Musings of a Toxicologist
Safety Assessment
Ria Falvo, BSc, DABT

Musings of a Toxicologist

The daily lessons of a toxicologist are perpetual and transferable to the next "expedition"

The alarm clock is ticking its way ‘round to 6 am. Just seconds before, my hand drapes over and silences its tune. My eyes are already adjusting to the winter’s gray morning light because I’ve been awake for almost 45 boundless minutes. Eagerness, blended with conflicting notes of tension and tranquility, energize me to climb out of bed and start my day. It’s Tuesday, but not just any Tuesday. In four hours, I will be starting a new study; the first dose administration of a 26-week study. Six months of daily dosing, timed sample collections, coordination of sample shipments. What could go wrong?

I can’t help but wonder if every item was covered. Did I review and approve the dosing volumes for each animal? Yes. Did I review and approve the times for the toxicokinetic blood sample collections? Yes. Did I review the calculations for the preparation of the dosing formulations? Yes. Did I review the prestudy clinical observations, body weights, food consumption, and clinical pathology data to confirm the animals’ good health and suitability for the study? Yes. My study plan is signed and I have IACUC’s approval. Yes. Yes. Yes! I think the day will go well!

A Strange Formulation

It’s about two hours before the study begins. My morning routine is uninterrupted: my laptop is waking up and the emails are loading, documents in my mailbox are sorted out, and my cup is filled with aromatic, hot coffee. I double check that all the appropriate working sheets are signed for the study start and call up the Research Associate to confirm we are all set. Moments later, the Formulation department calls, probably to let me know the dosing formulations are ready. But no, quite the opposite! Following overnight stirring, the test item formulations amalgamated into lumps, imperturbably floating at the surface of the otherwise clear formulation. I rush down to the lab, suit up, and inundate the Team Leader with all the expected questions. The Certificate of Analysis, preparation instructions, and stability documents are studied again; all squared out. A suitable option is to homogenize the suspensions, but not without the Sponsor’s approval. An email is required to document their approval (or disapproval), but a phone call would be swifter. I call the Sponsor and explain the issue; they agree to call me back in a few minutes after confirming with their chemist. Each second feels like a minute as I stand by the phone. The approval comes through and the email follows. Once homogenized, the formulations are perfect suspensions and I am thrilled!

Lesson learned: Proactively think about potential challenges and solutions. This would also be a good conversation to have with your Formulation Specialist and Chemist before the first prep. They may think of possible issues within their experience and expertise. As an example, consider a scaled up pre-study trial preparation during the study’s setup period, if test item availability permits.

Same Difference?

I’m back in my office, sipping my now lukewarm coffee, but that is extraneous to the averted scene. It’s about an hour from the start of the dose administration. The hour is swiftly charged with addressing emails and writing a report. Fifteen minutes before the dosing start of this Day 1, I head to the animal room to confirm with the team all activities are ongoing or scheduled, the blood samples collection tubes are in order, and the dosing formulations are indeed homogenously stirring. The room is busy; there is the dosing technician and the animal handling technician at the front, another set of technicians responsible for the blood sample collections at the back, and the runner technician, who is picking up the first set of samples of the day. Also, there are the Research Associate orchestrating the activities, a Quality Assurance Auditor, and me. This “organized chaos” is the footsteps of outstanding work by the technical staff; it’s complicated and fast, buzzing yet calm. I stand back and appreciatively watch them at their best.

Just before the start of the dose administration process, one rat has to be replaced due to an inconsistent body weight. Connected with each individual rat are its dosing, blood sample, and sample processing worksheets, sample collection tubes, and previously-collected data, including body weight and food consumption measurements. Because each blood sample collection is timed against the dosing minute, there is merely 15 minutes to complete the replacement without disturbing the day’s scheduled activities. The Research Associate prepares the new worksheets and tubes, and enters the new animal’s identification number and body weight (for dose calculation purposes) in the automatic data capture system. I follow the Research Associate to document my verification. Presuming the body weight of the new rat is similar to the previous one, the dose volume calculation is made, but the number is suspiciously larger to me. It is quickly revealed this new rat is heavier, a potentially impactful amount that would use up more of the dosing formulation!

The Research Associate and I exclaimed the same transient moment of panic in synchronicity: was enough prepared? We take a few seconds to ground ourselves to process the facts: 1) the worst case scenario: an additional volume of the dosing formulation is prepared, but this is not optimal because all scheduled activities would require postponement; 2) verify the body weights of the remaining spare rats for a lighter one, but also not optimal as all is arranged for the currently-selected rat; and 3) sum up the group’s dosing volumes with the confidence that an overage volume was prepared as per standard procedure. The sum is calculated and, indeed, there is a sufficient volume in the jar. The dosing of the animals is subsequently completed faultlessly. A team effort with my oversight to ensure all aspects of the study were adhered to, including the Study Plan and regulations. Done!

Lesson learned: Never assume anything and always double-check everything. Although we work dependently, anything imperative and impactful to the study, including the precious welfare of our animals, should not be assumed as conducted or acceptable without your affirmation. And despite feeling paranoid (or being told you are; during my almost 20 years’ experience, I’ve embraced this as a proven quality), do take the opportunity to recheck whatever you feel is warranted. 

The rest of the day’s activities progress well. A message is relayed to the Sponsor informing them the formulations were homogenous and administered, the animals are well and monitored, and samples and data appropriately collected and recorded.

Indeed, it was a day challenged with encounters commanding our immediate and prudent actions, but it was reciprocated with eruditions for tomorrow. 

Reflecting on the eventful day with each sip of a pacifying Merlot, I am reminded that the daily lessons of a Toxicologist are perpetual and transferable to our next expedition.

Be in the moment. Be intentional. Be inspired. A good way to journey through each day.