Challenges and Trends in Vaccine Manufacturing - An evaluation of the technologies and process parameters needed to develop a safe, effective, and economically efficient vaccine. This article is part
An evaluation of the technologies and process parameters needed to develop a safe, effective, and economically efficient vaccine. This article is part of a special section on vaccines.
Oct 2, 2011 By:
Suma Ray, PhD BioPharm International Supplements
Volume 24,
Issue 10,
pp. s3-s11
Figure 3: A generic process for animal cell culture based vaccine manufacturing using platform technologies. HCP is host cell
protein.
One way to eliminate bottlenecks, especially in downstream-process development, is to use purification platforms. The biopharmaceutical
manufacturing industry has communicated timesavings of 3–8 months using a fast-track development approach when technology
platforms are applied in all key aspects of development. This includes upstream as well as downstream processing, such as
cell-line development, cell culture, downstream processing, analytical concepts, and filling (3). Major considerations when
designing a manufacturing platform include the infrastructure, resources and manufacturing capacity available, the degree
of scalability and productivity desired, the time available for producing the first dose and the dosing regime. Figures 2
and 3 illustrate some platform processes for vaccine manufacturing in eggs and in animal cell culture. A complete platform
for downstream processing as noted in one study includes three steps: depth filtration, ultra/diafiltration (UF/DF), and membrane
adsorption for purification of recombinant baculoviruses. Global recovery yields reached 40% at purities over 98% (12).
VACCINE STABILITY AND SUPPLY-CHAIN MANAGEMENT
Another important parameter to consider when manufacturing a vaccine is its thermostability. All vaccines lose potency over
time, and the rate of potency loss is temperature dependent. Hence, there is a need to develop, monitor, and maintain cold-chain
systems to ensure that the potency of vaccines is maintained under refrigerated conditions (mostly between 2–8 °C) until the
point of use. The World Health Organizaion (WHO) recommends that reconstituted vaccines be kept cold and that any unused vaccine
from a multidose vial be discarded after 6 h (14). This is primarily due to the instability of reconstituted vaccines and
also due to the chances of bacterial contamination because live vaccines do not contain preservatives (15). New approaches
to develop thermostable vaccine formulations that are resistant to damage caused by freezing or overheating are necessary
to eliminate dependence on a cold chain. Such approaches could have great economic benefits in terms of reducing vaccine wastage
and preventing adverse health consequences of administering damaged vaccines to recipients. Furthermore, such approaches would
improve the effectiveness of vaccines and enable delivery of the vaccine to remote populations (15).
In addition to ensuring vaccine stability, optimizing the vaccine supply chain through quality management in vaccine manufacturing
plays a key role in safe and effective vaccine manufacturing. In this context, performing a risk analysis for the manufacturing-process
parameters that affect product quality, as well as an assessment of each validation step, including cleaning protocols, monitoring
of the air filters, and assurance of sterility of the source materials, are also crucial to a quality management process (16).
Suma Ray, PhD, is a process development scientist, viral clearance and cell line development, Global Purification Technologies Group at Sartorius Stedim Biotech
Articles by Suma Ray, PhD
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