Biologics Feature: Part 3
With biologics, the maxim is “process is the product,” and suppliers are meeting the technologies demanded by developers with an equal amount of innovation.
Reliably manufacturing large molecules at commercial scale requires both technical and operational acumen that only the best can muster; such sophistication comes at a price. McKinsey analysts note that large-scale biotech-manufacturing facilities require anywhere from $200 million to over $500 million to build and can take around four to five years to complete, compared with $30 million to $100 million for similar-scale small molecule facilities.1
Where the Money Goes …
The biopharmaceutical industry has an extremely mature technological supply chain, supporting its quest to engineer and field more flexible, cost-efficient and reliable commercial-scale capacity. ‘Commercial-scale’ is a totally relative construct in this industry, however, ranging from fielding enough processing capacity to win approval for an orphan-category therapy before it is sold upmarket, or meeting global, expanding demand for a popular biosimilar.
Regardless of scale, biopharmaceutical manufacturers are adopting multiple, increasingly affordable technologies to help them transition from inflexible, proprietary, fixed-scale batch processing platforms to the more flexible, modular, automated and flow-optimized process essential to sustain successful and cost-efficient processing capacity.2
The 2017 Nice Insight Pharmaceutical Equipment Survey revealed that 64% of respondents have a focused interest in purchasing biopharmaceutical processing equipment. Of those that have a particular interest in pursuing downstream bioprocessing equipment, 43% are interested in filtration equipment, 40% in purification equipment and 39% in separation equipment. For those interested in upstream bioprocessing equipment, 37% mentioned mixers/blenders/millers being of interest, 34% cited incubators and 29% expressed interest in fermenters.3
BioPlan Associates’ 13th Annual Biopharmaceutical Manufacturing Survey indicated that, for the first time, respondents felt that continuous manufacturing should be the focus of equipment supplier innovation R&D efforts.4
Long-Term Affair
Regardless of pharma’s alliances with bioprocessing technology, suppliers are becoming more strategic and long-term. For example, in June 2016, GE Healthcare’s Life Sciences business agreed to acquire IP relating to a proprietary yellow fever inactive vaccine platform from PnuVax. The deal was predicated on the purchase of GE’s single-use FlexFactoryTM biomanufacturing platform.5
Development with technical partners is often intensive and in the moment. To solve a particular processing problem, a Parker Dominick Hunter Technical support group, along with its R&D team, developed a new filter for a drug intermediate. The company said that involving the customer directly in the product development phase ensured that the filter was developed rapidly to the required specification and solved the customer’s problem.6
Speed-to-market and the need for ‘instant’ capacity are driving the uptake of modular single-use technologies and prefabricated processing units. Available to meet that demand is another recent GE offering: the KUBio, a prefabricated, prevalidated modular cGMP-compliant facility and process solution designed for scalable monoclonal antibody production. The units can be transported, assembled on site and made ready to operate in 14 to 18 months.7
Biopharmaceutical manufacturing spending has funded an extremely mature technological supply chain, one actively supporting the industry’s quest to engineer and field more flexible, cost-efficient and reliable commercial-scale manufacturing capacity.
Following the flexibility and automation themes in technology development, MilliporeSigma was similarly recognized at Interphex as ‘Efficiency Champion’ for its Mobius® 1,000 L Single-use Bioreactor. A stirred-tank bioreactor design, it configures software, hardware and single-use assemblies for suspension and adherent cell culture applications, either as a stand-alone system or integrated into a facility automation platform.
Modularity and flexibility were highlighted for another aspect of downstream process — fill-finish — with Interphex Biotech Innovation award winner Bausch+Stroebel recognized for its VarioSys® flexible processing line. The automated, scalable fill-finish platform emphasizes the integration of critical final processing routines through a modular design, standardized subassemblies and isolation technologies.
Downstream Performance
The real battle for efficiency and cost control comes by configuring downstream processes and ordering filtration, purification and similar molecule-finishing operations successfully. Various high-throughput instruments have been developed over the last 25 years to support downstream process development, notably in the purification of vaccine candidates.8
Automated liquid handling systems like predictor plate or ‘robo’ columns for the screening of chromatography resins and Design of Experiment studies — high-throughput sample preparation (compact liquid handling systems), high-throughput analytical tools (microfluidic electrophoresis, ultra-performance liquid chromatography and bio-layer interferometry label-free technology) — provide biopharmaceutical processors feedback for process development and facilitate vaccine purification development.8
Finally, commercially viable technologies situated a little deeper in downstream processing are already supporting the continuous processing movement identified by BioPlan Associates.9 Named ‘Technology of The Decade’ by Bioprocess International, Asahi Kasei’s inline buffer dilution system automates expensive, time-consuming buffer production, integrating quality by design into fluid processing through a real-time process analytical technology platform.9
For the near term, biopharmaceutical processors will continue spending to develop their capacity and improve their ability to successfully manufacture biologic drug products without defect and at whatever volumes the market demands. This investment is driving technical development as well as the breakthroughs the industry needs to bring these life-changing therapies to patients everywhere.
References
- Otto, Ralf, Alberto Santagostino, Ulf Schrader. “Rapid Growth in Biopharma: Challenges & Opportunities.” McKinsey. Dec. 2014. Web.
- Langer, Eric S., Jean-Claude Lupis. “Bio Pharma Manufacturing’s Top 15 Trends for 2015.” Pharmaceutical Manufacturing. 26 Aug. 2015. Web.
- The 2017 Nice Insight Pharmaceutical Equipment Annual Survey.
- Langer, Eric S. “4 Key Trends in Biopharmaceutical Manufacturing in 2016.” Bioprocess Online. 16 Mar. 2016. Web.
- Stanton, Dan. “GE and PnuVax Ink Vaccine Deal and Say Single-Use Will Change the Industry.” Biopharma Reporter. 10 Jun. 2016. Web.
- Kelly, Andrew. “A Case for Collaborative Filter Product Development.” Parker Dominick Hunter. 3 Mar. 2016. Web.
- Interphex 2016 Exhibitor Awards: Six Companies Recognized for Efforts in Cutting-Edge Pharma/Biopharma Technologies. Interphex. 26 Apr. 2016. Web.
- Yang, Yan-Ping. “Advances in Purification Technologies Accelerate Vaccine Development.” American Pharmaceutical Review. 30 Jul. 2016. Web.
- Sanderson, Kimo, Guy Tiene. “Innovating Equipment: Inline Buffer Dilution Technology.” Pharma’s Almanac. 1 Aug. 2016. Web.