ADC Biotechnology is making a new method that will present a new paradigm in Antibody Drug Conjugate (ADC) development and manufacturing, called for now ‘downstream bioconjugation’.
As the ways now in use, undertake bioconjugation after both the mAb and cytotoxic have been manufactured, according to ADCBio, this new approach moves the conjugation step into the later stages of the downstream processing (DSP), with conjugation and antibody purification carried out concurrently.
Charlie Johnson, CEO of ADC Bio, said: “The major benefit, and the reason this approach will prove so disruptive, is that it will save several months of manufacturing time and up to 25% of the overall costs. But it will require much of the industry, with its current ingrained manufacturing methods, to reevaluate exactly how it structures the supply chain that often uses three CMOs.”
ADC explains that, using this ‘downstream bioconjugation’ approach, it could mean less time at the antibody manufacturer (i.e. less time in traditional downstream processing), with the remaining downstream processing and conjugation service both transferring to the bioconjugation CMO. The result is a refined, simpler and much more efficient system – saving up to three months of development time and resources plus creating large cost savings.
Under the Company’s new process, the starting point for the conjugation will no longer be post-creation of purified antibodies and will instead begin with antibody supernatants. This persuasive approach forgoes the need for extensive chromatographic purification techniques to deliver purified antibody.
The production technique – yet to be formally named – would also remove the need for expensive Protein A resins. The new solution will be replaced with capture resins, the main part of the ‘Lock-Release’ technology, the drug purification process that eliminates several steps. In ADC manufacturing, the Protein A capture step is the most costly in downstream processing, delivering semi-purified antibody. Now, starting from antibody supernatant, ADC Bio’s approach will see ‘Lock-Release’ technology be used with the antibody capture step and subsequent conjugation to the ADC payload – replacing the Protein A resin and assembling the ADC. The subsequent viral inactivation, removal and polishing will then occur post-conjugation, the company explained.
Johnson also explained that, the company will be telescoping antibody DSP and conjugation, providing just one set of analytical development and release processes, whilst bringing in the use of much more cost effective and safer resins. “We have already successfully piloted our new development process in a number of applications. As the next step, we have just launched our Specialist Process Innovation Group – which will be responsible for fostering all further technological innovations moving forwards – with its first project being to validate our new downstream conjugation approach over the course of the next 18 months,” he said.