ICH Q13, the continuous-manufacturing quality guideline that sits alongside Q8 through Q12 in the CMC lifecycle stack, reached Step 4 at the ICH Assembly in November 2022. The EMA published its Step 5 version on 6 January 2023 and the guideline came into effect in the EU on 10 July 2023. The FDA announced availability of the harmonised text in March 2023. Three years after the earlier of those dates, the question is no longer whether the framework exists but whether sponsors are filing under it and whether reviewers are handling those filings the way the framework anticipates.
The short answer, drawn from FDA presentations, the Emerging Technology Program (ETP) tallies and the ISPE commentary that followed adoption, is that uptake is real but narrow. A double-digit number of continuous-manufactured products carry FDA approvals. Continuous manufacturing is the most-accepted category inside the ETP. Outside that concentrated cluster of sponsors, the rest of the industry has yet to convert intent into filings.
This piece tracks where Q13 stands across the ICH regulatory members, what the FDA numbers say about approvals and pre-submission engagement, and which pieces of the guideline are shaping the analytical control strategies that reviewers now expect to see.
Regional status
In the European Union, the EMA published the Step 5 version of ICH Q13 in January 2023 and it came into effect on 10 July 2023. The scope covers continuous manufacturing of drug substances and drug products for chemical entities and therapeutic proteins, and applies to new products, existing products moving from batch to continuous, and to segments of an otherwise batch process operated continuously. The EMA’s scientific guideline page is the entry point for the Step 5 text and the related Q&A track.
In the United States, the FDA published the guidance in March 2023 as “Q13 Continuous Manufacturing of Drug Substances and Drug Products”. The agency treats it as a harmonised ICH guidance, non-binding but describing the agency’s current thinking, with no US-specific transition arrangements. Filings that predate the guidance and used the earlier draft Quality Considerations text have not been re-opened, but new filings are expected to align with Q13’s structure.
Japan’s PMDA, an ICH founding member, aligned with the harmonised text on the same schedule. Continuous manufacturing has been on the PMDA’s radar since the agency’s Innovative Manufacturing Technology working group produced its early position papers, and Q13 formalises the vocabulary the agency was already using in scientific advice.
Outside the ICH regulatory members, adoption has followed the Q14 pattern: Switzerland’s Swissmedic, China’s NMPA and Health Canada have implemented the text, while several observers have adopted it in principle without codifying inspection expectations. Sponsors filing globally are working from a single scientific framework but with regional variation in how detailed the control-strategy narrative needs to be.
What the approval and ETP data show
The clearest public window into US uptake is the FDA’s Office of Pharmaceutical Quality. In a 2024 update covered by RAPS, Adam Fisher, staff director of the CDER Office of Pharmaceutical Quality, said 17 drugs had been approved using continuous manufacturing. Inside the ETP - the FDA’s front door for novel technology discussions ahead of a filing - continuous manufacturing was the most-accepted category, with 72 technology acceptances against 27 for novel unit operations, 25 for novel analytical technologies, 24 for aseptic technologies, 13 for novel container-closure systems and 6 for distributed or point-of-care manufacturing models. The mix is the more informative number: it tells you that CM engagement is not a single-vendor phenomenon and that the pipeline of pre-submission conversations is deeper than the approvals ledger suggests.
The approvals themselves remain concentrated among a small number of sponsors and product classes: solid-oral small molecules dominate, biologics are a minority, and the same handful of names - Janssen, Vertex, Pfizer, Lilly, Merck and a few contract manufacturers - reappear across filings. The FDA does not publish a per-sponsor breakdown, but the ISPE analysis in ICH Q13 and What Is Next for Continuous Manufacturing tracks the public case examples that anchor the community’s shared understanding of what a Q13-conformant control strategy looks like.
What Q13 actually changed in filings
Three concepts in the guideline are doing most of the work in day-to-day submissions. First, the definition of a “batch”. Q13 formalises that a batch in a continuous process is defined by a specified quantity produced during a defined run time or period of operation, not by a physical vessel volume. That shift lets sponsors design a control strategy around residence-time distribution and material-tracing logic rather than around discrete step-change points.
Second, the state of control and the associated concept of process dynamics. Q13 asks sponsors to describe how the system enters, maintains and exits a state of control, and how transient disturbances are detected and handled. The practical consequence is that PAT and real-time release testing move from optional embellishments to load-bearing pieces of the file. The chemometric model lifecycle across the FDA, EMA and PMDA is a useful companion here, because the model-maintenance obligations that Q13 implies are the same ones that Q14 formalises for the underlying analytical procedures.
Third, material diversion and traceability. Q13 sets an expectation that sponsors can identify and divert non-conforming material during operation, and that the diversion logic is part of the control strategy - not a separate deviation procedure. That is the piece of the guideline most likely to drive facility investment, because retrofitting diversion into a legacy skid is harder than adding a probe.
What is blocking wider uptake
The barriers are consistent across sponsor interviews at PDA, ISPE and the AAPS-PQRI PAT groups. Legacy facilities are the largest single item: converting a validated batch line to continuous is a capex decision that competes against new-product programmes and against the batch line’s own paid-off depreciation. Chemometric-model maintenance is the next: several early CM sponsors have reported that PAT-model drift and re-validation are absorbing more analytical-chemistry headcount than the original submission budgeted for, a pattern also visible in the broader terminology evolution across Q8 to Q14. Supply-chain concentration is the third: the number of vendors capable of supplying integrated PAT-plus-diversion instrumentation at pharma-grade documentation levels is small, and the lead times are long.
None of these are guideline problems. Q13 has done its job in that it is now the shared reference sponsors and reviewers argue from. The remaining friction sits in the plants and in the vendor bench.
What to watch through 2027
Two threads are worth tracking. First, whether the FDA publishes an updated tally of CM approvals or an ETP report that breaks the technology-acceptance numbers down by therapeutic modality. The 17-approvals figure is now two years old and the gap between ETP engagement and filed applications is the number that will show whether the pre-submission pipeline is converting. Second, whether the EMA issues a Q&A extending Q13’s language to biologics-specific process considerations - the guideline formally covers therapeutic proteins, but the case-example base is still overwhelmingly small-molecule.
For the broader status of continuous manufacturing in pharma production - beyond the regulatory-file view - our status report through early 2026 sets the operational context, and the ETP refresh piece covers how the FDA’s front door has evolved alongside the guideline.
Three years in, Q13 is on the books in every ICH regulatory member and in a growing set of observers. The next 12 months will show whether the concentrated cluster of CM filers widens - or whether continuous manufacturing settles into a durable niche around solid-oral small molecules with a slow drip of biologics behind it.