Decisions, Decisions. The top four API Manufacturing Decisions That Lower Cost and Avoid Delays

What decisions are most important in keeping API projects moving swiftly?

CDMOs favorite sponsors tend to be those who have the knowledge to make rapid, informed decisions. Here’s why. CMOs are busy, dynamic organizations.  Every chemistry suite, every piece of equipment, every staff member if fully engaged in projects in progress, racing to meet critical sponsor deadlines.

There are certainly decisions to be made along the way: new chemical entities (NCEs) can surprise at any stage, and any problems identified require solutions, rethinking and perhaps process changes. Often these are tweaks that the sponsor and CMO teams can rapidly resolve. That’s a good thing: CMOs simply don’t have the flexibility to stop and let the equipment sit idle when joint decisions are needed.  But when sponsors dawdle, that’s a problem. Stopping a project causes traffic jams every bit as disruptive as a car accident that closes a major highway in Boston or Lyon during rush hour. 

This article will focus on the four most important decisions sponsors should make to keep projects running smoothly.

  1.  Work with your CMO to make rapid informed decisions
    Not only can slow decision-making delay projects, but they can be costly for sponsors.  Take for example a sponsor who wants only one batch of material made. Our standard operating procedure is to make three batches to assure quality and reproducibility.  Sure, we can make just one batch, but we will then need to clean the equipment for the next project, backtracking later to make the rest of the batches. The cost of cleaning will double:  one cleaning after the first batch, and again later when we make the requisite two additional batches.  Added equipment cleaning costs are not the only reason. We recommend making all three batches sequentially to keep total project costs as low as we possibly can and the project moving as quickly as we can. These are best practices that avoid delays.
  2.  Decide to communicate fully
    We have stressed the importance of open and transparent communication time and again.  One thing sponsors should always communicate is the full timeline for the API: when does it need to be shipped; when do the trials for which it is intended initiate.  Advance notice of timelines is critical information for a CMO.  All too often, a customer calls to say they’ve scheduled a formulator for this or that date, without discussing it with us in advance.  With the new chemistry we’re working with, anything can happen. There could be a scale-up problem. Or the analytical method may need more work. An impurity might surface. There are a million reasons we need to collaborate with sponsors on a shipping date for the API, or the entire clinical trials timeline can be thrown off kilter.
  3. Share previous failures
    Not sharing failures that have occurred previously is almost certain to cause delays.  Anything at all that affected the project at another CMO needs to be disclosed. This of course includes safety issues.  In addition, you do not want your CMO to reinvent the wheel—it adds unnecessary costs.

    As one example, we had a project come to us for manufacturing that has taken 12 weeks of development work at a cost of approximately $1.5 million.  As we were scaling the drug substance for the first time, the product oiled out.  We couldn’t backtrack a few steps because the physical form had changed.  It was ruined. Everything went down the drain. It was only afterward that we learned from the customer that they had worked with a CMO overseas and knew about the—but never shared it, never discussed it with us.  Nor did they give us the batch records. Had we received those, and known about the problem, we might have been able to save the project.
  4. If the CMO doesn’t agree with your consultant, listen to the CMO
    There are excellent consultants and there are some who lack the specific knowledge a project requires. When sponsors rely on the latter, delays are sure to ensue.  A dose of healthy skepticism by sponsors is called for when consultants disagree with highly experienced CMOs who have created similar chemistry, have a multitude of in-house experts and know what needs to be done—and what doesn’t.

There are also consultants paid by the hour who benefit from prolonging projects, often creating more work than necessary. Many are not qualified. They don’t understand the science, or they had peripheral jobs at a big pharma company where their responsibilities were narrowly focused on a small piece of the drug development process. They do have some expertise—in that one thing they know. They don’t have the experience or knowledge to see an entire project through to a successful API.  A sponsor would be hard pressed to find a consultant that has as much experience as Seqens has.

Bottom line: in most disagreements between consultants and CDMOs, tip the scale to the CMO to avoid delays and unnecessary costs. But above all, be decisive.

If you have any questions, please call us at (978) 462-5555.