Quotient Sciences’ Alnwick, UK, facility employs over 200 people across a range of scientific disciplines, including process chemistry, solid-state characterization, and radiosynthesis, to support the development and manufacture of drug substance programs at the site. Over the past 2 years, the Alnwick site’s workforce has grown by 20%, which was fueled most recently by the completion of a major £6 million expansion of our drug substance manufacturing facility that created an additional 80–100 new scientific and technical jobs.
In our latest article, we interview Max Critchlow, a Process Development Chemist on the Drug Substance team at the Alnwick site, to give those interested in exploring a role in the drug substance space some insight into a typical day in the life of a PR&D chemist at Quotient Sciences.
What is your background in chemistry?
I studied chemistry at Bangor University in Wales, where I graduated with an MChem degree in 2020. Following my undergraduate degree, I began a PhD investigating direct enzyme prodrug therapy at XJTLU in September 2020. XJTLU is a leading international joint venture university in China, based on a partnership between Xi'an Jiaotong University and the University of Liverpool. Unfortunately, given the COVID-19 pandemic and travel restrictions, after 5 months of desk-based research, I had to stop my PhD. This led me to consider other options, the first being a laboratory technician role within a local school in 2021. During this time, I was able to think about my next move with regards to my chemistry career. During the school summer holiday, I was able to investigate various contract drug development and manufacturing organizations (CDMOs) and contract research organizations (CROs), as well as investigating an alternative PhD possibility. It was at this point I discovered Quotient Sciences’ Alnwick site.
What is your role at Quotient Sciences?
I began my career at Quotient Sciences’ Alnwick site in September 2021 as a Process Development Chemist within the Drug Substance department. My team is comprised of Process Development Chemists and Senior Process Development Chemists, in which we all report to a Process Chemistry Team Leader and the Head of Process Research and Development. We get additional support from our Laboratory Technician, who works closely with the team to ensure things run smoothly on a day-to-day basis.
Within my role as a Process Development Chemist, I primarily design and execute synthetic routes to target molecules, with a clear emphasis on developing safe, compliant, scalable, and economically viable processes for the downstream manufacture of intermediates and, ultimately, active pharmaceutical ingredients (APIs).
My responsibilities outside of the lab consist of typical desk-based work, such as maintaining laboratory notebooks and creating summary reports. I also present written and oral updates on project progress to clients and my colleagues.
What does a typical day at Quotient Sciences look like for you?
As I’m currently working a 4-day schedule, I usually arrive to work fairly early between 07:00 and 07:30. This is something offered by Quotient Sciences’ Alnwick site as a flexible work option.
I start my day by checking my emails, notifications, and meetings for the day. I usually run my analysis, such as high-performance liquid chromatography (HPLC), overnight as it’s automated, so I spend time in the morning reviewing this data from my desk. I then head into the lab to either sample or work up a reaction from the day before, and also set up a new experiment I have planned for that day. Once the whole team has arrived at site, we hold a quick meeting to touch base and raise any issues that have been encountered.
In addition to my lab work, I usually have various meetings throughout the day. This might include a Drug Substance team meeting, which typically involves a technical discussion on a particular project presented by the project chemists, a health and safety update, a briefing on the group/site and overall business performance, along with a general discussion of any other business. However, no two days are the same, and my role is ever changing with interesting new challenges each day. The one thing that stays consistent is the time I have my coffee and second breakfast! As PR&D chemists, we’re able to plan our time to what best suits us to get the relevant work done. This gives us the freedom and flexibility to perform our best work.
What typical challenges do you come across in your role, and how do you overcome them?
The main challenge within my role, and shared across the whole PR&D community, is the need to develop a synthesis and process that not only affords high-yielding and high-purity chemistry, but also avoid using traditional, small-scale organic synthetic techniques that are not suitable for scale-up.
For example, concentrating solutions to dryness is almost impossible to achieve on plant scale, where the vessels are fixed to the floor. Instead, distillation is commonly used to concentrate solutions, but there is a limit to the amount of solvent that can be removed. Usually, concentrating to dryness is for one of two purposes, to isolate your product or to swap to a different solvent. For the former, being able to crystallize your product is a huge advantage and will allow you to filter your drug substance relatively easily. For the latter, taking advantage of solvent azeotropes or a series of distillations can be used to swap from one solvent to the other without the need to go to complete dryness.
Column chromatography, which is a fundamental purification method, is almost entirely avoided when scaling up. It typically uses large quantities of solvent to purify modest amounts of material and requires a large quantity of solid support (silica gel), among other issues. In order to get around this, being able to crystallize your product is again the best option. This not only allows for simpler isolation, but crystallizations in the optimal solvent systems can realize high-purity drug substance, even for upgrading chiral purity in some instances.
Stability is also an important consideration. As we begin to scale up, the processing time of the reactions increases significantly, and understanding the representative holding points and stability of the reaction mixtures is vitally important.
Finally, it’s of paramount importance that before any large-scale process is undertaken, not only are the general chemical hazards assessed but also their inherent thermodynamic properties and reactivity are fully evaluated. With regards to general chemical hazards, reagent screening and route selection alternatives are considered to identify if certain high-potency, high-toxicity reagents or intermediates can be replaced with safer alternatives. With regards to thermochemical hazards, given that the cooling of a reaction vessel becomes less efficient as we increase scale due to the change in surface area-to-volume ratio, understanding the thermodynamics of the chemicals and reagents involved in these typically exothermic reactions is of upmost importance to avoid a thermal runaway and thus loss of containment.
What do you enjoy most about being a PR&D chemist at Quotient Sciences?
Overall, being a PR&D chemist involves facing new issues every day, which can be challenging but also satisfying, especially when I solve a problem. As a chemist at the forefront of PR&D, having a direct impact on the development of novel drug substances as APIs is very rewarding. I’m pleased that my work contributes to the company’s overall mission to develop new molecules fast.
In my role, there is also the opportunity to discover new chemistry, not only confined to new reactions, but new techniques, equipment, and methods too. Furthermore, I find it fulfilling to present my research and findings to not only my colleagues internally, but also externally to customers. This gives me a sense of pride and ownership with my work, which I think is important. I also appreciate the ability to collaborate with not only chemists on my project and within my department, but also with colleagues in other departments across the business, such as the analytical and manufacturing teams. This provides an authentic feeling of unity.
I’m lucky to find myself within a team of colleagues who are a pleasure to work alongside. Everyone is supportive and maintains a really positive culture, which breeds confidence in my role and my future career development. This culture is consistent throughout the Alnwick site and makes for a brilliant atmosphere and energy. I feel this site and its energy is a product of the people within, something I’m proud to be part of.
What would your advice be to a chemistry student/graduate looking to start their career in the pharmaceutical industry?
It goes without saying, to establish yourself within the pharmaceutical industry and more specifically towards PR&D, it’s essential that you understand the basics and fundamentals of organic chemistry, as learnt in your degree. Within the PR&D team, we often set monthly synthesis/process problems in order to develop and improve our knowledge. You also need to appreciate the problem-solving nature of this industry and understand the challenges of scaling up chemistry.
Other ways to begin developing your career within the pharmaceutical industry would be to investigate opportunities to gain work experience, such as summer placements, and it’s likely that your university tutors may have contacts or knowledge of a given opportunity. In addition, a year in industry as part of your degree course is an excellent way to gain work experience. At the Alnwick site, we offer industrial placements for undergraduate chemistry students, which you can apply for in the autumn for the following academic year.
Furthermore, keeping up to date with pharmaceutical companies, CDMOs, and CROs, along with relevant publications, can be a great way to understand how these businesses operate and what novel solutions are implemented to some intricate and complex problems.
It’s also worth investigating other areas of chemistry outside of PR&D. The pharmaceutical industry provides a huge variety of job opportunities for chemists in areas such as analytical sciences, formulation development, solid-state chemistry, and clinical or commercial manufacturing, to name just a few.