As the pharmaceutical industry tirelessly seeks to accelerate its medicines to market, drug manufacturing remains a key opportunity area for it to reduce costs and improve quality. The technology advances promised from Pharma 4.0 -- such as big data, interconnectivity, robotics and artificial intelligence -- and smart manufacturing techniques have given business leaders greater visibility into their pipelines and processes. Meanwhile the ability to manufacture more complex therapeutics spells relief for non-communicable disease patient populations.
Latest Advances in API Manufacturing
High-potency API products continue to be a hot topic in pharmaceutical manufacturing. The GlobalData/PharmSource trend report, “Contract Small Molecule API Manufacturing Industry by the Numbers – 2019 Edition,”[i] identifies strong demand for high-containment API manufacturing. This demand is predicted to increase in the foreseeable future as the oncology drug development pipeline continues to grow. IQVIA Institute, in its “Global Oncology Trends 2019” report[ii], says more than 700 companies are active in late-stage oncology R&D, working on nearly 850 products – the vast majority targeting small molecule and biologic therapies.
The GlobalData/PharmSource report also highlights a corresponding increased demand for CDMOs with specialized HP-API capabilities, as many pharma companies do not possess the ability or expertise to carry out such manufacturing. Considering that nine in 10 drug candidates fail in early-stage clinical trials, the use of an outsourced partner for HP-API development and manufacturing can be a good choice as it minimizes upfront expenditures. The benefits of such an approach include cost savings from not investing in high-containment equipment, partner management of complex supply chains and reduced tech-transfer costs and knowledge loss if using a fully integrated CDMO all the way to large-scale implementation.
With so much riding on early success, careful consideration should be taken when selecting a manufacturing partner in the HP-API space. Critical to success is assessing the provider’s technical expertise (e.g. previous experience with HP-API), quality and regulatory track record, facilities/equipment availability, as well as factors such as price.
Pharma 4.0 and Smart Manufacturing
The Industrial Internet of Things (IIoT) – an extension of use of the more widely known internet of things in industrial sectors and applications – and the Pharma 4.0 operating model are also being discussed extensively within the pharmaceutical manufacturing world. The use of artificial intelligence (AI) – the simulation of human intelligence in machines so that they mimic human thinking and logic -- not only applies to API development, but also to the design of more intelligent manufacturing processes. According to Deloitte, biopharma manufacturing currently produces troves of underutilized data, which AI is ready to unleash for real-time data processing and decision making.
“The potential for end-to-end visibility in manufacturing and supply chains will allow biopharma companies to improve their supply chain planning, inventory management, demand forecasting, logistics optimization, workforce planning and procurement,” Deloitte analysts write in an article, “The rise of artificial intelligence across biopharma.”[iii]
While the start-up costs for AI and Pharma 4.0 can be significant – purchasing new equipment, training staff, revamping infrastructure – economic analyses have shown the potential for significant savings and value creation in the long-term. One study shows the global Pharma 4.0 market is projected to grow at a compounded annual rate of 15 to 20 percent from 2019 to 2025.[iv]
Smart manufacturing technologies reinforce efforts for continuous manufacturing processes. Among its advantages is flexible batch sizes, which can be based on production period, the quantity of material processed and produced and production variation, such as different incoming lots of material. This flexibility is especially helpful with changes in market demand for a particular drug.
Additionally, continuous manufacturing is based on closed processes, making them easier to control than traditional batch manufacturing, with its discrete starts and stops that can introduce complexity and uncertainty.
“Continuous manufacturing has been praised by regulators for producing products of consistent quality and reducing production costs – which is why it has been adopted by the non-pharma fine chemistry industry for decades.” says Fiona Barry, Associate Editor at PharmSource, a GlobalData company.
Changing over from one product to another remains a concern. The goal is to be able to switch from one short production run of one product to another in a day or less. Depending on the systems involved, however, this may take a week or more as the lines need to be disassembled, cleaned, and reassembled. Optimizing the order of disassembly and reassembly has helped in this regard but requires additional training of operators involved.
It is worth noting that smaller, portable systems, such as Pfizer’s portable, continuous, miniature and modular (PCMM) pod and GEA’s Consigma technology, have been useful for this optimization and allow for the system to be easily moved once a run is complete.
New Technology Required for Continuous Biomanufacturing
While today’s blockbuster drugs relied on bioprocesses developed several decades ago, the drugs of the future require modernization to bioprocessing. The continuous operations in upstream processing are just now reaching downstream operations, thanks to recent advances that now give companies a completely integrated and continuous bioprocess platform that is more efficient for production.
With this in mind, several organizations have shown enthusiasm for continuous manufacturing in biopharma, driven by a need for a reduction in manufacturing costs and flexibility in their processes. Several leading CDMOs are investing in continuous manufacturing, and NIH has awarded grants in this field[v] [vi]. In July 2019, the University of Delaware, the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), and the FDA entered a Collaborative Research and Development Agreement (CRADA) focused on biopharmaceutical manufacturing investment and research, including continuous manufacturing.
“Biopharmaceuticals are more challenging to manufacture than traditional pharmaceuticals, and NIIMBL seeks to enhance patient access by innovating the biopharmaceutical manufacturing technologies and processes,” Kelvin Lee, institute director at NIIMBL, said. “This CRADA establishes a framework for FDA engagement in NIIMBL projects and initiatives that strengthens the existing NIIMBL-FDA relationship and supports the development of advanced biopharmaceutical manufacturing innovations.”[vii]
As with all other components of the pharmaceutical product lifecycle, drug manufacturing is evolving, and we are likely to see digitization, automation and AI all come very much to the fore. With Big Pharma increasingly focusing on R&D and marketing as its core competencies, it is very much falling on CDMOs to blaze a trail in redefining manufacturing. The winners in the industry are likely to be those who can successfully balance the requisite amount of standardization to reduce process complexity while affording enough flexibility in the design to cater for the growing complexity of biologics development and of course, individual clients’ needs.