Cosponsored by CASSS (an international separation science society) and the US Food and Drug Administration (FDA), the January 2010 CMC Strategy Forum explored antibody–drug conjugates (ADCs), which are monoclonal antibodies (MAbs) coupled to cytotoxic agents. The ADC platform of products is being used more and more for clinical evaluation in oncology. More than a dozen companies are developing several types, including products conjugated with calicheamicin, auristatins, and maytansinoids. Such products use the specificity of a MAb to deliver…
Analytical
Comparing H1N1 Virus Quantification with a Unique Flow Cytometer and Quantitative PCR
A novel influenza A (H1N1) virus was discovered in Mexico in early 2009 (1). Infections from this strain led to declaration of a pandemic midyear, with about 61 million patients and 13,000 deaths reported by the US Centers for Disease Control (2). Although the pandemic officially ended in August 2010 (3), vaccines are still in demand to protect people against the H1N1 strain that is now expected to circulate seasonally for years to come. To best respond to…
Meeting Increased Demands on Cell-Based Processes By Using Defined Media Supplements
Rapidly increasing demand for cell-derived products has placed huge pressures on the biomanufacturing industry’s production capacity requirements. Media development strategies continue to be a primary focus for optimizing output from cell culture systems. Animal cells used in manufacturing protein products have complex nutrient requirements specific for each cell type, clone, and product. Individual nutrient requirements were once addressed by using serum-based media rich in growth factors and supplements, which provided an optimal culture environment for cell growth and productivity (1).…
A World of Innovation
The world faces a clear need for innovative biological products to treat and prevent diseases that cause significant health burdens. What might be less obvious is a need for innovation in biomanufacturing processes. If these products are to be made more efficiently and cost-effectively through less wasteful and safer means, then improvements are definitely needed. “We need innovations in downstream bioprocessing, whether the products are vaccines, recombinant proteins, or other bioproducts,” said Uwe Gottschalk, vice president of purification technologies at…
Streamlining Downstream Process Development
Normal-flow filtration is used throughout downstream processes for biologics including depth, sterile, and viral filtration applications. Because of its ubiquity in large-scale biomanufacturing, using the most efficient normal-flow filter media area and type can lead to significant cost savings. To determine the most effective media type and area, developers use a scaled-down process model is used in bioprocess laboratories to minimize material requirements. Constant–flow-rate filter evaluations involve direct scale-down parameters that match manufacturing-scale process conditions. This type of evaluation can…
Rapid Process Development for Purification of a MAb
Time and flexibility are essential in purification process development for biopharmaceuticals. Easy translation of experimental ideas into process steps and insight into the effects of changes in chromatography parameters both help speed development and contribute toward achieving quality by design (QbD) objectives. An ability to scientifically design product and process characteristics that meet specific objectives is crucial. Opportunities to eliminate manually intensive steps all support an enhanced development process. A typical monoclonal antibody (MAb) purification process includes three chromatographic purification…
Top 10 Changes in FDA’s Process Validation Guidance
Two years after drafting a comprehensive revision of the 1987 process validation guidance, the FDA finalized the document this year. The revision elaborates on modern quality by design (QbD) techniques for developing a process, analyzing risks, and monitoring for control. The initial draft update remains largely intact, with some important adjustments focused on clarifying the FDA’s intent for how the industry is expected to validate its processes. 1 — Minor Changes: The guidance includes more references to the Code of…
Glycosylation of Therapeutic Proteins
ACMC Strategy Forum held in Washington, DC, on Sunday 28 January 2007, focused on two topics related to protein structure and function. First, analytical techniques used in the glycan analysis characterization included recent advances and correlations among the various tools. And second, current understanding glycosylation’s functional relevance to therapeutic proteins was discussed in the context of its effects on biological activity, pharmacokinetics, and Fc effector functions (for monoclonal antibodies, MAbs). Progress has been made in the field of…
An Update on Cell-Based Technologies
It’s always exciting to find out where the next meeting of the European Society for Animal Cell Technology will be. This venerable conference happens somewhere in Europe every other year. Recent sites have included Dublin, Ireland (2009); Dresden, Germany (2007); Harrogate, England (2005); Granada, Spain (2003); and Tylösand, Sweden (2001). This May, the gathering of animal cell culture scientists and engineers will convene in the palatial setting of the historic Hofburg Congress Center, formerly the Hapsburgs’ imperial residence…
Validation of Intermediate Hold Times
Because of the molecular complexity and relative fragility of biotherapeutics, validated intermediate hold times are critical for their commercial manufacture. Manufacturers typically conduct studies to define acceptable hold times for process intermediates to determine acceptable hold times for in-process production samples. A validation study defines maximum allowable hold times for all intermediate process stages based on product-specific data obtained during a hold study. A systematic risk assessment can determine which intermediate hold points should be validated (1). Hold…