API capabilities

 

Since all drug development activities depend on the reliable supply of the Active Pharmaceutical Ingredients (APIs), a foremost Evotec capability is its comprehensive global API service. 

These services span from the interaction with our discovery team to commercial production of API at up to 1,600 L scale.

The spread of our capabilities allows Evotec team to cater for multiple need: From the preparation of advance intermediate to support the drug discovery programme to the development and manufacture of late phase manufacturing process for commercial application in our fully compliant and audited plants.

A notable aspect of Evotec’s API capabilities is the ability to manufacture highly potent compounds as well as manufacture and distribute controlled substances.

Chemical development activities

To achieve the successful support of the drug development cycle, starting from pre-clinical to clinical and commercial supply, Evotec will involve chemists from its pool of more than 60 development chemists, all bringing in their own expertise to support the key steps of the development of our partner’s API:

  • Route scouting and identification of a new route to enable efficient scale-up
  • Custom synthesis
  • Analytical method development and validation
  • Process development to enable scale-up
  • Genotoxic risk assessment according to ICH M7 guidances
  • Synthesis of reference standards and impurity markers as well as Stable Labelled Isotope Standard (SIL)

Our customers are asking us to use our expertise to support different development strategies going from "Fit For Purpose" for the pre-clinical to early phase to generate more knowledge and process understanding when the programmes are moving through the clinical phases. 
Our main objective is the development of a process that will be scaled to deliver the material of required quality and support successful regulatory interaction.

Using more than a quarter of century of experience, the teams have developed approaches enabling efficient and seamless transfer of the procedures from the laboratory to the pilot plant. 
An in-depth understanding of the API process chemistry enables Evotec scientists to develop efficient and sustainable synthetic processes to whatever level is required by our sponsors.  Such activities require strong links between our organic chemists, our physico chemists, our analysts but also our sourcing and quality assurance teams.

From our multiples sites, we can call on a broad array of techniques that are getting embedded in our development activity:
  • Generate the required knowledge of the solid state property of our intermediate and API and deliver a robust crystallisation procedure securing purity, polymorphic and particle size control as needed
  • Identify a suitable salt to support isolation/purification but also as means to achieve chiral separation
  • Hydrogenation capacity (pressure up to 40 bars) and ability to rely on our screening experience and designated equipment supported by our specialised analytical group
  • Use of preparative chiral of achiral HPLC /SFC systems
  • Chiral synthesis, with an expertise in designing suitable processes that can be really and seamlessly scaled-up to dozen of kilos relying on the historical patrimony of some of our sites
  • The design of safe chemistry processes is guaranteed using our thermo hazard specialists relying on their experience and specific equipment (calorimeters type RC1, DSC, ARC)
  • Bring its skills to bear on detailed process studies, applying parallel experimentation, statistical tools (MVA, PCA, PLS), Design of Experiment (DoE), kinetics studies and Process Analytical Technology (PAT), either as part of QbD based strategy or as individual tools

As an average, the Evotec teams developed approximately 100-150 stages of chemistry a year for scale-up prior to operate them in kilo lab and about 50 stages of chemistry to be scale-up to plant scale. 

Our teams have developed a broad experience in many chemistry areas: 
  • Chiral chemistry
  • Organo-metallic, metal mediated transformation/coupling, hydrogenation
  • Hazardous chemistry:  Pyrophoric reagents (tBuLi); Azide Chemistry; toxic reagents (e.g. alkylating agents such as dimethyl sulphate)
  • Sugar chemistry at scale including azide chemistry
  • Developed processes with intermediates without UV chromophores
  • Impurity control via efficient work-up as well as a purification system for the early phase of the process life cycle

Evotec teams are composed of high standard chemists selected based on their scientific knowledge and experience. With a low turnover and a high ratio of PhD >75%, knowledge, experience, ability to understand our customer needs and communicate with our customer are probably our strongest tools.

Pilot Plant Manufacturing

As a clinical programme progresses and demand for API grows, Evotec is well positioned to seamlessly transfer suitable processes from its development laboratories to pilot facilities, all of which operate to the highest regulatory standards. Over the last decade Evotec has made and isolated literally thousands of intermediates, starting materials and final products to appropriate levels of cGMP, with API prepared from a single stages but up to more than 20 stages, involving most of the known chemical transformations.

Key aspects of Evotec’s pilot plant offering:
  • Facilities operating 18 reactions vessels up to 1,600 L and a total volume of >8,000 L
  • Filtration system from enclosed filters to filter dryers and centrifuge with fully contained off-loading
  • FDA, MHRA and AIFA inspected
  • Manufacture of non-cGMP material for pre-clinical support
  • Manufacture of clinical trial material and commercial supply up to several hundred kilos
  • Certified ISO14001 environmental quality standard
  • Class 100,000 clean rooms
  • Hydrogenation: high pressure vessel at up 20 L and from atmospheric pressure up to 7 bar at 1,600 L scale-also applicable for the use of other gases (CO, NH3..)
  • Cryogenic capability to –80°C and  up to +160°C
  • Supply of potent and toxic materials (HAPI) with OEL>0.5mg/m3
  • Use, manufacture and supply of controlled substances to Schedule 1

Commercial manufacturing

Evotec has licenses to perform commercial manufacture and accordingly, dependent on the volume of material required, can provide clients with the option of ongoing commercial supply for small volume APIs. 
Smooth scale-up of chemical processes is assured through reactor capacities up to 1,600 L that can produce kilogram to metric ton batches, both cGMP and non-GMP. 
High-potency APIs can be produced in capacities that range from 20 L to 1,500 L.

Highly potent APIs

A further distinction that supports Evotec’s leading industry position in API development is our ability to handle highly potent compounds (HPAPIs) at multiple global sites. HPAPI capabilities feature:

  • State-of-the-art containment facilities for both drug substance and drug product development and production
  • Class 100,000 clean rooms
  • Clean-in-place systems
  • Gram to kilogram capacities
  • Barrier (isolator) technology on reactors and solid handling systems
  • Automated and validated computer controls
  • Containment suites for the formulation of potent drug compounds
  • Separate HEPA-filtered air handling systems
  • Exposure and environmental monitoring
Clinical Phase I
Clinical Phase II/III
Commercial manufacture
Batch sizes
1 to 2 kg
3 to 50 kg
up to 120 kg
Scale
20/50 L glass vessels
20 to 1,600 L, glass, glass lined steel, Hastelloy
100 to 1,600 L
Equipment
Pressure hydrogenation up to 40 bar, Cryogenic up to -80°C, PAT tools: Lasentec, Raman 
Cryogenic up to -80°C (OXF - 400 L), Hydrogenation (OXF – up to 1,600 L & 7 bar), enclosed Hastelloy filter dryers, high-potent handling from 0.5 µg/m3 at up to 1,600 L scale (Abingdon), Centrifuge, Lasentec
Same as clinical Phase II/III
Containment
OEB 4
OEB 4 up to 1,600 L 
OEB 5 up to 1,600 L 
Batch sizes
Clinical Phase I 1 to 2 kg
Clinical Phase II/III 3 to 50 kg
Commercial manufacture up to 120 kg
Scale
Clinical Phase I 20/50 L glass vessels
Clinical Phase II/III 20 to 1,600 L, glass, glass lined steel, Hastelloy
Commercial manufacture 100 to 1,600 L
Equipment
Clinical Phase I Pressure hydrogenation up to 40 bar, Cryogenic up to -80°C, PAT tools: Lasentec, Raman 
Clinical Phase II/III Cryogenic up to -80°C (OXF - 400 L), Hydrogenation (OXF – up to 1,600 L & 7 bar), enclosed Hastelloy filter dryers, high-potent handling from 0.5 µg/m3 at up to 1,600 L scale (Abingdon), Centrifuge, Lasentec
Commercial manufacture Same as clinical Phase II/III
Containment
Clinical Phase I OEB 4
Clinical Phase II/III OEB 4 up to 1,600 L 
Commercial manufacture OEB 5 up to 1,600 L 

Contact us

Evotec

Business Development

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