The high potency CMO market is booming, from HPAPIs to clinical development to commercial scale manufacturing. We spoke with a number of players across the spectrum to get their perspectives on market trends. Driven by developments in oncological therapeutics, antibody drug conjugates (ADCs) and liposomal formulations were cited as key client needs.

Laura L. Parks, Ph.D., senior vice president Marketing & Sales at DSM Pharmaceuticals, noted that cytotoxic manufacturing is an important piece of DSM’s total portfolio in finished dosage. “We see a lot of market opportunity in high potency,” she remarked. “We remain excited about our prospects and have investment in place for more filling of cytotoxic products.”

Dr. Parks noted that, after Ben Venue Laboratories’ recent announcement that it will exit the CMO business, DSM is the sole U.S. commercial supplier of cytotoxic dosage form manufacturing, from its Greenville, NC site. “We’re actively involved in helping facilitate transfers of primary and secondary manufacturing clients of BV.”

The Greenville site, which opened in 2008, handles two commercial products and a number of Phase III projects. Dr. Parks pointed out that both of those commercial approvals had good Pre-Approval Inspections from the FDA.

Asked about the possibility of another major player trying to add commercial high potency operations in the U.S., Dr. Parks said that she wasn’t aware of anyone trying to make a move on that scale. The other providers we spoke to echoed that sentiment, noting that the regulatory burden was large and the timelines for facility approval were so long as to preclude anyone from making a major cytotoxin finished dosage investment.

But that doesn’t mean that expansion isn’t happening. Robert Felicelli, Global Franchise Head at Baxter’s BioPharma Solutions business, commented, “Baxter continues to invest in our cytotoxic and high potency manufacturing capabilities based upon growing demand from our pharmaceutical clients for high quality manufacturing. Most recently, we completed our latest expansion of a fourth large-scale lyophilization unit to support commercially marketed oncology therapies.”

That site, in Halle, Germany, offers lyophilization, process development, aseptic filling of cytotoxic, non-cytotoxic and highly potent liquid and sterile powder vials in clinical and commercial batch sizes, and sterile crystallization of cytotoxic APIs. Mr. Felicelli added, “With the high costs of equipment, containment standards and personnel training, it continues to make economical sense for many pharmaceutical companies to continue to outsource.”

Tom Gelineau, director, Business Development at SAFC, said that his company is seeing interest in several high potency areas. The company has 40kg and 200kg HPAPI capacity at its Madison and Verona, WI facilities, respectively, and has HPAPI fermentation capacity in its Jerusalem site.

The company also makes conjugated HPAPIs out of its facility in St. Louis, MO. “We’re seeing that capacity fill very nicely,” said Mr. Gelineau. He added that the company plans to expand its HPAPI drug conjugation capacity, noting, “Potent ADCs are probably our most rapidly developing business.”

Mr. Gelineau noted that the ADC client base has an interesting makeup: “For potent compounds, we see a mix of emerging to mid-sized to large pharma companies; for the ADCs, however, we are seeing a surprising number of large pharma companies taking licenses to specific ADC drug linker technologies. So for general non-targeted potent compounds, it is across the board, but for ADCs, I would say it is largely big pharma companies that are entering that space.”

SCM Pharma, a UK-based CDMO that specializes in sterile manufacturing and filling of radiopharma and cytotoxics and cytostatics, announced an expansion of its potent handling capacity earlier this year. The company has won several clinical and commercial contracts in the past several months, including the supply agreement for Plenaxis, a highly potent GnRH blocker for prostate cancer.

Neal Wesley, SCM’s technical director, commented, “Over the last few years, we have worked on increasing numbers of high potency contract manufacturing projects, which have involved the fill/finish of drug products into vials and ampoules. One particular project we carried out also required a c14 radiolabeled potent product, which naturally brought additional challenges to our technical team.”

Dianne Sharp, SCM’s managing director, added, “Our research has indicated that the sterile manufacturing market will continue to grow over the next few years. Likewise, the oncology market also continues to grow, which presents an opportunity for those like SCM Pharma that specialize in the development and manufacture of highly potent injectable products. Furthermore, smaller patient populations require smaller more nimble manufacturing capabilities than the traditional large scale, which again fits with our set-up.”

Scott Silaika, director, Business Development, East Coast, for Aesica, a UK-based CMO founded in 2004, also sees continued growth in the high potency market for both API and finished dosage. Aesica recently completed construction of a purpose-built high containment suite at its Queenborough, UK facility. “This unit is segregated from other manufacturing areas, has its own analytical laboratory, and the design is based upon engineering containment to minimize the need for personal protective equipment,” said Mr. Silaika. “Aesica is targeting the manufacture of Safebridge Category 3 Formulated Products in this facility, and already has a tablet production and packaging contract.”

Aesica is also in the process of validating other potent compounds within its API facility in Cramlington, UK. “These API and finished products were awarded to Aesica based on many factors, including our outstanding regulatory compliance record and ability to manage industrial hygiene at a competitive cost. As compound potency increases, the required volumes may decrease, so our ability to manage many SKU’s provides clients with a cost advantage.” 

Also on the API side, Carbogen Amcis and parent company Dishman have made a $40 million-plus investment in high potency manufacturing in China and India. Mark Griffiths, chief executive officer of Carbogen Amcis, remarked, “The facility in Shanghai, China, supplies drug substances down to category III, up to 50 metric tons, whilst the facility in Ahmedabad, India, manufactures down to category IV, up to one metric-ton per year. Both facilities extend the capacity at our existing high-potency plant in Switzerland, which is focused on R&D and niche commercial supply.”

Mr. Griffiths added, “Control over particle size distribution (PSD) by pin-milling, jet micronization, and wet-milling is paramount for low-dosage drugs. PSD in the range of 1,000 microns down to one micron can increase the bioavailability of low water-soluble oral drugs. Drug innovators prefer to partner with companies offering milling and wet-milling as a core particle sizing technology.” He said that the company has invested massively in milling technologies to control particle size.

SafeBridge Consultants is an occupational health and safety firm that evaluates manufacturers for Potent Compound Safety Certification, so the firm is in a position to answer some of the meta-questions throughout the high potency handling area: who’s looking for certification, what services do they cover, and where are they located?

John Farris, SafeBridge’s president and chief executive officer, said that one of the trends he’s noticed is integrated companies seeking SafeBridge certification. “We’re seeing more companies that handle both HPAPI and formulation.” Mr. Farris said that the majority of these integrated operations were large pharma spinoffs or other sites that had captive API capabilities and were performing formulation as a sideline.

Mr. Farris also said that the consultancy has received several inquiries about SafeBridge certification from companies in Asia, and the firm is involved in a design review for an aspiring ADC maker in that region. “ADC manufacturing has provoked a lot of activity in multiple regions,” he commented, before highlighting some of the obstacles that manufacturers face.

“Traditional API manufacturers haven’t dealt with biologicals before, so they have a learning curve. Meanwhile, antibody producers are generally unfamiliar with potent compound handling, so they have an even more challenging path.”

In all, he noted, there is more activity in potent drugs by CMOs than ever, driven by clients from emerging biotechs. “Most of our CMO clients are going gangbusters,” he remarked.  

Gil Roth has been the editor of Contract Pharma since its debut in 1999. He can be reached at gil@rodpub.com.