Cell therapies are being developed for a rapidly expanding range of indications. Genzyme Corporation has a treatment of cartilage in joints in long-term follow-up stage (Genzyme Corporation,
www.genzyme.com
). Cell Therapies are being investigated successfully in applications to treat infectious diseases such as AIDS, repair spinal cord injuries, strengthen immune systems, and treat neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and epilepsy. Positive results have been reported in treating arteriosclerosis and other cardiovascular diseases, congenital defects, breast reconstruction, and liver insufficiency. Successes have also been reported in development of autologous cancer vaccines (
1
).
Developers of such products logically seek safety and efficacy in clinical trials. Strong positive results are highlighting the ever-widening fields of application and increasing numbers of registered clinical trials.
Contract Manufacturing Support of Clinical Trials:
Many developers are us...
Defining the optimal market entry strategy for a vaccine is challenging. Worldwide, vaccine markets are commoditized andvery heterogeneous. In addition, with growth and evolving technology, the business model in the vaccines sector is changing. From the traditional vaccine model, constituted mainly of pediatric vaccines used to prevent a well-known series of viral and bacterial infections in large cohorts of healthy patients, we are seeing the emergence of a more pharma-like model that has been stimulated by new technologies, innovation, and growth. This new model involves higher R&D expenditure, a primary commercial focus on developed countries, and premium prices.
The vaccine market was estimated at US $16.3 billion in 2007 and is growing fast with an expected compound annual rate of 13.1% during 2008–2013 compared with 6% for the rest of the pharmaceutical sector. The recent approval of Sanofi Pasteur’s meningitis vaccine (and its release of six other inoculations including one for bird flu) illustrate...
The recent product recalls of PedvaxHib and Comvax vaccine batches are a reminder that the control of vaccine manufacturing processes is of the highest importance. This rings especially true because the target population for these two products is children under the age of five.
The Hib vaccine guards against meningitis and other serious infections caused by the bacterium
Haemophilus influenzae.
In this particular recall, type b vaccine was tested and determined to be free of contaminating microorganisms before being released to the market. However, postrelease surveillance of the sterilization methods used in the manufacturing process showed that the presence of
Bacillus cereus
bacteria in the batch could not be ruled out.
A Quality Risk Management Approach
Earlier this year the European authority published new guidance for the control of aseptic processing and for quality risk assessment. Because these two new documents affect the manufacturing of biopharmaceuticals, the guidance for the preparation ...
The biotechnology industry has from the start been characterized by its dependence on innovation. New therapeutics, new indications, new technologies — and the continual drive toward new approaches for optimizing processes — all contribute to getting novel products to the market (and to patients) efficiently and cost-effectively.
Most of the technical literature reports on development processes for the therapeutic products themselves. But one element largely ignored forms an essential foundation to the work of the biotechnology industry: How are products developed for use by those manufacturers? Beyond a company’s proprietary product/molecule are the various equipment types and “ingredients” — columns, resins, and other raw materials, single-use bags and fittings, and commercially available platform technologies. Such products do not come about by chance but from various suppliers’ responses to market needs and their own decisions to develop, manufacture, and commercialize them. How do those companies dec...
Mixing Options
Product:
PSU-20 microcompressor
Application:
Biotechnology/biopharmaceutical development and academic research
Features:
A new bench-top heavy-duty platform shaker provides three mixing functions (orbital motion, reciprocation, and vibration) and the flexibility of a range of interchangeable platforms. It includes a high-capacity, four-level “hotel” format platform to minimize its footprint. The mixing functions are fully programmable and can be set for continuous or timed operation from one minute to 96 hours to achieve optimum mixing in a single mode or in different combinations of the three functions. The unit comes with interchangeable platforms to accommodate different sized flasks, beakers, Petri dishes, and other laboratory vessels. It measures 140 × 485 × 520 mm and features a loading capacity of 15kg, a two-line 16-character LCD display, and a powerful but quiet motor.
Contact
Grant
www.grant.co.uk
Small Batch Filling
Product:
FPC50 filling machine
Application:
Clinical tria...
Statistical Approach to IgG Binding on a Strong Cation Exchanger
+4Many proteins are regulated by posttranslational modifications (PTMs) such as deamidation, phosphorylation, and glycosylation. Documented effects of PTMs include changes in enzymatic activity, interactions with other proteins, subcellular localization, and targeted degradation (
1
,
2
). Also these physicochemical modifications may also affect receptor binding (
3
) or higher order structure (
4
) and result in clinical effects such as changes to bioactivity, immunogenicity, and bioavailability (
5
). The development of analytical technologies to rapidly interrogate protein structure also has direct relevance to the biopharmaceutical industry because protein production processes can significantly affect a protein product’s PTMs and higher order structure (
6
,
7
). Such changes may have an impact on the ratio of different subpopulations of a protein product and hence alter the safety and efficacy profile of a biopharmaceutical. Easy identification of protein characteristics may facilitate engineering in...
+3 The biologics and natural product industries rely heavily on separation technology. Sample analyses are undertaken on the analytical scale, and isolation and purification are undertaken at the preparative scale. Key target components are often isolated to provide standard reference materials for future product quality assurance testing. These products are often very complex mixtures, requiring separation systems to have a high peak capacity for both analytical and preparative scale separations. A technique gaining popularity among companies that require the isolation of pure compounds from complex sample matrices is two-dimensional liquid chromatography, which can be conducted at either the analytical (2D-HPLC) or preparative scale (2D-PHPLC). Operated in a heart-cutting mode, 2D-PHPLC is a technique for which the first dimension essentially serves as an extraction step, simplifying the sample matrix before separation of target analyte(s) in the second dimension. In the comprehensive mode (LC × LC), it is...
Column chromatography remains a key unit operation in downstream processing of biopharmaceuticals. For most commercial processes, two to three chromatography steps are used to remove process-and product-related proteins, DNA and adventitious agents. As the biopharmaceutical industry has increased its product offerings and related demands, downstream processes have fast become a bottleneck (
1
,
2
). Many commercial and clinical processes include a number of cycles on one or more chromatography steps to process the harvest from a single production batch.
PRODUCT FOCUS:
ALL BIOLOGICS
PROCESS FOCUS:
DOWNSTREAAM PROCESSING
WHO SHOULD READ:
MANUFACTURING, PROCESS DEVELOPMENT, AND ANALYTICAL PERSONNEL
KEYWORDS:
FLOW DISTRIBUTION, CFD, SIMULATIONS, COLUMN CHROMATOGRAPHY, PACKED BED, DYE STUDIES
LEVEL:
ADVANCED
Up-scaling of chromatography steps has been the natural response. Theoretically, scale-up is elegantly achieved by increasing the diameter of a column (1–2 m), maintaining the same linear velocity, a...
+4 Implement Disposables and Operational Excellence Strategies to Optimize Facility Use and Achieve Cost and Waste Reduction
Cost pressures on the biopharmaceutical industry are mounting from domestic consumer demand, the growth of biosimilars, and emerging manufacturers around the globe. For organizations to remain competitive and gain sustainable cost reductions, they must drive innovation and accelerate their rate of implementation of novel technologies.
IBC’s fourth international BMD Summit once again provides the latest case studies, regulatory updates, and new strategies for incorporating disposables into biopharmaceutical manufacturing for the companies who continue to adopt this technology or expand their use of it. Learn how to integrate disposables into manufacturing facilities, and hear updates on facilities in general — improving flexibility, productivity, and economics of biopharmaceutical manufacturing facilities while maintaining or enhancing product quality. The biotech industry is beginning ...
The analytical program for a given biotherapeutic has a life-cycle analogous to that of a manufacturing process used to prepare material for clinical and commercial use. This two-part article discusses analytical activities associated with the progression of biotherapeutic candidates from the early stages of clinical development through their appearance as licensed drugs on the market. In Part One, we examined the stages of the analytical life-cycle. Here we conclude by going into more detail on challenges associated with method qualification, validation, and remediation.
Important Concepts in Method Qualification and Validation
Method qualification (MQ) has frequently been viewed as a “box-checking” exercise with no inherent value other than in nonrigorously demonstrating an analytical method’s suitability for its application. In many cases, qualification has been approached without target expectations regarding method performance. We advocate the establishment of target expectations for qualification of...
Adopting an effective strategy for data and knowledge management throughout the drug development and clinical manufacturing lifecycle is key to maintaining a competitive edge. Significant challenges face each organization seeking to improve efficiency in this area, and they can mostly be attributed to the complex nature of pharmaceutical drug development.
Managing both data and knowledge is complicated by the different groups, sites, and partner organizations involved with developing and manufacturing a new drug product. To further compound the problem, a significant proportion of data is most often stored in Microsoft Excel spreadsheets, paper-based systems, and disparate data silos, which makes location of information a particularly labor intensive chore. Under these conditions it becomes extremely difficult to extract any of the value locked within development data.
Novel IT solutions break down existing barriers and help significantly improve communication, data visibility, compliance, and operational...
Combined advances in molecular biology, cell biology, and genomics have led to a wealth of new information about cellular processes. A growing understanding of the fundamentals of cell biology is now being translated into products that use an approach to exert a biological effect that is different from that of most biologicals currently on the market.
To date, most biological products consist of highly purified proteins with a specific activity that alleviates or stops the symptoms of a certain condition. Increasingly, however, the “next generation” biologics exploit knowledge gained in cell biology to directly interact with specific cell types or receptors. Such highly specific interaction can direct them to activate or inhibit the signaling cascade of a specific pathway, generating a specific local or systemic biological effect. Another application would be in exploiting metabolic capabilities of an organism or occupying a niche that would otherwise be occupied by a pathogen.
What most of these second-g...
It appears that it will take more than just the subprime mortgage crisis to put a dent in biopharmaceutical manufacturing. Based on results of our latest annual report, capacity use in 2007 remained essentially steady for mammalian cell culture: at nearly two-thirds, 63.3% compared with 63.9% the year before (
1
).
Capacity use
represents the percentage of an industry’s production capacity that is actually in use. It measures how effectively manufacturers and industries are making use of their fixed assets. This leveling-off of the formerly fluctuating percentages suggests that companies are using their existing capacity more efficiently and are planning more effectively to handle shifts in demand for additional capacity.
This number is important to help planners and investors determine whether capacity will be available for production of pipeline drugs that may be reaching approval. In 2003, the biopharmaceutical industry’s use rates exceeded 76%. It was a capacity-crunch time that led to many facility...
In biopharmaceutical manufacturing, single-use components and systems can offer distinct advantages over reusable, cleanable systems. Deciding whether to move to a single-use approach, however, depends on many factors. In a recent review of biomanufacturers and CMOs, the risk of leachable materials entering drug products was highest on a list of end-user concerns, as shown in Figure 1 (
1
). That’s not surprising in view of the high organic polymer content of disposable components, a general inexperience with such polymeric materials in process contact, and the need to ensure that safety and regulatory requirements are satisfied.
For example, the US FDA’s GMP requirements for finished pharmaceuticals states, “Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements” (
Chromatography media and methods have evolved continuously since their introduction a half century ago. Traditional methods use columns packed with porous particles. They still dominate chromatography applications in the field of virus purification, but the past 20 years have witnessed the ascendance of alternative supports, namely membranes and monoliths. These newer media exploit the familiar surface chemistries — ion exchange, hydrophobic interaction, and affinity — but they use unique architectures that offer compelling performance features.
The Architecture of Chromatography Media
A
monolith
can be defined as a continuous stationary phase cast as a homogeneous column in a single piece (
1
,
2
,
3
). Monoliths are further characterized by a highly interconnected network of channels with sizes ranging 1–5 µm. The adsorptive surface is directly accessible to solutes as they pass through the column. The current generation of preparative monoliths have bed heights ranging from a few millimeters to a few...
