Stem cells have potential as a readily available, consistent source of many differentiated cell types. This unique property can be leveraged both for therapeutic purposes and for facilitating and improving a number of drug discovery and development processes. Large-scale, “industrialized” production of human stem cells in tightly controlled conditions will be required to deliver the quantity and quality of cells needed to support clinical trials and drug discovery development activities (Figure 1). Achieving this level of production while meeting rigorous quality and regulatory standards will depend on further progress in cell culture and scale-up, characterization, enrichment, purification, and process control to safely and cost-effectively deliver a consistent and reproducible supply of cells.
From Bench Scale to Large Scale
Cell culture can seem to be as much an art as a science, sometimes calling for a “whatever works” approach. Every cell type has unique needs when grown in vitro, and stem cells are ...
Containers and administration devices are integral to the safety and efficacy of biopharmaceutical therapies and must be key considerations for all new drugs coming on the market. By partnering with packaging manufacturers early in development, biopharmaceutical manufacturers can increase efficiencies in their production processes while gaining expert advice and counsel throughout a drug’s lifecycle. Such an alignment can also improve product quality, enhance regulatory compliance, and contribute to the overall state of control by preserving biopharmaceutical stability, ensuring sterilization, and customizing delivery systems for market differentiation.
Biopharmaceutical Packaging Concerns
In recent years, an increasing number of biotherapeutics has received regulatory approval. This drives a need for continuous improvement and creates new requirements for primary packaging components. Enhanced regulations and new guidance on current good manufacturing practices (CGMP) are also driving drug and packaging ...
Cation-exchange chromatography is the third most used industrial method for antibody purification after anion-exchange and protein A affinity chromatography. It is most commonly used as an intermediate step but continues to attract attention as a capture method. This offers obvious cost and cleaning advantages over protein A but also imposes some sacrifices, all of which are discussed in a number of recent articles (
1
,
2
,
3
,
4
,
5
). Whichever application may be intended, end users seek a common set of performance characteristics. They include high capacity and recovery, high purification factor, a high degree of process control, high lot-to-lot reproducibility, and easy cleanability and sanitizability.
Chromatography media vendors have responded by introducing a continuum of new cation exchangers to better serve those applications. Given that they all strive to offer the ideal product, it might be expected that their capabilities would converge over time. That may happen, but the present selection of...
Part 1 of this two-part article introduced the need to reduce the environmental footprint of bioprocesses and evaluated the impact of solid-waste disposal. Part 2 continues by describing the effects of the remaining elements of the bioprocess footprint: wastewater, electricity, and air emissions.
Wastewater
Process Waste Streams:
Generally, raw materials to produce and purify biopharmaceuticals fall into one of the following categories: inorganic/organic salts, sugars/polyols, trace elements, vitamins, amino acids, surface active agents, or complex (undefined) ingredients (Table 1). Most bioreactor media components are either life-supporting or life-promoting and thus likely to have a low intrinsic toxicity. However, when used at concentrations necessary to achieve commercially viable processes, these compounds can be toxic to aquatic life. Overall guidance for fermentation broth and downstream isolation component selection during early process development is best based on each component’s concentration ...
Monoclonal antibodies (MAbs) are increasingly formulated at concentrations >100 mg/mL as a means to deliver a high dose in a low volume (1,
2
). Such high-concentration solutions are commonly opalescent (
3
,
4
), an undesirable characteristic of biopharmaceutical products for several reasons. Although it may be only aesthetic, opalescent products are not considered pharmaceutically “elegant.” Of more serious concern, opalescence may be a precursor to aggregation and indicate a propensity toward decreased product stability or quality.
The term
opalescent
refers to a uniform haze or turbidity in a solution as opposed to the presence of distinguishable particles. Filtering opalescent solutions generally does not decrease their turbidity. The main challenge in studying such protein formulations stems from their forming only at high concentrations (
5
). Most biophysical characterization techniques require dilution to
PRODUCT FOCUS: HIGH-CONCENTRATION ANTIBODIES AND OTHER PROTEINS
PROCESS FOCUS: MANUFACTUR...
High-throughput screening and process development methods are becoming more widely used in the biopharmaceutical industry. Recent development of high-expression (high–target-titer) recombinant culture methods has enhanced the need to also develop more effective separation products, methods, and processes (
1
). Part of the solution would be chromatographic resins offering higher capacities and flow rates.
However, developing an optimized purification process that involves several chromatographic steps can consume significant time and samples. In addition, a purification process developed at small scale often has to be further optimized before being used at larger scale. One strategy is the use of a platform approach (
2
,
3
,
4
,
5
,
6
), in which the need for optimization is fairly limited and only minor adjustments are necessary. Purification of monoclonal antibody (MAb) targets using protein A affinity chromatography as a capture step is an example that provides purified target material at high yields....
+3Automated Osmometry
Product:
Advanced 20G high-throughput osmometer
Applications:
Cell culture process development and optimization
Features:
The Advanced 20G high-throughput osmometer combines state-of-the art osmometry technology and robotics within a parallel sample processing scheme. Samples can be analyzed in a 96-well format within 35 minutes with the same accuracy as stand-alone osmometers. The 20G system supports osmolality testing in even the most demanding cell culture process development schemes in the biopharmaceutical industry.
Contact Advanced Instruments Inc.
www.aicompanies.com
UV Calibration
Product:
Calibration accessories for Optek AF16/AF26 sensors and AS16 probes
Applications:
Visible (Vis) and near-infrared (NIR) analyzer calibration
Features:
Optek delivers new, nonintrusive Vis and NIR calibration filters traceable to NIST. They test photometric accuracy and linearity by attenuating 0.45, 0.90, and 1.80 AU of light. A unique design architecture eliminates stray light for incr...
The BMD Summit comprises two in-depth tracks, a combination of programming that will help you increase your manufacturing agility, reduce process variability, and achieve your manufacturing and development goals.
Tracks and Session Topics
Preconference Workshop:
“Mitigating the Risk and Impact of Viral Contaminations: Technical Aspects” (new this year)
Track #1, Enabling Efficient Facilities:
This track provides you with insights on how to achieve scale and product flexibility. You will hear perspectives from major biopharmaceutical companies on when and where to implement disposables — and the latest novel downstream technologies that can help you improve your plant’s flexibility and efficiency.
A plenary session on critical industry updates includes Genzyme’s adventitious agent control, Biocon’s economic strategies, Baxter’s inventory tips, and Pfizer’s operational excellence practices. Other sessions address
COLOCATED CONFERENCE
Preclinical Scale Bioprocessing
provides the strategies you need to nav...
May 2010 marked the 30th anniversary of the World Health Organization’s declaration that the world had won freedom from smallpox. An intensive two-year search had discovered no evidence of the disease since the last case on 26 October 1977. It was a historic moment — no disease had ever before been eradicated. Smallpox had terrorized humans for more than 3,500 years and in the 20th century alone had been responsible for 300 million deaths.
The success of the effort stands as an exemplar of the potential of public health and medicine when countries work together to achieve common goals and when research and technology play an ongoing, integral role. A professional staff of more than 70 nationalities worked across international borders to find cases and stop outbreaks. Even during the Cold War years, collaboration replaced confrontation.
Eradication Timeline:
Why did eradication take so long? Smallpox vaccine was the world’s first vaccine. It was developed 180 years before eradication was achieved. One vac...
