MAb

Preparedness Ahead of Pandemic Outbreaks

Lively debate in 2012 concerned the risks and benefits of laboratory studies that created a contagious H5N1 avian pandemic influenza (flu) laboratory-strain virus. One benefit of the public debate is that it reminded governments of the increasingly likely and disastrous possibility of a devastating flu pandemic on the scale of the Spanish influenza outbreak of 1918. Natural evolution of circulating H5N1 viruses could lead to emergence of a deadly and contagious strain (1). Here we outline conventional flu vaccine options…

Development of Protein Capsular Matrix Vaccine Platform Technology

Polysaccharide vaccines account for about 30% of the total >$20-billion/year vaccine market. Despite efficacious vaccines in the field, diseases such as invasive Streptococcus pneumoniae and typhoid fever persist. Development of multivalent polysaccharide conjugate vaccines requires complex chemistries and multiple, expensive good manufacturing practice (GMP) process steps. Matrivax Research and Development Corporation is developing a protein capsular matrix vaccine (PCMV) technology that simplifies synthesis of polysaccharide vaccines with fewer process steps than are required by typical conjugation vaccine processes. Polysaccharide Vaccine…

Emerging Challenges to Protein A

Protein A affinity chromatography has been a target for replacement since its commercial debut, mainly because of its high acquisition cost. The technique became established despite the cost because it was born into an industrial culture that favored speed to market over manufacturing economy (1). Vendors have since strengthened protein A’s position with incremental but worthy improvements such as higher capacity, lower ligand leaching, and modest tolerance of NaOH. Collateral improvements in polishing technologies, such as the high throughput and…

Spray-Dry Manufacture of Vaccine Formulations

Development of vaccines and immunotherapeutics has expanded rapidly due to technological advances in the fields of molecular biology and bioprocess engineering, as well as a smoothing of management and material logistics worldwide. Expression platforms and novel cell lines have enabled creation of increasingly complex vaccines. The advancement of vaccine formulation development is also capitalizing on new advances in manufacturing that use model-based methodologies gleaned from physiochemical principles, process analytical tools, and systematic approaches to problem solving. Herein we highlight recent…

Container–Closure Integrity

An increasing number of biopharmaceuticals — including vaccines, stem cells, and proteins — require cold storage to maintain efficacy before use. However, the ability to maintain container–closure integrity (CCI) during cold storage is not completely understood. Concerns about CCI failure have been raised for storage and shipment of such products in rubber-stoppered vials under cold conditions (e.g., −80 °C or on dry ice). Commonly used butyl stoppers are believed to lose their elastic properties below their glass transition temperature (Tg),…

Virus Risk Mitigation for Raw Materials

Recombinant protein–based medicinal products and modern cell-based vaccines have a very strong safety history with respect to viral and microbial contamination. However, virus contamination incidents do occur occasionally in manufacturing processes, and they can consume many resources and be expensive to rectify. The root cause of contamination incidents in recent years is most likely the use of contaminated raw materials. These include bovine serum contaminated with reovirus, epizootic hemorrhagic disease virus, Cache valley virus or vesivirus 2117; porcine trypsin contaminated…

Development Strategies for Novel Vaccines for Infectious Diseases

In a vaccine development program, the probability of success at each transition decreases, even though the actual probability of moving from one phase to another can be 50–80% (Figure 1). Many compounds and vaccine candidates are screened out even before they get into preclinical studies. Developers can implement different approaches to reduce product failure risk before a program gets expensive, including Establishing a product development plan (PDP) Identifying and mitigating risk with gap analysis Learning from the mistakes of others…

Protein A

The number of blockbuster monoclonal antibody (MAb) drugs continues to grow. In 2008, MAbs generated revenues in excess of US$15 billion (1), making them the highest-earning category of all biotherapeutics. The world MAb market will reach $62.3 billion in 2015, with next-generation therapeutic antibody revenues reaching $2.3 billion in 2015 according to Visiongain reports published in September and November 2011 (2, 3). Biosimilar antibodies will also begin to enter established markets as regulatory authorities clear approval pathways for them. Most…

Upstream Chemistry Analysis in Cell-Based Process Development

Cell line selection is important to any pharmaceutical company’s development pathway for biological compounds (1). In cell-line selection laboratories, many different, slightly variable cell lines are tested in parallel for desired characteristics. Candidate cell lines are chosen for further development on the basis of their performance in basic tests of critical quality attributes (CQAs). Historically, such cell lines were selected in large-volume containers because it was necessary to have sufficient volume in culture to allow repeated sampling without damaging the…

Automation of Microbioreactors

Current methodologies in genetics and microbiology enable researchers to influence metabolic pathways of microbial cells in many directions. Beside the academic interest in investigating fundamental functions in metabolic pathways, commercial production of valuable compounds by microbial hosts is state of the art. For example, such products include enzymes (lipases, proteases, phytases), therapeutic agents (insulin, antibodies), bulk chemicals (lysine, glutamate, citric acid), or the microbial cells themselves (used in brewing or milk processing), with therapeutic agents probably the fastest growing market.…