Pharmaceutical researchers feel real pressure to increase their R&D productivity by ‘doing more with less’. Despite having limited internal resources and specialized expertise, discovery chemistry research labs are expected to be increasingly effective and efficient, and deliver drug targets faster to advance projects rapidly. However, a lack of effective tools and technologies results in low efficiency workflows, with slow and laborious lead generation and optimization as a result. To boost productivity, the iterative cycle of design-make-test-analyze (DMTA) must move to a ‘best-practices’ state to become faster, more predictable and less time-consuming. A key factor is availability of reliable purification systems from dependable vendors.
Zeroing in on the problem
As we have seen from our interviews, the most prominent activities in the discovery chemist’s working day are synthesis and purification, both of which are included in the make (or M) portion of the DMTA cycle. Synthesis and purification are regarded as the most challenging aspects of their work. Since chemists spend most of their time performing synthesis and purification, one might assume they enjoy these activities. In fact, chemists feel that making novel compounds is the most satisfying part of their job. On the other hand, while purifying the molecules is the most critical aspect of their work, this step is regarded as time consuming and the least popular part of the working day. The take-away message here is that chemists cannot afford to spend the majority of their time and energy purifying target molecules as this slows down the discovery chemistry process.
Driving forward a step change in the chemistry process
What does it take to achieve this step change in the purification process? When I worked in a high-throughput synthesis environment in pharmaceutical research I saw that it was essential that all the compounds in any given compound library were purified to high purity (and recovery) standards to ensure reliability in the in vitro biological screens. In contrast, my experience in contract research showed me that purifying compounds quickly and reliably meant meeting demanding client timelines, securing my firm’s ability to invoice for services (having a direct impact to their profitability), and having satisfied clients who could then advance their compounds towards in vitro or in vivo biological testing.
High vendor quality is everything
The question is, how could the purification step be accelerated in discovery chemistry and made simpler to ensure more predictable outcomes? If this were possible then target compounds could be delivered more rapidly and reliably to help drive drug discovery projects faster. In addition, discovery chemists would find purification to be less of a challenge and not dread it as they do.
I saw that accelerating purification in the pharma and CRO environments means 1) having high quality automated systems that 2) incorporate intelligent software developed for purpose (by vendors with experts and application chemists who understood my needs), and 3) are supplied by a responsible vendor that backs its products and cares about my productivity as a scientist and satisfaction as a customer. Specifically, the vendor of choice is responsive and has a service organization that I know I can trust to be there when I need them, every time.
Like many, I have experienced the pain of time- and product loss due to problems with vendors. One experience comes to mind with a particular vendor that causes my blood to boil to this day. First, the system’s software, developed in conjunction with spectroscopists instead of chromatographers, had valve-switching timing that wasted 30% of the sample during every run. The vendor was completely unresponsive to service requests. After much discussion, the service manager finally said to me “Ok, so we screwed up, what can I do now to make this right by you?” Without hesitation I uttered, “Well, I’m done trying to get the equipment to perform as advertised and you have clearly complete disregard for my work. I expect a full refund and for you to come take the systems away now, hopefully before I push them off the lab bench.”
Another traumatic experience was with a consumables vendor sold highly discounted columns that failed, resulting in loss of precious compounds. Fearing that our methods were the cause of the problem, I tried unsuccessfully to discuss the issue with an applications chemist but was always referred to the sales organization.
How to choose a vendor that will give you confidence to commit
Having had these very process-impacting experiences, I was really motivated to make changes in my decision-making. I became extremely selective in my choice of vendor, which enabled me to achieve a high level of reliability in my purifications. Only then did my process improve markedly. This gave me the confidence I needed to commit to compound delivery dates and know that I could meet the requirements for purity and recovery that my organization expected.
So, how do I know I will get the confidence I need from a prospective supplier? It is easy enough to get the answers from them I need by asking the right questions. First, I find out the extent of QC procedures they have in place in manufacturing of both equipment and consumables. I then ask about how they support their products, i.e. what is the extent of their warranty and how are systems serviced. Specifically, I want to know how (and with what timing) a service engineer is deployed and how they know I am satisfied with the support. An important thing to note here is whether they even have their own service team or is this function outsourced.
I also find out who is the best contact for discussing applications, or product development. Vendors that have quality control processes in place love to talk about them and generally have documentation on hand. I have found that vendors that are concerned about producing quality products stand behind them with solid warrantees and have formal processes in place to handle issues with product defects. Vendors that care about the customer experience are responsive and provide a mechanism to reach technical and expert support. Such vendors know their customers expect immediate response with technical support and full applications, and even training services. In fact, vendors that know they fulfill customer expectations will readily share testimonials and have client references available to contact directly for referral.
Having reliable purification systems sourced from dependable vendors can certainly boost discovery efforts. In the next article in this series we will look more into how Biotage measures customer expectations in order to build confidence in our products.