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.
Join me at #BPIconf
Contact me at nick.hutchinson@parker.com
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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1 comment :
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