Handling of Highly Potent Compounds

Objectives

The main focus of this conference is on the connection of handling highly potent APIs and the usage of disposable equipment. GMP and safety aspects will be covered and examples from real life will be shown. Amongst others, the following topics will be discussed:

• Definition of the appropriate containment level
• Available single-use components and solutions
• GMP and ATEX requirements for single-use equipment
• Implementation of disposables in pharmaceutical processes
• Qualification of disposable equipment
• Risk handling strategies

Background

The usage of disposable and single-use equipment in the biopharmaceutical production has been growing for years. Well-known examples are disposable bags, hoses and bioreactors. But also in the manufacture of small molecule APIs, the usage of single-use equipment is increasing.

The pharmaceutical industry is now facing a new challenge after a long-time experience had been won with product contact interaction of stainless steel, ceramics or other alloys. Whereas the compatibility of traditional materials is (almost) no topic, plastic material raises discussions. Leachables and Extractables are the big topic here. Many studies have been done already, focusing on effects in aqueous buffer solutions. But coming to the production of small molecule APIs much fiercer conditions have to be considered with respect to organic solvents.
Another issue is caused by the advantages of single-use equipment. It is ready to use and does not have to be cleaned before use. So GMP-relevant steps are shifted towards the supplier of the plastic equipment who has to take care of the GMP-compliant production of his equipment, an appropriate packaging and the necessary documentation. The responsibility remains with the pharmaceutical manufacturer though. Also the handling of disposable equipment is much more demanding compared to robust stainless steel equipment. The training of the production staff gets thus even more important.
Furthermore, the SU equipment does not have to be cleaned after use which is - of course - one of the biggest advantages.

The containment aspect when manufacturing or handling potent APIs is independent from the material of the equipment. The production equipment has to be tight, not only from the GMP aspect to protect the product from the environment, but also from the occupational health point of view to protect the worker from the product. Both have to be proven by measurements.
Yet, with the flexible plastic equipment being much more sensitive to injuries compared to stainless steel equipment, optimised accident scenarios have to be in place.

Besides, there is another advantage of disposable systems. The shift to more single-use systems also brings a higher flexibility to production. More and more single-use isolators are used instead of fixed and immobile isolators - not only to avoid cleaning effort but also to minimize change-over times.