Highly potent APIs: can lean manufacturing ever be safe?

By Fiona BARRY

- Last updated on GMT

Highly potent APIs: can lean manufacturing ever be safe?

Related tags Manufacturing

The phrase “lean manufacturing” conjures up job cuts and not much more for many people, but managers can use the method to drastically simplify HPAPI (highly potent active pharmaceutical ingredients) production, says an expert.

James Burke, director of manufacturing at Irish CNS company Alkermes, said that, far from lay-offs, lean manufacturing on HPAPI lines means inventing equipment and innovative ways of working to limit the spread of hazardous waste.

One of the biggest ways plant managers drive up their expenses is unnecessarily placing safe materials in contact with HPAPIs, turning them into potentially dangerous products which are cumbersome to dispose of securely.

It’s not just excipients. Anything you can do outside the [HPAPI] suite, you should. In true lean thinking you should only send into the suite what touches the product. If it touches the product it then becomes potent.​”

Accordingly, Alkermes prepares its finished product drum for tablets outside the sealed manufacturing suite.

In standard HPAPI manufacturing where this does not happen, the cardboard boxes and paper bags that store inner packaging materials like liner bags and desiccant bags, will be contaminated by the potent substances and have to be disposed of as hazardous waste, often by shipping it to a specialist.

Sealed system

As part of these efforts to lower contamination, Burke said Alkermes created completely powder-free production lines, with ingredients kept within sealed machines throughout the process.

After 24 months, we now have enough data to assume the powder isn’t airborne and we can take our associates out of respirators.​” Simplifying workers’ protective gear in this way also creates less waste and is easier for employees.


While companies like Alkermes are catching on to lean manufacturing of HPAPIs, equipment makers may be lagging behind. Burke told us Alkermes has had to make its own parts, or modify those of other companies’, to create a completely sealed system.

Alkermes modified an ECM (exchangeable compression model) modulated tablet press made by Courtoy, so that repairs can be made without shutting down the line section to avoid contamination.

To change one of the machine’s punches and maintain containment without replacing them all, Alkermes made a unit that seals over the expired punch and pulls it up inside a plastic sleeve.

They move a clip over to the side to contain it, and they drop in the new punch, they haven’t breached containment. The old sealed punch connects with a tap and fills with water. It can’t become airborne if it’s wet.

Other people are going to take the whole product off. That way you lose product and waste time.​”

Burke said Courtoy has asked Alkermes for the punch-changing design and is likely to commercialise it.

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