The Common Technical Document quality section hasn't been updated since 2002. Twenty-three years. The same Module 3 structure we've been using was designed before biosimilars were a regulatory pathway, before ADCs became a real drug class, before anyone was filing submissions for cell and gene therapies.
ICH M4Q(R2) changes that. It's the first major revision of the CTD quality section, and it's on track for final adoption in June 2027. If you're filing INDs or NDAs, this affects how you organize every piece of CMC data in your submission.
I've been reading the draft and the industry feedback. Here's what's actually changing and what you should be doing now.
What M4Q(R2) replaces
The original M4Q(R1) from 2002 defined the CTD quality structure that every regulatory agency in the ICH regions uses. Module 2.3 (Quality Overall Summary) and Module 3 (Quality Body of Data) — those formats came from M4Q(R1).
The revision doesn't touch Modules 1, 4, or 5. It doesn't change the nonclinical or clinical sections. This is purely about the quality/CMC data: drug substance, drug product, and how it all gets summarized in Module 2.3.
The big structural change: Module 2.3 gets six subsections
Old Module 2.3 was a single narrative document. You wrote one Quality Overall Summary that covered everything. The new M4Q(R2) breaks it into six distinct subsections, each with a specific job:
| Section | Name | What it does |
|---|---|---|
| 2.3.1 | General Information | Product identification — names, structures, basic descriptors |
| 2.3.2 | Overall Development and Control Strategy | Your QbD framework: QTPP, CQAs, how each control element fits together |
| 2.3.3 | Core Quality Information (CQI) | The authoritative quality dataset — everything subject to lifecycle management |
| 2.3.4 | Development Summary and Justification | Scientific rationale for your specs, control strategy, process choices |
| 2.3.5 | Product Lifecycle Management (PLCM) | Science-based data supporting ongoing lifecycle management per ICH Q12 |
| 2.3.6 | Product Quality Benefit Risk | Optional — how quality risks are mitigated (relevant for expedited pathways) |
Sections 2.3.3 and 2.3.5 are genuinely new concepts, not just reorganized content.
Core Quality Information (CQI) is the big one. It's meant to be the single authoritative source of quality data that must be kept current throughout the product's lifecycle. Think of it as the quality equivalent of what the Investigator's Brochure is for clinical data — the living document that FDA and other agencies reference for current quality status.
Product Lifecycle Management links your quality data to ICH Q12 Established Conditions. If you've been following Q12, this is where it connects to the submission format. If you haven't been following Q12... you probably should start.
DMCS: the new template for everything
Both Module 2.3 and Module 3 now follow a standardized template called DMCS:
- Description — what is this material, what are its key characteristics
- Manufacture — production process and process controls
- Control — specifications, analytical testing, quality control
- Storage — stability, container closure, shelf life
Drug substance sections follow DMCS. Drug product sections follow DMCS. Intermediates, starting materials, excipients — all DMCS. The consistency makes cross-referencing easier, but it means restructuring how you organize data if your current Module 3 doesn't follow this pattern.
For your Quality Overall Summary, this is the most significant change. Instead of a free-form narrative, you'll need structured subsections that each serve a defined regulatory purpose.
Module 3 becomes pure supporting data
Under the old format, Module 3 contained both summary information and detailed data. It was never fully clear where summary ended and data began. M4Q(R2) draws a hard line: Module 2.3 holds the core quality information and summaries. Module 3.2 is exclusively the repository for supporting data with cross-references back to 2.3.
In practice: your drug substance specifications live in Module 2.3.3 (CQI). The validation reports, batch analyses, and method descriptions that support those specs live in Module 3.2. No more duplicating information across both modules.
This sounds cleaner on paper. The transition is the hard part. Every existing submission has data organized the old way, and somebody has to reorganize it.
Timeline
| When | What happens |
|---|---|
| May 2025 | ICH endorses draft (Step 2) |
| June-October 2025 | Public comment period |
| Late 2026 | Comments reviewed, final draft prepared |
| June 2027 | Step 4 adoption — final guideline |
| June 2027 | Effective for all new product submissions |
| ~2028 | Full implementation expected, aligned with eCTD 4.0 |
| TBD | Legacy product conversion timeline |
The legacy product question is the biggest open issue. Industry groups are requesting up to five years for converting existing dossiers to the new format. ICH hasn't given a definitive answer yet.
What this means for you right now
If you're filing a new IND or NDA before June 2027, you file under the current M4Q(R1) format. No changes required. Your existing Module 3 structure works.
If you're planning a submission after June 2027, you'll need to follow M4Q(R2). That means:
Your Module 2.3 needs restructuring. Six subsections instead of one narrative. CQI as a standalone section. Lifecycle management content. If you've been writing the Quality Overall Summary as a long document that mixes development history with specifications with stability conclusions, you'll need to separate those into distinct sections.
Your Module 3.2 needs to be a data repository, not a hybrid. Remove summary content from Module 3 that should now live in Module 2.3. Add cross-references. This is grunt work but it's not optional.
Your SOPs need updating. Any SOP that references "Module 3 format per ICH M4Q(R1)" needs to say M4Q(R2). Template documents, review checklists, submission procedures — audit everything that references the CTD quality format.
Start tracking ICH Q12. The lifecycle management subsection (2.3.5) connects directly to Q12's concept of Established Conditions. If your company hasn't engaged with Q12 yet, M4Q(R2) forces the issue.
The eCTD 4.0 connection
M4Q(R2) was designed to work with eCTD 4.0, the next version of the electronic CTD format. The two are meant to roll out together. The DMCS template, the structured subsections, the machine-readable format — all of this feeds into FDA's push toward structured data submissions.
If you're currently submitting in eCTD 3.x (which is everyone), the transition to eCTD 4.0 + M4Q(R2) is a combined effort. Don't plan them separately.
What we're doing at Regfo
Our CTD Library currently maps requirements to the M4Q(R1) structure. When M4Q(R2) is finalized, we'll update the mapping — new section numbers, new cross-references, updated drug substance and drug product structures.
The compliance checker will flag documents organized under the old format when you're targeting a post-June 2027 submission date. It'll also check whether your Module 2.3 has the required six subsections and whether CQI content is properly separated from supporting data.
Who this hits hardest
Large pharma companies have regulatory operations teams that do nothing but manage CTD structure. They'll handle this transition. It'll be expensive and annoying, but they have the people.
Small biotechs filing their first or second IND? This is where it gets interesting. If you're filing after June 2027, your CMC consultant or regulatory writer needs to know M4Q(R2). Not "heard of it" — actually know how to write a CQI section and structure Module 2.3 with six subsections.
I'd ask your CMC team or consultant directly: have you read the M4Q(R2) draft? Can you walk me through what changes in Module 2.3? If the answer is vague, that's a red flag. You don't want to discover formatting issues during a review cycle.
CROs preparing CMC sections for sponsors should be getting ahead of this. If your CRO's submission templates still reference M4Q(R1) and they don't have a transition plan, bring it up now. Not in 2027 when the deadline hits.
The practical first step
Read sections 2.3.3 (Core Quality Information) and the DMCS template description in the draft. Those are the conceptually new pieces. The rest is restructuring you can figure out once you understand the framework.
Then look at your current Module 3 and ask: where does the same information appear in both Module 2.3 and Module 3? That duplication is exactly what M4Q(R2) eliminates, and mapping it is the first step toward transition.
For now, the draft is 200+ pages. The parts that matter most for small biotech CMC teams are Core Quality Information and the DMCS template. Start there.
Related: FDA IND Submission Checklist 2026 | ICH Q1 Revision: Stability Testing
We'll be publishing more detailed breakdowns of each M4Q(R2) subsection as the final guideline approaches. If you want to stay ahead of the transition, keep an eye on our blog or check the CTD Library — we update it as guideline changes are confirmed.
ICH M4Q(R2) is currently at Step 2 (draft for public comment). Final guideline expected June 2027. This article is based on the draft — final version may differ. Sources: ICH M4Q(R2) Draft, RAPS Coverage.