FDA Creates New Regulatory (Pilot) Pathways for Earlier Review

September brought several important CMC and manufacturing developments that point to a broader shift in FDA’s approach to drug development and regulatory review.

The common thread is earlier regulatory engagement and earlier identification of CMC risk.

From reviewing portions of an IND before the complete submission is filed, to providing additional CMC interactions for accelerated programs, to proposing earlier discussions around manufacturing-facility readiness, FDA is creating and considering new mechanisms for sponsors to address issues before they become critical-path delays.

At the same time, recent enforcement activity reinforces that the fundamentals of scientifically justified specifications, robust stability programs, effective investigations, and strong Quality oversight remain just as important.

The Key Take Away: FDA Is Moving Review Upstream

These September developments illustrate an evolution in how FDA is approaching CMC and manufacturing oversight.

At the IND stage, the Expedited IND Pilot tests rolling review before the complete IND is submitted.

During accelerated clinical development, CDRP provides additional opportunities to resolve CMC issues before they become critical-path constraints.

Approaching NDA or BLA submission, the proposed PDUFA VIII facility lifecycle framework would create new opportunities to discuss manufacturing-site risks before filing and potentially resolve inspection issues during the review cycle.

And FDA’s latest enforcement activity demonstrates that earlier interaction does not diminish expectations around analytical controls, stability, investigations, and Quality oversight.

The common denominator is earlier identification and management of risk.

For sponsors, this raises an important question:

Are we identifying and resolving the CMC risks associated with our next development milestone early enough?

Here are four recent developments sponsors should have on their radar.

1. FDA Launches a New Expedited IND Pilot

On September 15, FDA launched its new Expedited Investigational New Drug (IND) Pilot Program, designed to shorten the path from IND-enabling development to initiation of first-in-human clinical trials.

Under the traditional process, FDA generally begins its formal IND review once the complete application has been submitted. The new pilot tests a different approach.

Participating sponsors will work with qualified research institutions that provide multidisciplinary scientific input across CMC, pharmacology and toxicology, clinical development, and regulatory strategy. Individual sections of the IND can then be reviewed on a rolling basis during the pre-IND phase, before the full IND is submitted.

The approach is intended to identify scientific and regulatory issues earlier and reduce delays between drug development and initiation of first-in-human studies.

FDA expects to select approximately 8–10 sponsor–research institution pairs for the initial cohort. Applications opened September 15 and close October 30, 2026.

FDA Expedited IND Pilot Program

What this means: Sponsors preparing first-in-human programs may have a new opportunity to identify CMC, nonclinical, and clinical deficiencies before the formal IND review begins. Even outside the pilot, the initiative reinforces the value of phase-appropriate CMC planning well ahead of IND submission.

2. FDA Opens Year Five of the CMC Development and Readiness Pilot

On September 21, FDA announced year five of the Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) for products moving through accelerated clinical-development timelines.

The CDRP is not a new program, it was originally established in 2022 under PDUFA VII but the September announcement opens another opportunity for sponsors to participate beginning October 1, 2026.

Sponsors accepted into the pilot receive two pre-designated CMC-focused Type B meetings, along with opportunities for follow-up discussions with FDA.

The goal is to help sponsors address CMC challenges that can arise when clinical development advances faster than process development, analytical development, stability work, scale-up, or other manufacturing activities.

FDA will select no more than nine proposals during the year, with approximately two-thirds expected to involve CBER-regulated products and one-third CDER-regulated products. The pilot will continue through the end of PDUFA VII in FY2027.

FDA CMC Development and Readiness Pilot Program

What this means: Sponsors on accelerated timelines should identify their highest-risk CMC questions early enough to use FDA interactions strategically. The objective is not simply to obtain another meeting it is to resolve issues that could otherwise become late-stage development or filing constraints.

3. PDUFA VIII Proposes Earlier Engagement on Manufacturing-Facility Readiness

FDA’s proposed PDUFA VIII commitments for fiscal years 2028–2032 could move earlier regulatory engagement beyond product CMC and into manufacturing-facility readiness.

The proposed commitments were released in August and discussed publicly by FDA on September 16. They include a new CMC Facility Lifecycle Program intended to identify and address manufacturing-facility issues earlier in the application-review process.

One of the most significant elements is a proposed CMC Facility Pre-submission Meeting.

Sponsors could request a meeting with FDA to discuss manufacturing facilities associated with an upcoming NDA or BLA. These meetings would generally occur three to six months before submission and could address manufacturing supply chains, relationships and interdependencies between facilities, known risks, and lessons from prior regulatory inspections.

The proposal would also introduce post-PAI and post-PLI meetings in certain circumstances, giving sponsors an opportunity to discuss significant inspection findings and potential corrective actions during the application-review cycle.

FDA’s proposed commitments also include a goal of communicating its intent to conduct certain NDA pre-approval or BLA pre-license inspections at least 60 days in advance, while preserving the Agency’s ability to inspect with less notice when needed.

FDA plans to issue draft guidance describing manufacturing-facility readiness expectations and implementation of the lifecycle program by October 1, 2028.

FDA PDUFA VIII: Fiscal Years 2028–2032

What this means: This is a proposed future framework rather than a current requirement. But the direction is important: facility readiness is increasingly being integrated with submission readiness rather than treated primarily as an issue to address once FDA schedules an inspection.

4. September Enforcement Reinforces the Importance of Analytical and Stability Readiness

Earlier regulatory engagement does not reduce expectations around fundamental CMC and Quality controls.

A September 8 FDA warning letter to kdc/one Chatsworth provides a useful example.

FDA cited significant CGMP deficiencies involving finished-product release testing and the company’s stability program. Among the observations, FDA found that the company had not established scientifically sound finished-product specifications and had not maintained an adequate written stability-testing program with reliable, meaningful, and specific methods for assessing product stability.

FDA also identified inadequate investigation of out-of-specification results and deficiencies related to storage conditions.

In its requested remediation, FDA called for measures including:

• scientifically appropriate chemical and microbiological specifications;
• qualified analytical methods;
• a comprehensive assessment of laboratory systems;
• stability-indicating methods;
• stability studies in marketed container-closure systems;
• an ongoing stability program; and
• stronger investigation and CAPA processes.

FDA Warning Letter: kdc/one Chatsworth

What this means: Specifications and stability programs should evolve with product and process knowledge. Sponsors and manufacturers should ensure that emerging degradation risks, unexpected analytical results, storage conditions, and other quality signals are incorporated into specifications, testing strategies, investigations, and lifecycle risk assessments.

How Verta Can Help

Verta Life Sciences helps pharmaceutical and biotechnology companies prepare for critical CMC, Quality, manufacturing, and regulatory milestones across the product lifecycle.

Our teams support organizations with CMC strategy and gap assessments, IND/IMPD/NDA/BLA readiness, analytical and stability strategy, process validation, manufacturing and facility readiness, CDMO oversight, Quality systems, inspection readiness, remediation, and regulatory CMC support.

Whether the next milestone is a first-in-human IND, an accelerated development program, technology transfer, an NDA/BLA submission, or a pre-approval inspection, identifying potential CMC gaps early can provide more options and more time to resolve them.