The need for Viral Clearance studies on tissue derived medical products
Caitlin Bubb, Principal Scientist/Group Leader, Viral Clearance Services
While it is common knowledge that Viral Clearance needs to be performed on products such as monoclonal antibodies, it is not as well known that Viral Clearance should also be performed on tissue-derived medical products. When a company is told that they need a Viral Clearance study for a tissue-based product, they might not be aware of all the critical elements that need to be considered in the design, execution and interpretation of a tissue Viral Clearance study. They may also not be aware of the challenges unique to a tissue product study as compared to a study performed on a product in solution. At Eurofins Lancaster Laboratories, we have over 60 years of cumulative experience working with many different types of tissue derived products and can lend our expertise to help guide you through your Viral Clearance needs.
Companies will need to begin by taking a look at the physical nature of their product along with the origin of the materials used in product manufacture. A risk assessment should be performed to determine what viruses the tissue has the potential to introduce into the process, and what level of risk these viruses would present to a patient. Once the risk assessment has been performed, Eurofins Lancaster Laboratories then helps finalize a panel of viruses to be used in the viral clearance study. The next step in study design is to evaluate the overall manufacturing process for steps that are most likely to effectively clear virus through inactivation, removal or both.
Scaling down these steps for a tissue-based product can sometimes prove to be a challenge. Unlike monoclonal antibodies which often have several industry standard removal or inactivation steps, tissue manufacturing processes can vary significantly. In addition, it is important to make sure that the mechanism by which the virus is being inactivated or removed is not repeated between steps.
After both the virus panel and the process steps have been selected, a spike recovery feasibility study must be performed on the material both before and after the process steps being evaluated as the nature of the tissue may change dramatically after processing. The spike recovery test allows us to ensure that if virus is present we would be able to recover it from the tissue. Obtaining samples for spike recovery testing often requires coordination with the client or third-party vendor to be able to receive a small amount of material that has already been through a single process step. Spike recovery testing is performed prior to the process step since this is often where issues are identified. Tissue sourced from vaccinated animals, or infected with viruses that routinely circulate through these animal herds (e.g., PPV, PCV, BVDV) may contain neutralizing antibodies that will prevent recovery of infectious virus from the tissue. Occasionally there are issues were the virus is not able to be recovered from the tissue, and the reason is not clear. At this point some research and development work and adjustments to the study would need to be made. This is where having all the previous risk assessment information proves critical.
Once all the pre-testing is complete the viral clearance steps can be executed. By working closely with the client, as well as encouraging clients to visit our site, we can work together to ensure a successful viral clearance study from start to finish. With the completion of the study, clients will receive their data package as well as support through their entire filing process.