Pharmalot: So why did you get this grant? Basu: The FDA gave us this grant to fund research that will led to developing the kind of science that’s very badly needed for pharmaceutical development and manufacturing. Right now, all the problems we see with manufacturing are because everybody has had their own way of doing things. We need well-proven science that everybody can use. So we were awarded $35 million for five years, although there is no guarantee NIPTE will receive it. It will depend on the FDA’s own funding. But if they have enough money, it will be up to $35 million.
Pharmalot: What kind of problems do you hope to rectify exactly? Basu: Most manufacturing problems are residual problems from drug development. This is not toxicity or clinical testing involving a drug. I’m taking about the process part. If development is imperfect, you’ll see problems creep up in manufacturing. One cannot isolate the two. The question is how to develop formulation and robust API (active pharmaceutical ingredient) processes and then how to do proper manufacturing. But our scope will be limited to how to take the molecule from the bench to the marketplace in that it will be the science behind the manufacturing.
Pharmalot: What kind of manufacturing problems are we talking about? Basu: Recalls, for instance. And the other problem the FDA faces a lot of the time involves applications that are submitted with very little science back up. And so it takes time to review those applications. If the science was more readily available, we could develop science-based applications and companies could provide evidence as to why they would manufacture a certain way. And then, the approval process could move much faster.
The other problem is that pharmaceutical manufacturing is becoming global and there’s very little one can do to stop outsourcing. The only thing we can do is to make sure products coming into the country are of high quality, beyond having inspectors on the ground, is to use proper science to make good products so there are minimum defects.
The heparin crisis could have been avoided if there were better analytic al tools. In my opinion, people trying to adulterate these products are very smart and we can avoid another heparin if we have proper scientific tools and methods available to identity the impurities ahead of time…And some of the processes we hope to develop could be incorporated in the USP standards.
Pharmalot: How exactly would the money be used? Basu: The FDA will identify some areas of research. They could they say want to improve protein analytics or how a solid dosage formulation is to be designed. Once they identify these broad areas, NIPTE will send out RFPs to the schools involved in our network – there 11 schools – although we may go outside to other schools, too. The proposals will be reviewed by external panels and the best proposals will be chosen from there. But everything will have to be published in journals, so everything will be out there. Our goal is to lift scientific design in pharmaceutical manufacturing to a new level.
Pharmalot: You mentioned recalls. Do you mean the sort of problem J&J experienced? Basu: The J&J problems were mostly due to substandard GMP issues at its plants. NIPTE is not going to be able to help that very much. Those recalls were happening because they did not maintain their plants and update GMP standards. But recalls happen because products are not made at the right strength or size. It’s a different kind of recall. In fact, 75 percent of recalls are due to manufacturing and can be traced to some kind of defect. Our goal would be to develop the technology that will improve the science so that recalls are reduced.
Pharmalot: Defects? Tell me about that. Basu: I did a study showing a very high percentage of human errors can be traced to some process not being right. We often tend to blame operator error, but most of the time it can be tied to a system that failed. There’s really human error, because the operator may not be trained properly or the manufacturing process was so variable that even those errors were caused.
Pharmalot: And heparin? How could something like that be prevented? Basu: They came up with this synthetic compound and normal analytical methods could not detect it as adulterated, which means our system is not sophisticated enough to detect this. Sure, they’re trying to make other products in a similar way. So we need to develop analytics tools and characterization tools so we can detect impurities much more rapidly and integrate them into product acceptance testing. That means if I’m importing heparin from China, then tests to accept or release the product to this country are not good enough. It means existing test methods have failed me.
Pharmalot: How would this work? Would drugmakers be involved? Basu: In the aerospace industry, the science is very well developed. Not so much in the pharmaceutical industry. There are hardly any good textbooks available on how to design API formulation and processes. Hopefully, by improving basic science, people will develop better tools. In the future, we may get industry involved, but we need to deal with conflicts of interest issues with the FDA. We don’t know if that’s possible. Right now, we’re structured so that we can’t accept any industry funding.