Portable and Continuous Miniature and Modular System

4-Apr-2016

Developed by a consortium of GEA, G-Con and Pfizer, PCMM is a portable, autonomous manufacturing environment for continuous oral solid dosage (OSD) production that answers many of the flexibility needs of the pharma industry, while also enhancing quality and compliance

Today's chemical and pharmaceutical markets are rapidly changing and highly volatile. Pharmaceutical manufacturers face many challenges when developing products and getting them to market in a timely, safe and cost-effective way. When formulating new molecular entities, improving generic drug production and/or extending the lifecycle of existing oral solid dosage (OSD) forms, issues such as increasing patient safety, reducing the cost-per-tablet and optimising the price/performance balance are common concerns. To face these challenges, flexibility is seen as a key element, and one way to address this requirement is implementing portable, continuous, miniature and modular (PCMM) manufacturing facilities.

Many articles have been published in recent years that explain the benefits of multipurpose and modular plants for the chemical, pharmaceutical and biopharmaceutical industry, including shorter time to market, growth in emerging geographies, lower capital expenditure and on-demand drug production.^1,5,6

Beyond the general challenges facing the chemical and pharmaceutical industries, drug manufacturers also need to overcome specific quality and compliance issues. Notwithstanding the financial and competitive hurdles that affect every manufacturing sector, pharmaceutical companies are under constant pressure to optimise performance and maximise output. 'As payers recognise the problem of reliability in the drug supply chain, they will gravitate toward the most reliable suppliers and, ultimately perhaps, to an entirely different supply-chain model,' notes Janet Woodcock, Director of the FDA's Center for Drug Evaluation and Research (CDER).

Highly efficient production will be the key to success as profit margins erode and the much-debated research and development pipeline continues to falter. The development of personalised medicines, products developed for specific populations or subgroups and/or treatments will certainly result in a decline in the need for batch-produced 'generic' drugs and may well instigate a completely new paradigm of supply chain practices throughout the pharmaceutical industry. Woodcock asks: 'Are you ready for the concept of continuous drug production?' If not, get ready, she advises.^2,3

POD-based mini factories

To create the next generation of OSD processing technologies and to address the rapidly changing requirements of drug manufacturers, Pfizer, GEA and G-Con Manufacturing formed a consortium to design and build a portable, autonomous manufacturing environment for continuous OSD production using GEA's ConsiGma continuous manufacturing (CM) system and G-Con's modular cleanroom POD system. Continuous processing with GEA's ConsiGma platform enables entire lines to be miniaturised and made both modular and portable. Furthermore, CM provides advanced process control resulting in more consistent and higher quality products. The result – PCMM – is a standardised production technology platform that can be used for product development and commercial manufacture; a key advantage of which is being able to use the same equipment throughout the entire product lifecycle.

The PCMM platform combines equipment design, PAT, advanced process control and engineering expertise to deliver a fully integrated cGMP facility

The PCMM platform offers a process analytical technology (PAT)-compatible process control solution for continuous wet granulation and continuous mixing/direct compression, enabling efficient transfer from development to clinical and commercial production without scale-up. The system is easy to deploy and ship. In addition, the PCMM platform combines equipment design, PAT, advanced process control and engineering expertise to deliver a fully integrated cGMP facility.

PCMM embodies the idea of portability in pharmaceutical development and manufacturing. Continuous processing enables miniaturisation, which increases the amount of accessible locations, reduces energy consumption and enables modularity, which subsequently enables rapid processing and product changeover. The platform also facilitates rapid deployment and redeployment, reduced capital investment, enhanced safety and environmental isolation. Multi-company POD installations in one host facility can also be created, providing greater opportunities for low overhead and localised pharmaceutical manufacturing.

The new OSD paradigm will generate significant cost savings and greatly simplify transfer/scale-up from R&D to commercial manufacturing. Using the same equipment for development, clinical supply and commercial production will maximise manufacturing efficiencies, providing the following benefits: improved quality assurance (QA), improved time to market, improved operational efficiency and improved supply chain agility.

PCMM in a nutshell

This first-of-a-kind manufacturing system accelerates the speed at which tablets are produced. By miniaturising the equipment, the continuous process can be enclosed in a portable, modular facility, which can be shipped by truck to any location in the world and quickly assembled. Once up and running, the system will deliver the capability to transform powders into uncoated tablets in minutes, which can take days or weeks with current technology.

To further highlight the significant role that CM will play in the evolution of pharmaceutical manufacturing, Pfizer was recently presented with the International Society for Pharmaceutical Engineering's 2016 Facility of the Year Award (FOYA) for 'Equipment Innovation' for its work on establishing the PCMM concept as a standardised development and manufacturing technology platform.

In addition, the consortium has announced a next-generation collaboration with GlaxoSmithKline (GSK) to further advance these self-contained, POD-based mini-factories.

PCMM has the potential to transform the future of pharmaceutical development and manufacturing, and deliver customised quantities of on-demand medicines to patients in need in a quick and more efficient way.

Regulatory support

Regulators are increasingly supportive of CM and manufacturers are recognising that current quality assurance costs are disproportionately large compared with other industries, wherein the production, detection and removal of out-of-specification product is vanishingly small. Potential API savings of more than 60% and time-to-market reductions of more than a year have been identified by companies using small-scale CM systems. In 10 years, it is predicted, the vast majority of tablets will be produced on CM lines installed in modular facilities that are a fraction of the size of current plants.

To meet the requirements of the current and future pharmaceutical industry, facilities must have:

• Capacity flexibility: a plant should be able to produce both small and large quantities in a cost-effective way, without the need for time-consuming and costly scale-up or -down
• Product flexibility: a plant should be easily adaptable to different products
• Innovation flexibility: research and development (R&D) plants must easily accommodate new and innovative products and processes
• Location flexibility: the plants should be easily movable from one place to another
• Feedstock flexibility: the plant should be able to handle different kinds of feedstock.¹

With lower upfront investment costs compared with traditional facility design and build approaches, lower energy and resource requirements, while at the same time enhancing quality, POD-based mini-factories are the solution to many of these needs. Additional benefits include increased OEE, optimised R&D (10 times less material use, 10 times faster than conventional batch equipment), multiple formulations and flexible batch sizes, and reduced cleaning costs and materials.

Conclusion

A concept that is applicable across a spectrum of biologics, small molecules, APIs and drug product, PCMM is the factory of the future.⁴ For more than 20 years, the batch-based production of blockbuster solid dosage forms dominated the industry. Profitability was such that companies were not incentivised to innovate or risk developing new manufacturing technology. In the post-blockbuster era, however, it is increasingly recognised that material costs during drug development are significant, new drug products are likely to be manufactured in much smaller quantities and that, for novel treatments, the development of a commercial manufacturing process is not guaranteed.

With the goal of achieving more consistent process control and, ultimately, higher quality end products, manufacturers are increasingly moving away from batch-based systems

Such pressures have put the costs, risks and timelines associated with traditional batch-based development and manufacturing under scrutiny. In most industries, CM is seen as the low-cost solution to producing low value, high volume products in which there is little need to focus on the cost of materials used in process development and, often, little need for product changeover.

Furthermore, process intensification in the pharmaceutical industry has led to the development of smaller and more compact equipment. With the goal of achieving more consistent process control and, ultimately, higher quality end products, manufacturers are increasingly moving away from batch-based systems and switching to CM. Providing increased yields, lower utility consumption and reduced waste, continuous manufacturing presents a paradigm shift in drug production and meets the industry's demands for faster product development, reduced costs, improved production economics and increased manufacturing flexibility.

References

1. Van Kranenburg K, Sofra C, Verdoes D, de Graaff M., Whitepaper: Small-Scale Flexible Plants. Towards a More Agile and Competitive EU Chemical Industry. TNO innovation for life. June 2015.

2. Koberstein W. Janet Woodcock's Quality Agenda at CDER. Pharmaceutical Online, 2 February 2014: http://www.pharmaceuticalonline.com/doc/janet-woodcock-s-quality-agenda-at-cder-0001 (last accessed 6/7/2015).

3. Brennan Z. FDA calls on manufacturers to begin switch from batch to continuous production. In-Pharmatechnologist.com (1 May 2015): www.in-pharmatechnologist.com/Processing/FDA-calls-on-manufacturers-to-begin-switch-from-batch-to-continuous-production (last accessed 6/7/2015).

4. Nixon P. Broad Implementation of Continuous Manufacturing for Solid Oral Drug Products: What Can the Future Look Like? Presentation at 50th Arden Conference, March 16–18, 2015. Baltimore, USA.

5. Estapé D. Production Progress. Innovations in Pharmaceutical Technology, Issue 5.1, 2014

6. Almhem P., Lilja J., Järvi K. Outside the box. Innovations in Pharmaceutical Technology, Issue 5.1, 2014.

The PCMM installation at Pfizer was presented with the 2016 Facility of the Year Award (FOYA) for Equipment Innovation by the International Society for Pharmaceutical Engineering (ISPE)

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See also

• Pfizer
• G-CON Manufacturing

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Source: https://www.manufacturingchemist.com/news/article_page/Portable_continuous_miniature_and_modular_the_pharma_factory_of_the_future/117046

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