The Exchange: Colony Management Solutions

I am Anjli Venkateswaran and it is my pleasure to introduce Kristin Sapp, who will be joining me today. Kristin is the senior program director for the genetically modified animal program at the Biomere site in Worcester, Massachusetts. She holds a bachelor’s degree from the University of Massachusetts and a master’s degree from the University of Maryland Global Campus. With over 30 years of experience in the biopharma and CRO sectors, 18 of those years have been dedicated to animal markets.

Biomere is a preclinical CRO with locations in Worcester, Massachusetts; Richmond, California; and several sites in China. Their services include discovery, ADME, and GLP toxicology. More information about Biomere’s services can be found at www.biomere.com. We will be discussing colony management solutions at Biomere. 

Anjili: Welcome, Kristin. Could you provide a brief overview of Biomere’s Vivarium facility and your team? I know you have an amazing team, and I would love to learn more about the facility and the team you manage.

Kristin: It’s great to be here. As you mentioned, we are based in Worcester, Massachusetts. My team consists of 14 people, and we are responsible for all client breeding colonies. We have two facilities at Biomere: one is a complete shower-in clean barrier and the other is specific pathogen-free.

Anjili: When you refer to a “complete shower-in barrier,” is that for immunodeficient animals, or what kind of animals are housed in that facility? 

Kristin: The facility houses rodents. We all shower in to protect the health status of the animals. We are essentially “dirty” to them, so we take a physical shower, dress in facility clothes, and wear four gowns along with our PPE. All procedures are performed very cleanly. Animals are only opened under laminar flow hoods. The purpose is to protect the animals, whether they are immunocompromised or not.

Anjili: That’s very important because it doesn’t take much for something to go wrong in a vivarium. The stringent standards you have in place provide a lot of comfort to clients who have breeding populations at your facility. It sounds like you have a well-established facility and a team of 14 people, which is very impressive. Let’s discuss some of the technical capabilities you have been promoting, specifically reproductive assistance, which I think sounds very impressive. Many people may not be fully aware of these capabilities or their importance. So, could you tell me about the reproductive assistance capabilities at Biomere?

Kristin: Certainly. Many of our strains come from commercial vendors and are very clean. However, a lot of our clients want to bring in animals from academia, which may not have shower-in facilities. These animals might be considered “dirty” or have some pathogens. To clean them up so they can be housed in our facility, we perform embryology.

We offer IVF and traditional embryo transfer surgery. My team and I collect oocytes or embryos, clean them using media steps, and then surgically implant them into pseudo-pregnant females that are clean and inside our breeding barrier. Three weeks later, they give birth to clean pups, allowing our clients to start their studies with a fresh slate.

Anjili: And those would be the F0s?

Kristin: Yes, you could call them that. It is like restarting their colony. They would be considered F0 for all intents and purposes when they enter our facility.

Anjili: That makes sense. With your extensive experience, have you ever encountered a difficult-to-breed strain that required a tricky or challenging embryology protocol? 

Kristin: Yes, I’ve had some of those recently. Sometimes we get shipments of a small number of animals, perhaps just two, and you have to come up with creative solutions because you don’t want to use them all for IVF and then lose the animals. We’ve had instances where we breed them, but they aren’t breeding as expected. The original plan may have been for a classic embryo transfer, and we have to step back and think outside the box to get the animal model ready for our client as quickly as possible.

We have had scenarios where we’re breeding animals in isolation while also doing IVF and classic embryo transfer at the same time. We try everything we can to get the model ready for our clients and work with their timelines. We also recognize when the timeline has been extended because the animals are not reproductively behaving as we want them to. In these cases, we will do small pilot studies for the client while the animals are in isolation. It is a very difficult environment to work in, but my team is trained to perform various manipulations there.

Anjili: That’s amazing. Biology rarely behaves as planned. It is reassuring to know that you and your team are prepared for different eventualities and are trained to come up with a plan B or plan C. 

I have a question about the stringent protocols you mentioned, like showering and using PPE. For colonies that are maintained for some time, what kind of testing do you do to ensure they remain specific pathogen-free? What is the typical testing cadence?

Kristin: My group is responsible for all health monitoring and surveillance of all rodents in the entire facility. For any rodents that have been in the building for more than three months, my team will come in and do the sampling. We have moved to a media-based system where we mix dirty bedding with media per colony. We also take direct samples, such as fecal oral swabs and fur swabs. The type of sampling depends on the project’s size and location, but for the most part, every cage gets tested over a three-month span. We send out testing every three months, or every quarter, based on our pathogen exclusion list for each area.

When we bring animals from isolation, their vendor testing sometimes does not comply with our pathogen exclusion list. I work with the investigator and our veterinarians to get the animals into isolation, and they are tested when they arrive. They are released if they pass all the tests. If they do not pass, the investigator can decide if they want to proceed with the model, and if so, my team performs a derivation through embryo transfer. Our team has a hand in many of the rodent programs here because we are often called upon for health monitoring or to remedy a colony that does not pass the pathogen exclusion tests.

Anjili: This is so important. You can only use healthy animals that meet specifications in studies and get actionable data from them. It is easy to forget this when everything goes smoothly, but having a solid game plan for when things go wrong is crucial to avoid derailing a program or study.

Speaking of studies, one of the interesting things about Biomere is that it is a one-stop-shop for in vivo studies. Clients can outsource not only the animal management but also pharmacology and ADME programs. What are the advantages for clients who take advantage of this one-stop approach? Why would a company want to outsource both aspects to Biomere?

Kristin: From a colony management perspective, if a client brings a line in for us to breed, they get priority scheduling. We can’t control reproduction, so when a client needs a cohort of, for example, 15 homozygous females, and we only get 14, we can roll them into the study in a rolling admissions type of way. We don’t know exactly when they will be born. For a two-week-old neonatal study we are preparing for, for instance, if it has to start on day 12, then it has to start on day 12. We have to be flexible and stagger the cohort. We work with our clients because it’s important to us to use the animals from a 3R perspective and for our clients to get the data they need without delay.

Another advantage is that my team breeds the animals and knows how the model behaves, and we also do the studies. We do a lot of neonate studies inside our vivarium. This is easier because we don’t have to ship the dams out with the neonates, as they would not be able to return to the barrier once they are out. By doing the studies inside the breeding barrier, we can save the dams to use them for another litter, which adheres to the 3Rs. We are already in there, we know the model, and we can do the study there. It is a one-stop shop. We get the animals, do the study, and keep things moving.

Anjili: One thing that has always intrigued me is that when animals, especially dams with neonates, are shipped, they experience stress. Does this stress impact the studies?

Kristin: It always does. We always build in acclimation periods. This becomes difficult with neonatal study if you have to ship them outside of Biomere. Your protocol might require a minimum of 72 hours or even five days for acclimation. The animals will be stressed. It’s not to say that you cannot do it, as we do ship animals to clients domestically and internationally. However, it is better for the animals to stay in their home environment. This ensures consistency in their care and housing, which leads to consistency in your data.

Anjili: I completely agree. When you have the option to do everything in one place, you save time, save costs, and adhere to the 3R principles. This makes a lot of sense. Priority scheduling is also very important for biopharma clients because of the pressure to move fast and get data quickly for IND submissions or other milestones. Some safety studies can take a long time, and you might be waiting for data on long-term toxic effects. With the trend of outsourcing, people have to wait in line, and you don’t want to have to do that.

Kristin: That’s the good thing about having a colony with us; you don’t have to wait in line. We have a regular small animal team that does studies and my team also does studies, and between us, we get things done. We pull from both areas of expertise. If my team has a new procedure they haven’t done before, but the other team has, they will come in and do it for us. It is a very flexible collaboration, and we get what the client wants as soon as possible.

While I feel it is best to keep everything in one place, I want to point out that we regularly ship animals out domestically and internationally. We have many clients in the Boston and Cambridge area, and we have a courier that works Monday to Friday to bring animals and tissue collections to investigators on the same day. So, in addition to priority scheduling, you get your materials on the same day. I think that’s a big draw for our program and sets us above the rest.

Anjili: I think so too. The concept of flexibility is huge, and it’s a perfect segue into one of the challenges in drug discovery. I challenge anyone to show me a study design that is the same at the end as it was at the beginning. Study designs often change based on unexpected data. How does your group manage these changes efficiently?

Kristin: The team is very nimble, and I think it comes down to their attitude. They are all animal lovers and want to see the animals they care for used for the greater good. They understand that things change and take everything in stride. Managing a breeding colony is like “managed chaos” because you don’t know what you are going to get. So, you prepare for all the different possibilities.

I think that’s what sets my team apart. They are ready to do whatever is asked of them because they do it every day. I am in the vivarium at least three times a week. I walk in with a plan, but I usually only accomplish one of the things I set out to do because it is a constant process of talking, collaborating, and ensuring everything is going well, especially at the start of a study. It’s easy for us to be flexible because we want to be flexible for our clients. This isn’t just a cliche; we really care about what we do.

Anjili: It’s true. Flexibility is a good buzzword, but your team practices what they preach, and that is very important. Colony management is a long-term commitment that can last for months or even years. There is so much going on, including derivation, breeding, genotyping, and keeping the animals healthy to meet study requirements. I appreciate that your team is flexible and nimble, but how do biopharma clients get information about what is happening with their animals?

I ask because some clients’ animal models are so precious to them. They are putting a huge amount of trust in outsourcing their colony management and want to know everything that is going on. How is your team structured to interact with clients without giving too much or too little information?

Kristin: I built this team from the ground up in 2019. I used to be a Biomere client and ran a transgenic core, so I knew what I wanted as a client. Every client starts with me. I talk to them and we build their flexible statements of work based on what they plan to do. The statements of work are not cookie-cutter.

For consistency, clients are introduced to a project coordinator who is their first point of contact after the statement of work is set up. The project coordinator is their lifeline to their colony. I am usually on all the emails in the background so that I know what is going on and can be aware of what everybody is doing. I still go in there and breed and wean animals sometimes.

Clients tell us how they want to be updated. If they want us to manage everything and they are not “rodent people,” that’s fine. Each client has one project coordinator, even if they have multiple colonies. Beneath the project coordinator are one or two technicians, depending on the number of colonies. It is always the same technicians, as we do not use a rotation schedule. The project coordinators and technicians check the cages every day. We send clients inventories every week, two weeks, or month, based on their preference.

My team probably gets 20 to 50 emails a day from their clients. The volume of communication is due to the back-and-forth nature of breeding colonies. The way it’s set up is so that if someone calls me on the weekend with an issue, I or our project coordinator will know what they are talking about because we are physically in the cages every day.

Anjili: The fact that you were on the other side and understand the client’s perspective is a huge advantage. You can translate the client’s needs and likely have a solution ready because you’ve had the same questions yourself. This is a unique characteristic of Biomere.

On a related note, many vivariums use software solutions to manage their operations. I believe you use SoftMouse. How has SoftMouse helped you and your team?

Kristin: It has definitely helped. I brought it over from my old company. A Biomere technician, who is now a project coordinator, was my tech at the time as a client. She went to a conference and came back asking if we could get SoftMouse because it would make her life so much easier. It was a new program at the time, and we liked it so much that I brought it over to Biomere in 2019. A lot of our record-keeping was Excel-based, with thousands of animals on a spreadsheet, and it was too burdensome.

It was hard for some of the people who had been on the team for a long time to convert to it. But once they did, they wondered why they had been stuck with spreadsheets for so long. We were early adopters and picked up almost every module they have, and it has just gotten better. I still see the creators at conferences, and they know my first name. This shows the relationship we have built and the ideas we have shared with them to improve the software.

SoftMouse is an easy tool because it’s secure, and we can log in from any computer to see what happened on a weekend. I can run reports and pedigrees, and our genotyping data automatically uploads to it. This removes the need for manual data entry. It also keeps track of inventories. If a client asks how many cages we have, I can just pull it up and tell them. It’s a great tool that has made us more efficient and allows us to provide information to clients at our fingertips without any number crunching. I can send them a report within minutes, and people really like that. I have even had clients who use SoftMouse in their own vivariums, so they can upload our data in the same format.

Anjili: It seems to be a time saver, a cost saver, and it removes the potential for human error. In academic settings, it was easy to end up with unscheduled breeding or incorrect animals if Excel spreadsheets were not updated daily. These mistakes could delay studies and increase costs. I’m glad you brought it in early, as this is where the field is heading. The people who resisted the change eventually realize how much easier it is. With a QR scanner, you can just scan a cage, and the software makes the adjustments and prints a new cage card. Biomere wasn’t doing that five or six years ago, but they are now. This efficiency in time is a benefit to the client, as our technical hours are decreased.

Kristin: That’s a great point. For biopharma clients, it’s all about de-risking. The fact that they have a dedicated project coordinator builds trust. The team at Biomere becomes an extension of the client’s group, which is the best form of collaboration.

Anjili: We are running out of time, so thank you so much, Kristin, for sharing this information. It is wonderful to hear about your flexible, experienced, and dedicated colony management team. That dedication is key to continuous improvements and the adoption of technology to improve processes. Thank you for speaking with me, and to our viewers, if you’re interested in learning more, you can email BD@biomere.com or visit the website at www.biomere.com. 

Kristin: Thank you.