CEPiA WHITE PAPERS
INNOVATIVE PLATFORM
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
LIQUID & SOLID PHASE CHEMISTRY
PEPTIDES & OLIGONUCLEOTIDES
From a unique state-of-the-art platform for development and scale-up of Peptides in Frankfurt (Germany) and Oligonucleotides in Frankfurt (Germany) & Haverhill (United Kingdom), CEPiA offers customized services (manufacturing and analytical) and can provide the full scope of development activities from clinical phase up to submission and launch, including regulatory support, as well as commercial supplies. Both sites are regularly inspected by FDA, International and European agencies. In Frankfurt, cGMP API manufacturing can be combined with Drug Product and Devices Technology (Fill & Finish on our « TIDES » platform).
Figure 1 : Oligo Process synthesizer
Figure 2 : Industrial scale equipment
www.cepia-sanofi.com
INNOVATIVE PLATFORM
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
Through Sanofi’s 25-yearsexperience in the field of oligonucleotides, CEPiA can provide different classes of Oligonucleotides such as DNA, 2’-O-Modified, phosphorothiolate derivatives via solid phase chemistry.
LIQUID & SOLID PHASE CHEMISTRY
CEPiA can develop your Oligonucleotides from g scale up to kg quantities. We operate a variety of different Oligonucleotide synthesizers (with our “Oligo Process” performing up to 600 mmole batches. This synthesizer is equipped with 12 independent amidite ports. Figure 3 : Oligonucleotides :process & equipment
The purification is performed at industrial scale by Ion Exchange or Reverse Phase chromatography. The final lyophilization is handled in freeze dryers with a capacity up to 100 kg ice.
Within our peptide plant in Frankfurt, we manufacture different classes of peptides. CEPiA offer Solid-Phase Peptide Synthesis and / or Solution phase peptide synthesis from g up to approximately 3 digit kg possible (depending on molecule size). Peptides up to ~ 50 mers are synthesized using solid phase technology using equipment from 10 L to 280 L. Purification is conveniently accomplished after each step by a simple wash and filtration. Small peptides are synthesized by solution phase peptide chemistry using equipment from 50 L to 1200 L. Figure 4 : Peptides : process & equipment
For the purification, we can develop isolation techniques (Precipitation / Lyophilization) and chromatographic Purification Processes (Reverse phase, ion exchange, etc.).
www.cepia-sanofi.com
INNOVATIVE PLATFORM
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
LIQUID & SOLID PHASE CHEMISTRY
Figure 5 : Seamless scale-up from mg to kg
CEPiA provides a full analytical service: • Structural characterization • Development and validation of analytical methods (SM, IPC, DS ) • Determination of column lifetime and leachables • Holding time studies • Characterization of amidites and PNS • Sequence investigation / confirmation for impurities and target compound [ap plying mass spectrometry & enzymatic digestions] • Melting temperature analysis • Reaction Monitoring (“IPC”) and impurity tracking based on MS • Purification of Reference Materials and Reference Standards • Stability Studies to ICH standards • QC testing for batch release This full analytical service benefit from the following equipment: • Chromatography: HPLC (UV, light scattering and MS detection), GC (FID, MS and WLD detection, headspace injection), IC, prep HPLC, CE, LC-MS • Water content: KF (headspace) • Mass spectrometry: MALDI-TOF; Q-TOF; TOF; Ion Trap • NMR: 600 MHz & 400 MHz (1H / 13C / 19F / 31P/...), (solution, gel and solid probes) • AAS (graphite oven): Pd, Rh, Pb, Cu, Ni, Zn, Pt, Fe • Extensive PAT capabilities – in line FT-IR, NIR, Raman, UV-vis, Conductivity, RI, NMR, MS, density, etc. with experience of integration with Unicorn software. • Sequence guarantee using PAT in accordance with QbD principles. • Imaging of synthesis and purification columns • Polymer support analysis CEPiA can offer the full scope of analytical studies needed for filing and the support for the redaction of CMC dossier following the latest regulatory expectations.
www.cepia-sanofi.com
INNOVATIVE PLATFORM
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
We noticed, that CMC development has become increasingly challenging in the last years requiring not only to meet scientific/technical but also financial criteria. The “typical” project does not exist anymore. We see early development compounds from start–up companies as well as late stage projects with correspondingly very different expectations and timelines. CEPIA is discussing these topics with the customer within the common project team as the central communication platform for development activities, in order to identify the optimum development approach. LIQUID & SOLID PHASE CHEMISTRY
Besides the technical aspects, work on regulatory strategy has become one of the key success factors. Oligonucleotides and Peptides are between the known small molecules and the large biomolecules. Regulatory strategy can therefore not be deduced from small molecule or biomolecule approaches. We worked on new successful regulatory strategies in close cooperation with Regulatory Authorities. Being the transition zone between small and large molecules we also have the impression, that the formerly strictly separated areas start to “network” to generate more value: Bioprocess are combined with chemical transformations, online analysis embedded into the manufacturing process, oligonucleotides with peptides to come? We are excited about the next steps in science to come...
Figure 6 : Industrial scale equipment
Figure 7 : Laboratory scale equipment
[email protected]
www.cepia-sanofi.com
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
LIQUID & SOLID PHASE CHEMISTRY
PEPTIDES & OLIGONUCLEOTIDES
From a unique state-of-the-art platform for development and scale-up of Peptides in Frankfurt (Germany) and Oligonucleotides in Frankfurt (Germany) & Haverhill (United Kingdom), CEPiA offers customized services (manufacturing and analytical) and can provide the full scope of development activities from clinical phase up to submission and launch, including regulatory support, as well as commercial supplies. Both sites are regularly inspected by FDA, International and European agencies. In Frankfurt, cGMP API manufacturing can be combined with Drug Product and Devices Technology (Fill & Finish on our « TIDES » platform).
Figure 1 : Oligo Process synthesizer
Figure 2 : Industrial scale equipment
www.cepia-sanofi.com
INNOVATIVE PLATFORM
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
Through Sanofi’s 25-yearsexperience in the field of oligonucleotides, CEPiA can provide different classes of Oligonucleotides such as DNA, 2’-O-Modified, phosphorothiolate derivatives via solid phase chemistry.
LIQUID & SOLID PHASE CHEMISTRY
CEPiA can develop your Oligonucleotides from g scale up to kg quantities. We operate a variety of different Oligonucleotide synthesizers (with our “Oligo Process” performing up to 600 mmole batches. This synthesizer is equipped with 12 independent amidite ports. Figure 3 : Oligonucleotides :process & equipment
The purification is performed at industrial scale by Ion Exchange or Reverse Phase chromatography. The final lyophilization is handled in freeze dryers with a capacity up to 100 kg ice.
Within our peptide plant in Frankfurt, we manufacture different classes of peptides. CEPiA offer Solid-Phase Peptide Synthesis and / or Solution phase peptide synthesis from g up to approximately 3 digit kg possible (depending on molecule size). Peptides up to ~ 50 mers are synthesized using solid phase technology using equipment from 10 L to 280 L. Purification is conveniently accomplished after each step by a simple wash and filtration. Small peptides are synthesized by solution phase peptide chemistry using equipment from 50 L to 1200 L. Figure 4 : Peptides : process & equipment
For the purification, we can develop isolation techniques (Precipitation / Lyophilization) and chromatographic Purification Processes (Reverse phase, ion exchange, etc.).
www.cepia-sanofi.com
INNOVATIVE PLATFORM
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
LIQUID & SOLID PHASE CHEMISTRY
Figure 5 : Seamless scale-up from mg to kg
CEPiA provides a full analytical service: • Structural characterization • Development and validation of analytical methods (SM, IPC, DS ) • Determination of column lifetime and leachables • Holding time studies • Characterization of amidites and PNS • Sequence investigation / confirmation for impurities and target compound [ap plying mass spectrometry & enzymatic digestions] • Melting temperature analysis • Reaction Monitoring (“IPC”) and impurity tracking based on MS • Purification of Reference Materials and Reference Standards • Stability Studies to ICH standards • QC testing for batch release This full analytical service benefit from the following equipment: • Chromatography: HPLC (UV, light scattering and MS detection), GC (FID, MS and WLD detection, headspace injection), IC, prep HPLC, CE, LC-MS • Water content: KF (headspace) • Mass spectrometry: MALDI-TOF; Q-TOF; TOF; Ion Trap • NMR: 600 MHz & 400 MHz (1H / 13C / 19F / 31P/...), (solution, gel and solid probes) • AAS (graphite oven): Pd, Rh, Pb, Cu, Ni, Zn, Pt, Fe • Extensive PAT capabilities – in line FT-IR, NIR, Raman, UV-vis, Conductivity, RI, NMR, MS, density, etc. with experience of integration with Unicorn software. • Sequence guarantee using PAT in accordance with QbD principles. • Imaging of synthesis and purification columns • Polymer support analysis CEPiA can offer the full scope of analytical studies needed for filing and the support for the redaction of CMC dossier following the latest regulatory expectations.
www.cepia-sanofi.com
INNOVATIVE PLATFORM
CEPiA WHITE PAPERS
SCIENTIFIC EXPERTISE
STATE-OF-THE-ART EQUIPMENT
We noticed, that CMC development has become increasingly challenging in the last years requiring not only to meet scientific/technical but also financial criteria. The “typical” project does not exist anymore. We see early development compounds from start–up companies as well as late stage projects with correspondingly very different expectations and timelines. CEPIA is discussing these topics with the customer within the common project team as the central communication platform for development activities, in order to identify the optimum development approach. LIQUID & SOLID PHASE CHEMISTRY
Besides the technical aspects, work on regulatory strategy has become one of the key success factors. Oligonucleotides and Peptides are between the known small molecules and the large biomolecules. Regulatory strategy can therefore not be deduced from small molecule or biomolecule approaches. We worked on new successful regulatory strategies in close cooperation with Regulatory Authorities. Being the transition zone between small and large molecules we also have the impression, that the formerly strictly separated areas start to “network” to generate more value: Bioprocess are combined with chemical transformations, online analysis embedded into the manufacturing process, oligonucleotides with peptides to come? We are excited about the next steps in science to come...
Figure 6 : Industrial scale equipment
Figure 7 : Laboratory scale equipment
[email protected]
www.cepia-sanofi.com
