Q&A Case studyContinuous Manufacturing
From Batch to Continuous: Rewiring an OSD Product for Steady-State Manufacture
Bayer's Leverkusen site converted a commercial oral solid dosage product from traditional batch to continuous direct compression — and cut cycle time by more than a third.
Reduction in end-to-end cycle time
38%
The practitioner
Thomas Wagner
Head of Continuous Manufacturing, Bayer
Interview by Mrudula Kulkarni
Managing Editor - Pharma Now
14 Jul 2026 · 11 min read
The challenge
The product in question sold in high volumes but suffered persistent inter-batch variability on assay uniformity, forcing an expensive…
The approach
A Quality by Design programme mapped the critical material and process parameters, then built a continuous direct compression line with…
The result
Post-conversion, cycle time dropped 38 percent, rework rate collapsed to under 0.5 percent, and the product was released under real-time…
The challenge
The product in question sold in high volumes but suffered persistent inter-batch variability on assay uniformity, forcing an expensive rework rate above 4 percent. Batch manufacturing was also constrained by cleaning turnarounds that pushed cycle times past what supply planning could tolerate for the growing forecast.
The approach
A Quality by Design programme mapped the critical material and process parameters, then built a continuous direct compression line with in-line NIR and RTRT capability. Regulatory prior approval was sought as a comparability protocol, and the team ran a nine-month parallel manufacturing period to build the evidence package.
The result
Post-conversion, cycle time dropped 38 percent, rework rate collapsed to under 0.5 percent, and the product was released under real-time release testing within eighteen months. The site now uses the resulting playbook to evaluate two additional OSD candidates for conversion.
Q
Why continuous direct compression rather than continuous wet granulation?
The API blend was already well characterised for direct compression and had no compaction issues in batch. Adding a wet-granulation step would have introduced a whole new set of critical process parameters and a longer regulatory conversation.
Direct compression let us reuse most of the existing formulation knowledge while getting the continuous benefits — shorter cycle time, in-line PAT, RTRT eligibility.
Q
How did you build the regulatory package?
We filed a comparability protocol up front — that gave the agency visibility into the plan and let us define the acceptance criteria for the switchover in advance.
The nine-month parallel run generated the actual comparability data. Every batch was manufactured in parallel on both lines, tested against the same specifications, and the results were tabulated in a single package the agency reviewed at the end.
Q
What did the operators need to learn that surprised you?
Reading the PAT signals in real time. In batch, they were used to reviewing quality at the end of a step. In continuous, if you wait until the end you have thousands of tablets you can't recover.
We built a two-week hands-on training programme with the PAT vendor and made every operator run at least four full campaigns before certification.
The parallel run was expensive, but it turned a comparability protocol into a data conversation.
Thomas Wagner, Head of Continuous Manufacturing
Measured impact
38%
Reduction in end-to-end cycle time
<0.5%
Post-conversion rework rate
18 mo
Time to real-time release testing
The method, in brief
1
Map critical process parameters via QbD — Started with a formal QbD exercise across the existing batch process. Identified which parameters would be genuinely critical in continuous mode — turns out only about half of the batch CPPs mattered at steady state.
2
File a comparability protocol early — Submitted the comparability protocol to the agency before ordering the continuous line hardware. Locked in the acceptance criteria for the eventual switchover.
3
Install in-line NIR sized for RTRT — Sized the NIR instrumentation for real-time release testing from day one. Cheaper to over-spec once than to retrofit after the line is qualified.
4
Run 9-month parallel manufacturing — Every commercial batch was manufactured in parallel on both the batch and continuous lines for nine months. Same specs, same testing, single evidence package for the regulator.
5
Retrain operators on real-time PAT — Two-week hands-on training programme with the PAT vendor. Every operator completed at least four full campaigns before certification.
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