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 advancements in spray-dried vaccine formulation, which has been successfully applied to develop stable and effective formulations across a spectrum of vaccine types.
Vaccine development has been incorporated into the era of biotechnology. The field of vaccines is as old as small-molecule therapeutics, with Jenner’s smallpox vaccinations in 1796 and Withering’s dosing of digitalis in 1785. Novel approaches to...
Chinese hamster ovary (CHO) cells attached on macrocarriers extracted from the iCELLis bioreactor fixed bed
Human and veterinary vaccines are divided into five main categories: conjugate, toxoid, subunit, inactivated (killed), and live (attenuated) vaccines (
1
). The vast majority of currently licensed human and veterinary vaccines are inactivated or live (
2
,
3
). They are produced mostly using adherent cells: primary cells such as chicken embryo fibroblasts (CEF), human diploid cells such as MRC-5, or continuous cell lines such as Vero and MDCK (
4
). The pioneering legacy inherited by vaccine manufacturing development has led to strategies for cultivation of those anchorage-dependent cells. Those strategies rely on two approaches: either two-dimensional (2-D) systems (e.g., T flasks, roller bottles, Cell Factory, CellSTACK, and other stacked systems) or microcarrier cultures in stirred bioreactors.
Two-dimensional supports are quick and easy to implement with limited expertise. But scaling them up (...
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 and their limitations with regard to pandemic influenza preparedness. We also describe a new approach provided by BiondVax’s M-001 technology for preparedness ahead of pandemic influenza outbreaks.
Background:
Countless influenza strains arise as the flu virus mutates unpredictably and frequently, making flu the most common infectious disease. Conventional vaccines rely predominantly on triggering antibody responses to variable regions in the influenza envelope protein hemagglutinin (H...
+1If current efforts to eradicate polioviruses worldwide are successful, then the oral poliovirus vaccine (OPV) currently used for routine immunization in low- and middle-income countries (LMICs) will be replaced by inactivated poliovirus vaccine (IPV). IPV will become the only option for such countries if they want to continue to vaccinate against polio (
1
). Because IPV is currently considered to be too expensive for use in LMICs, strategies are being undertaken to make IPV more affordable (
2
). Some experts estimate that in 5–10 years there will be a lack of IPV manufacturing capacity worldwide (
3
). That will most affect LMICs, which depend on external vaccine supplies. So expansion of existing facilities (or building new ones) will be key to meet future demand. Here we examine the use of alternative technologies such as modular manufacturing facilities and single-use equipment as means to improve IPV affordability and capacity.
Main Drivers for Implementation of Modular Facilities and Disposables in...
With the approaching holiday season and the end of the year — how can that be? — we find ourselves pretty well settled into plans for our 2014 editorial calendar. As a team, we’ve met during the summer to brainstorm and share the results of our research into the subjects of next year’s special reports and supplements. What should we focus on next? What old themes and supplement topics need to be revisited, and what new topics should we highlight? Is there another trend to follow such as we did with early promotion of single-use technologies? Such planning is always a combination of market studies, reader and advisor suggestions, our own editorial interests, advertiser and sponsor recommendations … and a bit of cautious guesswork (that is, prognostication). We’ve tried always to help present bigger-picture views into how various advances can encourage progress across more than one industry segment, but we also don’t want to oversimplify matters.
With its downstream theme, this issue follows a number of top...
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
Product Development Planning
Developing vaccines is risky, so prudent companies take efforts to mitigate risk. A robust plan is critical to robust product development. One approach is to begin by envisioning the final vaccine product. A gap analysis is important to identify potential problems. Then you can establish a mitigation strategy to prevent potential difficulties or to discuss different options to reduce that risk.
A robust document should gather everything together in one place (e.g., preclinical data and processes used). That helps you focus resources where they’re needed.
A PDP can be used to...
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 Market
Pneumococcal vaccines
account for a major part of the current polysaccharide vaccine market.
S. pneumoniae
infections lead to at least a million deaths annually worldwide. In the United States, the infection causes ∼3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7 million cases of otitis media.
The 23-valent Pneumova...
+2 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 (
T
g
), which poses a risk to sealability (
1
,
2
).
Temporary loss of CCI under cold conditions could allow cold, dense gas from the surrounding low-temperature storage environment to leak into stored vials. Such an ingress of gas could contribute to loss of efficacy of stored drug products due to interaction with the gas as well as vial overpressurization. That occurs when cold, dense gas becomes trapped within a vial as its rubber stopper warms to a >
T
g
temperature...
+2 
