Outsourcing
“A group of six biopharmaceutical firms researching monoclonal antibody candidates recently sought permission under antitrust law to exchange ‘technical information’ on each other’s manufacturing processes and platforms,” noted a recent paper entitled ‘Knowledge transfer for large- scale vaccine manufacturing’.
“A focus on rapid information exchange of the sort recently encouraged by the [US Department of Justice] will not only be critical for the current crisis, but could also create the foundation for fewer silos, improved standardisation and less secrecy over manufacturing information in the future,” the report says.
Delays can be deadly
More open knowledge transfer can greatly increase the speed and scale of manufacturing processes, but in normal times this is a competitive market with closely guarded intellectual property. The pandemic has shown the need to bend traditional rules, though there have still been some notable refusals. For instance, Inovio claimed in a June 2020 court filing that its own experimental vaccine was being “held hostage” by a contract manufacturer unwilling to share details of its manufacturing process. Even when lines of communication between pharma companies and their contract manufacturers are open, the transfer of technical know-how can still cause delays. A recent McKinsey report, based on from a survey of vaccine manufacturers, highlighted that the technical transfer process can typically take between 18 and 30 months. That’s too long under normal circumstances, so it’s certainly too long during a pandemic. Technical transfer is the bridge between development and manufacturing. It determines how quickly a new product will come to market, but until recently its importance has, it seems, been underappreciated – not least because it is not front of mind during the development stage. Ensuring adequate and timely supplies of Covid-19 vaccines has required unprecedented collaboration between global institutions, pharma companies and their contract development and manufacturing companies (CDMOs). This is proof that the tech transfer phase can be expedited when necessary. “The relationships we have with CDMOs are very important for us, as we rely on outsourcing for all process development, analytical characterisation, quality control and manufacturing,” says Michael Mulkerrin, vice-president and head of chemistry manufacturing and control (CMC) at ADC Therapeutics. “We look for a partner who has significant expertise in their area. We depend on the contractor or CDMO to be able to develop assays or processes and contribute to the understanding of the development.”
World Pharmaceutical Frontiers /
www.worldpharmaceuticals.net Production process challenges for biopharmaceuticals
■Molecule or virus complexity: 2,500–25,000 atoms in protein-based vaccines; even greater complexity in virus-based vaccines, creating a high- value product.
■Molecule or virus stability: great sensitivity to heat, pH and organic solvents, possibly resulting in a relatively short shelf life.
■Production principle: recombinant technology, typically with >15 steps or sterile design for drug substance and drug product, involving complicated and expensive production requirements.
■Scalability: difficult, up to approximately 20,000L, meaning there is limited output per production line.
■Cell banking: sterile handling and master cell banks needing to be maintained at temperatures as low as –120°C.
■Raw materials: typically >50 raw materials with many critical specs, creating a heavy test load on raw materials and difficult quality control.
■Purification: multistep chromatography, an expensive step with high- cost consumables.
■Lead time to drug substance: often long, measured in weeks or months. ■Storage: cold room (2–8°C) and frozen storage mean tight supply chain control is required.
■Transport: cold chain transport in frozen state for drug substance and at 2–8°C for drug products mean tight transport control is required.
Source: McKinsey & Company
Mulkerrin is emphasising the critical nature of the CDMO relationship, which has been accentuated across the industry, with the crisis of Covid-19 acting as a catalyst to bring vaccines to market much faster than usual. As the McKinsey report noted, large biopharmaceutical companies are now willing to share information that they would have previously seen as a threat to their competitive advantage.
“We depend on the contractor or CDMO to be able to develop assays or processes and contribute to the understanding of the development.”
They may even be willing to pursue some standardisation of how such information is shared, which could lead to a more uniform vaccine manufacturing process. As some platforms, such as mRNA, have never been produced at scale before, this could prove crucial in the future. Though the pandemic does represent a set of exceptional circumstances, in which secrecy around manufacturing processes would have been catastrophic, it also shows how sharing relevant information can lead to the quick and effective scale- up of production. The next step is ensuring that the CDMO responsible for production can handle the processes and ramp up production swiftly without compromising quality. As Mulkerrin suggests, the quality of the relationship with the CDMO is of paramount importance. His company, which creates antibody-drug conjugates (ADCs) to deliver pyrrolobenzodiazepine (PBD) dimers for cancer therapy, has a carefully planned approach to the
18–30
Number of months the technical transfer process can typically take.
McKinsey & Company 25
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