Quality control isn’t only a scientific priority; editorial QC, proofreading, and knowing when and what to question is becoming more and more complicated, even as (ironically) the Internet facilitates research and information sharing. Plagiarism can be entirely unintentional. Most accomplished editors notice when a paper seems pieced together and styles clash — one reason that we copyedit fairly rigorously in BPI. But you have to work harder to infringe a copyright. Editors worry whether authors have acquired proper permissions to use graphics submitted with their manuscripts. I would like to say that we at BPI always err on the side of caution; but, sadly, everyone is forced to work faster than we would like these days on too many projects at a time, with accelerated timelines and conflicting priorities. That can make it hard to proceed with caution.
No longer do you have to physically type an infringing passage or hard-code a link — both actions seeming somehow more “intentional” than simply copying and...
Microorganisms play a vital role in modern life — with applications ranging from wine fermentation to biofuel production to solutions for complex mathematical problems (
1
). During the past decade, microbial fermentation for protein production reached a higher level of sophistication and wider adoption. When BPI was first published in 2003, the physical and biological characteristics of many microbial cells and the attributes of their fermentation processes were well known. Nonetheless, the economic environment at that time created immense pressure on the industry to drive innovation and emphasize manufacturing efficiency (
2
).
BPI’s
Protein Expressions
supplement in 2004 reviewed microbial fermentation, its advantages over mammalian cell expression (e.g., lower generation time, growth time, media costs, robustness), and its shortfalls (e.g., for most systems, glycosylation and posttranslational modifications) (
3
). Our 2008 coverage of microbial expressions confirmed that companies continued to use ...
Off-label marketing occurs when doctors prescribe a drug or device for a use that has not received FDA approval (
1
). Physicians have the unfettered right to prescribe the best drugs or devices for their patients, including approved drugs and devices for unapproved uses. Pharmaceutical and medical device manufacturers, however, cannot promote their products for such uses — even if those are supported in medical literature. Companies cross the line when their sales representatives sell physicians on the idea of using drugs for off-label purposes, sometimes with inducements and misrepresentations.
Civil and Criminal Penalties
During the past five years, the Department of Justice has exacted substantial criminal and civil penalties through settlements with several of the nation’s largest biopharmaceutical and medical device companies arising from wide-ranging allegations of healthcare fraud. Eight of the 10 largest settlements by the Department of Justice involved pharmaceutical companies. Drug maker Allerg...
Companies trying to market cell therapy products face a number of challenges in communicating highly technical knowledge, understanding the nature and complexity of their products, and trying to understand the global regulatory environment within which they must operate. The role standards development organizations (SDOs) play is key to overcoming some of those challenges through a standardization process. The British Standards Institution (BSI) sits at the forefront, developing a number of documents that will increase the chances of cell therapies for commercialization.
Standardization
Standardization has long been an important aspect in the emergence of new technologies (
1
,–
3
). Development and implementation of standards by companies working toward product launch and encouraging adoption of those products by key end users often gives those product developers an advantage over their competitors. This is for a number of reasons, including establishment of common vocabularies in previously disparate, m...
+4Downstream problems for biomanufacturers finally appear to be lessening. Over the past six years, demand for better purification has topped the list of biomanufacturing areas in need of improvement. This year, however, it appears that purification woes — though still a hot topic — are cooling off. After seven years of measuring the impact on capacity of specific biomanufacturing operations, preliminary data from BioPlan Associates’ ninth annual survey shows that activities associated with both optimizing internal downstream processes (DSPs) and evaluating external, novel DSP technologies are holding steady or declining (
1
). This is probably the result of incremental improvements in process design with the ongoing impact of excess industry capacity. Despite incremental improvements, however, downstream processing remains a top area of concern.
“Develop better downstream purification technologies” took the top spot this year, as before, marked by 47.9% of respondents this year and 51.4% in 2011. Each year...
It is estimated that hundreds of new recombinant proteins and monoclonal antibodies (MAbs) enter preclinical and clinical development each year (
1
,
2
). Concomitant global competition in biologics manufacturing has put immense pressure to shorten the time to market. Over the years, cells from various origins have been used for therapeutic protein production (
2
,
3
,–
5
). One of the most economical choices is
Escherichia coli,
used to make proteins such as human insulin and growth hormone. But the bacteria have some serious shortcomings, such as an inability to perform posttranslational protein modifications (
6
). Mammalian cell lines such as Chinese hamster ovary (CHO) cells, baby hamster kidney (BHK) cells, or human fibrosarcoma cells have addressed necessary glycosylation in production of certain therapeutic proteins (
6
). For MAbs, CHO and NS0 cell lines are the most commonly used expression hosts (
2
,
4
).
PRODUCT FOCUS:
ANTIBODIES AND OTHER PROTEINS FROM MAMMALIAN CELLS
PROCESS FOCUS:
P...
Risk of cell-culture contamination is a common concern whenever materials are added to or removed from a bioreactor. It is essential to maintain a sterile barrier and provide containment against intruding organisms during such operations. Many R&D and pilot-scale manufacturing tasks involve flexible, single-use processes with presterilized containment systems in nonclassified laboratory areas.
Here, we examine a process that requires substantial manipulation of a culture — first completely removing and later returning the culture to a bioreactor during media exchange — using individual presterilized, single-use bioprocessing components. Bags, sensors, and filters all needed to be assembled together and connected to the bioreactor beforehand (without laminar-flow hood) in a nonclassified laboratory. In addition, we tested a new method combining media exchange and clarification using a single filter sequentially in both operations.
PRODUCT FOCUS:
Mammalian cell–derived proteins
PROCESS FOCUS:
PRODUCTION
W...
+3 During one development meeting early in my industrial career, a process development group member asked me whether the value my group had reported in one result was okay to use. I confidently replied “Yes, it’s fine. It’s about 40, somewhere between 38 and 42. The other person raised his eyebrows. “About 40?” In response, I somewhat awkwardly mumbled “Yes, probably…about that” — an answer not met with full understanding, but rather concern.
My answer hadn’t been incorrect. The result was about 40, give or take a bit. Perhaps I should have said the word
exactly
in those circumstances, but that would not have reflected my confidence at the time. The exchange bothered me. I knew I was “about” right and understood the variance around our result, but I didn’t articulate it clearly. After some thought, I concluded that my understanding was inadequate, so I needed to try better understanding biostatistics. At the time, I never questioned whether doing so would add value to my part in the business of making medi...
Cell therapies and related cell-based technologies constitute an emerging, fast-growing market with a total value expected to exceed US$100 billion by 2019 (
1
). Cell therapy is defined as the process of introducing cells to a patient’s tissue for disease treatment. These therapies generally require cryopreservation to maintain sufficient product quality and shelf life. As a common practice, cell therapy manufacturers use controlled-rate freezers to optimize cooling profiles. The goal is to preserve final products in cryopreservation media with the highest possible cell viability while also achieving a consistent product from sample to sample and batch to batch.
Traditional controlled-rate freezers on the market are optimized for small-scale operations. As market demand increases and companies aim to control costs by increasing batch sizes, currently available controlled-rate freezers may fall short of achieving the uniform, controlled freezing processes necessary to obtain high yields and consistent pro...
+2 Live Cell Imaging
Product:
DeltaVision OMX Blaze system
Applications:
Cell and protein research
Features:
Applied Precision, a GE Healthcare company, offers the world’s first microscopy system for capturing high-resolution video of live cells in three dimensions. The DeltaVision OMX Blaze system’s speed of image acquisitions enables researchers to follow tagged proteins within the same living cell over time in 3D space at near-molecular resolution. The 3D structured illumination microscopy technology roughly doubles the resolution of fluorescent microscopy methods — for an 8× improvement in volume resolution over conventional microscopy. The UC Davis–based Center for Biophotonics Science and Technology (CBST) collaborated early in beta testing, and the system is installed at other early adopter sites around the world.
Contact
Applied Precision, Inc.
www.api.com
Automated Quality Control
Product:
QC Kit
Applications:
Performance verification of liquid-handling workstations
Features:
Tecan integrate...
Recent achievements driven by the application of novel approaches and tools have caused significant savings in time and money for cell-line selection and development. This conference will report on the latest applications of automated tools, “-omics” technologies, analytical methods, and engineering strategies to help you understand and improve the stability, quality, and workability of your cell lines. Hear the latest case studies and unpublished data from industry and academia, and collaborate with your peers during strategic discussion groups and interactive roundtables to overcome pressing challenges.
With the recent completion of the Chinese hamster ovary (CHO) cell genome sequencing project, companies are now challenged to work on the genome information. They are using -omic technologies to advance their understanding of cell lines and improve their predictability. This event will deliver answers to your questions about how to apply information provided by the CHO genome and show you how to deal wit...
Biological experiments must be performed correctly. A textual method description doesn’t always capture the myriad techniques involved in even a fairly simple study. So the inability of researchers to reproduce published results is becoming a problem. And it is being addressed by video methods that show exactly how scientific results are achieved, helping future researchers learn new techniques and replicate scientific results.
The ability to reproduce and confirm a study’s results and conclusions is a foundation of scientific research. And the pharmaceutical industry relies heavily on research to identify early drug projects. Drug manufacturers spend millions of dollars conducting human trials based on data published in peer-reviewed scientific journals. But that money could be wasted because of an inability to reproduce experimental results.
In a December 2011 story by Gautam Naik (“Scientists’ Elusive Goal: Reproducing Study Results”),
The Wall Street Journal
highlighted a case in which a research te...
