Novasep was approached by a top 10 pharmaceutical company to help with the manufacture of a cGMP antibody drug conjugate. The ADC was in clinical trial Phase I to treat solid tumors, and the customer required a quantity of ADC within 4 months starting from 100g monoclonal antibody.
Technology: ADC conjugation
Clinical phase: Phase I
Project scope: Process development and cGMP manufacturing
Timing: 4 months
> Successful process development and cGMP manufacture of a Phase I ADC, including a chromatography step
> Fast process transfer from mg to g scale
> Effective transfer of analytical methods
Manufacturing ADCs is very complex. Indeed, in-house ADC manufacture requires unique facility design and know-how. This is why an estimated 70 to 80% of the ADC manufacturing market is outsourced. But finding the right partner for ADC supply is not easy!
Novasep was approached by a top 10 pharmaceutical company looking for a reliable partner to help with the manufacture of a cGMP antibody drug conjugate. The ADC was in clinical trial Phase I to treat solid tumors, and the customer required a quantity of ADC within 4 months starting from 100g monoclonal antibody.
Novasep proposed a work plan for the familiarization, development and cGMP manufacture of this new Phase I ADC, comprising the following key steps:
After optimization of the chromatographic purification parameters, Novasep delivered a gram scale representative sample in the R&D lab. The Master Batch Record was then prepared and submitted to the client for approval.
For a robust process transfer from R&D to cGMP production, a non-GMP 25g scale batch was produced in the bioconjugation suite.
Finally, cGMP production was successfully done on 100g scale.
The cGMP manufacturing process required 6 different steps:
1- mAb was first thawed under biological safety cabinet and pooled using single-use mixing bags.
2- Then, a single-use TFF (Tangential Flow Filtration System) equipment was used to exchange the buffer from mAb storage to conjugation buffer.
3- The stochastic conjugation step was successfully conducted in a glass reactor.
4- Our experts took care of the ADC purification, with a chromatography step using the Novasep Hipersep® Bio equipment for toxin and aggregate removal. ADC monomer level was successfully increased from <95% to >95% and toxin was removed according to specification level.
5- A formulation TFF step was conducted with a single-use TFF equipment to exchange buffer from chromatographic buffer to ADC formulation buffer. Product was stored in a single-use container.
6- Finally, the ADC was filtered on a 0.22µm sterile filter to obtain the final batch.
> Deliverables: One representative sample, one non-GMP batch and one GMP batch were produced in 4 months.
> All client product CQA* were within client specifications (including concentration, DAR, purity by SEC, pH, endotoxin and bioburden).
> Yield obtained at scale was over 75% for after 2 TFF and one 1 chromatographic purification.
> Product was used by customer in a clinical study.
*CQA: Critical Quality Attributes
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