Thursday, September 3, 2015

Containment and the challenges of ADC Manufacture

Monoclonal antibody therapeutics are a leading class of biopharmaceutical which have been very successful in the clinic and commercially for their sponsors. The key attribute of these medicines that has led to their success has been their very high degree of specificity enabling monoclonal antibody therapies to target antigens found only on cells that clinicians are seeking to destroy such as cancerous cells without damaging a patient’s healthy cells and tissues. In this way life threatening diseases can be treated with far fewer side effects than has traditionally been possible.

Antibody Drug Conjugates

To capitalize on this success, leading biopharmaceutical companies have sought to enhance the therapeutic effect of antibodies by linking highly potent toxophore molecules to antibodies through a conjugation step in the manufacturing process. These antibody-drug conjugates or ADCs benefit patients because they achieve the best of both worlds; high specificity that targets the drug to diseased tissue and minimizes side effects and high potency with the potential to destroy the targeted tissue with a high degree of efficiency.
The manufacture of ADCs presents some additional complexities on top of those typically experienced during the production of biopharmaceuticals. Conjugation steps are typically performed towards the end of the downstream process where linker and toxophore molecules entities must be added to purified antibodies in a reactor. Those molecules that do not conjugate must then be removed from the conjugated antibody which is often performed by an ultrafiltration operation. Once formulation steps are completed the ADC can be filtered and filled

Challenges of ADC Manufacture

The high potency of the ADC drugs themselves and the intermediates used in their production requires manufacturers to consider the issue of containment to an even greater extent than they might for a non-ADC antibody. ADCs and toxophores might be present in very small amounts and can therefore be difficult to detect yet may still represent a potential hazard as a contaminant in the environment or facility, to operators and a cross contaminant in other processes in multi-product operations.

Biomanufacturers may look to perform steps in isolators or within equipment that allows for closed system processing. In a previous post I have described how single-use technologies canallow for processing while maintaining a closed processing environment.

ADCs at BPI Boston 2015

The BioProcessInternational Conference & Exposition to be held in Boston on 26-29 October 2015 will dedicate a pre-conference symposium to ADC Development and Production and will have additional presentations throughout the conference such as Berthold Boedeker of Bayer Pharma’s talk entitled “ADC Production: Integration of the Conjugation Step in a Standard Protein Plant Using Closed System” which is part of the Closed System Manufacturing Track.

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Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker's strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.

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