July 23, 2019

Tools and Processes for Mature and Emerging Therapies

New technologies and thought trends provide innovative biomanufacturing approaches for a range of therapies.

By Rita Peters  

Conference sessions and new technology introductions at recent trade shows addressed ongoing and emerging trends in the development and manufacture of biologic-based drugs. While technology advances for more traditional biologic-based drugs such as monoclonal antibodies are evolutionary, the processing requirements for emerging cell therapies and gene therapies may require revolutionary changes to the industry’s approach to making drugs.

In April 2019, at the INTERPHEX trade show in New York City, vendors of bioprocessing equipment and materials announced improvements to existing platforms, added options for upstream and downstream systems, and introduced equipment, supplies, columns, media, buffers, single-use systems, and ancillary equipment to promote process capabilities and reliability.

New technologies for aseptic processing—a frequent source of quality problems—were in evidence at INTERPHEX. To control contamination threats during transfer and fill/finish steps for bulk, vial, and syringe filling, companies introduced improvements to existing technologies and processes such as restricted access barrier systems and isolators, and also recommended single-use disposable systems. Automated processing continues to play a role in high-speed applications; however, robotic systems are gaining a foothold in closed systems, offering smaller footprints and the flexibility to handle multiple container sizes.

Focus on data

Capturing process data and applying that information to control process operations was a major theme at INTERPHEX. Notable announcements include the application of artificial intelligence to control manufacturing processes, track raw materials, and troubleshoot equipment and process problems via a virtual system.

A digital data exchange collaboration program between Cytiva and Amgen was developed to understand of the relationship between raw material variability and manufacturing process performance. The companies will use a connection for data transfer between Cytiva’s raw-material manufacturing sites and Amgen’s process development center in Cambridge, MA.

Cytiva also announced a partnership with Rockwell Automation to use augmented reality technology; biopharma companies will be able to monitor production processes, review equipment setup, provide instructions to operators, and detect potential problems remotely using a tablet-based system. The collaboration will integrate Cytiva’s FlexFactory single-use equipment and Rockwell’s bioprocess automation systems.

Processing challenges

During a panel discussion sponsored by BioPharm International, representatives of bioprocessing equipment manufacturers and contract manufacturing organizations debated the challenges associated with meeting bioprocessing manufacturing capacity demands for traditional biologic-based drugs, such as monoclonal antibodies.

Topics discussed included the decision process for manufacturing drugs in-house versus using a contract service provider, single-use bioprocessing systems for commercial manufacturing, and challenges with technology adoption. Budget constraints, uncertainty about unproven technology, and concerns about gaining regulatory approval were some reasons biopharma companies hesitate to adopt new technologies.

Emerging therapies

As biologic drugs mature and biosimilars move to market, bioprocessing technologies are expected build on current technologies to improve efficiencies. For emerging therapies, particularly personalized medicines, the challenge is to adapt—or reinvent—proven manufacturing technologies to meet the requirements of these new treatments.

While the approvals of cell therapies and gene therapies has been exciting, turning clinical processes into operational processes will prove challenging, said Eric Langer, managing partner, BioPlan Associates, in an interview with BioPharm International. For example, with autologous cell therapies, the one patient–one therapy approach can be a manufacturing challenge. The one patient­–one treatment approach using current biologic manufacturing processes is not sustainable for large groups of patients. The likelihood that manufacturing gene therapies or cell therapies in a cost-effective manner using current manufacturing methods is very unlikely.

Speakers at the BIO International convention in Philadelphia in June 2019 echoed these concerns. Peter Marks, director of the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA) told the audience at an FDA Town Hall session that the agency is gearing up for an increase in applications for gene therapies. While gene therapies are promising, he said, manufacturing capabilities and capacity are not sufficient. He encouraged industry involvement in pre-competitive efforts to resolve and de-risk development challenges.

Backing from the investment community in innovator companies and investments by major contract development and manufacturing organizations in cell and gene therapy capacity are strong indicators the biopharma is committed to development of in this area.

Tags: aseptic, automation, gene therapy, cell therapy