Navigating the Complex Risks of Accelerated Pharmaceutical Launches

Raj Puri, chief commercial officer at Argonaut Manufacturing, explores the complex balance between speed and risk in pharmaceutical product launches. Puri explains that while getting a product to market quickly is vital for patient access and commercial survival, compressed timelines introduce significant regulatory and financial hurdles. He notes that, "As a biotech or pharma company, getting product to market as quickly as possible is critical”.

One of the primary challenges discussed is the "gamble" of mass production. Puri highlights that accelerated timelines often force companies to decide whether to manufacture commercial-scale products before receiving indicative guidance from regulatory agencies. He explains, "The compressed review timeline actually forces the biotech and pharma companies into taking a bit of a gamble, and that decision really is, do you start mass production before you have indicative regulatory feedback?". This financial risk is compounded by the need to negotiate proactively with agencies for allowances, such as submitting manufacturing data on a rolling basis.

Puri also shares a personal case study involving a life-saving biologic where the Phase 3 study was discontinued early due to "overwhelming efficacy". While a positive outcome, this created a gap in patient access during the submission window and led to clinical utilization challenges. Because the study ended early, the resulting regulatory label required ICU clinicians to use unfamiliar clinical trial tools, necessitating a massive educational effort.

Finally, the interview addresses the global implications of accelerated launches. Different requirements from the FDA, EMA, and Japanese Health Authorities often force companies to prioritize one jurisdiction over others. Puri concludes that while compressed timelines are highly desirable, they necessitate robust contingency strategies and a deep, collaborative relationship with regulatory bodies to ensure alignment on all requirements.

Transcript:

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Good morning. My name is Raj Puri. I'm the Chief Commercial Officer at Argonaut manufacturing. Argonaut is a contract manufacturing company based in Carlsbad, California. We have two separate divisions within the company. One division is focused on the production of life science and diagnostic products, and then the second division is focused on aseptic filling of drug product. So again, pleasure to be here today.

As a biotech or pharma company, getting product to market as quickly as possible is critical. Both from a patient access perspective, you want to save or improve lives of many patients as possible, as quickly as possible, but also from a commercial perspective, we basically burn cash until we get to market. So, from a commercial perspective, getting there as quickly as possible is obviously desirable. It can have significant challenges, these compressed timelines, and I've gone through them, personally, myself, from a regulatory perspective, what you can often see is that you're able to negotiate proactively with the agencies allowances regarding the data required on submission. And so again, you have to work very closely with the agency to determine what allowances will be made. But for example, in your PPQ package, which is essentially the manufacturing data that's provided on your submission, you may have the opportunity to reduce the amount of data provided and provided on a rolling basis, rather than everything has to go in at once on the submission date. So again, it takes close coordination with the regulatory body to negotiate those allowances.

From a commercial risk perspective, the compressed review timeline actually forces the biotech and pharma companies into taking a bit of a gamble, and that decision really is, do you start mass production before you have indicative regulatory feedback? So typically, let's say you have a year review timeline. After six months, you probably have some guidance whether or not your clinical package is acceptable or not. You then can say, after six months, everything looks good, we're going to pull the trigger. There's some risk here. But, clinical data looks pretty good. We're going to make the decision to manufacture and have product ready for launch. When you have a compressed timeline, you can't actually make that decision. You may actually have to make a decision on actual submission before you have any indicative guidance about whether or not you're going to make product to be ready for commercial launch. So there's a significant financial risk associated with making that decision at the time of submission versus when you have some indicative guidance from the agency. Personally, early in my career, I was part of a team at one of the big pharma companies responsible for setting regulatory strategy for a lifesaving biologic. The phase three study was actually discontinued due to overwhelming efficacy, which again, was a fantastic outcome. We were very, very excited the product was saving lives, and it became not ethical now to treat patients with a placebo when we knew that the active was extremely effective.

So we're very excited, but it did create some significant challenges for us on the back end. So, one of those challenges was actually a patient access issue. We discontinued study due to overwhelming efficacy, and it took us probably six to eight months to actually make a submission to the regulatory agency. You have to compile all the data, do the analysis, and then you have a review time on top of that. We did not have a scalable program in place where we continue to have availability for patients to access this product. So that was a major challenge from a patient access perspective, in that window between study discontinuation and commercial approval. And then from a clinical utilization perspective, we also had a challenge in that, because the study was discontinued early, we had a much smaller patient population than we had anticipated. What ended up happening was that the regulatory agencies then integrated into our label, the use of a clinical trial severity score.

What that meant is that you now had, commercially, you had clinicians that weren't involved in clinical trials were being asked to use a tool that they never used before. And so from a commercial perspective, we're now trying to educate the ICU doctors and nurses on how to actually assess patients effectively using this tool. And it's something they'd never done before. And so that also created a major challenge for us, again, somewhat precipitated by the compressed timeline. At the end of the day, the compressed outlines, while extremely desirable, they really do force companies to have a very robust contingency strategy developed prior to submission, and really forces them to work very closely with the regulatory agencies to make sure that they have alignment regarding requirements. It also may have the unintended effect of forcing companies to prioritize certain jurisdictions over others. Because, what the FDA may require might be quite different than what the EMA require, which may be different than what the Japanese Health Authority requires. And so now you have to say, Okay, which of these are the priority market? Because frankly, we can only really meet one. And so that's another peripheral outcome of going through a compressed review timeline.