Biologics in FDA’s 2025 Approvals: Implications for Future CMC Strategies

For years, the pharma industry has anticipated a "biologics-first" world. While small molecules still remain a significant cornerstone of the market, the FDA’s 2025 New Drug Therapy Approvals report signifies that biologics will continue to evolve, with highly engineered, complex biomolecules featuring heavily. With 46 novel drug approvals from FDA’s Center for Drug Evaluation and Research (CDER) in 2025, alongside additional biologics approvals across the agency, the message is clear: standard monoclonal antibody (mAb) workflows are no longer enough.

As these molecules become more structurally intricate, the "process is the product" principle has never been more relevant. To navigate this evolving landscape, large-molecule developers must shift from reactive troubleshooting to a proactive, science-first CMC strategy centered on robust process characterisation, analytical depth, and platform-flexible manufacturing. 

 For CMC leaders, the implication is straightforward: when molecular sophistication rises and timelines compress, “process is the product” stops being a principle and becomes a regulatory requirement.

The 2025 Signals CMC Teams Can’t Ignore, Complexity is the New Baseline

The 2025 data reveals the continuing shift away from "simple" biologics toward high-engineered modalities designed for precision. Key highlights include: 

• The ADC Renaissance: After a brief hiatus, 2025 saw the approval of two major ADCs (Datroway and Emrelis) targeting TROP2 and c-Met. These molecules demand a dual-competency CMC strategy that masters both large-molecule protein engineering and small-molecule potent payload chemistry. 

• Beyond the Antibody Framework: The approval of Lerochol (lerodalcibep), the first Adnectin-based biologic, validates the move toward non-antibody scaffolds. These smaller, more stable proteins offer manufacturing advantages but require bespoke purification and formulation strategies. 

• Subcutaneous Dominance: A major trend in 2025 was a visible shift toward subcutaneous options for some therapies like Keytruda Qlex and Leqembi Iqlik. This places immense pressure on CMC teams to achieve high-concentration formulations without compromising stability or sterility. 

Strategic Imperatives for Future Large Molecule Development 

To meet the rising regulatory bar and the speed of accelerated pathways (which 72% of 2025 approvals utilized), CMC strategies must evolve in three critical areas: 

1. Analytical Rigor: Moving Beyond "Good Enough" 

The complexity of 2025’s approvals, particularly bispecifics and ADCs, means that traditional "release testing" is too slow and too late. 

• The Risk: Heterogeneity in drug-to-antibody ratios (DAR) or mismatched light chains in bispecifics can lead to clinical failure or manufacturing delays. 

• The APC & VLE Approach: We advocate for the use of Orthogonal Analytical Methods (OAM) and real-time Process Analytical Technology (PAT).  By leveraging independent, cross-verifying datasets to monitor critical quality attributes, we provide the molecular clarity required to move from "testing quality in" to "designing quality in” 

2. Process Intensification: MVDA and Continuous Manufacturing 

As titers rise and molecules become more labile, the traditional 2,000L fed-batch model is being challenged by more agile systems. 

• The Risk: Long residence times in batch reactors can lead to product degradation or unfavourable glycosylation profiles for sensitive novel scaffolds. 

• The APC and VLE Approach: We utilize process intensification and statistical modelling (e.g. MVDA) to reduce footprint and improve product consistency. Going forward, the goal is to maximize yield while maintaining a fingerprint-perfect molecular profile. 

3. Integrated ADC and Conjugation Readiness 

The return of ADCs requires a CMC strategy that bridges the gap between biologics and high-potency small molecules. 

• The Risk: Siloed development of the antibody, the linker, and the payload often leads to late-stage "conjugation surprises" that derail IND or BLA timelines. 

• The APC & VLE Approach: Our integrated CMC strategy treats the ADC as a single, holistic entity from day one. We align the protein’s site-specific chemistry with the payload’s solubility and potency requirements to ensure a stable, scalable conjugation process. 

4. "Right First Time" for Accelerated Pathways 

With the FDA increasingly using Fast Track and Breakthrough designations, the time between Phase 1 and BLA is shrinking. 

• The Risk: Inadequate process characterization during early phases leads to CMC-related Complete Response Letters (CRLs) or post-approval commitment burdens. 

• The APC & VLE Approach: We prioritize Digital Twin modeling and high-throughput screening early in development. This allows us to map the design space rapidly, ensuring that the process used for clinical trials is commercially viable and regulatory-ready. 

Conclusion: Designing for the Future Regulatory Reality 

The FDA’s 2025 approvals prove that the targeted mechanisms, complex biomolecules, and novel biologic scaffolds are where the industry is thriving. However, these successes are only possible when backed by a CMC strategy that is as innovative as the science itself. 

As you evaluate your milestones in 2026 and beyond, the question is no longer just "can we make this molecule?" but "can we make it with the precision and speed required by today's regulatory environment?" 

Navigating the 2026 large-molecule landscape requires more than just capacity; it demands a data-driven, science-first partner.  The CMC organizations that win in 2026 will be the ones that can do both:

1. develop with deep process understanding, and

2. make decisions that hold up in GMP manufacturing, not just in development.

That is the advantage of an integrated development-to-GMP model:

• APC helps teams generate the process and analytical evidence needed to reduce uncertainty early

• VLE ensures that what you build can be executed under GMP conditions with the rigor required for late-stage and commercial supply

• iAchieve (digital CMC backbone): captures experimental context and CMC decisions in a structured, queryable system, enabling faster root-cause analysis, stronger comparability narratives, and transfer-ready packages that connect development data to GMP execution.

In practice, the goal is simple: fewer avoidable pivots, faster confidence, and a CMC narrative that stands up to scrutiny.