The contract manufacturing business is moving into a new phase, according to Villax, one that has little to do with the hardware. “Now, you simply can’t just buy the differentiator,” he says. “Success is the result of experience and accumulated knowledge and databases.”
Data are no small part of the equation, he adds, noting that data-based quality management principles, such as quality by design, are gaining momentum in process development. Design of experiment, a statistical method of multivariable analysis in R&D and process engineering, will be a critical practice as data and statistical analysis become the common ground of chemistry and engineering, Villax says.
“And it’s not just chemistry and engineering,” says Villax, who is in his 50s. “A lot of what I am describing involves computer simulation skills, things people my age don’t know about. It also requires that an organization have the DNA to accept change. One needs to open the doors to people who are 20 years younger.”I sure wish I knew what Mr. Villax meant by "computer simulation" -- also, that people in their 50s don't know about computers is, in my opinion, rather an odd thing to think.
Here's Rudolf Hanko of Siegfried, dreaming big:
Rudolf Hanko, CEO of Siegfried, a Swiss CMO, wants even further development of the chemistry needed for API production. The challenge posed by complex drugs, he says, “is that organic chemistry, despite progress over the past 150 years, is still not a science that allows you to synthesize molecules in a convergent way.” Rather than extol the virtues of being able to manage a complex, multistep synthesis, Hanko says, CMOs should seek to design routes that reduce the number of steps or allow them to be taken simultaneously.
Hanko uses an auto assembly line, that paragon of efficient manufacturing, as a model. “The API is the car in our example,” he says. “It’s impossible to convolute that molecule into eight or 10 components and then say, ‘I have a final step that brings these eight to 10 components together, and after six hours reaction time and six hours of clean-up we have our API.’ ”
In some exceptional cases two components can be brought to a final reaction stage, he acknowledges, “but then each of these elements has 10, 15, maybe 20 linear steps behind it. That leads to a situation where each step requires two or three days, and the entire pathway might require four weeks, or eight weeks, or for some molecules, four months.”
The result, Hanko explains, is molecules that cost $60,000 to $100,000 per kg.
“Yes, organic chemistry has made enormous advances over the past 20 years, but it is still far, far away from where it would ideally be,” Hanko says. “That is why we need the best people, the most talented chemists, and why we need good contact with academia.”I am kind of confused by which molecules Hanko is talking about (e.g. 15 to 20 linear steps), but nevertheless, the point about truly convergent syntheses is well-taken.