Lots of behind-the-scenes technology is required for discovering, developing, and manufacturing pharmaceuticals. Ideally, a company would be able to get the technology it needs off the shelf. But sometimes it doesn’t exist.
▸ Year launched: 2016
▸ Annual membership fee: $20,000
▸ Members: 13 (AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly & Co., Genentech, GlaxoSmithKline, Merck & Co., Pfizer, Takeda Pharmaceutical)
▸ Working groups: 7 (analytical and purification, automated lab reactors, crystallization, drying, high-throughput experimentation, mathematical modeling, solubility)
That’s where the Enabling Technologies Consortium (ETC) comes in. It’s a group of pharmaceutical companies that have banded together to accelerate the process of creating the technologies they need by working with third parties to bring them to market.
Those technologies include analytical instruments and laboratory and production tools. During a symposium at Pittcon, held Feb. 26–March 1 in Orlando, ETC representatives gave the audience a look inside the organization. It’s not perfect, but it is starting to yield new technology in several key areas.
The consortium started inside the International Consortium for Innovation & Quality (the IQ Consortium), which works to build consensus among member companies on scientific and regulatory issues related to drug development. “One of the working groups in IQ was identifying gaps in technology and finding ways to work together,” said James M. Vergis, director for science and technology at law firm Drinker Biddle & Reath and coordinator of ETC’s activities. But the IQ Consortium wasn’t set up to work with outside vendors.
So that working group spun off into a consortium of its own. Currently, 13 pharmaceutical companies are ETC members. The group focuses on so-called precompetitive technologies, ones for which the companies have no plans to obtain intellectual property, so that all member companies—and perhaps even the broader chemistry community in some cases—can benefit from them (Org. Process Res. Dev. 2017, DOI: 10.1021/acs.oprd.6b00427).
The consortium’s goal is to streamline the process of working with outside vendors on new technologies and to share resources so no single company must shoulder the cost of any project. The drug companies hammer out legal language for their projects. ETC then uses those agreements to negotiate directly with the vendors, reducing a potential many-on-one interaction to a one-on-one interaction.
The consortium has seven working groups for different technologies. Member companies participate only in groups and projects that interest them. On top of an annual membership fee, they pitch in with money, expertise, and other resources.
The working groups have set up a three-phase process. In the first phase, participants brainstorm to identify technology gaps and projects that could fill them. For a project to move forward, at least two companies need to agree to collaborate.
In the second phase, a working group solicits information from potential academic or commercial partners. In the third, the working group selects a vendor or academic collaborator as a partner to carry out the project.
Although ETC members need consensus on the language in their agreements, they don’t reach that consensus in a vacuum isolated from the vendor. “We don’t want to kick an agreement over the fence to a vendor and have them basically draw a big X over it and say we can’t agree to any of this,” Vergis told C&EN.
So far, three projects have reached the third phase. In one of them, a working group for analytical and purification problems has joined with the instrument maker Shimadzu to develop a new preparative-scale supercritical-fluid chromatography (SFC) system, according to Mirlinda Biba, a researcher at Merck & Co. and member of the working group.
SFC is the preferred method for purifying small molecules in the drug industry, she said. Many companies’ SFC equipment is aging, and the Berger Instruments system that most of them use is no longer available. They were worried about the performance and dependability of the newer systems, which focus on smaller, analytical-scale separations, and wanted to develop a new one.
At Pittcon, Biba described the long road to get to that third phase. The analytical and purification working group kicked off in April 2015 while still part of the IQ Consortium. Moving through the three phases of ETC’s process, they reached a final agreement in March 2017, and the project officially got under way the following month. Team members meet monthly and provide feedback on the hardware and software that Shimadzu is developing. They expect the first prototypes later this year.
Vergis, the ETC coordinator, acknowledged that three-plus years is a long time. “The project teams were excited to move forward, but they couldn’t because the infrastructure for the ETC wasn’t fully signed off on by the members,” he said. “Things will get more efficient as companies have already reviewed the language in the legal agreements we have.” He expects much shorter timelines in the future.
Other working groups are not yet that far along. A group for high-throughput experimentation is focused on equipment for dispensing powders, which is a bottleneck in the process, according to Matthew Bahr of GlaxoSmithKline, one of the group’s leaders. Such equipment is key for doing quantitative experiments to determine drug properties.
The group tested existing commercial equipment across a range of powders, configurations, and lab settings. It used a set of seven powders at three doses.
“We concluded that there is still a gap in the sub-milligram dispensing range, and we are asking that the vendors consider looking into designing equipment to fill this gap,” Bahr told C&EN.
If any vendors express interest in working with ETC on the issue, the group will probably move on to the second stage of the ETC process. Otherwise, the group plans to wrap up its activities with a submission to Organic Process Research & Development detailing the findings, Bahr said.
Now in the second phase is the solubility working group. Predicting compound solubility in various solvents under a range of conditions is a bottleneck for scientists. “However much capacity we have to measure solubility, it will never be enough,” said Simon Yates, a researcher at AstraZeneca and member of the solubility working group.
The solubility group is taking both experimental and modeling approaches to speed up solubility determinations. On the experimental side, the group is looking for partners to develop a next-generation automated solubility system. Proposals were due earlier this month, and the group hopes to have a working system sometime in 2019. On the modeling side, the team is evaluating commercially available software packages for predicting solubility.
And after drug molecules have been in solution, they have to be dried. “Drying has been an afterthought,” said Joshua Engstrom, a researcher at Bristol-Myers Squibb and leader of ETC’s drying working group. The group seeks to improve understanding of how various parameters affect drying and to develop better monitoring technologies.
The process of going from solution to a solid active ingredient is complex. The drug needs to be in the right form with the right properties. The working group is in the process of identifying vendors to develop better systems for collecting spectroscopic data during the drying process.
As these and other projects advance, ETC is slowly making progress on filling technology gaps in discovering, developing, and making drugs. If all goes according to plan, pharmaceutical companies may finally be able to get the equipment they want off the shelf.