Risk Management in Viral Safety

Recently I spoke with editorial advisor Hazel Aranha (manager of viral clearance and safety at Catalent Pharma Solutions) about viral contaminants and risk management. A recognized expert in the field, Aranha contributed “Current Issues in Assuring Virological Safety of Biopharmaceuticals” to BPI's March 2012 issue and was interviewed by Ellen Martin for her September 2012 article, “Legacies in Bioprocessing.”

Spotlight on the Industry

BPI: Have there been any recent viral transmission incidents that you can share to highlight the concern over this issue?

Aranha: Fortunately, to date, biopharmaceutical products have had an excellent safety record, and we have not had any virus transmission of pathogenic virus — and I stress the word pathogenic — associated with their administration. That said, there have been instances of contaminated manufacturing batches and environments. There have been reports of batch contamination with mouse minute virus (MMV) and other adventitious virus contamination of manufacturing environments. Even a marketed vaccine product (rotavirus vaccine) was shown to be contaminated with a virus that was, in fact, traced to a reagent (porcine trypsin) used when the master cell banks were set up decades ago. It was not negligence on the part of the manufacturer; it's just that our detection methods are considerably more sensitive today than they were in the past. This has shone the spotlight on the vulnerability of all biopharmaceutical operations.

Viral Safety Methods

BPI: What common methods are used to remove viral contamination?

Aranha: Essentially, virus clearance methods can be classified as virus inactivation or virus removal methods. Inactivation methods such as pH inactivation and heat inactivation disrupt virus infectivity. Viruses would be detected by molecular methods such as PCR that detect nucleic acid (both infectious and noninfectious).

Common virus removal methods are chromatography and virus filtration. Several chromatography methods are currently in use, and some are relatively robust. Methods such as protein A chromatography and anion-exchange chromatography have been shown to reliably remove viruses. Virus removal with some methods such as cation-exchange chromatography is more process dependent.

Virus filtration is another key method. Size-based virus removal filters provide robust virus clearance, especially in terms of large-virus removal. However, we are concerned about smaller viruses such as parvovirus. Studies have to be performed to ensure no bleed-through when virus filters are used. Currently there is a lot of development in virus-filter membrane technology toward improved flow rates and enhancement of virus removal.

Taking a Risk Management Approach

BPI: What new trends in viral clearance and safety may be of interest to readers?

Aranha: Supply-chain management has gained considerable focus. With increased globalization, there are multiple tiers of raw-material sourcing. In some cases, the exact origin of a raw material may not be available. So most companies need a very robust supply-chain management program to ensure that adventitious viruses are not entering the raw material stream. The days of “Take my word for it” are long gone. And suppliers can no longer hide behind the “That is proprietary information” approach. More and more suppliers are being asked to provide pharmaceutical companies with data regarding sourcing or any testing done before procurement.

Another area of focus is the use of upstream barriers such as irradiation, high-temperature–short-time (HTST) treatment, and UV-C inactivation. Although upstream virus barriers are not an absolute requirement, I essentially equate their use with having business insurance because of the significant consequences that come with a contamination incident. Not only does a company have legal, financial, and regulatory losses, but I think most important are drug shortages to patients. As we all acknowledge, considerable drug shortages can significantly influence patient morbidity and mortality.

Fortunately for us, some current industry initiatives seek to leverage biopharmaceutical industry knowledge and experience and share industry risk and prevention strategies regarding risk mitigation and management of adventitious agent contamination. We have moved away from our past paradigm that was responsive and disaster-led to a preemptive approach.

Virus safety assurance is a moving target. New and emerging viruses will continue to threaten the safety of our biopharmaceuticals. We need a robust virus safety management program, which should be based on strong scientific reasoning, benefit/risk assessment, and knowledge management. This is the only way we can continue to maintain a high level of virus safety assurance.

American author and playwright Alfred Sheinwold, with whom I agree, expressed this eloquently: “Learn all you can from the mistakes of others. You won't have time to make them all yourself.”

Author Details

Leah Rosin is marketing and digital content strategist for BioProcess International, 1-508-614-1167; [email protected].