By Wayne Koberstein, Contributing Editor
The Strategic Use of Cutting-Edge Suppliers in Early Drug Characterization and Development
Years ago, the subhead for this piece would have made little or no sense to me. For one, I would not have thought the words “strategic, characterization, and development” belonged together. And how suppliers entered the picture, especially on the “cutting edge,” would not have been obvious. Then, there’s the title. Smart Sourcing? The Outset of What? Today it all seems almost too obvious, even though companies still struggle with applying the concept: Corporate strategy and product strategy must begin with the very definition of a product as a molecule worthy of scale-up and production, continuing through process development and beyond. When companies don’t have the in-house resources to characterize and refine truly novel compounds, they must rely on suppliers who do.
More recently, I have had an education, thanks to my assignments for Life Science Leader. In particular, two conferences I covered for the magazine — the USP Biologics Standards Seminar and the AAPS National Biotechnology Conference — impressed me with the strategic importance of purity and potency in novel molecules. Those qualities affect safety and efficacy, of course.
But there are so many other characteristics of strategic importance that constitute or surpass them: pharmacokinetics, immunogenicity, bioavailability, delivery, stability, aggregation, fill-finish, and more. Such factors can have enormous effects on the strategic viability of the product in preclinical and clinical trials, manufacturing at all scales, reimbursement, regulation, and potentially medical practice. Again, once stated, the proposition sounds perfectly self-evident, but I have the feeling many companies and executives still find it difficult to assimilate such thinking into their strategic plans.
This is not a pitch for outsourcing, however. It is reinforcement for anyone who has yet to embrace the idea of early, painstaking characterization — using the most well-equipped and innovative suppliers as needed to put your product and company on sound strategic footing. That means, before all else, recruiting the right talent and expertise into the company to separate the supplier wheat from the chaff. The COO and CSO should work together to guide internal managers through selection, setup, and ongoing relations with the external party. That expertise should include advanced knowledge of new technologies, standards, assays, processes, and other components of drug characterization and early development.
Getting those experts is an investment, admittedly, and investors seldom place much value on the early stages of compound development, especially related to manufacturing. It follows that the investment must be carefully justified at the conception of the company and development project and fortified as much as possible with an IP strategy. One model that covers both of those bases is a codevelopment partnership of company and supplier. As the two parties work together to develop assays, processes, and compositions unique to the product, the company may retain the resulting IP as an asset in its valuation. Meanwhile, the supplier may improve its capabilities, and thus its business generally.
Insight From Recent Conferences
So far, I am only using logic to support my thesis, so I have not yet transgressed my outsider status in the outsourcing field. My reasoning is also grounded, however, in some of the examples I encountered at the aforementioned events. Given the general themes, most concerned biologic molecules, but with the oft-heard refrain that the lessons apply to many new small molecules as well.
USP’s event centered on standards, yet it was clear the real driver of change in early development is technology. In simple terms, we can test new compounds in ever more sophisticated and accurate ways and increase our understanding of how purity vectors and potency attributes interact. The hunt for biosimilars has fostered recognition of “attributes and combinatorics” such as deamidation, methionine oxidation, glycation, high mannose fucosylation, sialylation, and so on. “Each term represents almost endless permutations adding to the complex challenge of characterizing large biomolecules and comparing one to another,” I said in my report on the event.
The AAPS conference included testimonials from companies and suppliers on the relationships between parameters such as concentration, charge interaction, viscosity, and aggregation — and their influence on everything from patient immune response to injectable needle size.
Bernard Helk of Novartis reported on the company’s use of spatial aggregation propensity (SAP) technology, molecular simulations that predict formulation characteristics that can aid the screening and stabilization of biological therapeutic candidates. Other speakers, from a full range of company types and sizes, described using various new tools to analyze new molecules for potential toxicity, immunity effects, stability, comparability, fill-finish issues, and many other key attributes that can guide optimization.
This is an experience I believe all pharma/biopharma company executives should have. Go to a USP or AAPS event or any other one that you think might be technically over your head or if not that, too technical to suit your lofty strategic concerns. Now, I’m sure I’m talking to a very small crowd here and that most of our readers are much too sophisticated to need so didactic an exercise. Still, you might consider doing it anyway, no matter how hip you think you are. There is a value to walking on the street as compared to just imagining it. Everything moves much faster, and changes come with every step. You may well leave with a deeper understanding of why early development is critically important, and thus better prepared to justify investing in it.
The Importance Of Supplier Choice
Back to suppliers. The ones you are looking for have applied original, scientifically validated insights to solving the problems you will face as you optimize your compound before sending it off into the real world of development and manufacturing. Again, sounds obvious, right? Well, this is where it gets difficult, because now you must do your homework, putting your company’s time, expertise, and money on the line. And I can’t help you there. I can just say this as you begin the journey: Make it a strategic exercise with the same priority as the design of a Phase 3 trial — which, of course, is a whole other subject.
Although some CMOs are certainly on the cutting edge of early development technology, not all such suppliers think of themselves as CMOs — or even as suppliers. Many regard themselves as biotech companies developing platforms or helping others develop products with those platforms. Others are academics, if particularly active ones. The SAP system used by Novartis came out of MIT. And the Novartis example also shows how the need for cutting-edge suppliers in this space is not confined to small startups. Large companies, at best playing catch-up in the manufacturing game, also have strategic reasons to find, select, and use them for maximum advantage.