Overcoming Bottlenecks and Designing Universal Development and Manufacturing Solutions

A recap of the major points from the afternoon sessions during day 2 of BPI in Boston, MA.

A key component of the process in commercializing a new product is the scaling-up of production from research production volumes to volumes appropriate to supply the market.

 Lentiviral Vector Manufacturing Strategy to Supply the Market – Scale Up Considerations

James E. Misken Ph.D., Chief Technical Officer at Oxford Biomedica (OXB) a biotechnology company based in the United Kingdom, opened the afternoon session with a discussion on the considerations required for scaling-up of therapeutics based on OXBs experiences. OXB was formed out of Oxford University and has been active in the field of gene and cell therapy for approximately 20 years. According to Dr. Misken the key factors towards successful commercialization of gene and cell therapies are to:

  1. Establish the method of action (MOA) of the product
  2. Get clinical proof of the concept
  3. Manufacturing cost of goods must be acceptable

Dr. Misken then spoke of the considerations needed to develop a manufacturing strategy to satisfy current/future demands. These include, process complexity (multiple vessels vs single), manual handling requirements vs single use closed systems, reliance on raw material supply, and output per clean-room suite, To illustrate these points he used, as a case study, OXBs experience in scaling-up production of one of their products OXB-102, a therapeutic developed to combat Parkinson’s Disease. He concluded with a lengthy discussion on upstream and downstream process considerations for scaling-up production.

Considerations for the Design and Deployment of End-to-End Solutions in Cell, Gene, and Immunotherapy Manufacturing.

In the second presentation, Kim Nguyen Ph.D., Senior Scientist in Cell Processing at Terumo Medical Corporation, introduced a number of products that the company manufactures that are used in the harvesting and scaling-up of cells from patients. Dr. Nguyen began by introducing a regenerative medicine that the company had developed called HeartShield. HeartShield is an autologous cell therapy for patients with severe ischemic heart failure in patients that are non-reative to conventional drugs. Essentially, five skeletal muscle cell sheets are transplanted on the surface of the heart. She then gave an in-depth introduction to the Spectra Apheresis and Spectra Optica Apheresis systems that are used to harvest mononuclear cells from patients, and gave a brief overview to how they worked. She then introduced the Elutra Cell Separation system, which is used to further separate the Apheresis products to more pure fractions based on cell diameter or densisty. The next product introduced was the Quantum Cell Expansion System, a single-use, hollow-fibre bioreactor system. One interesting point raised was the use of CoBots, collaborative robots, by Terumo Medical Corporation in their manufacturing lines. Dr. Nguyen explained that they had many benefits including, low cost, easily trainable, multi-axis, integrated sensors, and force limited joints.

Platform Solutions for Cell Therapy Manufacturing

To conclude the session, Eytan Abraham Ph.D., the Head of Immerging Technologies at Lonza spoke about custom process development and the manufacture of therapeutic agents. She stated that one of the main considerations was in choosing an appropriate cell therapy platform and that there were three main points that had to be considered:

  1. Quantity – how much product is produced per unit of volume
  2. Cost of product – need to consider patient affordability
  3. Quality – consistently, high quality production

Additionally, platforms needed to be scalable and robust. She then went on to introduce the Lonza bioreactor system and presented data showing that the system increased cell production with a smaller footprint, resulting in more efficiency in production. She discussed the need to consider the use of smooth, microporous, and/or macroporous microcarriers if scaling-up from 2D to 3D culture methods, and the advantages and disadvantages of each, but concluded that the ultimate choice depends on the overall goal of production.

One over-aching theme in all three presentations was the desirability of using single-use bioreactors for commercial production. The benefits include decreased cleaning and sterilization demands, reduced risk of cross contamination, decreased labor cost, and reduced maintenance costs.

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