Ensuring Tabletting Safety For High Potency APIs

The main challenge for tablet manufacturers processing highly potent APIs (HPAPIs) is to protect equipment operators from the inhalation of airborne particles and prevent skin contact with the product during the entire production process: dispensing, granulation, tablet compression, coating and packaging.

One of the earliest solutions was the use of air suits, but these are not at all ergonomic and protect only the operator. A tremendous amount of cleaning is also still required; all process equipment is contaminated, as are the processing rooms and corridors. Furthermore, in most Western countries, health and safety laws only allow personal protective equipment as a last resort.

Jan Vogeleer

To that end, isolators were introduced, which got the operator out of the air suit and reduced the amount of cleaning work. Operations, from dispensing to packaging, were integrated into large, sophisticated and highly contained isolators. However, as well as requiring large amounts of space and being impractical in terms of cleaning and product changeover, this solution quickly proved to be very expensive. WIP and CIP capabilities were integrated as much as possible, but this made installations even more complex. Moreover, in many cases, such isolator technology proved to be excessive in relation to HPAPI containment and the concentrations being processed.

One newer, more cost-effective and practical approach is to design inherently closed process equipment using 'containment at the source'. With this technique, the section of the machine in contact with the product is small and carefully isolated from both the electromechanical part of the machine and the environment. Additionally, it is easy to clean without breaching containment.

A more rational approach can also be adopted towards containment requirements in the various production stages. Indeed, the containment level required of equipment used at the dispensing stage (where the material handled is pure HPAPI in powder phase) is different from that needed in tablet coating (where the HPAPI is diluted and compressed into a tablet). The concentration of airborne API particles also varies during the different operational steps of the tablet production process. The only correct way to assess risk and determine the appropriate containment level for the various process steps/equipment is to calculate real daily intake (RDI) and compare this with the allowable daily intake (ADI).

Equipment considerations

Tablet presses for highly potent drugs need to have a compression zone that:

• is as small as possible
• is highly isolated from the remainder of the machine
• contains the smallest possible number of mechanical components (in no case should it contain the cam tracks or compression rollers)
• features automatic underpressure monitoring and control
• is easily removable from the machine for fast product change-over
• can be washed down off-line without breaking containment.

These requirements also apply to downstream equipment, including the tablet deduster, metal detector and the automatic tablet sampler (and tester).

The feeding of powder into the tablet press and the collection of tablets into drums or intermediate bulk containers (IBCs) also need to be conducted in a contained way. I recommend split butterfly valves as a solution to achieve this because such valves offer the requisite containment level, and allow for reliable and fast connection and disconnection, while maintaining containment. In view of this, a highly integrated solution is preferable from powder in-feed to tablet collection, with high-containment interfaces and connections between them.

With a growing number of increasingly potent new APIs often targeted at specific niche therapeutic applications, the pharma industry will need flexible medium- to small-scale, highcontainment tablet presses that enable swift product changeover with no risk of product cross-contamination. It follows that future design improvements for potent tablet manufacturing equipment will focus on these trends.