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API Process Development
One team on the route from the first scouting experiment to process validation.
The early-phase trade-off
The fastest route to first-in-human is rarely the route that survives to commercial supply. A route chosen for speed alone usually has to be rebuilt later, with the comparability work that brings; a route optimized too early for the commercial process delays the IND.
Early-phase process development manages the trade-off: deciding which simplifications carry no cost at scale, and which will have to be undone.
3,500+ process chemists and analytical scientists support synthetic drugs from preclinical through clinical to commercial launch, across starting materials, intermediates and API, including high potency compounds at an occupational exposure limit of 10 ng/m³.
Timelines in weeks per step
Process development and manufacturing runs at about 2.5 weeks per step for the API, and 1.5 weeks per step for regulatory starting materials. The number of steps per route determines the timeline.
We have supported more than 2,000 molecules from preclinical through Phase II.
Route scouting
Before a route is committed, we look for the one that can be run at scale: fewer steps, safer reagents, controllable impurities, and starting materials that can be purchased.
That work includes isolating, characterizing, and controlling process impurities, validating both the synthetic and analytical protocols, and running stress tests and safety evaluation before a step goes into a kilo lab.
Process development
Condition optimization, in-process controls, and the analytical methods that will stay with the molecule through to commercial supply. Our enabling technologies are available from the first campaign: crystallization and particle engineering, flow chemistry, biocatalysis, chemocatalysis, and preparative HPLC, SFC, and SMB chromatography.
High-potency compounds are handled on the same platform, down to an occupational exposure limit of 10 ng/m³, and every enabling technology is available inside containment.
Regulatory starting material designation
Where the regulatory starting material is designated determines how much of the synthesis sits inside the filing and under GMP. A designation too late in the route carries unnecessary GMP cost for the life of the product, and one too early is likely to be challenged by the agency.
We assess the proposed designation against ICH guidance and FDA, EMA, and NMPA expectations, and where a challenge is likely, we build the development data to defend it. If a challenge does come, the response takes about 12 weeks, including the quality-by-design study and the PPQ manufacturing behind it.
Late phase process optimization
Until Phase II, the process is only to make material; from Phase II onward, it has to be defensible. Every choice made quickly in early development is re-examined: where the regulatory starting material sits, whether the impurity profile is controlled or only observed, and whether the route gives the same result on a different scale with a different team.
A team of more than 700 process chemists and analytical scientists works exclusively on late-phase programs, from Phase II through marketing application submission and commercial launch, across regulatory starting materials, API intermediates, APIs and high potency products.
Step count, solvent volumes and cycle time are all worked on in late phase, because at commercial scale each determines cost of goods and process mass intensity for the life of the product.
Timeline to process validation and commercial launch runs 15 to 20 months, shorter than a typical industry timeline. An established workflow accelerates analytical validation alongside it.
Process validation
We have taken more than 180 new chemical entities through process performance qualification since 2018, with a 100% success rate.
Validation is the point at which every earlier shortcut becomes visible, which is why most of the work behind a successful PPQ is done in late-phase development.
Analytical services and quality control
Analytical development runs alongside the chemistry rather than behind it. More than 750 analytical scientists develop the methods, and more than 920 QC analysts release the batches, at every manufacturing site.
Where cost of goods is set
By late phase the question is what the process costs, and the answer usually sits in the three or four steps that have not been revisited since the first campaign.
Finding those steps is a matter of having optimized many similar processes before, which is why a process that already works is still worth putting in front of the late-phase team.
Speed that holds at Phase III
A route that reaches IND quickly and cannot be scaled has to be reworked in Phase II, when any process change brings comparability data with it.
Route scouting is given the time the route needs, and the workstreams downstream of it, analytical development, stability and dossier preparation, run in parallel.