Viral Clearance Studies Made Easy
by Doug Rea, Research Fellow
Viral clearance studies are a necessary component of any regulatory submission for clinical trials or commercial product approval for a biopharmaceutical product. These studies are performed to evaluate the capability of the purification process to remove or inactivate viruses that could potentially contaminate the starting material. These are complex studies and require substantial financial and personnel resources to perform. They are usually performed at a contract testing company rather than in-house, which adds to the complexity. From both financial and timeline standpoints, it is important to get a viral clearance study done right the first time.
There are some obvious questions to ask when planning a study, including which steps of the process to test with which viruses, and what the spiking percentage should be. However, addressing additional questions early in the planning process will ensure that there are no surprises during the execution of the study.
How soon do I need to begin my planning? As early as possible! Decisions made during development of the purification process can have an impact on the design and results from the viral clearance study. If you have been considering the needs for your viral clearance study all along, you will be in a good position when it is time to conduct it.
Who is responsible for what? Will you be performing the study, or will the contract lab be performing it? Who is performing the scale-down purification validation? If the contract lab will be performing either part, they will need detailed information on the process steps. They will also need time to develop the study design and prepare the documentation.
What materials are needed? Samples and solutions are often pulled from a Pilot / GMP purification that may occur months before the clearance study. Not only is it necessary to ensure that there is enough sample to load the unit operations to the target goal, you must also ensure that the amounts collected are enough to provide sample volume adequate for assay. You must also take into account viral assay sampling losses, and sampling for toxicity/interference testing. In addition, it is prudent to collect extra samples for possible repeats.
What supplies will be needed? If your process needs special items such as filters or housings, don’t assume the testing lab has them – it is important to check.
What are the parameters of the scaled-down process? Discuss your process with the viral clearance lab, especially if the lab will be executing your process, but even if your staff is going to the viral clearance lab to execute the process. The viral clearance lab will need to know volumes used and generated during the process in order to calculate clearance. Often these volumes are obvious, but not always. This is especially true for inactivation steps; they may be simple to execute, but planning can be challenging.
If the viral clearance lab staff will be executing some or all of the unit operations, remember, they have not lived with the process as you have. So details of specifications, limitations, and quirks need to be communicated.
What is your schedule for performing the study? It is important to share your daily schedule with your testing lab. The viral plaque assays used for most clearance determinations require growing indicator cells, which must be used within a fairly narrow time frame. Knowing how long the unit operations take allows the sponsor and the viral clearance lab to come up with a schedule within the resources available.
Every company has its own jargon. Remember that just because doing something a certain way is standard for you and your company, that not everyone understands that this is the way you do it. Communications of details are important to success. Even when flexibility is acceptable, the viral clearance laboratory needs to know this. The more the viral clearance laboratory knows and understands about your process, the smoother your study will run.