April 7, 2017

Speed and Flexibility Are Dual Goals for Biopharma Operations


Bioprocessing facilities, equipment, and materials, as well as strategies to improve biopharmaceutical development and manufacturing, were featured at INTERPHEX 2017, held in March in New York City. Rita Peters, editorial director of BioPharm International shares insight on technologies and trends observed at the show.

What trends did the BioPharm International editorial team observe about manufacturing facilities and operations?
As demand for biologics drug manufacturing increases capacity, contract manufacturers and drug sponsors are investing in facilities and production lines to accommodate clinical trial and commercial needs for innovator and biosimilar drugs. With speed to market a prime objective, prefabricated and modular production facilities, with shorter construction times, are being viewed as alternatives to conventional construction. Specialized therapies, with smaller patient populations and—therefore, smaller drug volumes—can be accommodated in smaller production facilities.

In addition, biopharma companies and contract manufacturers seek the flexibility to produce multiple products on a single line with minimal downtime for cleaning and changeover.
Modular processing equipment and single-use technologies are positioned for flexible production operations and replication in other locations.

For example, FujiFilm Diosynth expanded its contract manufacturing capacity by mirroring an existing North Carolina-based single-use facility at a second site in Billingham, UK. The facilities, built in partnership with Cytiva, offer cGMP manufacturing based on mammalian cell culture technologies to meet customer demand for Phase II/III clinical trials. In addition, the single-use technologies facilitate easy tech transfer between sites, company representatives said in an interview at INTERPHEX.

What new technologies and products are impacting bioprocessing operations?
Recent product introductions for bioprocessing operations—such as advances in bioreactor technology, media, buffers, and cell lines that produce higher titers in smaller systems—reflected an evolution in technology. Other product introductions included new chromatography columns, inline process monitoring sensors, lab and pilot-scale filtration systems, and pumps and fluid handling systems. Suppliers also introduced features to assist companies with tracking inventories of supplies and materials.
To assist the adoption of single-use systems, industry organizations, such as the BioPhorum Operations Group and Bio-Process Systems Alliance, are addressing concerns about extractables and leachables, disposal costs, and sustainability.

The use of modeling to develop bioprocessing operations and systems—spurred by quality-by-design efforts—can help biopharma companies to better understand processes and equipment and to optimize manufacturing output.

What are some challenges in bringing new manufacturing technologies to commercial operations?
Developing a process to produce a biologic-based drug—and gaining regulatory approval for that process—is complex and time-consuming. If the process involves emerging manufacturing technologies, approval may be delayed as the regulatory authority representatives learn about the new systems during review of the chemistry, manufacturing, and controls (CMC) submission.

To expedite the review of new manufacturing technologies, FDA has initiated efforts to promote early discussion between drug sponsors and the agency to address manufacturing design and development issues. In a draft guidance for industry, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base (December 2015), the agency outlined a process for biopharmaceutical companies to open a dialog prior to the CMC filing with the Emerging Technology Team (ETT) at the Center for Drug Evaluation and Research (CDER). The ETT’s role, as defined in the draft guidance, is to answer sponsor questions about information FDA expects to see in a submission and to facilitate regulatory review of a new manufacturing technology.

While new manufacturing technologies can improve production processes for approved drugs, the challenges associated with obtaining post-approval changes may discourage biopharma companies from upgrading systems, especially when the drug is marketed in multiple regulatory jurisdictions.

The Parenteral Drug Association (PDA) is investigating options to reduce barriers to innovation imposed by post-approval change requirements. The association is also investigating the harmonization of post-approval change criteria of various regulatory authorities.

How can technology advances resolve data integrity problems?
Data integrity is a major focus of FDA; the agency routinely cites firms in warning letters for failure to accurately record, report, and protect data associated with laboratory and production operations. Instrument manufacturers and providers of laboratory information systems are incorporating more controls to protect data. Some are offering cloud-based services; others are incorporating advanced features and workflows to make their systems easier to use. Despite these technology advances, a successful data integrity program will be contingent upon human factors: employee training, implementation, and oversight.

Read more Q&As here