Speciality Chemicals Magazine spoke with Platform Directors Dr. Mimoun Ayoub, Global Head of Peptides, and Dr. John Cameron, Global Head of Injectables, on CordenPharma’s investment covering the whole peptide-injectable supply chain.
In recent years peptides have accelerated away from already high 8-10%/year growth rates, thanks mainly but by no means entirely to the success of GLP-1s in the treatment of diabetes and obesity. That has led to new challenges, most obviously the sheer capacities needed to supply them at tonne-scale, but also during the early stages.
Even more than most APIs and finished dosage forms, peptides have become more sophisticated in recent years. Many peptides are conjugated with fatty acids or small molecules, which requires skills in lipid and small molecule chemistry as well as peptide chemistry. That has made their supply chain more complex too, which CDMOs like CordenPharma are addressing.
“The beauty of CordenPharma is that we cover all of these technologies within our six technology platforms,” says Dr Mimoun Ayoub, global head of the company’s peptides and oligonucleotides platforms. “We reduce that complexity by having all of these skills under the same roof. We have small molecule sites that can support the production of non-peptide parts such as side-chains, and sites for peptide development, manufacturing and conjugation.”
All of these services are integrated into drug product (DP) manufacturing, Ayoub adds. The company also has capabilities in injectables and oral solid dose (OSD) formulations for peptides in close proximity to each other in Europe. The company also has high potency and peptide manufacturing capabilities in the US, currently lacking only DP there.
For first-in-human (FIH) clinical trials, CordenPharma’s site in Frankfurt carries out stand-alone early peptide synthesis, focusing on pre-clinical and Phase I-II supply with the emphasis on agility, flexibility and speed. These services are deliberately kept apart from late-phase validation and commercial, where the objectives are completely different. Instead, the small and medium scale site at Liestal, Switzerland, along with the very large-scale facility in Boulder, Colorado, handle these.
“The goal at Frankfurt is to support customers with speed-to-market. You can only keep that agility if you don’t have that mix of commercial and early phase at the same site,” Ayoub says. “We don’t want to give customers the perception that we are only a large-scale manufacturer. We have a very wide bandwidth from very small to very large.”
The Frankfurt’s site’s capabilities span solid- and liquid-phase peptide synthesis (SPPS and LPPS), plus all kinds of conjugations. Batch sizes range from a few tens of grams up to a few kilos. It also has all the downstream capabilities required.
In addition to Frankfurt, the injectables site at Capanago, Italy, has seen major investment in the last three to four years. The formulation development laboratory there has doubled in size and can now house about 50 R&D scientists handling pre-formulation, formulation and analytical development.
“We found that not getting access to these types of development capabilities was quite often the bottleneck customers were experiencing,” says Dr John Cameron, global head of the injectables platform. “Almost all injectable projects require some formulation development before they can go into GMP manufacturing.”
Two new lines will come onstream at Capanago in 2028 and 2027 respectively: a high-speed, late-stage line for prefilled syringes (PFS) and cartridges; and a flexible line that will handle Phase I and II projects but will also be able to do small-scale Phase III and commercial campaigns.
In addition to early phase API and DP, Cameron adds, CordenPharma can support customers with Qualified Person release of the DP and clinical trial services like secondary packaging and shipping to trial sites.
Complexity in the drugs themselves and their supply chains brings other challenges for innovators. There is no shortage of potential manufacturing partners for innovators, but it is preferable that they be able to supply both the peptide and the DP, which CordenPharma can.
Currently over 95% of all peptide drugs are injectables and the company can offer both the formulation development and the GMP and non-GMP manufacture for these. “That really streamlines the process and helps innovators go to clinical trials quickly,” Cameron says.
Both Ayoub and Cameron believe that the company is unique in having capabilities in both peptide APIs and DP across injectables and OSD. Building on synergies and eliminating redundancies takes out costs and saves time, the former says.
It typically takes CordenPharma nine to 12 months to deliver a fully integrated project of API and Drug Product, depending on the complexity of the drug. This can save at least three months of development time and speed is critical in FIH, because time is money in this industry.
“In pharma, it’s all about getting your product to market as soon as possible” Cameron notes. The first stage is getting it into clinical trials and the vast majority of clients in this field are biotechs funded by venture capital or similar means and seeking to hit certain milestones to unlock further funding. If they are delayed, they are still burning through investors’ money and it might run out before a promising therapy comes to market.
Another aspect of the challenge, Ayoub says, is risk mitigation in supply. He cites one example in the company portfolio of a peptide conjugated through a small molecule linker to a lipid moiety. This requires other sites to work on the lipid part and deliver it to the peptide site, sharing all the necessary knowledge and the methods in an integrated timeline.
“Imagine a customer who has to handle different partners for the peptide, the small molecule partner, the linker and the injectable or OSD manufacturing, and potentially also the packaging. It is hugely complex and if anything goes wrong or is delayed, they will have to co-ordinate all of the CDMOs to find a new manufacturing slot. CordenPharma manages all that for you.”
An integrated offer like this means that the process can be governed by a single master services agreement (MSA), which reduces bureaucracy and costs and frees up time to do more productive work. Whilst some believe that artificial intelligence (AI) will greatly simplify the process, there is little evidence of it yet in CordenPharma’s experience.
“There are a lot of synergies between API manufacturing and DP manufacturing but the two simplest are communication and analytics,” says Cameron. The process starts, in peptide drug substance, with making gram-scale amounts of API and the development of analytical methods.
“Once this is done, they can be transferred to Caponago, which can then start working straight away on analytics for the DP. If there is enough peptide available, they can also start to do the formulation development, which is often the critical part before you get into GMP manufacturing of the DP.”
Effective planning is critical here. If a customer comes with an integrated supply project for the peptide and the injectable, CordenPharma also supplies a global project manager in addition to those at the API and DP sites, who will be responsible for the entire global timeline, including communication between sites, ensuring that time and budget are met.
“A lot of small biotechs don’t have a lot of manpower and would find it challenging to manage an API and a DP site,” Cameron says. Whilst this is on offer to every customer, most of the interest comes from small to medium-sized biotechs.
Looking ahead, Ayoub stresses the need to stay ahead of the curve as the growth in demand for peptide development and manufacturing services shows no signs of slowing down. “We always invest hand-in-hand with customers. We need to anticipate their needs, which is why we always seek their input with regard to their projections for the next few years so we can build the right capacities and put the right assets in place,” he concludes.
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