Shared or divided manufacturing is certainly possible. Be aware that under our regulations those
have specific meanings. Divided manufacturing to regulators means both manufacturers are
capable of doing the entire process, that is, A to Z. A shared manufacturing arrangement means
that you would be licensed for part of the manufacturing process. Say, a manufacturer would be
doing the initial inoculation and fermentation, maybe even up through purification, and then
sending the API perhaps to another company for additional processing, and then fill and finish
activities. So, yes, and if you take a look at one of CBER’s guidance documents that came out in
August 1999, that talked about the Center’s [i.e., CBER] policies on shared manufacturing
arrangements.
The other possibility is contract manufacturing. A number of years ago, we changed the definition
of applicant. It used to be that an applicant had to be a manufacturer, that is, doing some of the
manufacturing steps. We realized, with the way the technology was going, it wasn’t possible in a
lot of cases for one manufacturer to be doing all the significant manufacturing steps. So, we
redefined the license holder to be an applicant. Essentially, at this point, you could have a virtual
company, with all the manufacturing steps contracted out. That may be another possibility if
you’re looking for a licensing scenario. You could be the applicant and contract out all the
manufacturing steps. With respect to Drug Master Files, our Center handles and reviews Drug
Master Files, as well. I think the caution we have with Master Files is, Master Files, while they can
be used to submit a lot of supporting information, when it comes to some of the process-specific
information, I would tend to shy away from those. Those should be in the application. I’ll step over
into the application world for a minute and talk about some of the problems we’ve had with Drug
Master Files. We had one for a product, it was a contract manufacturer that had a Drug Master
File, and they submitted some of the information for the container closure system and some of
the sterilization. The information that they submitted wasn’t what was in the application. The
application was for a 5 ml vial and what was in the DMF was for a 100 ml vial. I think you have to
be careful on how you’re relying on the Drug Master File. I think there’s going to be additional
discussion on this, but the Drug Master File is really appropriate for general things: procedures,
facility overview, and those sorts of things. But, when it comes to specifics of container closures,
sterilization parameters, those are things that are best left for the application.
