ADCs: Requirements in terms of GMP and occupational safety – PART 1 The challenges presented by a new generation of highly active pharmaceutical products for cancer treatment
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.
WHAT ARE ADCS, AND WHAT MAKES THEM SO DANGEROUS?
Antibody drug conjugates (ADCs) are macromolecules that typically consist of a monoclonal antibody (mAb) linked to a number of molecules of an antineoplastic agent. These small-molecule antineoplastic agents are also referred to as “toxins”, “warheads” or “payloads”. The bond between the mAb and the antineoplastic agent is created by a linker. The task of the mAb in these ADCs is to deliver the “payload” as accurately as possible to the tumour, with a view to ensuring that as little damage as possible is done to healthy tissue. The linker is intended to prevent the payload from splitting off from the mAb before it reaches the tumour.
There are also ADCs currently in the R&D stage in which the small molecule (e.g. an antibiotic) has no antineoplastic effect. These are then generally less toxic than those used to treat cancer. In the future, therefore, it will be necessary to ask what exactly the “drug” in the ADC is in each individual case. Researchers are also working on constructs in which mAbs, or parts of them, are bound to other highly active proteins or to peptide ...