The 505(b)(2) New Drug Application (NDA) regulatory pathway offers a unique strategic opportunity for sponsors to streamline development plans, accelerate approval timelines, and potentially reduce clinical costs. But success with this complex regulatory strategy demands more than knowledge of regulatory requirements — it requires historical insight, discernment of regulatory precedents, strategic foresight, creative strategic thinking and deep familiarity with FDA expectations.

At Premier Research, we bring unrivalled 505(b)(2) development experience to the table — and in this space, experience matters. Premier acquired Camargo Pharmaceuticals Services in 2021 and in doing so, expanded its wealth of 505(b)(2) experience. We’ve supported a wide range of products through the full 505(b)(2) lifecycle, giving us unmatched visibility into what works, what doesn’t, and how to take advantage of opportunities for smaller programs that others miss.

More Experience, Smarter Strategy

505(b)(2) development is rarely one-size-fits-all. This pathway lacks a preset playbook, which means each product demands a tailored strategic approach to bridge to existing data to address regulatory requirements for a repurposed product. If not done right, a sponsor will end up conducting more studies than they need for approval.  Premier’s historical involvement across therapeutic areas, FDA Divisions, and molecule types gives us a deep bench of precedent and perspective — allowing us to proactively design leaner, expedited programs while anticipating and avoiding costly missteps.

Whether you’re repositioning a known molecule, modifying a route of administration, including a new excipient, considering an Rx to OTC switch, or exploring new combinations, or planning a bioavailability/bioequivalence (BA/BE) bridging study, our seasoned regulatory strategists will guide your approach with insights drawn from real-world success.

To best prepare for accelerated development programs, our cross-functional experts bring expertise in specific 505(b)(2) pharmacokinetic bridging studies, nonclinical strategy, clinical, and chemistry, manufacturing, and controls (CMC) plans that address regulatory and clinical expectations. In partnership with our regulatory strategists, they deliver the holistic, team-based approach required for a successful program. Our cross-functional teams have experience with programs involving new salt forms, polymorphs, enantiomers, prodrugs, active metabolites, and nanoparticle formulations, and more.

Comprehensive 505(b)(2) Services – From Strategy to Submission

Regulatory Strategy & FDA Engagement: Overcoming 505(b)(2) Complexities

Clinical development for 505(b)(2) programs is highly drug product—as well as indication-dependent—and requires extensive regulatory and clinical expertise to understand the program gaps between the new drug product and the listed drug and how to strategically leverage the published literature.

We leverage decades of regulatory experience to build persuasive strategies that align with FDA expectations — not just theoretically but based on direct precedent from numerous successful 505(b)(2) submissions and regular engagement with the Agency. We help sponsors:

• Identify reference product(s) and bridging strategies
• Justify data reliance approaches
• Assess for eligibility for FDAs expedited review programs such as Breakthrough Therapy and Fast Track designations, orphan and other rare disease programs
• Identify potential for marketing exclusivities
• Provide a roadmap for an optimal development program to reduce cost and time to market
• Prepare for pre-IND, Type A, C, D, end-of-phase, and pre-NDA meetings with confidence

Clinical Pharmacology & PK Expertise: The Critical Role of PK Modeling & Simulation

Clinical pharmacologists play a critical role in 505(b)(2) drug development by evaluating the adequacy of existing data, identifying opportunities to obtain the required PK or clinical pharmacology studies without conducting additional studies, and designing optimal bioavailability/bioequivalence (BA/BE) studies or biowaiver strategies. Establishing a successful PK bridge to an approved reference product allows sponsors to leverage prior FDA findings on safety and efficacy. But they must be conducted in alignment with FDA expectations.

In addition to specific experience in 505(b)(2) programs, our clinical pharmacology team are experts in identifying situations in which PK modeling and/or simulation can replace the need for additional studies, reduce the number of patients required in clinical studies, or optimize sampling to reduce the number of samples required. This reduces the burden on study participants and reduces cost for the sponsor. From data sourcing and modeling to biowaiver justification, we know what FDA reviewers expect — and we find custom solutions to meet these requirements while reducing the size and scope of your development program.

Nonclinical Strategy: Identifying the Need for Nonclinical Studies

Many 505(b)(2) products could be approved, or have their IND-opened, with reduced or even no nonclinical studies — but knowing which studies could be avoided and providing an appropriate scientific justification is critical. Our toxicologists propose credibly aggressive but reasonable nonclinical programs based on experience in negotiating 505(b)(2) programs with FDA.

Premier’s long history of  experience with 505(b)(2) programs and frequent engagement with FDA in milestone meetings allows us to identify data gaps early and craft nonclinical strategies that satisfy regulatory requirements while reducing timelines and costs.

Chemistry, Manufacturing, and Controls (CMC): Critical to Differentiation and Approval

For 505(b)(2) NDAs, CMC differences from the reference product are often central to both risk and value. Differences between an investigational asset and its reference product—such as dosage form, strength, route of administration, or combination features—can significantly impact critical quality attributes and pose challenges to demonstrating manufacturing robustness and reproducibility. Ultimately, it is crucial to ensure that the content and timing of the CMC program matches the accelerated pace of 505(b)(2) programs.

We help clients navigate critical CMC considerations such as:

• New dosage forms, delivery systems, and routes of administration
• Manufacturing challenges and regulatory timing alignment
• Phase appropriate quality requirements by clinical program development stage
• Device and combination product attributes and compliance

Our in-depth knowledge of FDA expectations based on past regulatory submissions helps ensure your CMC program supports product quality, consistency, and approval readiness.

Combination Products: We Have Seen Them All

Whether it is drug-device combination products, or fixed-dose combinations (eg. drug-drug), these programs are frequently approved via the 505(b)(2) pathway. With Premier’s years of experience in 505(b)(2) programs, we have taken all types of combinations to the FDA to negotiate custom yet streamlined programs that comply with drug and device regulations, or 21CR 300.50 Fixed Combination Prescription Drugs for Humans (commonly known as the Combination Rule).

Why Experience Matters in 505(b)(2) Development

Unlike CROs or consulting firms that dabble in this space, Premier has a proven track record with 505(b)(2) programs—including many that are now FDA-approved and commercially successful. We don’t just know the theory; we know the history, the pitfalls, the workarounds, and advantages. This extensive experience translates directly into more effective, efficient, and successful development programs. Premier’s clinical experts across multiple therapeutic areas ensure that your 505(b)(2) program becomes a reality.

Work With the Experts

When it comes to 505(b)(2), experience isn’t optional, it will be your asset’s competitive advantage. Contact Premier today for help navigating this unique regulatory pathway with confidence, clarity, and access to a team that’s known for 505(b)2 success. Read more about the 505(b)(2) pathway here.