What Would You Do in the Case of a Virus Breakout in Your Manufacturing Plant?
The porcine circovirus contamination of GSK’s Rotarix vaccine in March of this year, and previous contaminations in both Baxter and Genzyme biological products in 2009, have highlighted the issue of viral safety in biologics more than ever before. In a recent interview Dr. Mark Plavsic, Senior Director, Gene Therapy Development Genzyme, spoke with Andrea Charles from Pharma IQ, about the latest techniques for ensuring effective viral clearance.
Please could tell us a bit about your current role at Genzyme?
My current role at Genzyme is in the field of viral safety. I am a global microbiological and viral safety expert with the company.
How would say that evolving regulatory guidances have impacted on viral clearance studies for biologicals?
Firstly, I think they are very helpful, they provide relatively good guidance in terms of how these should be conducted, and also how they should be designed. I think that there has to be more clarity with regards to selection of virus, and maybe better delineation between so called laboratory adaptive strains against, so called field isolates, which are more likely to be encountered in a real case scenario. I also think a bit more clarification as to expectations of quality of viral preparations (e.g. purity, characterisation, age, minum titer, IU/particle ratio, etc) to be used in studies, will be required.
What lessons would you say you have learnt since the vesivirus virus contamination?
I think we learnt several lessons, first of all biotech companies are not immune to viral contaminations in the first place. Secondly, that these events are not always readily detected by the current viral testing protocols, accepted as industry standards today. We also learnt that we need to do more in terms of preventing these events in the first place, and finally, should they happen how to respond swiftly and effectively.
Leading on from that what steps can we take to reduce the risk of viral contamination?
There are a number of steps that can be considered. Procurement of critical / vital raw materials is important upstream step - looking at the way critical raw materials are manufactured, and making sure that they are manufactured in compliance with GMP with adequate controls built into the process, including certain viral clearance steps, and relevant and meaningful viral testing technologies at the raw material level. Beyond that, certainly a number of steps can be taken in terms of controlling manufacturing processes, replacement of animal origin components, treatment of raw materials where appropriate, built-in robust viral clearance steps, single use disposables, the facility and equipment design, cleaning processes, periodic risk evaluation, etc – all of these in concert could contribute in preventing these potential issues.
Similarly operators and employees should also be adequately trained and made aware of these issues.
Which emerging detection technologies do you think hold the most potential?
Out of the many current technologies that exist, I think one of the most promising technologies, probably centres around deep sequencing. It is broad range method in that one can detect virus, or any other microbial agent if present at a detectable level. Presently, the method is still in its early stage, and is rather expensive for routine use. It requires more development and understanding before wider industry application and adoption.
You are going to be speaking at our ensuring viral clearance and safety for biologics conference in 2010, for anyone interested in attending the event, what will be your key take home message?
First, I will touch briefly on how we identified the virus. I will also touch base briefly on the weakness of the existing viral testing methods. Then, I will highlight the viral biology of this particular viral agent. Finally, I will underline what you and I spoke about earlier, viable options for the industry today to prevent these contaminations and, if they happen, how to respond.
How can we optimise the response to contaminations? What are the best ways to ensure an effective response?
The best ways is not to have them at all in the first place. Prevention, prevention, prevention! To really build in the elements to prevent them, but even that is not going to lead to risk elimination. There is no 100% guarantee that everything is going to be safe. So the next thing, beyond the prevention plan, to do is put in place a well organised, well written response plan. In other words, outlining what you do if it happens, so that you respond quickly and effectively.