Supporting innovators’ complex modalities 26th October 2023
By Stephen Houldsworth, PhD, Senior VP of Platform Management & Marketing, CordenPharma International*
CordenPharma’s 2023 investments and global platform approach to CDMO development and commercialisation support pharma innovators with expanded end-to-end services to address their drug lifecycle gaps and reach patients faster.
CordenPharma provides CDMO services that elevate pharma and biotech customers to support complex modalities across the drug development spectrum. By aligning its facilities and technology platforms to anticipate the challenges innovators often encounter as they work through development phases towards commercial markets and patients, CordenPharma offers bespoke end-to-end services designed to promote the rapid scale-up of pre-clinical, clinical and commercial manufacturing capabilities, and the latest technology to accelerate development of today’s most advanced large and small-molecule therapeutics.
With its fully-integrated supply model as an overarching focus, CordenPharma has made recent, significant investments across all five previous technology platforms (Highly Potent and Oncology – Lipids & Carbohydrates – Peptides – Injectables – Small Molecules), and as of May, 2023, the company announced its re-entry into the Oligonucleotide manufacturing market to create a sixth Oligonucleotide Technology Platform.
All six 2023 technology platform service offerings are further bolstered by the creation of a new Technology and Science Advisory Board (TSAB) in July, 2023. By harnessing the knowledge and insights of eight renowned scientists and industry leaders coming from both academia and commercial sectors, CordenPharma aims to enhance capabilities in the efficient development and manufacturing of APIs, Lipid Excipients and Drug Products to support its broad pharmaceutical customer base. The new TSAB helps generate an unparalleled, fully-integrated service offering across its current Good Manufacturing Practice (cGMP) facility network to create the stable, streamlined outsourcing the pharma industry needs to develop and commercialise critical medications and reach global patients successfully.
Following the signature of a multi-year large scale peptide manufacturing agreement in early 2023, CordenPharma was pleased to announce in September, 2023, the inauguration of commercial peptide production with extensive investments in newly-upgraded facilities and increased capacity at CordenPharma Colorado, the largest Solid-Phase Peptide Synthesis (SPPS) manufacturing plant worldwide. The capital investments included a series of modernisations such as upgrades to an existing 10,000 litre reactor volume, which have increased the efficiency and throughput of SPPS peptide production to a batch size exceeding 400 kg (> 35 Amino Acids) and a yearly capacity of > 2 metric tons of peptide.
Additionally, full downstream capabilities, implementation of PAT for amino acid identification, greater efficiency for solvent delivery and effluent removal with reduced environmental impact and automation upgrades allow increased peptide capacity with a reduction in overall cycle time, improved scale-up consistency and the elimination of human error to service current and future customers across a growing pharmaceutical innovator base.
In addition to enhanced large-scale manufacturing, the company’s multi-pronged approach to becoming the #1 peptide CDMO supplier extends to small-scale capabilities, which started with expansions of non-GMP peptide capacity back in Q4 2020. Now, CordenPharma’s Peptide Centre of Excellence in Frankfurt, Germany is in the process of adding GMP manufacturing capacity to serve early-phase customers with first-in-human supplies.
The manufacturing line, which started construction at the end of 2022, will be available in H1 2024 and will consist of:
- 2 SPPS lines, 1 cleavage line and 1 liquid-phase reactor.
- Downstream process capabilities, including HPLC, concentration equipment (thin film, nanofiltration) and isolation equipment (filter & freeze dryer).
- Clean room concept and utilities.
The manufacturing area will be supported by a new fully-fitted QC laboratory that will support API release and stability studies. This fully-compliant area will receive local authority approval in Q2 2024 and will accommodate production up to kg scale supporting customers’ regulated toxicology studies, Phase 1 human clinical trials and Phase 2 resupply batches.
This newly built capacity, together with CordenPharma’s well-established injectable Fill and Finish services at CordenPharma Caponago, Italy, will jointly launch a unique, fully-integrated Drug Substance/Drug Product peptide offering in Q4 2023. Customers targeting First-In-Human clinical trials will be fully supported – from end of discovery phase to first GMP clinical supply – with a customised approach directed by experts in peptide chemistry, formulation and CMC preparation and strategy. CordenPharma believes this end-to-end approach will increase its customers’ chance of success in their IND submission, all while minimising their time to clinical trial.
New oligonucleotide platform
After an initial exit of the oligo market in 2018 due to shifting CapEx investments, CordenPharma was pleased to announce in 2023 that it has re-entered the oligonucleotide manufacturing space with an initial $25 million budget in two phases, backed by a record year-over-year sales growth in 2022 and reinforced with new Private Equity owners Astorg and scientific strategies to support innovative, complex modalities.
Phase one is the reconditioning of existing laboratory space, purchase of development equipment and the hiring of an expert team to set up process and analytical development capabilities, with a target completion in Q4 2023. Phase two, which is also underway in parallel, includes the redesign of existing manufacturing space to create a fully GMP-compliant manufacturing area housing synthesis, cleavage, downstream processing and lyophilisation at 10-160 mmol scale. These manufacturing assets will provide early to mid-phase clinical trial supply for customer demands and are envisioned to come on stream in mid-2024. Future expansions are being investigated to cover increased capacity and scale capability strategically designed to supply customers with validation and commercial supply solutions to address the largest gaps in the oligonucleotide market.
As a stand-alone service offering for customers in the early clinical phases, CordenPharma believes this two-phased approach will have great benefit. However, when taken in combination with its recently- expanded sterile injectable filling capability, full Lipid NanoParticle (LNP) formulation development and manufacturing services, specialised custom and catalog lipid synthesis, and extensive oral drug product services, the company is confident customers will discover the unique potential that comes with a fully-integrated, bespoke service offering a truly end-to-end experience.
Lipids and carbohydrates platform
CordenPharma stands as a global leader in pioneering lipid-based products for pharmaceutical development. With a remarkable track record over three decades, CordenPharma has collaborated extensively with the research, pharmaceutical and diagnostic sectors to deliver cutting-edge solutions that push the boundaries of science and support pharmaceutical innovators’ complex modalities for their life-saving medications.
CordenPharma’s continuous pursuit of specialised lipid innovation has resulted in an expanded 2023 portfolio of diverse custom and catalog lipids that draw upon its legacy of excellence in synthetic lipid process development. As a leader in the scale-up and large-scale manufacturing of commercial lipids, CordenPharma was an early innovator, holding Drug Master Files (DMFs) on some of the industry’s most utilised lipids that have been proven efficient and effective for Lipid NanoParticle (LNP) formulation.
Its ongoing, substantial capital investment and development efforts in custom lipid synthesis are demonstrating efficacy and utility in delivering advanced complex mRNA therapeutics. CordenPharma supports mRNA vaccine development with four classes of high purity lipids required to formulate LNPs:
- Cationic lipids that encapsulate the negatively charged mRNA.
- PEGylated lipids that help form a protective hydrophilic layer that sterically stabilises the LNP.
- Distearoylphosphatidylcholine (DSPC) phospholipids that provide a stable bilayer-forming structure.
- BotaniChol®, CordenPharma’s non-animal origin cholesterol that stabilises the LNP structure and facilitates endosome escape.
High-purity, complex lipids play an increasingly significant role in today’s xRNA pharmaceutical development landscape. As part of this long-term strategy, CordenPharma recently completed the expansion of its specialty lipids production at CordenPharma Chenôve (France), integrating Supercritical Fluid Chromatography (SFC) technology for compound separation. The beauty of SFC technology is that it does not use organic solvents, is a much faster process and allows for the direct recycling of over 95% of the CO2 used.
In light of market trends, CordenPharma’s Injectable platform recently advanced its sterile injectable drug product and xRNA capabilities at CordenPharma Caponago (IT). Investing over €10 million in new Lipid Nanoparticle (LNP) formulation, development and production capabilities, Caponago operations will soon be able to seamlessly progress programs from pre-clinical and clinical stages to full-scale commercial production.
CordenPharma’s LNP formulation operations offer two different cGMP LNP assembly technologies: Microfluidic and Jet-Impingement. Microfluidic technology controls the flow of two different solutions (water-based and lipid-based), then mixes them in a precise manner to deliver small, uniform particles capable of sterile formulation for proper introduction into the human body. In the second technology, CordenPharma deploys Jet-Impingement via a modified T-Junction. This technology is especially suited to accommodate larger-scale manufacturing and larger batch volumes.
The initial R&D phase of the LNP formulation program was built out and has been operational for over a year, enabling the production of development batches in the range of a few millilitres to litre sizes. The latest expansion is the construction of a state-of-the-art GMP plant that enables CordenPharma to scale up LNP formulations developed in the R&D facility to the multi-litre scale. By placing this new facility alongside its existing injectable filling lines in CordenPharma Caponago, it can now provide a fully-integrated service to easily develop and produce state-of-the-art LNP formulations and fill them into vials, cartridges or Pre-Filled Syringes (PFS) for clinical or commercial purposes.
Highly potent and oncology platform
Because Oral Solid Dose (OSD) capabilities are in high demand, CordenPharma made the strategic decision to enhance its offering with an investment of €9.7 million into the design and installation of a new Clinical Trial Development (CTD 4) facility located in CordenPharma Plankstadt (Germany). From early-stage lot development to clinical supply-scale process, Plankstadt has become CordenPharma’s Drug Product Innovation Centre of Excellence for the development and manufacture of highly potent OSD products for compounds with OEL levels as low as < 1 µg/m3.
Set to be qualified in late 2023, the facility investment came about in response to drug developers’ need for capabilities that specifically address issues of scale and process in early phase clinical supply. Focused on the formulation challenges often troubling insoluble APIs, CTD 4 is designed to incorporate technologies to enhance bioavailability and enable manufacture of highly complex OSD products.
Depending on clinical trial dosing needs, the new mini tableting capabilities are a practical way of delivering APIs to patients. Encapsulating these versatile forms has proven to be effective in adjusting dosage strengths and exploring modified release profiles. Among mini tablets’ distinct advantages, the form’s accurate incremental dosing can support more robust clinical trial data. This delivery system, however, requires experience in terms of developing a suitable tableting process and analytical methods to analyse these mighty mini tablets. With access to this technology early in development, researchers can take better advantage of the safety and efficacy this form can offer.
For much of recent development history, producing straight API-in-capsule clinical supply has been the go-to approach for rapid manufacture and entry for First-In-Human clinical trials and precision powder encapsulation systems that facilitate manufacture. At CordenPharma, Harro Höfliger encapsulation is deployed for clinical-scale production. These systems have the accuracy, speed and volume to meet today’s increasingly complex clinical supply needs cost-effectively.
In addition, Bioavailability Enhancement capabilities were added in response to customers’ demands and gaps in formulation technologies for solubility-challenged APIs were recognised. Already equipped with conventional small-scale OSD development processes, including blending, granulation, compression, coating and a tablet simulator, CordenPharma’s Drug Product Innovation Centre of Excellence has added spray drying, hot melt extrusion, nanomilling and micronisation technologies. Customers will also benefit from its fully-integrated Lipid Excipients offerings for SEDDS/SMEDDS formulations that can address permeability issues. The new Centre is capable of handling multiple projects in parallel, with open capacity to start projects immediately.
Small molecule platform
To help pharmaceutical developers bring their IP innovations to markets and patients even more successfully, CordenPharma expanded Small Molecule service offerings in 2023 to include solid-state development. By forming the Solid-State Centre of Excellence in CordenPharma Liestal (Switzerland), the company is now organised to solve challenges with solid-state form and isolation strategies, as well as help customers move their assets to a better physicochemical state suitable for subsequent processing and drug product finishing.
Obtaining a stable, validatable solid-state chemistry form is a central goal of OSD drug development. For many patient-centric reasons, the need to develop drugs for oral administration will likely continue unabated, despite the barriers presented by complex chemistries and formulations. The earlier those barriers are overcome, the better. Innovators increasingly need to find a good home for API solid-state characterisation.
Liestal’s approach to solid-state IP enhancement focuses on several distinct areas of study and evaluation utilising some of the industry’s most advanced analytical technologies and solid-state characterisation methodologies.
CordenPharma offers the opportunity for innovators to evaluate and characterise their API’s solid-state chemistries step-by-step, up or downstream of the processing chain. Even customers in later stages of development can benefit from a robust understanding of their API’s crystal polymorph and why it is optimal for their specific therapy and application.
Investments in 2023
Fully-integrated supply, continuous improvement and large investments in six technology platforms across the company’s network help customers span the gaps in development, commercialise their products more efficiently and reach patients faster. With expanded capacity, capabilities, expert teams and cutting-edge technology across Europe and the USA, CordenPharma brings bespoke end-to-end services tailored to support your innovative complex modalities for increased efficiency, faster time to market and better patient outcomes.