Completing construction of a cleanroom may seem like the end of a journey, but for many, it is just the beginning. Cleaning the area and maintaining that cleanliness requires a lot of effort and expertise, with whole teams of experts focused on environmental monitoring. Jessica Rayser is one such expert, who works as Global Product Manager for Charles River Laboratories.
Rayser manages Accugenix, which is the part of the business that specialises in microbial investigations to support environmental monitoring programmes and contamination investigations. "I make sure we have the right products and services to meet our customers' needs, which means I have to be an expert in pharmaceutical regulations and our technology," she explains.
To rise to such a role, Rayser had to have expertise in the microbiology that she would be overseeing. "I have a master's degree in cell biology and molecular genetics," she explains. "This gives me a deep understanding of Accugenix's processes for microbial identification, as well as the ability to evaluate new technology and potential applications in pharma."
Adoption of rapid methods is slow as pharma is reluctant to consider “viable but not culturable” organisms
This deep understanding and knowledge of microbiology really helps Rayser understand contamination control, testing workflows, and relate to the challenges that face her customers. "I still think people underestimate the importance of accurate microbial identification. There can be significant variability between methods and systems that impact accuracy, and that poses a challenge to risk assessments, contamination control, and operational decisions."
Rayser's background in molecular genetics means she is particularly positioned to evaluate the use of next-generation sequencing in pharmaceutical quality control applications.
"Next-generation sequencing (NGS) is often viewed as only for clinical applications or drug development, as it gives the ability to sequence whole genomes and microbial populations like the microbiome. But those capabilities could indeed play a role in the pharmaceutical QC lab, as the technology allows us to move away from cultivation."
Cultivation is a method that has its place in environmental monitoring, but using all the tools at one's disposal seems like the smart person's decision. "This could be a great tool for analysing flora in the manufacturing environment or water systems," Rayser suggests. "But I think adoption will be slow as pharma is reluctant to consider 'viable but not culturable' organisms. However, the technology could provide valuable information."
Get your crystal ball out
Like many who work with these tiny beings, Rayser is optimistic and excited about the potential of rapid microbial methods and the many benefits they may provide to those working in controlled environments. "There are some really interesting and creative technologies out there," she says.
The importance of pushing innovation in this area is compounded by new emerging markets that require them. "We're seeing a lot of growth in short shelf-life products and cell and gene therapy, all of which need those rapid methods."
Despite this excitement, Rayser echoes the concern of many, saying that the adoption rate has been very slow in pharma, as many companies seem hesitant to take on the validations. "However, I think the pace will increase as more and more precedents are set. The regulators are open and ready to approve these methods, as we see a push for 'modern methods' in Annex 1."
Strain typing isn’t utilised as often as it probably should
Rayser seems hesitantly enthusiastic for the 2020 EU Annex 1 draft and its revisions. She explains that there have been very real impacts revisions, which have certainly changed cleanroom operations around the world. "With the stricter standards, we're seeing an increase in the frequency of cleanroom validations, environmental monitoring, microbial identifications, and trending of data."
A fearless and innovative attitude is something Rayser doesn't just preach: "The best lesson I've learned in my career is to not be afraid of being uncomfortable," she says. "New opportunities and situations can feel scary and you may feel out of your element, but those experiences are necessary for learning and growth. Don't be afraid to ask questions or for help and be gracious to yourself!"
A bold position that displays Rayser's intrepid trait and reflects her specialist molecular genetics background is that environmental monitoring shouldn't stop at simple identification. "Another microbiological tool that isn't utilised as often as it probably should is strain typing," she puts forward. "This looks at strain-level differences between samples of the same species for contamination investigations to determine the root cause."
With the state of the pandemic as it is at the start of 2021, with mutations causing new strains left, right and centre, I am sure that even the layman can see that Rayser has a very valid point.
The virus that shall not be named
It would be impossible to talk to a microbiologist in 2021 and not discuss the virus that has consumed the world for close to a year; COVID-19. Rayser is brimming with tales about how the coronavirus has changed her daily work.
"The COVID-19 pandemic has created a whole new population of patients waiting for testing and treatment," Rayser says. She explains that Charles River used its technical expertise and resources to partner with many pharmaceutical companies in their COVID-19 effort. "We provided appropriate animal models, safety assessments for vaccine candidates, and microbiology QC support for rapid sterility testing and environmental monitoring - spanning the entire range of drug development."
We’ll look for ways to remove single-use plastics
Like many companies involved in essential work, Rayser talks about the balance with remote working. Work shifted to home as much as possible, but for microbiologists who need specific working conditions, this balance is key to ongoing operations. But for those who perform these services, the challenges do not stop here. "As a lab that provides critical services to pharmaceutical companies, we continue to strive to provide the best quality data with a fast turnaround time. However, we did experience staffing challenges as we tried to minimise COVID-19 risk to our technicians, allow for social distancing as much as possible, and maintain operations."
Not one to be a pessimist it seems though, Rayser says: "COVID has also challenged us to view our operations through a different perspective: how can we work more efficiently and effectively? How can we streamline our processes? The positive from this pandemic has been the way we've been forced to step back and re-evaluate and improve our processes, as well as the renewed camaraderie and care between employees."
On a personal note, Rayser talks about carving out a dedicated workspace with minimal distractions and setting boundaries for the work/life balance. These things were key in finding a good quality of life from the confines of the various lockdowns.
When one door closes
Aside from staffing issues, microbiological operations require many of the tools that have been in scarcity over the last year. Plastic consumables are one of the main shortages that Rayser says is an issue, particularly pipette tips that are integral to many operations. "With some of the reagent and consumable shortages we've had, I think we'll take a closer look at sustainability initiatives," she says. "We'll look for ways to remove single-use plastics from our manufacturing."
Taking the 'what doesn't kill you makes you stronger' approach, these shortages are being used to really drive home the sustainability message. Rayser looks back over recent years and sees there has certainly been a drive for companies to think outside the box. "We've broadened our view of what [sustainability] really looks like, from recycling programmes to alternative energies and conservation to all matters of waste reduction."
Speaking about pharmaceutical applications specifically, Rayser explains seeing people work to reduce hazardous chemicals and waste and consider the role of single-use consumables and systems. However, a measure that is almost uniquely applied to microbiologists is the adoption of LAL (Limulus amebocyte lysate) cartridges for endotoxin testing. The important chemical is sourced directly from the horseshoe crab, and this has a direct impact on the ecology of the oceans. Cartridges use significantly less LAL, and with synthetic options still not getting the full backing of regulatory agencies due to safety concerns, this is a great step in mitigating the impact.
Cartridges use significantly less LAL
The root cause of shortages is, ironically, also the root cause of increased demand. Borders and plants shutting, whilst the need for sterile environments skyrocketed exacerbated the problem. In Rayser's view, the increase in cleanroom uptake across all industries is not going anywhere. The mass vaccinations are not the be-all and end-all of the pandemic efforts. "We're already learning about the long-term side effects of COVID-19 and there will be more treatment needs in the future," she says.
With a pandemic that Rayser thinks will continue until the latter stages of 2021 and a continuing ageing population, she says that science has more of a need than ever for advancing treatments. "A trend which is really interesting is the increased collaboration between pharmaceutical companies as they all work towards the common goal of a COVID-19 treatment and vaccine," Rayser adds happily. "I will be curious to see how long the cooperation lasts, and if it will result in faster drug development and time to market."
