New FDA CMC Guidance (2026): What Sponsors Must Do Differently

The regulatory landscape for Chemistry, Manufacturing, and Controls (CMC) is undergoing a rapid transformation. The FDA is rolling out new initiatives and pilot programs to ensure CMC development keeps pace with accelerated clinical timelines and to modernize how CMC data is submitted.

For biotech and pharma companies, especially those targeting expedited pathways (e.g. Breakthrough Therapy, Fast Track, RMAT), these changes have profound implications for CMC strategy and operations. Regulatory leaders and CMC executives must now integrate early CMC readiness planning, structured data submissions, and digital formats into their development and lifecycle management strategies.

This white paper provides an in-depth look at key FDA policy initiatives, including the CMC Development and Readiness Pilot (CDRP) and the Pharmaceutical Quality/CMC (PQ/CMC) data standards effort – and offers guidance on how to align CMC plans with this evolving landscape.

CMC Development and Readiness Pilot (CDRP)

The CMC Development and Readiness Pilot (CDRP) is an FDA program launched under PDUFA VII (FY 2023–2027) to facilitate CMC development for products with expedited clinical development timelines. The pilot’s core purpose is to prevent CMC activities from becoming the critical bottleneck for breakthrough therapies by increasing communication between sponsors and the FDA and exploring risk-based CMC approaches. Key features of CDRP include:

• Eligibility and Scope: The pilot is open to certain fast-tracked products – including those with Breakthrough, Fast Track, or Regenerative Medicine Advanced Therapy (RMAT) designations – that have accelerated clinical programs. Both CDER and CBER-regulated products are included, reflecting a broad scope across drugs and biologics. Sponsors must have an active commercial IND (generally prior to end of Phase 2) and a product addressing a serious unmet need to qualify. Starting in FY 2023, FDA began accepting up to nine sponsors per year into CDRP (approximately 2/3 CBER and 1/3 CDER products).

• Pilot Benefits: Selected IND sponsors gain two additional CMC-focused Type B meetings with FDA review teams (beyond the standard meetings) at critical development milestones. In these meetings, sponsors and regulators align on CMC strategy – for example, agreeing on which CMC data must be included in the eventual NDA/BLA versus what might be provided later (e.g. by end of review or post-approval) without delaying approval. FDA also allows a limited number of follow-up discussions to address arising questions, fostering a continuous dialogue. This intense communication helps sponsors shape CMC plans that keep up with rapid clinical progress, ensuring earlier patient access to promising therapies without compromising quality.

• Application and Selection: To participate, sponsors submit a request as an IND amendment with a cover letter “Request to participate in the CMC Development and Readiness Pilot” The FDA has published Federal Register notices detailing eligibility and how to apply. Notably, sponsors must acknowledge that certain CMC information from the pilot may be publicly disclosed (e.g. as case studies), since the program’s intent is to share lessons learned. Each year’s participants are chosen based on criteria like the product’s potential clinical benefit and the need for accelerated CMC development. FDA has continued to announce new enrollment periods via the Federal Register; for example, Year 4 of CDRP opened on October 1, 2025 to new applicants.

• Timeline and PDUFA Commitment: CDRP is a time-limited pilot aligned with PDUFA VII. It began in FY 2023 and will run through FY 2027 (the end of PDUFA VII). This multi-year pilot allows the FDA to iteratively learn and refine approaches for CMC in accelerated programs. A major public workshop in September 2025 (“Lessons Learned from the CDRP”) gathered feedback from industry and FDA on the pilot’s outcomes. Common themes from participants included calls for even greater flexibility – e.g. the option for more frequent but focused CMC check-ins, faster turnaround on FDA feedback, and additional clarity on pilot structure and confidentiality. Indeed, industry stakeholders suggested that CDRP meetings could be more rapid and targeted (potentially a new meeting format with limited questions and 30-day FDA turnaround) to better match the pace of ultra-rapid developments.

• 2026 Strategy Document: As mandated in the PDUFA VII commitment, the FDA will publish a CMC Strategy Document in 2026 to capture the pilot’s lessons and outline future strategy. This forthcoming white paper from FDA is expected to provide guidance on CMC approaches for expedited programs, potentially institutionalizing best practices from CDRP. Regulatory leaders should anticipate recommendations on early CMC planning, communication pathways, and risk-based flexibility (e.g. use of regulatory tools to defer certain CMC elements to post-approval when appropriate). The 2026 strategy document will likely serve as a blueprint for sponsors to integrate “CMC readiness” into development programs even outside the pilot. In the meantime, lessons from CDRP are already emerging: for instance, one sponsor in the pilot reported that early FDA feedback was “critical to de-risk Phase 3 initiation” – it enabled them to begin validation of key assays earlier, rather than waiting for formal Phase 3 IND amendments. Such examples underscore how proactive CMC engagement can accelerate later-stage development.

Implications for CMC Strategy: The CDRP’s emphasis on upfront planning and frequent FDA interaction signals a broader regulatory expectation: CMC should no longer be left to catch up at the end. Companies pursuing accelerated pathways must ensure their CMC timelines are aligned with clinical milestones from the start. Even sponsors not in the pilot can take a page from its playbook by requesting early CMC meetings (e.g. pre-IND, end-of-Phase 1) to discuss manufacturing preparedness. The pilot also highlights the value of risk-based regulatory approaches – for example, leveraging draft guidance on expedited programs and applying scientific flexibility (with FDA agreement) to advance CMC in step with clinical progress. Sponsors should watch for the FDA’s 2026 CMC strategy publication and be prepared to adapt internal practices accordingly, as the Agency formalizes new expectations for CMC in accelerated development.

Modernizing CMC Submissions: The PQ/CMC Structured Data Initiative

In parallel with fostering early CMC readiness, FDA is modernizing how CMC data is submitted and reviewed. The Pharmaceutical Quality/Chemistry, Manufacturing & Controls (PQ/CMC) data standards initiative is a cross-center effort to transition portions of Module 3 of the eCTD from document-based submissions to structured, standardized data. This initiative aims to replace static PDF documents with searchable, computer-readable data that can streamline both submission assembly and FDA review. Key aspects of the PQ/CMC modernization include:

• Scope of Structured Data: FDA has identified specific domains of CMC information that are “amenable to structuring and would bring value to the quality review process”. The scope initially focuses on elements of Module 3 (and corresponding summaries in Module 2.3) such as product composition, components, manufacturing process details, and quality attributes – starting with solid oral dosage forms as the first model case. The goal is not to structure all CMC content at once, but to prioritize high-impact areas (e.g. formulation ingredients, batch data, specifications) where standardized data can increase review efficiency. Over time, additional product types (like biologics, parenterals, etc.) will be tackled in phases. In fact, FDA has begun exploring data standards for therapeutic protein products as a next stage – an “Informational Chapter A” published in late 2024 drafts controlled vocabularies for biologic product quality attributes and seeks industry feedback.

• Objectives and Benefits: The PQ/CMC project’s primary objective is to develop electronic standards for submitting CMC data in regulatory applications. This involves two components: (1) defining structured data elements and controlled terminology for CMC information, and (2) creating a data exchange standard to transmit this data to FDA in a consistent way. By introducing structured data into Module 3 of NDAs, BLAs, INDs, and other applications, FDA expects to increase the efficiency of CMC reviews. Reviewers would be able to auto-validate datasets, quickly query specific parameters (e.g. assay results, ingredient attributes), and more easily compare across submissions or lifecycle updates. Automation and analytics could flag issues faster than manually reading hundreds of pages of text. In essence, this transition from PDFs to data eases the burden on both sponsors and regulators by reducing repetitive manual work and enabling data-driven submission assembly and review. Over the long term, widespread adoption of structured content management is envisioned to speed up regulatory filings and approvals across the board, not only for expedited products but for standard submissions as well.

• HL7 FHIR Data Standard: To implement these structured submissions, FDA has partnered with the Health Level 7 (HL7) standards organization. The data exchange format being used is HL7’s Fast Healthcare Interoperability Resources (FHIR) standard – widely used in healthcare data exchange, now being applied to pharmaceutical quality data. An HL7 project, “PQ/CMC Submissions to FDA,” is developing a FHIR Implementation Guide (IG) that defines how to represent CMC data (e.g. a formulation composition, a manufacturing site, a test result) as structured FHIR resources. The work is iterative and transparent: HL7 working groups hold public calls and periodic “Connectathons” to test draft standards. Progress to date: Stage 1 of the PQ/CMC FHIR Implementation Guide was published as a Standard for Trial Use (version 1.0.0) in 2024, covering foundational domains for solid oral products. Stage 2, which adds new content (such as enhanced manufacturing data), was successfully tested at an HL7 Connectathon in Sept 2024 and entered the HL7 ballot in early 2025. This staged approach will continue until all key Module 3 domains (for all dosage forms) are represented in FHIR. It’s important to note that these HL7 standards are not yet FDA requirements – they are draft specifications undergoing testing. FDA has emphasized that it will follow formal procedures to announce when it will accept regulatory submissions in a new format. Until then, the FHIR data standards are available for industry review and optional use in pilot settings, but not mandated for filings. Sponsors and vendors can engage now by reviewing the HL7 IGs and participating in comment periods, ensuring the standards are robust and fit for purpose.

• Federal Register Dockets and Feedback Opportunities: FDA has been actively seeking industry input on PQ/CMC data standards through Federal Register notices (FRNs) and an open public docket. Historic efforts date back to an initial 2017 FR notice where FDA first floated the idea of structured Module 3 data and received broad industry support. This was followed by a 2022 FR notice releasing an updated set of draft PQ/CMC data elements and controlled terminology (Phase 1) along with prototype mappings to FHIR, specifically to gather feedback on the proposed data fields and how they correlate to FHIR resources. The high volume of comments affirmed industry’s interest and provided detailed suggestions, which FDA has been incorporating. In May 2023, FDA established a new open docket (FDA-2022-N-0297) via Federal Register notice to allow continuous input as the standards evolve. Rather than occasional big notices, FDA switched to a model of releasing quarterly “chapters” of draft data standards on its website for public comment. For example, Chapters 1 and 2 (published May 2023) included foundational data standards for PQ/CMC (as initially outlined in 2022) plus new elements to support multi-layer tablets, capsules, and solid oral manufacturing processes. Subsequent updates are posted every three months (targeting end of March, June, September, December) – if new content is ready, a draft chapter is added for review; if not, FDA notes that no new content is available that quarter. Public comment opportunities are continuous via the open docket, but FDA typically specifies a 60-day window for each new chapter to concentrate feedback (e.g. comments on “Informational Chapter A” – therapeutic protein quality data – were requested by December 5, 2024). This agile, incremental approach allows FDA to refine data standards in collaboration with industry experts, ensuring that by the time formal guidance or requirements are issued, the standards have been vetted by real-world use and comment.

• Digital Submission Format: As structured data standards mature, the FDA is also considering the regulatory submission format that will carry this data. The Common Technical Document (CTD) framework (ICH M4) remains the backbone for organizing quality information, and the Electronic CTD (eCTD) specification (ICH M8) defines how dossiers are transmitted. FDA has indicated that FHIR-based CMC data will be submitted as part of eCTD, likely as specialized “study data” sections or attachments within Module 3. The HL7 Implementation Guide notes that FHIR-based PQ/CMC content is being aligned with the forthcoming eCTD v4.0 standard. In other words, future eCTD submissions could include FHIR data files (machine-readable JSON/XML) in lieu of certain PDF documents. Figure 1 from the HL7 guide illustrates a high-level data flow: industry will send CTD quality data in a FHIR format, within the eCTD exchange mechanism, to FDA’s review system. The timeline for FDA’s acceptance of such submissions is still to be determined; formal adoption will require FDA to issue guidance or technical specifications (likely after the HL7 standard reaches a stable, published state and pilot testing is completed). Nonetheless, regulatory teams should anticipate a transition to digital CMC submissions in coming years as part of FDA’s broader drive toward structured data across regulatory submissions. The Agency’s message is clear – sponsors should begin organizing their CMC data in databases and structured formats now so they can easily populate future electronic submission templates. Early adopters who embrace electronic data exchange may gain efficiencies in compiling variations of dossiers for global markets and enable FDA reviewers to assess their applications faster and more consistently.

Federal Register Notices, Guidance, and CMC Policy Trends

Beyond the flagship initiatives above, FDA has been active in releasing draft guidances and policy statements that impact CMC strategy. Regulatory and CMC executives need to stay vigilant in monitoring these developments via Federal Register notices and FDA announcements. Some recent policy documents and their CMC implications include:

• ICH Q12 Implementation: FDA’s adoption of ICH Q12: Pharmaceutical Product Lifecycle Management has introduced new tools for post-approval CMC change management. In 2021, FDA released a guidance on Q12 implementation, which provides a framework for managing post-approval changes in a more predictable and efficient manner. Key Q12 concepts such as Established Conditions (ECs) (explicitly defined CMC elements that require regulatory notification if changed) and Post-Approval Change Management Protocols (PACMPs) allow companies to gain upfront agreement on how certain changes will be handled post-approval. Embracing Q12 can significantly streamline post-approval operations: for example, a sponsor might utilize a PACMP (analogous to FDA’s traditional Comparability Protocol) to get FDA’s pre-approval on a plan to scale up manufacturing or change a process, so that when the change is executed, the reporting category is reduced (saving time and resources). CMC implication: Firms should incorporate Q12 principles into their regulatory submissions – identify ECs in dossiers and propose PACMPs for complex changes – to reduce supplementary filings and facilitate continual improvement without undue delay. This ties directly into the CDRP and expedited programs: by planning which CMC aspects can be flexibly managed post-approval under Q12, sponsors can prioritize what must be perfected for initial approval versus what can evolve later. The FDA’s encouragement of risk-based approaches in CDRP aligns with Q12’s philosophy of focusing regulatory scrutiny on critical elements while allowing more flexibility in lower-risk changes.

• Guidances on Advanced Manufacturing: FDA is also supporting CMC innovation through guidances on emerging technologies (continuous manufacturing, 3D printing, AI in process control, etc.). While not explicitly covered in this paper, such guidances are part of the evolving landscape that CMC teams must consider in strategy. For instance, FDA’s guidance on continuous manufacturing (ICH Q13, adopted in 2023) and on Artificial Intelligence in drug manufacturing (draft discussions) indicate regulators are receptive to new technology that can enhance quality. Sponsors leveraging advanced manufacturing should engage FDA early to incorporate any needed CMC regulatory considerations (control strategy, real-time release testing, etc.) into their submission planning. These forward-looking policies dovetail with the digital submission initiative – as more process data and monitoring information could be submitted in structured forms, enabling FDA to evaluate innovative processes more efficiently.

• Electronic Submission Requirements: FDA has longstanding requirements for electronic submissions in eCTD format for NDAs, BLAs, ANDAs, and INDs. Recently, the Agency has updated technical specifications and validation criteria for eCTD submissions (for example, new modules for Quality metrics or stability data). While these technical notices may seem granular, they can have practical CMC implications – e.g., requiring all datasets (like stability tables) to be submitted in specific formats. In the near future, as mentioned, FDA may put out guidance on submitting structured quality data once the PQ/CMC standards are ready. Sponsors should be prepared to comment on such draft guidances when they appear in the Federal Register. Staying engaged through industry trade associations or public workshops ensures that sponsor perspectives on feasibility are heard before new requirements become final.

• Federal Register Notices for Pilot Programs: In addition to guidance documents, keep an eye on Federal Register notices announcing pilot programs or requesting comments. For example, the yearly announcements for CDRP participation (first published 31 October 2022 and updated annually) not only invite participants but also often outline FDA’s expectations for CMC in accelerated programs. Similarly, FR notices for public workshops (such as the 2025 CDRP Lessons Learned workshop) can signal FDA’s areas of focus and concern – these workshops often precede new guidances or policy shifts. Engaging with these dockets (by attending meetings, submitting comments, or even volunteering for pilots) is a strategic move for sponsors to anticipate regulatory changes and help shape policies. FDA has explicitly stated that feedback from industry via the PQ/CMC open docket will be used to refine data standards, illustrating the value of proactive comment. As another example, if FDA were to request comment on a draft guidance about digital CMC submissions or stability data reporting, providing thoughtful input can both influence the final policy and prepare your organization for compliance.

In summary, the FDA’s recent dockets and guidance initiatives all point toward a more structured, data-driven, and proactive regulatory environment for CMC. Whether it’s through pilots like CDRP, data standardization efforts like PQ/CMC, or new guidances on lifecycle management, the common theme is encouraging sponsors to plan CMC early, provide data in more usable formats, and leverage risk-based flexibility. The implications for CMC operations are significant – companies need to invest in regulatory intelligence capabilities to track these changes and adapt internal processes ahead of the curve.

Strategic Planning for Sponsors: Recommendations for 2026 and Beyond

Given the evolving policy landscape, sponsors should update their CMC strategies to remain compliant and competitive. Below are key recommendations for aligning development and operations with FDA’s new CMC expectations:

1. Start CMC Planning Early and Align with Clinical Timelines: It is critical to synchronize CMC development with clinical development – especially for programs on accelerated pathways. Begin CMC readiness planning at the pre-IND stage or earlier. Map out major CMC deliverables (process scale-up, analytical method validation, stability data, etc.) against clinical milestones. If Phase 2 and Phase 3 will be compressed, identify which CMC activities need parallel execution (e.g. initiating process validation or building commercial manufacturing capacity during Phase 2). Early planning helps avoid situations where a breakthrough therapy’s approval is delayed due to CMC gaps. FDA’s CDRP and other communications have reinforced that “late-stage surprises” in CMC are no longer acceptable for expedited programs – by NDA/BLA submission time, CMC must either be complete or on a clear path with FDA agreement for any post-approval commitments. As an internal best practice, consider developing a CMC Development Plan that runs alongside the Clinical Development Plan, and update it continuously as data emerge.

2. Leverage FDA’s Pilot Programs and Early Engagement Opportunities: Take advantage of initiatives like CDRP or any future CMC-focused pilots. If your product is eligible for CDRP (or a similar program), strongly consider applying – the additional meeting opportunities and feedback can significantly de-risk your CMC program. Even if not in a pilot, proactively engage FDA through existing meeting types: Type C meetings can be requested to discuss CMC strategy questions; for complex biologics or gene therapies, use preliminary meetings (e.g. INTERACT meetings for advanced therapies) to get agency input on novel manufacturing aspects. The CDRP experience shows that more touchpoints with FDA can prevent missteps and facilitate agreement on novel approaches. When engaging, come prepared with specific questions and proposals – for instance, outline which steps you propose to defer to post-approval (with justification) versus which will be completed by filing, to get FDA’s concurrence. Early agreement on using tools like a Post-Approval Change Management Protocol (under ICH Q12) can allow you to file the initial application with a plan in place for future improvements.

3. Invest in Data Standardization and Digital Infrastructure: To prepare for the shift toward structured data submissions, companies should invest now in their CMC data management. This means moving away from relying solely on narrative Word documents and PDFs generated ad-hoc. Instead, establish structured data repositories for key CMC information – for example, a database for formulation composition and batch records, or a system for managing analytical method parameters and results. By structuring these data internally, you will be well-positioned to populate FDA’s future data submission templates (such as the PQ/CMC FHIR-based modules) with minimal re-work. It will also improve internal efficiency: teams can update a single source of truth for CMC data that automatically feeds various submission documents, reducing inconsistencies and errors. Evaluate tools that support Structured Content and Data Management (SCDM) in regulatory submissions – these can help chunk data and text into reusable elements, which is exactly the paradigm FDA is moving toward. Additionally, consider participating in standards development: join industry working groups or HL7 meetings related to PQ/CMC to stay informed and contribute your expertise (several pharma companies are already active in this area, helping ensure the standards work for real-world use). By embracing digital CMC practices early, you can gain a competitive edge – your submissions will be easier for regulators to review, and you’ll adapt faster as FDA mandates more electronic data in the future.

4. Implement Training and Change Management for Your Teams: The shift to early planning and structured data affects not just systems, but people and processes. Ensure that CMC and regulatory teams are trained on new guidances and data standards. For example, your regulatory affairs staff should be aware of how to use the new PQ/CMC data elements and what they mean, while your CMC scientists need to understand the importance of consistent data definitions (like controlled vocabulary for materials or processes). Establish internal guidelines or SOPs for CMC dossier preparation that reflect current FDA expectations: e.g., a guideline on using ICH Q12’s Established Conditions in submissions, or a template for CMC meeting requests that addresses the points FDA cares about (risk assessments, proposal for approval timing of each CMC element, etc.). Encourage a mindset of “regulatory readiness” in CMC teams – they should be considering regulatory impact at every development stage, not just at the time of writing the CTD. Some companies set up CMC regulatory sub-teams that shadow the technical teams from early development onward, ensuring alignment and readiness for regulatory milestones. This cross-functional integration is vital in an era where CMC can be on the critical path for fast programs.

5. Plan for Lifecycle and Post-Approval Change Early: With expedited approvals, it’s common that some CMC aspects (long-term stability, expanded process validation, second-source manufacturers, etc.) will continue to mature after approval. FDA policy now provides mechanisms to plan for this. Sponsors should incorporate a Lifecycle Management Plan (sometimes called Product Lifecycle Management (PLCM) document under Q12) as part of their submission package, outlining how post-approval changes will be handled. Identify areas where you might seek post-approval changes and consider preparing PACMPs for them ahead of time – for instance, a protocol for a future manufacturing site change or scale-up can be submitted with the BLA/NDA, so that when you execute it two years post-launch, the change can be approved quickly. Also make use of FDA’s guidance on comparability for biologics and small molecules to streamline post-approval comparability studies. By demonstrating to FDA that you have a handle on the product’s lifecycle (and that robust controls are in place), you build confidence and may secure greater flexibility in initial approval. In essence, think beyond the initial approval – consider the first several years of commercialization as part of your CMC strategy, and align those plans with FDA’s frameworks so that post-approval supplements or annual report changes are efficient.

6. Monitor and Adapt to Policy Updates: Finally, given how dynamic the regulatory environment is, put in place a robust regulatory intelligence and tracking process. Assign team members to monitor FDA announcements (guidance releases, FR notices, meetings) specifically for CMC/Quality topics. When new policies emerge – such as an update to FDA’s data standards catalog, a new draft guidance on stability data, or a revision to ICH guidelines – conduct impact assessments for your projects. It can be helpful to maintain a CMC policy tracker that maps upcoming or expected changes (like eCTD v4 requirements, or deadlines for using structured formats) and flags what actions your organization needs to take. By staying ahead of the curve, you can avoid last-minute scrambles and also capitalize on opportunities (for example, joining a pilot or adopting a new method that FDA endorses). In this regard, engaging consultants or tools that specialize in regulatory change management can be valuable to ensure nothing slips through the cracks.

Conclusion

The FDA’s evolving CMC policy landscape, characterized by initiatives like CDRP’s early engagement model, the PQ/CMC structured data transition, and new guidances on lifecycle management – is driving the industry toward greater proactivity, transparency, and digital innovation in CMC. Companies that adapt to these changes will not only mitigate regulatory risk but can also achieve faster time-to-market and more efficient post-market operations.

CMC executives should treat regulatory strategy as a front-end component of product development, investing in the processes, tools, and collaborations that will keep their CMC programs “submission-ready” at all times. As 2026 approaches, we can anticipate further clarity from FDA, the CDRP strategy document and continued PQ/CMC updates will shed more light on future expectations. The direction is set: early CMC readiness, structured data submissions, and continuous improvement are becoming the new normal.

For organizations navigating these complexities, it may be beneficial to seek external expertise or solutions. Enkrisi offers specialized consulting services and tools to help biotech and pharma companies stay ahead of regulatory changes.

For example, you can download Enkrisi’s free CMC Policy Tracker tool to keep track of FDA pilot programs, guidances, and data standard updates, or contact Enkrisi’s CMC regulatory experts for a personalized strategy session. By leveraging such resources, sponsors can confidently align their CMC strategy with the evolving FDA landscape, turning regulatory compliance into a strategic advantage in delivering high-quality therapies to patients faster.