Removing viral contaminants from animal cell-culture derived biologicals is a major challenge of downstream purification because
it involves laborious and time-consuming techniques that result in increased manufacturing costs. Updated regulatory guidelines
demanding higher safety margins and enforcing good manufacturing practices are leading to tighter specifications. This stresses
the need to implement robust and efficient orthogonal strategies for virus clearance to meet the requirements of a virus-clearance
approach based on risk assessment. Such technologies can involve virus removal by nanofiltration, inactivation by ultraviolet
C (UVC), and adsorption by membrane chromatography. Additionally, this three-tier platform should be characterized by using
disposables to meet the flexibility and low capital requirements needed in early-stage process development. All of these new
paradigms in virus clearance are scalable, economical, orthogonal, and disposable.
Today's downstream processing operations generally focus on two main areas: the initial recovery phase, when bulk purity is
achieved, and the subsequent polishing phase, which adds safety through orthogonal strategies for impurity and pathogen clearance.1 Commercial manufacturing of therapeutic antibodies requires robust and reliable processes that are economical and deliver
high yields of a product that is pure and safe for human use. One factor that poses a constant threat to product safety is
the presence of viruses in the finished product. Virus contamination of products derived from human or animal cells can have
disastrous clinical consequences causing diseases ranging from common colds and influenza, to acquired immune deficiency syndrome
(AIDS), hepatitis, herpes, measles, and poliomyelitis. Some viruses like Epstein-Barr, human papillomavirus, and retroviruses
are even oncogenic, causing the insertion of cancer-causing genes into cellular genomes.2 It is essential to review both the short-and long-term consequences of viral contaminants existing in biopharmaceutical
products. In this context, it is worthwhile to understand some important aspects of current and state-of-the-art methods for
inactivating and eliminating viruses from process streams that generate products intended for use by humans.
Sartorius Stedim Biotech
GENERAL STRUCTURE OF VIRUSES
Viruses are composed of small amounts of DNA or RNA, encapsulated by a protein coat, and may be enclosed in an envelope made
of proteins, carbohydrates, and lipids. Viruses exploit the enzymes and other host-cell machinery to replicate themselves.
The viral nucleic acid can be single-or double-strand DNA or RNA. A single virion is a completely developed virus particle
made of 1–50% nucleic acid and 50–99% proteins or glycoproteins and lipids. Virions range from about 15 to 450 nm in size.