Ensuring Adventitious Agent Safety in Biologics

By 2015, the global market for biologics is expected to reach $239 billion (£147 billion), thanks to more comprehensive drugs pipelines, development of biosimilars and innovations to slash production costs, according to research by Bharat Book.

Yet there is one area where the industry's knowledge is still limited; how to mitigate the risk or deal with contamination of adventitious agents.

High-profile cases involving GlaxoSmithKline and Genzyme in recent years have serve to highlight the consequences these virus contaminations have, even when they pose no safety risks to patients. And these are by no means the only cases.

"At least 17 incidences of viral contamination in biologics have been reported, but industry insiders say that many more go unreported," an editorial in the April 2011 issue of Nature noted.

In June 2009, Genzyme indentified a contamination at its Allston Landing manufacturing facility in the United States.  Vesivirus 2117 was found to be present in one of six bioreactors used at the facility and was shown to restrict cell growth.

Indeed, the virus was said to be the cause behind two previous instances of falls of cell productivity in 2008, but it was not until a specialised assay was developed, after standard tests proved fruitless, that the virus was detected this time.

"Genzyme is adding steps to increase the robustness of its raw materials screening and viral removal processes," the company said at the time.

Final terms of the FDA Consent Decree for revising standards at the Allston factory were put forward in May 2010, and Genzyme expects the changes to take two to three years to complete.

If milestones are not met, the FDA can fine the company $15,000 per day for each drug, on top of the upfront payment of $175 million, while five years of annual reports will have to be compiled and submitted.

Steps were taken to enhance manufacturing at the factory, including the relocation of senior managers, employment of manufacturing and quality leaders.

"Programs have been designed to evaluate and implement risk reduction strategies such as irradiation of serum as well as the potential elimination of serum from therapeutic protein processes," Genzyme added in its 2011 annual report.

But two years down the line supplies of drugs to treat rare and serious diseases is still running short.

The situation would be worse, however, if members of the pharmaceutical industry were not given the opportunity to learn from Genzyme's experience of successfully dealing with a contamination.

Biologics are making their way further into the mainstream, but the relatively immature state of the industry means mechanisms for sharing best practice in the area of contaminations are not yet properly developed.

The Center for Biomedical Innovation at Massachusetts Institute of Technology created the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) to help address this.

It noted current experience of dealing with contamination is restricted to the experiences of individual organisations, and the CAACB set about confidentially collecting and analysing contamination data from the industry.

"Specifically, the CAACB seeks to develop a comprehensive understanding of adventitious agents encountered, the source of such agents, and a risk-based analysis of the most effective barriers to contamination," it explains on its website.

Unfortunately, as of April 2011, just six companies has signed up the pilot scheme and CAACB needs at least 20 to be able to make meaningful conclusions from the information it collections, Nature reported.

The problem for pharmaceutical companies, is that even if the contamination poses no risk to human health, the bad publicity it brings with it and the precautions regulators are required to take negatively impacts business.

When GSK discovered PCV-1 in its oral rotavirus vaccine Rotarix the FDA recommended medical practitioners temporarily suspended its use as a precaution, despite there being no evidence the virus, found in everyday meat products, caused infections in humans.

Such effects mean efforts like those from the CAACB to create a better understanding of how to manage the risks of adventitious agents could prove invaluable for the pharmaceutical industry.