At the IBC Third Annual International Forum on Vaccine Production, I presented an outline of “Best Practices for Quality by Design (QbD) in Biological Products and How to Implement in Vaccines.” It covered process development and QbD principles, best practices used in biologics, how QbD fits in with process validation, how it applies to vaccines, and some thoughts on the potential for seasonal vaccines.
Shifts in Process Development
Classic process development (as practiced in the early days) generally involved rudimentary processes that were “patched together.” By performing sequential, single-parametric analysis, you could define general processing parameters. Generally, little attention was paid to the impact of raw materials unless a disaster occurred. Because of the limiting availability of resources and time, development was sparse and not fully complete. Then by rigorously controlling process parameters, operational staff hoped and prayed that the ensuing product was acceptable. In many situations,...
Life sciences company leaders need to put the right people, processes, and technologies in place to create evolutionary cultures. Such cultures would embrace advanced manufacturing process intelligence and reap related business benefits. Since the late 1990s, my software company has helped biomanufacturers improve their process understanding. In that time, we’ve seen regulatory drivers such as quality by design (QbD) and process analytical technology (PAT) guidances call for improved manufacturing process performance through better process understanding and optimization.
We define
process intelligence
as the technology and systems needed to design, commercialize, and sustain robust manufacturing processes that provide predictable high-quality outcomes cost-effectively based on scientific process understanding. Through our experiences, we see three key elements helping successful companies reach an advanced level of process intelligence: people, processes, and technologies. Combined correctly, those thre...
It’s no surprise that immunochemistry forms a broad and solid basis of biopharmaceutical analytical laboratory work. Immunochemicals include antibiotics and antigens, nucleic acids and nucleotides, enzymes, lipids, antioxidants, probes and dyes, and proteins and peptides. Available from companies such as Advanced Immunochemical, Immundiagnostik, Lampire Biological Laboratories, and Rockland Antibodies and Assays, their many uses include antibody isotyping and fragmentation. Adjuvants, buffers, assay kits, target biomolecules, and phage-display systems support those applications. Because background and off-target effects complicate the study of antibodies, quality and purity of these reagents are critical to accurate results.
Brief History
At its most basic, immunochemistry is the branch of chemistry that covers how our immune systems react to and make use of the biomolecules listed above. One of the earliest examples was the Wasserman antibody test for detection of syphilis. It was developed by August Pau...
Monoclonal antibodies (MAbs) have become the most prevalent therapeutics in the biopharmaceutical industry. Their downstream purification typically involves protein A chromatography as a capture step followed by one or two additional chromatographic polishing steps. Additional unit operations dedicated specifically for viral clearance (e.g., viral inactivation and filtration) are added to ensure product safety. According to a survey of Amgen processes, after processing through a protein A column, only trace amounts of impurities such as Chinese hamster ovary cell protein (CHOP) (<3,000 ppm), high–molecular-weight (HMW) aggregates (<6%), leached protein A (<10 ppm), and host-cell DNA (<1 ppm) need to be removed to meet final product purity specifications. Chromatographic polishing steps traditionally use packed-bed resins, but such media entail some difficulties: slow transport of solutes to binding sites within bead pores and high pressure drops through the column even at moderate flow rates.
PRODUCT FOCU...
+7The recent success of monoclonal antibodies (MAbs) as therapeutic agents to treat cancer, multiple sclerosis, rheumatoid arthritis, and other chronic inflammatory and autoimmune disorders (Table 1) has catapulted these once difficult-to-develop molecules to the forefront of modern molecular medicine (
1
,
2
). The size of the global MAb market in 2008 was valued at almost US$28 billion. Industry analysts predict that the size of the MAb market will grow to almost $68 billion by 2015, with the largest growth occurring in oncology and chronic inflammatory diseases (
2
).
Table 1: Commercialized monoclonal antibodies in the United States and European Union
From Chimeric to Fully Human MAbs
The first MAbs to be commercialized in the early 2000s were chimeric MAbs (genetically engineered hybrid molecules containing murine and human sequences) and “humanized” MAbs (containing 90–95% human antibody protein sequences). Since their introduction, many of those products — including Remicade, Enbrel, and other drugs...
As the adoption of single-use systems continues to expand beyond bags and tubing to complete process steps, a full range of sensing technologies will be needed to complement the resulting varied single-use applications. Single-use sensors must meet or exceed the performance of traditional sensing technologies in areas such as accuracy, response time, ease of use, control system integration, process compatibility, regulatory requirements, and cost. Single-use flow-through process sensors are currently available for pressure, temperature, flow, and conductivity. Here, we report results from a comparative study of a new single-use flow-through UV absorbance sensor against traditional UV detection equipment in a protein A capture chromatography application.
Elements of UV Detection
Several types of chromatography steps are routinely used to separate components during downstream processing in biopharmaceutical manufacture. Protein A affinity chromatography with UV spectroscopic detection is one of the most imp...
Our company carried out a preformulation study on a recombinant targeted secretion inhibitor (TSI) with contract research organization (CRO) Avacta Analytical. In this protein, the binding domain of botulinum toxin is replaced to broaden the toxin’s therapeutic potential and allow drug development to be targeted towards a specific disease. In our study, we took advantage of the high-throughput, microvolume protein analysis of Avacta’s Optim 1000 fluorescence and light-scattering instrument (which is distributed in the United States by Pall Corporation). It significantly reduced the volume of material required for testing and enabled large amounts of data to be acquired in a relatively short period of time.
Preformulation Testing
Preformulation studies are a vital stage of drug research and development. They fully explore the physical, chemical, and mechanical properties of a candidate drug to enable a stable, safe, and effective formulation to be produced. During this phase of drug development, the physic...
Hosted by the Biotechnology Industry Organization (BIO), this year’s global event for biotechnology — the BIO International Convention — will take place 22–25 April 2013 at the McCormick Place in Chicago, IL.
The 2013 BIO International Convention is where the global biotech community meets, showcasing and connecting the people, companies, and innovations that help fulfill the promise of biotechnology through healing, fueling, and feeding the world. The convention is expected to draw more than 16,500 industry leaders from 48 states and 65 countries.
Connect with Global Bioprocess Leaders
Partnering is the most efficient and economical way to find new business, promote your product or service, and explore licensing opportunities. In 2012, the BIO International Convention hosted a record-breaking >25,000 partnering meetings in the BIO Exhibition and BIO Business Forum. Exhibitor Booth Partnering was launched in 2012, allowing exhibitors to prequalify companies and leads by requesting and scheduling meetings ...
One strong take-away message from BPI’s flexible facilities supplement (December 2012) is that there is no single road to achieving a flexible manufacturing process. The ability to quickly modify a unit operation, process line, or entire facility to accommodate change certainly depends on several factors. Flexibility is no longer exclusively linked to single-use systems for one specific operation. It connects facility design, staffing models, and revamped technologies. Vendors and suppliers are hearing first-hand what the industry wants in flexible operations.
“Different customers have different needs,” says Dennis Powers (director of integrated solutions North America at Sartorius Stedim Biotech). “Some want to increase throughput within their facility and reduce turnover time for their manufacturing processes. For others, flexibility means they want to run multiple processes or products within their existing footprint. In other cases, flexibility means being able to rapidly scale up a manufacturing proc...
