If your organization is planning to create capacity for advanced therapy medicinal products (ATMP) or viral vector production, there are three key engineering considerations to take into account: Facility current good manufacturing practice (cGMP) flows, base efficiency and airflow control. These considerations are relatively easy to underestimate, because in many ways the technology behind viral vector production seems similar to production of monoclonal antibodies.
If your production requirements are higher than your available square footage, and a new build is not an option, design becomes a balancing act. You’ll need to come to grips with what you can sacrifice and still meet your original production goals, and ensure that any retrofit will not pigeonhole your facility’s future capabilities.
Historically, cGMP flows were about mitigating adventitious virus, whereas in viral vector manufacturing, we can’t avoid viruses or vectors, because that’s the product. But the facility design needs to account for viral vectors differently than in mAb production.
Testing surfaces and the environment to ensure that you’re not getting carryover nascent viruses from a previous process is not something that was considered previously. Today, you’re not just mitigating against whatever environmental virus gets floated into a room when people walk through; you are actually manufacturing viral vectors in the billions. How to design a facility around controlling this viral vector load is worth understanding in detail. Consider:
• How are you ensuring that the vectors you’re working with don’t escape equipment into the environment?
• Have equipment manufacturers given you enough specification data to know if you’re exposed to a potential problem?
• How are you ensuring that you’re mitigating any possible escape of material with room design and decontamination procedures?
Your facility should have a strict cGMP flow design because of uncertainty around the containment of manufacturing processes. There are specific design criteria and equipment that engineers can recommend to mitigate risk, on a case-by-case basis.
Careful upfront planning, including modeling flows for further optimization, determining decontamination procedures to mitigate vector exfiltration, and understanding all available equipment and design options are critical.
Vector technology expansion projects leverage a lot from the mAb space. People often think that because the technology looks familiar, the demands are the same. Consequently, they underestimate the square footage required for a multiproduct high-throughput facility.
If you’re starting with a facility that was designed around a throughput for a single product and now is being retrofitted for a range of products, ask yourself: What is the anticipated production requirement for every product? And, do we have the square footage to accommodate the equipment itself?
Often, companies can campaign between product lines throughout the year. In other cases, they may need multiple rooms because production requirements make sharing rooms impossible. As production expands, even more square footage is needed for required segregations.
Now that you’re producing viral vectors, how do you ensure that they aren’t spreading throughout your facility? Some process steps create the opportunity for particle aerosolization. You must ensure those aerosolized particles aren’t free floating through your HVAC system into adjacent spaces.
How does your design accommodate appropriate levels of air changes per hour? Which rooms do you zone together, and which are single pass? How do you handle pressurization considerations to maintain boundaries for where viral vectors are manufactured and contained? There are experts for whom these questions are more commonplace and the answers more nuanced. Ask these and every other possible question .
We might see facility flows, base efficiency and airflow controls become better understood in the future, as viral vector technology is improved. For now, understanding the basics of these design considerations will allow you to properly set up your facility to take on your new lines of viral vector business.