DEVELOP

Development of pre-GMP Manufacturing Processes for Oncolytic Measles Viruses

PI(s)
Sascha Bossow

Contributing CCU members
Stefanie Prien

Technological innovations to offer improved cancer therapeutics are major drivers of the immuno-oncology market. Oncolytic therapy is a novel approach using viruses that requires specialized manufacturing processes.

Challenges:

  1. Upscaling: Oncolytic virus therapy requires high-dose administration that needs large-scale production and efficient purification procedures. The development of a robust platform technology is a major challenge.
  2. Complexity: Viral particles are much more complex than other therapeutics such as monoclonal antibodies. Our focus is on developing a robust, scalable and efficient process for oncolytic measles virus (MeV) that can be transferred to cGMP-compliant manufacturing facilities.
  3. Quality: Worldwide approaches in clinical development of different virus therapeutics have led to global harmonization of regulatory requirements. The potential risk of process-related impurities and contaminations is a challenge in manufacturing biological products. Implementation of single-use technologies and aseptic, closed processing improves product quality. Well documented materials are essential for GMP manufacturing. The quality assessment of a viral drug product requires robust analytical assays.

Our goals:

  1. A robust pre-GMP manufacturing process for oncolytic therapeutics derived from our unique MeV-vectored platform.
  2. Large-scale oncolytic MeV batches in cGMP-compliant quality.
  3. Compliant documentation and quality assurance for our oncolytic virus products required for clinical batches.

Our tasks:

  1. Generation of a pre-GMP Master Cell Bank and Virus Seed Stocks.
  2. Determination of MeV productivity in multi-layer vessels and single-use bioreactors at small-scale (collaboration with PALL). Definition of parameters for a robust upstream process and evaluation of upscaling potential.
  3. Feasibility of different purification methods in the downstream processing (collaboration with P. Czermak, THM Giessen, and Merck KGaA Darmstadt).
  4. Establishment of robust analytical assays for quality assessment.

Publications
Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses. Ungerechts G, Bossow S, Leuchs B, Holm PS, Rommelaere J, Coffey M, Coffin R, Bell J, Nettelbeck DM. Mol Ther Methods Clin Dev. 2016; 3: 16018.

Funding
Industry Funding (CanVirex AG)

Contact Information
Dr. rer. nat. Sascha Bossow
Otto-Meyerhof-Zentrum (OMZ), Heidelberg University Hospital
Im Neuenheimer Feld 350
69120 Heidelberg
e-mail: sascha.bossow@med.uni-heidelberg.de 
phone: +49-6221-563438

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