Every drug development professional knows that bringing a new therapy to market is a high-stakes, complex, and highly regulated journey. Along the way, difficult and risky decisions must be made—each with the potential to impact cost, timelines, complexity, or even the ultimate success or failure of a project. There is no universal strategy that solves all challenges in this space. Instead, thoughtful, phase-appropriate decision-making is essential.
Contract Development and Manufacturing Organizations (CDMOs) play an important role here—as trusted partners, they help teams navigate the complex path to market and to increase development speed with agility and foresight.
CDMOs can support phase-appropriate choices by presenting realistic options for each stage. To simplify this, we like to frame it as a “Need vs. Want” list—a practical tool for distinguishing what is truly essential from what’s ideal but non-critical.
Below are five key considerations that should guide phase-appropriate decisions:
1. Regulatory strategy: Pre-clinical development
During the pre-clinical phase, using “good-enough” quality materials—rather than excessively pure compounds—can be a smart move. While early-stage companies may aim to meet the highest standards from the outset, this can backfire. Regulators may later expect the same standards in clinical phases, making scale-up more difficult and costly. This could create significant hurdles when scaling up production, where achieving such high purity at a larger volume can be technically challenging and economically prohibitive.
Similarly, including too much detail in early regulatory filings can limit flexibility. Overly specific information may require updates or re-filings if changes are needed later. Early-phase processes should be lean, compliant, and adaptable—not locked into commercially infeasible standards.
2. Route selection and process development: Clinical Phases I & II
Route selection and process development during Clinical Phases I & II are crucial for optimizing the synthesis of the active pharmaceutical ingredient (API) and ensuring its scalability, efficiency, and reproducibility for larger trials. Multiple synthetic routes may be available to access the active pharmaceutical ingredient (API). In early clinical stages, the focus should be on speed and feasibility—selecting a route that delivers APIs quickly to meet development timelines.
As the molecule progresses, attention should shift toward robustness and scalability yield improvement, impurity control, and solvent selection. Ideally, the synthetic pathway is flexible, with backup options. However, decisions around locking in the route for validation and filing should be made carefully because if control strategies become more refined, including in-process monitoring, critical quality attributes (CQAs), and regulatory-compliant batch records you may limit your ability to pivot later.
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3. Analytical development: Phase-appropriate approach
Analytical methods should evolve with the program, meaning the level of method validation, characterization, and regulatory compliance evolves as the drug advances through clinical development. In early stages, basic methods to confirm identity and purity are typically sufficient. Fit-for-purpose assays are developed, but don’t require full validation. Full validation or detailed impurity profiling is often unnecessary (and costly) at this point.
As development progresses, analytical rigor must increase accordingly. A balance must be struck between scientifically sound methods and fully validated ones.
4. Balancing GMP with practicality during scale-up
Phase-appropriate development focuses on what is required at each point, rather than what could be done. Balancing Good Manufacturing Practice (GMP) with practicality during scale-up is crucial to ensure both regulatory compliance and efficiency in production. GMP requires detailed records and traceability, which can slow down production if not streamlined. Of course, all processes could be carried out to GMP standards throughout, but it is not strictly necessary and adds both time and cost.
A 10-step synthesis, for instance, doesn’t require GMP compliance for every step. Identifying the regulatory starting material (RSM) is essential; GMP is required from that point forward.
5. Commercial manufacturing: Planning for scale & market realities
An important decision lies in when to invest in a commercial-scale process. Planning for commercial manufacturing requires a strategic balance between scale, efficiency, regulatory compliance, and market demands. While developing a scalable process early may increase upfront cost and time, it can offer long-term savings if the project advances.
That said, there’s risk involved. If the program fails, that investment may not yield returns. But if it succeeds, early investment pays off by enabling a smoother transition to later phases and market launch.
The Siegfried Acceleration Hub: A partner to support you in making phase-appropriate decisions to maximize speed to clinical
Drug development is filled with critical decision points. Not all challenges can be captured in a single document—but one truth stands out: choosing the right partner makes all the difference. At Siegfried’s Acceleration Hub in Grafton, Wisconsin, we are committed to supporting your journey through early-phase development with phase-appropriate guidance, speed, and expertise.
The Acceleration Hub is part of Siegfried's network of 13 sites globally. Siegfried is a leading CDMO offering development and manufacturing of pharmaceutical ingredients and finished dosage forms as an integrated supplier. Leveraging Siegfried’s vast experience in pharmaceutical development ensures robust processes, high-quality standards, and efficient project progression. Additionally, seamless transfer options within Siegfried’s worldwide network of pilot and launch plant enables a smooth transition from early development to commercial manufacturing.
The Siegfried Acceleration Hub team is committed to providing the support you need by partnering with you in your efforts to bring your drug candidate to market by providing suggestions and guidance that are collaborating with you to make the best phase-appropriate decisions. We work hand in hand with companies of all sizes, ensuring that your program is set on a fast and efficient path toward commercial launch.