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Manufacturing of antibody drug conjugates requires high-containment solutions, such as high-performance aseptic isolators.
Antibody drug conjugates (ADCs) are a new class of highly hazardous substances used for cancer treatment. Most ADCs have an occupational exposure limit (OEL) of less than 0.1 μg/m3 (100 nanograms/m3) and, therefore, require the most stringent containment classification (see Figure 1). The manufacture of pharmaceutical products in this range represents a challenge, particularly to aseptic production processes, which must be run in overpressure to meet GMP requirements for protecting the product, while also actively protecting operators from the substance.
Isolators have been used successfully for many years for product protection in aseptic manufacture, and now they are also being required to provide active personnel protection. In aseptic manufacture, isolators are operated in overpressure to protect the product. Containment, however, calls for negative pressure in the isolator to protect personnel by preventing the hazardous substance from escaping. High-performance aseptic isolators can do both, but innovative solutions, such as FilterPatrone (FiPa) filter technology and specific sealings on the gloves and glass panel, are needed to enable an isolator operated in overpressure to remain below an OEL of 0.1 μg/m3. This OEL can be verified on the basis of the International Society for Pharmaceutical Engineering (ISPE) Good Practice Guide "Assessing the Particulate Containment Performance of Pharmaceutical Equipment," also known as SMEPAC (1).
Integrated filter technology plays an important role in achieving this low level in an isolator operated in overpressure. As a rule, filters are installed after the exhaust air channels and then changed using bag in/bag out (BiBo) technology, but this arrangement has two serious problems. Not only do the exhaust air channels become contaminated, but BiBo technology does not offer the necessary level of containment in the nanogram range. Nanogram-level containment requires a technology that captures and filters the particles in the critical containment area to prevent them from reaching the exhaust air channels in the first place. Such technology is provided by a new type of isolation filter known as FiPa, which is shown in Figure 2. These filters are positioned in critical areas in such a way that particles released during production can be captured safely and via the shortest possible route. FiPa filters take the form of a mini-isolator in their own right, and they come with an integrated filter cartridge. During a product change, the FiPa can be sealed and removed safely for disposal.
1. ISPE, ISPE Good Practice Guide: Assessing the Particulate Containment Performance of Pharmaceutical Equipment (2012).
About the Author
Richard Denk is head of the Containment Group at SKAN AG, firstname.lastname@example.org.