The biomanufacturing industry is heavily invested in improvements in productivity and efficiency, and innovation is a critical component to ensuring gains in these areas. Yet that is not always the case. Suppliers and innovators in this market face greater challenges, and much longer product evaluation cycles than in other segments, for example the information technology or semiconductor industries. In the highly regulated biomanufacturing environment, changing any aspect of a process can potentially necessitate additional regulatory submissions to the US Food and Drug Administration (FDA) or other regulatory agencies. Any innovation or change to an existing process needs to be considered in terms of the regulatory aspects of adopting a new technology.
We asked our Biotechnology Industry Council to weigh in on the challenges of introducing new technologies (
1
). More than 300 senior biomanufacturing participants considered the question “What are the biggest problems you face in getting a supplier’s new i...
The California Separation Science Society (CASSS) held a Chemistry, Manufacturing, and Controls (CMC) Strategy Forum on drug products for biological medicines in July 2012 in Bethesda, MD. Topics included novel delivery devices, challenging formulations, and combination products. This CMC Strategy Forum aimed to promote an understanding of how best to increase the speed and effectiveness of drug product and device development for both large and small companies. Participants focused on areas that improve the likelihood for regulatory success, reduce risk, and decrease the time it takes to get a combination product through development. The forum included input from regulators on how to prevent delays during review of regulatory applications. Biopharmaceutical companies and regulatory agencies both presented case studies, and open discussions provided opportunities for all participants to gain common understanding and consensus on a range of topics.
PRODUCT FOCUS:
ALL BIOLOGICS, COMBINATION PRODUCTS, PARENT...
Comparability has become a routine exercise throughout the life cycle of biotechnological products. According to ICH Q5E, a comparability exercise should provide analytical evidence that a product has highly similar quality attributes before and after manufacturing process changes, with no adverse impact on safety or efficacy, including immunogenicity (
1
). Any doubt about data from such studies could translate into unforeseen pharmacological or nonclinical studies — or worse, clinical studies.
Selection of analytical methods and acceptance criteria that will be applied to demonstrate comparability can be the most difficult step in a comparability exercise. Defining where and how to begin is a time-saving approach to reduce the risk of not meeting deadlines. For that reason, we formalized a stepwise process aimed at expediting timelines while ensuring regulatory acceptance of our resulting comparability protocol.
The proposed process described here takes into consideration requirements of ICH Q5E, Q8, an...
In 2012, the United States Pharmacopeia (USP) published a complementary set of three guidance documents on the development, analysis, and validation of biological assays (
1
,
2
,
3
). USP chapter <1033> recommends a novel, systematic approach for bioassay validation using design of experiments (DoE) that incorporates robustness of critical parameters (
2
). Use of DoE to establish robustness has been reported (
4
,–
5
), but to our knowledge its use in qualification or validation protocols for assessing assay accuracy, precision, and linearity is not described in literature. A validation approach incorporating different levels of critical assay parameters provides a more realistic representation of how an assay will perform in routine testing.
After initial development of a cell-based bioassay to enable an investigational new drug (IND) application, we used a DoE-based approach to perform a comprehensive qualification of that bioassay to estimate its accuracy, precision, linearity, and robustness. Such a...
+2In most downstream purification processes designed for biopharmaceutical drug production, dilution and diafiltration sequences are unavoidable. Such operations are routinely used to adjust a feedstock or chromatographic fraction to the optimal conditions required for best process performances. Nevertheless, those steps are often time, water, and labor consuming without participating directly in final product purification. Because biopharmaceutical production is increasingly driven by cost reduction, a possible means for enhancing process economics is to streamline purification by eliminating these unit operations before or between chromatography steps as much possible.
Anion exchangers — quaternary amine (Q) or diethyl-amino-ethyl (DEAE)sorbents — are commonly used first purification steps in biomanufacturing. However, use of conventional anion exchangers requires low to moderate ionic strength to achieve sufficient capacity (
1
,
2
). Therefore, integrating chromatography sequences with anion-exchanger ...
+3 Join us in Boston this September to celebrate the 10th Anniversary of IBC’s “BioProcess International™ Conference and Exhibition,” a milestone event providing the tools and knowledge you need to meet the demands of increasingly diverse product portfolios in an evolving biomanufacturing landscape.
The inaugural BPI Conference in 2004 gave the industry’s an opportunity to exchange experiences and knowledge to optimize manufacturing processes and accelerate programs. Fast-forward 10 years, and this has become
the
industry meetingplace for product and process development and biomanufacturing scientists and executives to share technical, scientific, and strategic solutions across all phases of bioprocess development.
IBC Life Sciences and its colleagues at
BioProcess International
magazine are proud to announce this year’s program. This September will be your opportunity to join more than 1,400 colleagues in Boston to find superior tools and practical knowledge to help you accelerate your bioprocess develo...
Earlier this year, the Pharmaceutical Research and Manufacturers of America (PhRMA) released a report titled
2013 Report: Medicines in Development – Biologics.
It lists 907 biologics currently in development at “America’s biopharmaceutical research companies.” The list includes biologics targeting more than 100 diseases that either are currently in human clinical trials or are under review by the US Food and Drug Administration (FDA). Of those 907 product candidates, the most common types are monoclonal antibodies (MAbs, 338), vaccines (250), and other recombinant proteins (93). The largest therapeutic categories include cancer and related conditions (338), infectious diseases (176), and autoimmune disorders (71). It is no surprise that over half of those cancer therapies are MAb products, representing 170 of the 338 products in development.
Key Data
Biosimilars Are Moving Forward:
After regulators spent years discussing a potential pathway for biosimilars — with many arguments both for and against— se...
