Dateline: Long Branch, New Jersey
The day kicked off with a panel discussion on Quality by Design (QBD), a somewhat self-explanatory method of efficient process design associated with the quality management movement of the previous century. It has been revived with the FDA’s recent establishment of an enhanced submissions regimen based on QBD for drug companies filing new drug applications.
QBD comes with other quality sub-practices, including Design of Experiment (DOE), which was featured in an article in C&EN earlier this year. It also comes with additional costs in process design and R&D. As so often happens when something like a quality standard is established as a way to achieve regulatory approval, the industry has tended to focus efforts more on gaining that approval at the lowest cost rather than on designing the most efficient process.
Panelists agreed that cost concerns can lead to a lot of confusion on QBD, especially when dealing with a contract manufacturing organization. Emerging pharma companies that have little experience in advanced stages of process engineering are unlikely to employ QBD effectively.
According to panelist Kevin Siebert, senior research adviser at Eli Lilly & Company, Lilly has put together four enhanced submissions using QBD. “One was withdrawn, but FDA gave us feedback on it,” he says. “We’ve embraced the initiative. It’s an effort that we use in the early stages when we are looking at process robustness. But it is intended to deliver not only material but also information to support the advanced submissions.”
Panelists agreed that the opportunity to deliver on the information is often lost when dealing with a CMO.
From the perspective of an emerging pharmaceutical company, said panelist James Bruno, president of Pharmaceutical and Chemical Solutions, the focus is on minimizing the amount of work needed to reach clinical milestones. “There is a heavy reliance on CMOs, because few of these companies have strong tech groups. Many don’t understand scale up and process development. Their whole point is, ‘how much will it cost and when can you deliver.’”
The CMO, he said, is therefor under significant cost and time pressure, and will move a reasonable process along without the full QBD vetting. “There is a disconnect on expectations,” he said. “It’s a highly competitive market, and you want to make sure what you turn over to Merck and Lilly is a good package.” The CMO looks to the drug company, and vice versa, to get that together. “It is about money at end of day,” he says. “It’s about how can you minimize cost going forward.”
After the panel, Bruno told me that QBD will eventually be applied effectively, and that it will accelerate the use of efficient technology and process design that are beginning to transform drug chemical production—see his comment yesterday on the need for simple assets.
The panel was followed by a plenary presentation featuring Stefan Loren, managing director of Westwicke Partners. Loren reprised his plenary talk of 2010 on Wall Street’s view of emerging pharma, biotech, and pharma outsourcing.
That view has changed markedly since Loren’s last appearance, largely because money can be had at the moment.
Loren noted, however, that uncertainty is a dirty word on The Street. And there is a solid trace of it in the air right now. For example, there is concern that the upswing in productivity at Big Pharma results from in-licensed products, and that gains in drug approvals may not be sustainable.
Outsourcing, said Loren, has “matured” in Wall Street’s assessment in recent years. It is applauded now as a means of diversifying risk. This marks a welcome evolution from an earlier insistence on the one-stop-shop approach. He advised pristine due diligence in picking a contract manufacture, however, noting that a problem caused by a contractor can hit a drug firm’s stock hard and long.
One surprising bit of intelligence at ChemOutsourcing comes from Fabbrica Italiana Sintetici (FIS): Managing director Laura Coppi will be leaving for a position at CordenPharma in Milan after two years in the key business management role at the Vicenza-based pharma chemicals firm. Her replacement has not been named.
I haven’t spoken with Coppi since writing a C&EN Talks With feature about her earlier this year. But on hearing the news, I was reminded of the quote that ended that article: “I would have loved to have studied mathematics. But, I have to say, I am a chemist in the soul. Deep inside.”
Meanwhile FIS has been investing in Delmar, the Montreal, Quebec-area pharma chemical company it acquired shortly after Coppi came in, boosting capacity and adding significant new isolation and drying capabilities. Delmar will also be adding a kilo lab to its existing pilot plant and expanding its R&D lab to enhance small-scale cGMP synthesis. Delmar and FIS will continue to operate as separate companies, with Delmar making some material for FIS, says John Brady, business development manager. They will also coordinate on projects, leveraging their newly-established connection between Europe and North America, with Delmar passing some projects to FIS for larger-scale production.
FIS has invested about $19 million in developments at Delmar to date, with an additional $5 million per year slated for the next two years, according to Brady.
The day ended on the beach with the annual bonfire, which this year seemed to throw an inordinate quantity of sparks. Not enough to deter marshmallow roasting, however. The karaoke stage had a few takers. Fullish moon. All very nice.
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