From the cleanroom to the zip: 20 years of pharmaceutical technology in transition at the exhibition stand

Continuous production gains ground

The regulatory green light was given in 2004 by the FDA’s PAT Guidance: quality should no longer be assessed only at the end, but understood and controlled throughout the process. This was followed by two decades of regulatory tailwind – from Quality by Design, through the FDA’s Emerging Technology Programme, to the ICH Q13 guideline for continuous manufacturing processes. At the same time, the concept became industrial practice. In 2015, Vertex’s Orkambi became the first continuously manufactured medicinal product to receive marketing authorisation; a year later, Janssen was permitted to switch the production of Prezista from a batch-based to a continuous process.

Continuous manufacturing has thus moved beyond its pioneering phase. Particularly in the case of solid dosage forms, several traditional batch steps can now be combined into seamless process chains. Direct compression and dry granulation play a central role in this. The advantage is not merely greater productivity: fewer process steps mean fewer handover points – and thus fewer interfaces where product can leak or become contaminated.

Alexanderwerk demonstrates just how closely continuous processing and containment are now intertwined with its WP 120 Pharma OEB 4 roller press. It combines dry granulation with high standards of operator safety. Romaco contributes tableting technology with the Kilian KTP 1X. And because continuous processes can hardly function without continuous data, analytics is also becoming part of the production line: Sympatec is showcasing solutions for particle characterisation with HELOS and QICPIC/S, whilst further measurement technology is provided by Malvern Panalytical and Anton Paar, amongst others. Fette Compacting, one of the major suppliers in tablet production, is also represented at POWTECH TECHNOPHARM.

Containment is becoming a design principle

As the potency of active pharmaceutical ingredients increases, so does the problem of interface contamination. More than 57 per cent of the active pharmaceutical ingredients authorised between 2011 and 2020 are classified as Occupational Exposure Band 3 or higher; at the same time, the market for highly active pharmaceutical ingredients continues to grow strongly. High potency is therefore no longer an exotic special case.

Regulatory pressure is also mounting. The amended Hazardous Substances Ordinance and GMP Annex 1 are placing greater emphasis on closed processes, contamination control and barrier technology. The critical weak point is often not the closed reactor itself, but what lies in between: every transfer, every opening and every product change can lead to a contamination incident.

It is precisely at these interfaces, therefore, that a dedicated ecosystem has emerged. With the JEL SmartCon ES containment discharge station and the JEL Konti II CTM vibrating screen, Engelsmann demonstrates how big bags can be emptied whilst meeting high containment requirements and how the product can then be processed further. Rubitec and Air-Jet address similar challenges in filling and pressure vessels.

The direct transfer between two pieces of equipment remains a particularly critical point. This is where containment valves – such as Zermec’s Valve System or CO.RA.’s TABLET VALVE and SOLE VALVE, designed for tablets and capsules – come into play. They are intended to prevent the need to open the closed process precisely at the point of transfer.

And containment does not end at the product line. Air flow management is also part of the safety concept. AFC is showcasing a push-push filter system from the ConVaaC series for this purpose, whilst HET Filter and Infastaub close the air-side barrier with high-performance filtration and dust extraction technology.

The change is therefore more fundamental than the use of individual protective components: containment is evolving from an add-on for particularly critical applications into a design principle for entire process chains.

When the zip complements the stainless steel

The most striking change originally stems from the biopharmaceutical sector. Single-use technology has expanded from bioreactor bags to encompass ever more process steps – and has long since reached the field of containment for solid dosage forms.

There are not only regulatory but also economic reasons for this. Smaller batches, more frequent product changes and more highly personalised therapies increase the effort required for cleaning, changeover and revalidation. Pre-sterilised or pre-assembled single-use components can shorten these downtimes whilst simultaneously reducing the risk of cross-contamination. Even from an environmental perspective, stainless steel is not automatically superior: eliminating complex CIP and SIP cycles reduces water, steam and energy consumption – though this is offset by additional plastic waste.

Lugaia demonstrates just how far this principle has now progressed with its flexible film systems and the latest products, SafePort Evo and SafeSeal DuoPro. Instead of constructing a solid stainless steel process interface, the sealed connection here is formed from film, a port and a closure system.

Novindustra Containment follows the same logic with a new containment film system and a continuous film system: highly active products are transferred not via an open handover but within a flexible barrier. ChargePoint Technology combines single-use ChargeBags with aseptic split-butterfly valves, thereby linking single-use technology with sterile transfer processes. ILC Dover complements the range with ArmorFlex films, continuous liners and the CrimpLoc closure system. The fact that specialised containment service providers are now also emerging with isolators and discharge systems shows just how far this has developed into a market of its own.

This also shifts the long-standing fundamental question of ‘stainless steel or single-use?’. In practice, much of it boils down to a hybrid approach: durable stainless steel equipment where robust, continuous processes are required – flexible single-use components where frequent product changes, critical transfers or maximum separation are required.

So the ‘zipper’ is not replacing stainless steel. But it is appearing in more and more places where, twenty years ago, a rigid connection would have been the norm.

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