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Successful cGMP conjugation of a Novel ADC for phase I clinical trials

Successful cGMP conjugation of a Novel ADC for phase I clinical trials
15 Feb 2018

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
Scale: 100g
Project scope: Process development and cGMP manufacturing
Timing: 4 months      

Highlights:

  > 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 

The challenge

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.

The solution

Novasep proposed a work plan for the familiarization, development and cGMP manufacture of this new Phase I ADC, comprising the following key steps:

  • Transfer of process & analytical methods
  • Chromatographic purification development
  • 1 R&D sample
  • 1 non-GMP demo batch (Proof of Concept - POC)
  • 1 cGMP production batch

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.

  ADC Manufacturing Process

 

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.

The outcome

  > 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

 

Do you want to know more about Novasep Fully Integrated Services for ADCs? Contact us here or view our latest ADC webinar recording: 

C2A Webinar OK

 


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