month’s Biological Production Forum in Dublin, Ireland, especially in light of the firm’s $147,000 contract with the Biomedical Advanced Research and Development Authority (BARDA) to produce up to 50 million doses of Flublok within six months of a potential flu pandemic.
“Our launch site for Flublok is a very small plant with a 500L bioreactor capacity and we can only produce about 300-400,000 doses per year for this vaccine,” Fino told delegates, and though the firm has now set up home at an ex-Pfizer in Pearl River, New York, based on a 2,000L bioreactor, it was not the company’s first choice to launch commercially.
Greenfield and CMOs
“The first thing we looked at was a greenfield facility, but the primary concerns with constructing a new facility is time and money,” she continued, adding construction and validation would have taken up to five years, rather than the one-two years’ timeline the company was looking for.
Furthermore, in 2010 the cost of a new facility had been budgeted at $76m (€56m) which “is significant for a very small biotech company,” Fino said, and thus the firm looked at other avenues.
“The focus was then on contract manufacturing,” she said, saying a CMO is the most expedient way to launch a commercial product. “We looked at companies in the US primarily and we narrowed it down from 30 companies to just two,” with contract negotiations beginning in July/August 2012.
However, at the same time Pfizer was selling its biomanufacturing facility, in the wake of its megamerger with Wyeth, which offered a number of benefits for a biotech looking to control its own production without the outlay and validation of a new facility.
“[The Pfizer site] was a licensed manufacturing facility since 2000, just recently decommissioned and it had been fully qualified… There were relative minor expenses expected for equipment and it was ready for capacity expansion… and Pfizer offered very attractive lease terms,” so the firm moved in in December 2012.
Leveraging the qualifications already at the facility was described as a “fast-track into large scale manufacturing,” reducing time and re-work.
“46% of equipment we are using did not require additional qualification, 12% required modification, and about a quarter of equipment (especially in small scale) was new so had to go through full qualification. We have about 70% of the workload completed and we expect to finish within the next 3-5 months.”
“Bringing the facility in line took us about 10 weeks,” said Fino. “It was a very sharp focus, and we made a clear decision on what was needed to maintain the systems in place when operating and what will need to be done later as improvement or remediation of the utilities.”
The first batch was harvested within 100 days, she added, and the company confirmed over the next two batches the process and equipment was producing matching yields and purities to clinical production.
Whilst there was some work to be done in adapting upstream processes, focused mostly on changing the 2,000L bioreactor from a cell-culture control system and working on ensuring sterility of the media in high filtration, Fino said downstream adaptation was relatively simple with a Pfizer custom-made chromatography column being a “perfect fit” for Protein Sciences’ scale -up.