Advances in bioprocessing technology hardware and genetic engineering are expanding the geographic options for biologics manufacturing to include developing and emerging economies. Such advances are beginning to permit biopharmaceutical production in regions that previously lacked the technical expertise or quality processes to permit complex operations, monitoring, record-keeping, and oversight. Global demand by countries for in-country production of biological vaccines is increasing, so those products tend to be leading the way in terms of adoption of modern bioprocessing in developing countries.
Ongoing bioprocessing advances are enabling a diverse spectrum of companies worldwide to develop biosimilars (
1
). Although biosimilar trends tend to be more newsworthy, the long-established worldwide vaccine market is actually much larger — currently ~US$30 billion/year (
2
). This includes access to vaccines that many health authorities consider to be absolutely essential, even a basic human right. Products ...
Electrophoresis is the basis of all blotting methods, and BPI Lab covered it last month (
1
).
Electroblotting
is a method for transferring electrophoretically separated proteins or nucleic acids onto a polyvinylidene fluoride (PVDF) or nitrocellulose membrane for permanence using electric current and a transfer buffer solution. This allows for analysts to further study them using probes, ligands, or stains. Capillary blotting is a variation designed to work with capillary electrophoresis.
After electrophoresis the following are stacked in cathode-to-anode order: a sponge, filter paper soaked in transfer buffer, the gel, a membrane, more soaked filter paper, and another sponge. When current is applied, it drives proteins or nucleic acids from the gel onto the membrane, where they are typically stained using a dye such as Coomassie Brilliant Blue to confirm that a sufficient quantity of material has been transferred. Immunoblotting involves the addition of specific antibodies with which proteins will int...
Many technological advancements in recent years have enabled companies to shorten time to market, to better understand their manufacturing processes, and to characterize their products well. In BPI’s December 2013 issue (pages 47–50), I reported on the first half of an informal reader survey about those technologies, with commentary from some survey participants and others. This month concludes with my examination of analytical, formulation/fill–finish, and facilities technologies.
Analytical Technologies
After writing several installments of our new “BPI Lab” series this year, I’ve learned a lot about the many and varied analytical methods used in biopharmaceutical quality, discovery, and development laboratories. But I needed to keep my multiple-choice lists under each survey question short because long lists can make people change their minds about participating halfway through! And there are so many technologies in this category, it was difficult to choose just a few. So I half expected the “other” ca...
Abiological measurement of drug activity is perhaps the most critical step in the series of tests required for product release both for clinical trials and the market. This evaluation plays an important role in the stability assessment of drug candidates. According to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q6B document, measurements of biological activity can be performed in defined animal models that demonstrate a measurable physiological change in response to application of the drug (
1
). But animal studies are costly, time-consuming, and known to have high degrees of variability, thereby raising questions about their effectiveness. In addition, the reduction, refinement, or replacement of such in vivo assays is a common goal of the animal welfare community health authorities, and some pharmaceutical manufacturers (
2
,
3
,
4
).
PRODUCT FOCUS:
ALL BIOLOGICS
PROCESS FOCUS:
ANALYTICAL
WHO SHOULD READ:
PROCESS, D...
+2Hydroxyapatite (HA) has a long and successful history in the field of antibody purification, and it has worked well for immunoglobulin M (IgM) monoclonal antibodies (MAbs) (
1
,
2
,
3
,
4
,
5
,
6
,
7
,
8
). Applications range from initial capture to intermediate purification to final polishing. HA is best known for its superior ability to reduce antibody aggregates, but it also supports excellent reduction of DNA, viruses, and endotoxins. As IgM MAbs exhibit increasing potential in the fields of cancer and infectious disease and in stem-cell therapies, HA’s unique fractionation abilities take on greater importance. Meeting the needs of those new opportunities requires an understanding of how HA interacts with various classes of biomolecules and how such interactions can be coordinated to create selectivities that particularly support the unique requirements of IgM purification.
PRODUCT FOCUS:
ANTIBODIES
PROCESS FOCUS:
DOWNSTREAM PROCESSING
WHO SHOULD READ:
PROCESS DEVELOPMENT, MANUFACTURING, AND ANALYT...
+5 Commercial-scale viral vaccine manufacturing requires production of large quantities of virus as an antigenic source. To deliver those quantities, a number of systems are used for viral replication based on mammalian, avian, or insect cells. To overcome the inherent limitations in production outputs with serial propagation of cells, mammalian cells can be immortalized, which increases the number of times they can divide in culture. Modifications that immortalize cells are typically accomplished through mechanisms similar to those converting normal cells to cancer cells. Thus, the presence of residual host-cell nucleic acids in final vaccine products would create significant concerns about the potential for transfer and integration into a patient’s genetic material.
PRODUCT FOCUS:
VACCINES
PROCESS FOCUS:
DOWNSTREAM PROCESSING
WHO SHOULD READ:
PROCESS ENGINEERS, QA/QC, ANALYTICAL
KEYWORDS:
CHROMATOGRAPHY, BIOCATALYSIS, TANGENTIAL-FLOW FILTRATION, NUCLEIC ACID DETECTION ASSAYS
LEVEL:
INTERMEDIATE
Host-c...
+1 In the era of biologics manufacturing, chemical medicine production facilities are becoming the dinosaurs of the life sciences sector. Traditional chemical facility development and management systems are simply unequipped to support the highly sensitive — and highly regulated — process of developing and producing biological and biosimilar medicines. Renovating or building such facilities anew is a mammoth undertaking by any measure. All signs point to the value of evolving facility design and management to house more sophisticated biologic laboratory services.
Numbers Reveal Rising Demand
The biologics market is expected to skyrocket from US$162 billion in 2012 to $252 billion by 2017 — representing a projected compound annual growth rate (CAGR) of 9% over five years, according to a January 2013 BCC Research report. That reflects the growing interest in biosimilars and biobetters but covers all main product categories. Monoclonal antibodies (MAbs) are the fastest-growing segment, expected to grow at 11.8%...
