In the recent decade, the biotech manufacturing industry has evolved in fascinating ways. Cell and gene therapies are on the precipice of altering human life as we know it, potentially curing disease and extending lives. As we navigate this changing landscape, let’s talk about a topic that's critical and deserves our attention: preventing viral cross-contamination in multi-product facilities. The last thing any organization wants is to compromise the integrity of their products, not just because of the financial implications but more importantly, because of the potential impact on patient safety.
How Does Cross-Contamination Happen and Why is Preventing it So Important?
Viral vector therapies use a modified virus to carry genetic material into the cell. The virus is engineered to be safe and only serves as a delivery vehicle. When a viral cross-contamination event occurs, it means that viral particles from one product or batch have inadvertently been introduced into another, different product, or batch. Perhaps someone didn’t gown from one area to another appropriately and carried material with them. Or maybe shared equipment traveled between rooms without proper disinfection. However it may occur, it is a serious issue that can compromise the integrity, safety, and efficacy of the therapies being produced, and even shut down a facility all together.
In this blog we will only be discussing prevention controls. Generally, a holistic approach to avoiding cross-contamination events includes detection and removal strategies as well, so be sure to consider those.
1. Facility Layout: Segregation of Work Areas
Different viral vectors should never share the same workspace. Moreover, it is never a good idea to manufacture non-viral vector therapies in the same cleanrooms as viral vector therapies. Cross-contamination can occur even through airborne particles. This means airlocks, pressure differentials, and air supply extraction systems must all be functioning as expected. All individuals who will be accessing the cleanrooms, viral or non-viral, should be trained in the expectations for movement, disinfection, and handling of materials and waste. They should also be aware of what alarms they may encounter should any airlock or air pressure controls not be working properly. Review your procedures on these activities and make sure there is no ambiguity. There can be no shortcuts taken, so it is of the utmost importance that individuals not only have what they need to follow procedures, but also communicate when they do not. Attention activators, such as bright colored labeling and signage, will help serve as reminders of the right behaviors when navigating the facility.
2. Personal Protective Equipment (PPE): Gowning, Degowning, and Everything in Between
As we know, PPE acts as a physical barrier between us and the process. For those involved in viral vector manufacturing, the PPE is like a second skin. Traversing to different areas throughout the facility, such as shared material airlocks or hallways, can lead to the transfer of viral material. Best practice is to discard viral PPE in a designated area, and used gowning should never be brought into and left in the restroom or locker room areas. Some facilities may consider additional controls upon completing a shift, which may include having staff shower upon exit. Different style gowning or colored gowning for viral vector operators can also help in controlling movement and behaviors.
3. Rigorous Cleaning and Sterilization Processes: Consider the Flow
Any facility that manufactures viral vector therapies should perform a thorough risk assessment to develop a cleaning strategy that considers all the routes and sources of cross-contamination. The four typical pathways are mix-ups, retention, airborne, and mechanical transfer. Cleaning and sanitization procedures should be followed to the letter, and any concerns should be escalated. Even a small lapse in cleaning can be a potential source of cross-contamination. It is important to be mindful of the order in which cleanrooms and other areas are cleaned. For example, if a facility has both non-viral and viral manufacturing areas, cleaning should never start in viral areas and end in non-viral. This will increase the risk of spreading or transferring viral material from one location to another.
4. Regular Walkthroughs & Audits: Ensure Training Effectiveness
After individuals are trained in contamination control strategies and expected behaviors, organizations must conduct regular internal audits to ensure compliance. Even if the best procedures are written, they are useless if they are not followed. According to a study published in the European Journal of Social Psychology, it takes an average of 66 days to form a new habit, whether good or bad. However, the range can vary widely from 18 to 254 days depending on the individual and the complexity of the habit. Bad habits can form surprisingly quickly, often due to the brain's natural tendency to seek out shortcuts or easier ways of doing things. If walkthroughs or formal audits are not happening regularly, new behavioral norms that differ from the standard can be created, leading to a higher likelihood of contamination events. Coaching and correcting should be done in an empathetic and helpful way. Pointing fingers or applying blame will only exacerbate any engrained issues. By fostering an environment where learning and improving is celebrated, individuals will be happy to help one another and escalate concerns.
Preventing cross-contamination in facilities where viral vector manufacturing takes place is everyone's responsibility. It's not just about following procedures; it's about cultivating a culture of excellence and attention to detail. Lives depend on the quality of our products!
Sarah Boynton, a Consultant on the Quality Executive Partners team, has extensive experience in the biopharmaceutical/cell and gene therapy space, with a particular focus on cGMP training, human performance/error prevention, downstream processing, and non-conformance investigations. Prior to joining QxP, Sarah worked for Catalent Pharma Solutions, KBI Biopharma, AstraZeneca, MedImmune, and GlaxoSmithKline.
Check out Sarah’s recent blog: “6 Ways To Achieve Manufacturing Audit And Inspection Readiness.”