Feature article - CPHI Frankfurt: Strong markets, multiple modalities

Pharmaceutical CDMOs are continuing to invest in a buoyant market. We report from CPHI Frankfurt

The mood among CDMOs remained buoyant at the rebranded CPHI Frankfurt show, which took place on 1-3 November. There were several announcements of major investments and most of the exhibitors SCM spoke to were optimistic about continued rapid growth, particularly in new modalities of all kinds.

This feeling was reflected in new research from the CPHI Annual Report 2022, launched during the show, which forecasts that “huge volumes of venture capital and private equity cash reserves will drive significant expansion in demand for CRO and CDMO services in the next two years”. The cash ‘overhang’ stood at $1,049 million as of June 2022.

For the past two years, noted report author Brian Scanlan of Edgewater Capital says and previously with Cambridge Major Laboratories, forerunner to Alcami, this money has poured mostly into biotechs. Now, these companies have two to three years of cash reserves behind them. As they advance more targets within the time frame of their investors, they will be pouring cash into development and manufacturing services.

Among the most bullish of the CDMOs was India’s Aragen Life Sciences. Helped by a $350 million investment from Goldman Sachs, it has increased its revenues by 20% and its margins by 30% while employee numbers have risen from 2,400 to 4,000. This earned CEO Manni Kantipudi the CEO of the Year award at the CPHI Pharma Awards “for delivering outstanding performance with sustained growth and robust strategies”.

Among the investments have been two new buildings for drug discovery and development, plus acquisitions to fill gaps in drug product and toxicology capabilities. A new drug product facility will open in Bengaluru at the turn of the year. Aragen is the largest CDMO in India but, said CCO Dr Ramesh Subramanian, “we don’t want to be a CRO or CDMO, our aim is to be a modality-agnostic R&D partner of choice” for pharma and biotech companies.

Shortly before the show, Aragen had announced the launch of its newly optimised RapTr 2022 cell line development (CLD) platform. This royalty-free platform is said to offer a 33% reduction in CLD timelines and deliver increased titres up to 6g/L, helping to accelerates the process of cell line engineering from DNA transfection in the host cell lines to research cell bank within 18 weeks.

Chinese-based giant WuXi STA had made a large number of investments across the world in the last few years, the most recent being its first high potency oral drug product facility at its Wuxi city campus. This will complement two nearby HPAPI facilities in other cities. The firm will also open a new HP sterile parenteral production plant there in Q3 2023.

Kevin Li, senior director of marketing and communications, revealed that it will shortly announce a new continuous manufacturing line for drug product at the site. He described the firm as a “unique CRDMO” because of its wide range of capabilities at all stages of development.

At the time of CPHI Frankfurt, Thermo Fisher Scientific had just announced that it would acquire The Binding Site Group, a speciality diagnostics firm, for $2.6 billion. This, combined with a $1.0 billion share repurchase programme in Q4, will bring its capital deployment commitment in 2022 to $6.1 billion.

Other recent investments comprised a 28,000 m² viral vector facility in Plainville, Massachusetts and two new translational sciences labs in the US. A cell therapy development and cGMP manufacturing centre will open next year at the University of California San Francisco’s Mission Bay campus, while a new manufacturing facility for steriles and biologics manufacturing will open at Hangzhou, China, by the end of the year. “

We believe that new modalities are growing fastest, although small molecules are still of interest,” said Dr Anil Kane, global head of technical and scientific affairs. “Patient-centricity is an increasing focus for our Patheon business and its small molecules will continue to support patient requirements.”

Russell Kneipp, the new CEO of Spectrum Chemical, said that the last few years had been transformative for what had historically been a catalogue company active in many industries. “Customers no longer want a catalogue, they expect you to know what they need and to be able to supply all the relevant documentation,” he said.

Spectrum has increasingly focused on biopharma, notably through the recently launched BioCertified line of products, and has developed its portfolio to offer support from testing through to packing. However, it is also active in small molecules and other fields and expanding its services into China, which, Kneipp said, “has really taken off in biologics in the last three or four years”.

Biovectra revealed that it is now accepting projects at its manufacturing facility in Windsor, Nova Scotia, Canada, for its new, biologics fermentation suite. This contains 100 L and 1,000 L single-use fermenters and became fully operational during November.

“The new suite enables execution of a state-of-the-art process train that enhances Biovectra’s microbial fermentation capacity and supports the tech-transfer, optimisation, early/mid-stage clinical investigation and commercial-scale supply of highly specialised therapeutics and biologics,” the firm stated.

This followed the addition of two 17,000L stainless steel fermentation vessels with advanced control systems in Prince Edward Island, where the firm has four more sites, over the summer and many others into new modalities over five years, particularly the last two, noted CCO Heather Delage. These have already been used to produce recombinant proteins.

Among European CDMOs, Minakem has made a €40 million investment in multi-purpose capacity at its site in Beuvry-la-Foret in northern France. This should be ready for qualification by mid-2023, said general manager Sebastien Poncet. It will feature a high level of automation and computer control. In addition, Minakem is investing about €15 million in high potency HPLC to support HPAPI projects.

Also featuring in the CPHI Pharma Awards alongside Aragen was Lonza Capsules & Health Ingredients. It won in the Regulatory Procedures & Compliance category for its Capsugel TiO₂-free white gelatin capsule for intestinal drug delivery, which was launched at the show.

This is an opacifying technology that uses the functionality of crystallised salts to provide the same whiteness and masking as capsules containing TiO₂, which faces increasing restrictions in the EU. The capsule remains intact during stomach transit and only releases its contents in the intestine, while simplifying drug product manufacturing by mitigating the need for additional capsule coating or sealing.

Lonza also announced an agreement under which it will gain access to Singzyme’s enzymatic conjugation platform for site-specific binding of payloads with peptidic linkers to proteins of interest. This, said Stefan Egli, head of bioconjugates, “represents an attractive addition to Lonza’s bioconjugation toolbox”.

Evonik, meanwhile, won the Pharmaceutical Packaging & Drug Delivery award for its polymeric nucleic acid delivery systems. These comprise a new class of polymers that complement existing lipid nanoparticle-based delivery technologies.

The company has also entered into a long-term agreement under which it will supply large-scale volumes of vonoprazan from sites in the US and Germany to Phathom Pharmaceuticals, a US biopharma company focused on gastric acid-related diseases. Evonik used its expertise in heterogeneous catalysis to achieving high purity in the API used in vonoprazan.

In the week before the show, Curia hosted a groundbreaking ceremony to mark the beginning of construction of its expanded campus in Albuquerque, New Mexico. The additional space will house an isolated high-speed fill-finish vial line – which includes biosafety level 2 (BSL-2) containment, two lyophilisers for the high-speed fill-finish line and an isolated flexible filling line for vials, syringes and cartridges to support smaller-batch advanced therapies.

In response to increasing demand in the later stages of development, EuroAPI announced an initial €18 million investment in manufacturing capacity for peptides and oligonucleotides at its Frankfurt site as part of a multi-stage effort. The aim is to debottleneck current capacity and increase output to about 500 kg/year by 2025, without the need for any downtime.

Also in the peptide field, AmbioPharm announced a strategic partnership to supply of peptide conjugates to Ariceum for use in future clinical studies. Ariceum is based in Berlin and develops radiopharmaceutical products for the diagnosis and systemic targeted radiation therapy of certain hard-to-treat cancers.

In the run-up to CPHI Frankfurt, Dipharma Francis announced that the Italian Medicines Agency, AIFA, has approved its new production line at the cGMP pilot plant suite in Mereto di Tomba. This will double its capacity, both in generics and CDMO arena, while also enhancing operational safety and isolation technologies, the company said.

Likewise, Quotient Sciences completed the expansion of its drug substance manufacturing facility in Alnwick, UK. The £6 million expansion delivers multi-purpose capacity of up to 15 GMP reactor streams with reactor volumes ranging from 5 to 150L and tactical deployment of batch or continuous flow chemistry technologies to optimise manufacturing processes.

Univar Solutions announced the addition of four pharmaceutical ingredient labs at its ‘solution centres’ in Houston, Texas; Osasco - São Paulo, Brazil; Mexico City, Mexico; and Essen, Germany. They will provide services such as formulation and prototype development, performance and application testing, chemical and product performance analysis, and custom blending for various dosage forms including oral solid dose, semi-solid, liquid and topical.

Finally, in late October, Symeres acquired Exemplify BioPharma, another US-based CRO that provides integrated drug development services in process and analytical chemistry and formulation development from a 1,750 m² site at Cranbury, New Jersey. Earlier, Symeres had acquired Organix, a supplier of lipids for mRNA therapeutics and vaccines in the Boston area.