So in this industry, with its built-in inertia, new technology introductions can be tough. Investors expecting rapid returns on product innovations used in clinical or commercial therapeutic production can be quickly disappointed. Downstream processing, the bottleneck that everyone wants a solution for, is a prime example. In previous columns, we've discussed various technologies being developed to address this bottleneck, but we haven't addressed the strategies behind getting these new technologies into the market.
Preliminary data from BioPlan Associates' 7th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production clearly indicates that little has changed over the past seven years regarding solutions to address the downstream bottleneck. Many new technologies are under investigation, but these are being "actively considered" and not actively implemented. Many end users want to see new technology improvements used to manufacture a product approved by the FDA, but until this happens, regulatory challenges will continue to overshadow the benefits of reduced costs, fewer steps, more purification cycles, and disposability.REGULATORY CHALLENGES
To get a sense of where the trends are heading, we spoke to our Biotechnology Industry Council panel on downstream processing regarding regulatory hurdles. Their feedback is presented below.
Most Critical Downstream Regulatory Issues
Regulatory Approach to New Technologies
Being a first-adopter in this industry requires balancing the regulatory risk against the benefits of being first to integrate a new technology. According to our survey and our panel of experts, the industry continues its wait-and-see attitude. The problem is how receptive the FDA will continue to be to novel alternatives to chromatography. "When more single-use purification technologies start to penetrate the market, you'll also see increased focus on characterizing and managing robustness and scalability," says, Michael Kuczewski, scientist I, downstream process development, Percivia, LLC.
Others believe the FDA has already indicated a receptive attitude. Justin McCue, head engineer, bioprocess development at Biogen Idec says, "Membrane adsorbers have been readily accepted. One of the keys to acceptance is to ensure appropriate in-process controls and tests are established for alternative technologies." Acceptance, according to Amitava Kundu, associate director, process development, Genmab, Inc., is a function of comparability of processes, which "must be accompanied by an ability to probe for changes in secondary and tertiary structure of the protein as well as an ability to further understand and monitor the presence of large aggregates … that could potentially be created in the process."
A key problem in the approval process, says John Zeng, head of purification R&D at Lonza Biologics, will require that vendors and end-users work together to tackle problems such as the testing associated with new materials, matrices, and formats, "Developers need to work closely with vendors to overcome this hurdle by more testing," he said. Zeng believes that the first ones will take the biggest risk. However, given the merits of novel downstream technologies to improve selectivity, binding capacity, and throughput, the regulatory pathway should become relatively easier as agencies take a more positive approach to alternatives to chromatography.
The industry is asking for solutions that include clearer guidance from regulators and more partnering with vendors and industry associations to address the downstream bottleneck.
Being first in the water may be a challenge for new technology adoption, and before broad acceptance of novel downstream technologies take place, the industry will need to move forward to get to those early adopter success models.
Eric Langer is president and managing partner at BioPlan Associates, Inc., Rockville, MD. He also is the editor of Advances in Large-scale Biopharmaceutical Manufacturing, 301.921.5979, [email protected]