Informatics
Similarities and differences between small molecule and biologics drug discovery Both small molecule and biologics drug discovery share the fundamental cycle of design > make > test > analyse and report, and back to the next round of design. An informatics system to support either type should include the same core software appli- cations, comprised of data-capture applications, including an ELN and associated applications for compound and experiment design, a registration system for entity management and intellectual property (IP) protection, and laboratory instru- ment management and compound/consumable inventory application(s) to manage and support experimental execution. These are complemented by data management, analysis and visualisation applications such as an assay data management system for managing screening data and first-line analysis, and an analysis and visualisation applica- tion for in-depth analysis and interpretation of the data. Tying everything together should be an appli- cation to search and browse the current project sta- tus and data. Accessory software applications include tools for drawing and representing scientif- ic entities on users’ interfaces and in databases, tools for workflow management, and scientific plug-ins to non-scientific productivity applications such as Microsoft Office apps. When selecting the elements of an informatics system, it is critical to ensure that the elements can support the type of discovery being performed. In the case of entity registration systems, these have traditionally been distinct for small molecules and biologics because the nature of the entities themselves are so promi- nent in how the applications function and the underlying workflows differ due to the need to understand the lineage as part of determining the uniqueness of a biologic, compared with just knowing the structure for a small molecule. Conversely, assay data management systems often support both types of drug discovery, because the nature of the screening data may be less dependent on entity type and therefore a single system might work well in both cases. While the overarching processes involved in
small molecule and biologics discovery are similar, there are significant differences in operational details that impact the selection and implementa- tion of an informatics environment. First and fore- most, the nature of biologics entities are different from small molecules, being larger (up to three or more orders of magnitude) and designed and syn- thesised in diverse ways, which often involves live animals from which the initial creation of the can-
Drug Discovery World Spring 2018
didate biologic is not fully controllable in the way that synthetic chemistry allows. Even when the syn- thesis of biologic compounds is done artificially, it is usually a much more complicated process than for small molecules. Therefore, for small molecule discovery the chemical structure of the candidate(s) and related structures are essentially the entirety of the IP, in biologics the process by which the candi- date compound(s) are created also form part of the IP because they represent information about how to generate the compound(s) reproducibly. An infor- matics system for IP registration and protection must accommodate this distinction. Another key consideration is recognising that
comparing small molecules and biologics in the way the industry and informatics vendors support it is problematic. Small molecules represent a homoge- nous class of organic compounds of very similar size and composition, the synthesis of which occurs when two or more precursor molecules of the same class are combined in a reaction to create the target molecule. This means that informatics systems designed to support small molecules can be made very specific to deal with this type of entity. Biologics on the other hand represent a heteroge- nous class of compounds that can vary greatly in size, structure and composition. Learning from small molecule discovery, it is important to view each major class of biologics (ie antibodies, small peptides, vaccines, etc) as a class in its own right and develop informatics systems that can specifical- ly handle whichever entity type(s) are the focus of the discovery programme. Informatics vendors must support this approach as well. Biologics drug discovery occurs in two primary
organisational configurations. The first is organi- sations that are solely focused on biologics, often a single biologic entity type. While there are some long-established biologics-only companies, many are relatively young, small and often in start-up mode. The second organisation type is where an established small molecule drug discovery compa- ny has moved into developing biologics, or plans to do so. Although the desired endpoint may be similar in both cases, the trajectory for acquiring a biologics informatics environment in these two cases typically differs significantly. As noted above, biologics-only companies often need to replace a paper-based system, or one which is a non-scientif- ic, electronic system, such as Excel, PowerPoint and SharePoint. In this case the choices will focus on whether to implement a system iteratively, piece by piece, or take a more strategic view and create a vision for the end goal and develop a plan to get there (which can be done incrementally). In our
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