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ADCs: Requirements in terms of GMP and occupational safety – PART 2* – The challenges presented by a new generation of highly active pharmaceutical products for cancer treatment

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RICHARD DENK1, ANDREAS FLÜCKIGER2
1. Head of Sales Containment SKAN AG, Allschwil, CH
2. F. Hoffmann-La Roche AG, Basel, CH

Abstract

ADCs (antibody drug conjugates) are a new generation of highly active pharmaceutical products used, among other things, in the targeted treatment of cancer. For health and safety reasons, most of these ADCs require containment in the double or triple-digit ng/m3 range.

Manufacturing ADCs is a new challenge, particularly in aseptic production. While isolators have been used successfully in this area for many years, they are now being called on to provide active personal protection as well. A contradiction in terms? At first glance, yes. While the aseptic process must be operated in positive pressure in accordance with GMP (Good Manufacturing Practice) requirements, personal protection isolators are typically operated in negative pressure in order to prevent the hazardous substance from escaping. Special seals on the isolator, innovative filter technology and a well-conceived pressure-cascade concept with active mouseholes make it possible to protect both product and personnel.


HYGIENE DESIGN AND GLOVE TESTING

The concept of hygiene design refers to the optimal cleanability of the interior surfaces of the isolator or of devices built into the isolator. As mentioned earlier, cleanability is extremely important as product residues on these surfaces present a risk from a GMP perspective of cross-contamination between two different substances manufactured in sequence. Particularly important in the design of an isolator are the seals on the glass panels and doors. Static seals are the most straightforward option, as well as being seen as the most critical. Static seals have the disadvantage that they wear out over time and can allow dust to be deposited and penetrate critical areas. This process of wear can also affect the airtightness of the isolator. During or following cleaning in particular, opening the glass panel can cause the product residues deposited in the seals to become detached and escape from the isolator or into the interior. Inflatable seals are a better option in terms of hygienic design, and allow for highly accurate sealing of the glass panel. The seal and its functionality can also be tested using validated measuring equip ...