Kudos once again to our IBC colleagues for another excellent BioProcess International Conference and Exposition. Throughout the week of 31 October– 4 November more than 1,400 attendees and 125 exhibitors engaged in lively discussions on critical issues affecting our industry. The Long Beach, CA, convention center proved to be a comfortable and accessible venue for multiple session tracks, technical workshops, and seminars. Among the trends and topics that made frequent appearances in presentations were the ongoing challenges in developing chemically defined media, the expanding use of disposables into complete (or nearly complete) manufacturing processes, and the increasing interest in continuous processing.
My editorial staff and I appreciate chances to meet one-on-one with our authors, advisors, and advertisers. And we had quite a lot to talk about with everyone! As BPI (the magazine) heads into its tenth volume in 2012, we are planning a number of special activities to celebrate our decade of publishin...
Following up on its 28 June 2011 innovation forum, the Hamilton Project (an economic policy initiative of the Brookings Institution,
www.hamiltonproject.org
) created a new document detailing
A Dozen Economic Facts About Innovation
for the United States. Drawing from insightful comments by panelists during the event, authors Michael Greenstone and Adam Looney focused on three specific points:
“Since the 1970s,“ they wrote, “the pace of innovation has slowed, leading to lower overall wage growth for American workers. Moreover, those gains that have been made have not been shared equally across society.”
The Hamilton Project’s forum, “PhDs, Policies, and Patents: Innovation and America’s Future,” explored the evolving role of innovation in driving broad-based economic growth in the United States and creating a policy environment necessary to foster new ideas in science, technology, and business. For more information, download the full policy memo:
www.brookings.edu/∼/media/Files/rc/papers/2011/0805_inno...
University of Nevada, Reno, researchers reported in
Nature Biotechnology
this past summer on their survey of >2,000 Americans about stem cells and other controversial research topics. Supporters of using embryonic stem cells in disease research outnumbered opponents five to one. Most respondents (>66%) also approved of induced pluripotent stem cell treatments. But opponents of stem-cell–based cosmetic treatments outnumbered supporters by almost two to one.
The need for transformation is a powerful driving force in the biopharmaceutical industry. Opinions and predictions about the best way forward are plentiful. As drug developers seek to enhance productivity, reduce costs, and improve their return on investment in research and development, new ways of doing business are explored, evaluated, and acted upon — with varying degrees of success.
Faced with intense pressure to evolve, the biopharmaceutical industry is smart to leverage approaches that have driven success in other industries. Witness the growing interest among drug developers in applying continuous process improvement strategies that Toyota used to revolutionize automobile manufacturing (
1
).
In this turbulent environment, what other sources of inspiration can the industry call upon to guide new approaches? Over 20 years ago, the enormously popular self-help book
The 7 Habits of Highly Effective People
promised “powerful lessons in personal change” (
2
). Author Stephen Covey offered a blueprint...
Earlier this year, the FDA issued its long-awaited process validation guidance document, which had been several years in development. It is well written and effectively articulates what many progressive companies have been thinking and doing for years. But many people in the industry are asking questions.
Part 1 of this article described the history of process validation before the FDA’s quality by design (QbD) initiative and discussed QbD in general. It also described the new process validation paradigm according to the 2011 guidance in a QbD context. Part 2 concludes here with examples, a focus on postapproval activities, and general implications.
Two Examples
A Cell Culture Unit Operation:
After expansion of frozen cells from vials in vessels of increasing size, you have sufficient biomass to express a protein in your production reactor (production phase). This step in the manufacturing process will express a batch of protein that will be subsequently recovered and purified to yield the BDS. It is imp...
Review times for 510(k) submissions have increased by >55% since 2005 because of poor-quality submissions by medical device manufacturers, according to a US FDA July 2011 report (
1
). Such setbacks can debilitate research and development (R&D) budgets of medical device and pharmaceutical companies and significantly affect their return on investment. As the FDA increases scrutiny of submissions, organizations must ensure adequate controls in assessing drug and device efficacy for preclinical animal studies and clinical trials. Doing so lends validity to presented data in new product submissions (510k, premarket approval) and postmarket evaluations. It also assures reviewers that the necessary due diligence has been performed. Choosing proper controls for an FDA submission, however, can vary significantly depending on application and host.
In Vitro Imaging Studies
In vitro studies are commonly used to investigate the effects of drug treatments on specific cell types as a first-pass surrogate for in-vivo pe...
Immunoglobulin G (IgG) antibodies have been used to treat cancer for many years (
1
). Another class of antibodies—immunoglobulin M (IgM)—has been overlooked in spite of offering unique advantages that make them highly desirable as cancer therapeutics. Serving a valuable function in our innate immune system, IgM antibodies are the first to be secreted when an abnormal cell is present (
2
). These antibodies play a critical role in recognition and elimination of infectious particles (
3
,
4
), in removal of intracellular components, and in immunosurveillance mechanisms against malignant cells (
5
,
6
). IgMs also can bind to multiple copies of a target on a cancer cell surface. Such high avidity leads to cross-linking and more effective cell killing (
7
).
PRODUCT FOCUS: ANTIBODIES (IGM)
PROCESS FOCUS: MANUFACTURING
WHO SHOULD READ: PROCESS ENGINEERS, PRODUCT DEVELOPMENT, AND MANUFACTURING
KEYWORDS: PER.C6 CELLS, SCALE-UP, OPTIMIZATION, MONOLITHS, FED BATCH
LEVEL: INTERMEDIATE
In spite of all those desirab...
+4The conclusion of this CMC Forum continued to focus on the latest developments in detection and characterization of protein aggregates (1). Afternoon sessions detailed the most recent experiments probing the role of protein aggregates in immunogenicity, with discussions on the best models to use and initial results. Topics included potential thresholds for immunogenicity, linking laboratory and clinical data, and predicting and testing potential immunogenicity of products throughout a development lifecycle.
Afternoon Sessions
Amy Rosenberg (Division of Therapeutic Proteins, CDER, FDA) described a preponderance of data concerning the ability of aggregates to induce and enhance immune responses as well as their significance to the immunogenicity of therapeutic proteins. Her data came from both animal and human studies.
PRODUCT FOCUS: PARENTERAL PRODUCTS
PROCESS FOCUS: FORMULATION, QA/QC
WHO SHOULD READ: ANALYTICAL DEVELOPMENT, FORMULATION, AND MANUFACTURING
KEYWORDS: AGGREGATION, CHARACTERIZATION, IMMUNOGEN...
+6 Recombinant therapeutic protein production using cell culture systems is a US$70 billion market. Most biotherapeutic proteins, including monoclonal antibodies (MAbs), are produced in Chinese hamster ovary (CHO) cells, which can generate the posttranslational modifications required for full biological function. Single-cell cloning is an important step in generating homogenous recombinant protein-producing mammalian cell lines. Recent advances in media development technologies have enabled limiting dilution cloning (LDC) and protein production in a serum-free environment to meet regulatory requirements.
LDC allows homogeneity of a selected cell line. It involves diluting a pool of transfected cells down to a single cell per culture well and then expanding that single cell to a larger cell population called a
clonal cell population
or
cell line
. Success of this process requires a medium containing correctly balanced nutrients that promote cell growth at extremely low cell densities. To meet stringent reg...
+6 Although glass is widely considered to be the most traditional and cost-effective option for a parenteral drug container or delivery system, it may not always be the most economical or the best choice for certain products. With knowledge emerging about the suitability of materials in contact with drug products, it is time to look at alternatives that may offer a more appropriate choice and mitigate the risks associated with glass. As single-use technology finds its way into upstream and downstream processing, might such materials be useful in product containment as well?
PRODUCT FOCUS: PARENTERALS
PROCESS FOCUS: FORMULATION, FILL AND FINISH
WHO SHOULD READ: PRODUCT AND PROCESS DEVELOPMENT, MANUFACTURING
KEYWORDS: Container–closures, leachables, extractables, drug product formulation, contamination
LEVEL: BASIC
Other Product Recalls
Recalls related to glass delamination, particulate, and breakage issues have spurred the need for greater understanding of risks associated with materials used in container–clo...
High-Throughput Osmometry
Product:
Advanced 20G osmometer
Applications:
Cell culture process development and optimization
Features:
New approaches to accelerate cell culture process development and optimization require higher sample throughput for osmolality testing. The Advanced 20G high-throughput osmometer was developed by combining state-of-the-art osmometry technology and robotics within a parallel sample processing scheme. Samples can be analyzed in 96-well format within 35 minutes, with the same accuracy as provided by stand-alone osmometers. This system has been applied to support osmolality testing in several demanding cell culture process development schemes in the biopharmaceutical industry.
Contact Advanced Instruments Inc.
www.aicompanies.com
Disposable Containment
Product:
FluoroFlex biocontainers
Applications:
Biologic process solutions and active product ingredients
Features:
Meissner’s polyvinylidene fluoride (PVDF)–based FluoroFlex biocontainers are made of a multilayer coextruded ...
Antibody Development and Production covers the entire spectrum of topics related to development and production of the most promising therapeutics in the biopharmaceutical industry. An estimated 30% of new drug products likely to be licensed in the next decade will be antibodies. With the reality of their biosimilar equivalents getting closer, companies need to develop processes faster to preserve their time on the market free from generic competition and keep costs down. With that in mind, we developed the 2012 agenda to help you improve process development through innovation, integration, and optimization; improve product quality in process development; and develop and implement downstream approaches that capitalize on high-titer processes.
New This Year
For 2012, we expanded our coverage to include more diverse antibody-related products. Companies of all sizes will provide multiple perspectives on strategies and approaches that help overcome current and future bioprocessing challenges. For example, wher...
Biosimilars require comparative studies that are different from the typical placebo-control clinical trials for first-generation proteins. A typical clinical trial programs must show equivalence of a biosimilar to the originator protein. Hans-Peter Guler, senior vice president of clinical development at INC Research, recently discussed with me the primary objectives and approaches to conducting an equivalence design.
By contrast with trials for originator proteins, equivalence trials require a different statistical approach. The biosimilars company needs agreement from the competent regulatory agency on how the data will be analyzed. Because “similarity” or “equivalence” will depend to some extent on the type of protein and its indication, certain terms should be defined early. For example, the sample size and the parameters under which the two proteins can be declared similar must be determined, says Guler.
Another factor that needs to be determined early is the minimally clinically important difference ...
