Reducing drug development risks & timeline delays: An Integrated Bioanalytical & Pharmacokinetics (PK) Strategy
Delivering an effective integrated bioanalytical and pharmacokinetics (PK) strategy – in even the most challenging of circumstances.
Stuart McDougall, VP of Bioanalytical Services, Quotient Sciences, has been in this business since 1988. Here, he discusses the evolution of the company and how it has overcome the challenges thrown up by the Covid-19 pandemic.
As it stands today, bioanalytical departments or companies offering bioanalytical services, such as contract research organizations (CRO’s) are often separate from pharmacokinetic (PK) departments or companies that offer PK services. These industry silos create inefficiencies and time delays in getting data analyzed, resulting in slower decision-making in drug development. Being able to integrate bioanalysis (the sample analysis) and pharmacokinetic analysis (the data analysis and interpretation) under a single organization simplifies and streamlines the drug development process and accelerates timelines.
Q: What is your background in this sector?
A: I’ve been working in the pharmaceutical industry since 1988. Quotient’s Alnwick facility was part of Sterling Winthrop when I joined, which then became a Sanofi R&D site. My first job was in drug metabolism and pharmacokinetics, mainly working with radiolabelled drugs.
I then led the bioanalytical services group for over five years, and when a global CRO purchased this site in 2011, I remained in the same discipline but was also part of their bioanalytical services executive group. When Arcinova was formed in 2016, we massively increased headcount and there was a lot of investment in new mass spectrometers. We significantly grew as an organisation, I think it was nearly a five-fold increase in growth over five years and will continue to grow in both headcount and capacity now as Quotient Sciences.
Q: What are the components of a successful bioanalytical and pharmacokinetics strategy?
A: An essential piece of information from a clinical trial is the pharmacokinetic data, that’s where you make the decisions on drug absorption and exposure. But you only make the pharmacokinetic decisions if you have concentration data, and concentration data comes from the plasma blood samples from the patient. So, it’s that ‘bedside to bench’ part that we look after. And then our in-house pharmacokinetic experts take that data and interpret that into what it means for the drug.
Q: How does an integrated strategy help clients move from one stage of development to another (E.g. candidate selection to preclinical, preclinical to clinical, FIH to POC)?
A: You really need to understand what your customer’s needs are, and to understand what stage of drug development they are at. At Quotient, we have a very science-rich culture with a significant amount of knowledge in drug development, and we work with our clients in collaboration. We possess a dedicated method development team, most being PhD level, with more than 100 years of experience, who have developed over 400 bespoke mass spectrometry-based assays. They employ great science and agility to solve problems in order to arrive at a quality assay that achieves the exposure data for your drug, whether it’s supporting a preclinical or clinical study.
Speed is everything when it comes to developing our client’s drug programs. It’s part of Quotient Sciences’ manifesto: “Molecule to Cure. Fast.” If we can accelerate drug development, then that’s positive for patients, customers, as well as humanity in the broadest sense, obviously.
Q: Why are such strategies important for reducing risks and delays in drug development?
A: The attrition rate from non-clinical development into a registered drug is high, with typically, less than one in 250 molecules that will make it through the process
By integrating bioanalysis and pk analysis we are able to provide customers with a well-rounded view of their molecule’s behavior and provide them with critical data that will allow them to make informed decisions going toward their next milestone. This robust data package aids in developing biopharmaceutics strategies to optimize the chances of success of your molecule in the clinic.
Q: How has a bioanalytical capability helped Quotient Sciences reduce delays and streamline drug development?
A: Quotient was already a drug development accelerator, and their Translational Pharmaceutics™ platform allows clients to quickly develop, manufacture and test new dosage forms in clinical trials.
By adding bioanalysis to the already integrated clinical pharmacology and pharmaceutical development capabilities, we can seamlessly bridge from the clinic, through sample analysis, sample management and logistics all the way to data arriving at the pharmacokinetics team. And because we’re all part of one organization, a lot of those points can be very slick.
This ensures the right samples are collected at the bedside, then processed the right way. The samples are then shipped up with speed to the bioanalytical facility. Samples are then rapidly analyzed in an accelerated timeline. We will go through a single ascending dose (SAD) cohort in less than three days from point of receipt, to the day the audited data is sent to our pharmacokinetics (PK) experts, so they can then do the PK processing, and then feed back to the clinic with the exposure data and the safety data. It’s that speed of looking at the data, and then moving on to the next stage that’s incredibly beneficial to our customers.
Q: How have your customers reacted to broader service offerings?
A: Generally, it’s been a very positive reaction from our customers. We’re breaking down the traditional, inefficient siloes in industry. Customers are wanting to outsource more and are looking for a trusted partner who can seamlessly move them through stages of development. We are able to assist them by providing multi-disciplinary guidance and recommendations that span bioanalysis, drug metabolism & pharmacokinetics, clinical pharmacology, formulation development and product manufacturing all at one organization.
An ideal bioanalytical team would disappear into the background, only looking after the mechanics from bedside to bench. The people that are ‘on point’ are the pharmacokinetic team. We are active contributors across the lifecycle of the program, collaborating with our in-house clinical and development teams to ensure the best outcome for the product, the customer and the patient.
Q: How do you take risk out of the process?
A: For Quotient Sciences, it is literally that synergy between the clinic to the lab. Everything takes place at one organization, from sample management, to sample logistics, to discrepancy resolution. This offering takes a lot of uncertainty out of it, which in turn takes a lot of risk out of the client’s process.
I’ve been discussing internally how to streamline the process even more by using 2D barcoding, where the barcode is attached to the bottom of the sample tube. We then could design the whole process from beginning to end, including the data flow.
I’ve worked with a multitude of clients around the world – and they’ve shared that this hasn’t been done yet at any of the organizations that they’ve worked with. If we’re doing all those things internally at Quotient, we can use a 2D barcode process, and it would streamline the process for our customers and give them a clear sightline to where all their samples are. That’s the front end.
The next part of the process is the data that comes from the bioanalytical lab. The information that comes from the lab is essentially a concentration of data, nanograms per mL which are associated with a time point and a patient. The data goes to our in-house PK team in the format that they need, so that they can then bring it into their PK software, without any questions or discrepancies, or data interfacing problems. Since this takes place under one organization, we de-risk the possibility of any discrepancies or miscommunication because we’re now sending data back and forward between Quotient facilities and not to external organizations. That’s another synergy and a huge benefit to our customers.
Q: What about data transfer?
A: Every client has a very different way of delivering and accepting data. In Quotient, we have a data transfer agreement. We use a LIMS system for our bioanalytical services. This system allows us to use barcode scanning to check samples in, to easily track their chain of custody and allows us to send the data out quickly.
Q: How has Covid-19 affected Quotient Sciences’ business?
A: At Quotient, we have been very fortunate to have been able to sustain essential operations throughout the COVID-19 pandemic and support the continued progress of customer programs. Our internal teams have worked diligently to put in place procedures to ensure employee safety and awareness across all our global sites. Regarding our customers, many shared that they had experienced a slowdown with their patient trials as recruitment became more challenging.
Q: How does this affect business continuity?
A: Many of our clients are asking us about our business continuity plan for Covid. We implemented Covid procedures across all our global sites to help minimize exposure in the workplace and layer controls to reduce risk. These procedures have helped create a safe work environment for our colleagues, and support the continuity of business to ensure client projects continue to run smoothly.
Like every business, we had to work around various challenges, such as global shortages of PPE. Fortunately, we have been able to maintain of good supply chain and have a trusted set of suppliers that enabled us to source needed materials and continue supporting our customers’ programs without any downtime.