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Genentech Offers Insight To Increase CMC Development Efficiency – Courtesy (Pharmaceutical Online)
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CMC development costs

In April, the Kaiser Family Foundation released a poll about the public’s views on the Affordable Care Act (ACA) as well as what it believes the health care priorities of the President and Congress should be going forward. Out of a list of 16, 76 percent of Americans identified “making sure that high-cost drugs for chronic conditions … are affordable to those who need them” as the top priority. A close second at 60 percent is “government action to lower prescription drug prices.”

However, in order for pharmaceutical companies to meet these needs, they will need to focus on those efforts that can increase manufacturing efficiencies and reduce development costs. This would not only have an effect on the cost of developing and producing drugs, but overall, doing things more efficiently and better enables industry to test more therapeutic hypotheses in patients and correspondingly bring more therapeutics to market that make a difference. “Patients are relying on our industry to develop important new therapies, and we’ll need to do this as efficiently as possible to have the most impact,” says Dana Andersen, senior director of pharmaceutical development at Genentech.

Andersen, who recently delivered a keynote address at the 2015 BDP Week conference, began his presentation by highlighting the cost of developing a prescription drug that gains market approval. That number, $2.6 billion, is a 145 percent increase from when the Tufts Center for the Study of Drug Development (CSDD) last made an estimate in 2003. “Average drug development costs have risen steadily over the last three decades while rising costs pressures limit returns,” he tells the audience. “We need to do things differently and better in the future.” So the million dollar question is – how?

Approaches to Streamline CMC Development

For his presentation, Andersen focused on the CMC development costs, which are just one component of the overall development costs. While he stressed that each case will have different risks and constraints leading to product-specific CMC approaches, there are general opportunities where pharmaceutical development companies can streamline development and reduce these effects.

One opportunity Andersen says companies have to increase efficiency is fixing CMC issues upfront, so you can avoid unnecessary work later. “If you have issues with your molecules, you end up dealing with a lifetime of flaws, so it can really constrain manufacturing,” he explains. “Once you start development and it’s in the clinic, it almost never makes sense to stop and start over, so you end up living with things you know are a problem. By identifying them early, you can alleviate those future issues.”

He uses molecules that do not express well as an example. “Cell culture titer is often the biggest single factor that affects production costs for biologics,” he says. “If you get stuck with a sequence that just doesn’t express well, you may never be able to make a high titer cell line and will likely be stuck with a more expensive process for a given scale.” He suggests screening sequence candidates early for “expressibility,” purification fit, degradation hot spots, stability issues, and when relevant, viscosity. When possible fix liabilities or select the best version, and if the liabilities can’t be fixed, you know where to focus your efforts.

Another way he says companies can streamline development is by applying standard approaches to reduce the development work. “You learn from your past experience,” explains Andersen. “There are some standard approaches you can use so that each new molecule takes a little less work to develop than the last one.” By applying robust platforms to get into the clinic with minimal to no development work, he says you can minimize your resource spend until some clinical proof-of-concept has been achieved. “It’s also easier for manufacturing when the processes are similar,” says Andersen. “In some cases, the initial process may be commercializable or nearly so, which can greatly reduce later work.”

A tension in the industry Andersen discussed in his presentation was the expectation of data from the regulators, as the amount of information that’s filed today is much greater than it was decades ago. He asked the audience – how do we reconcile the need for increased efficiency with the desire for increased knowledge?  As he sees it, using automation is at least one way to do this. “There’s a lot of opportunity with robotics systems to generate a lot of data more cheaply and easily, which can give you a better understanding of your process,” he explains. “However, you need to be careful in knowing where automation can add value versus where it just adds complexity. Effective knowledge management becomes critical for capturing the full value of the data being generated.” He warns though that you should not underestimate the extra work that may be required to enable the transition to automation.

Breakthrough Therapy Offers Both Hope And Challenges

Andersen also reviewed the Breakthrough Therapy Designation during his presentation, including both its benefits as well as the challenges it creates. Through this legislation, the FDA and sponsor collaborate in what Andersen calls “a dynamic, multi-disciplinary process to determine the most efficient path forward.”

In this “all-hands-on-deck approach,” Andersen says some of the challenges associated with biologics development, such as overall development costs (because the drug gets to the market sooner), will be addressed; however, accelerated clinical timelines for products designated breakthrough therapies will necessitate new approaches to product and process development, commercial readiness, launch, and regulatory filings. “With a shorter timeline, you can’t always do everything you want to do,” he explains. “So how do you compress things and negotiate places where maybe you don’t have everything you typically have at the time of filing?”

With an ever-evolving landscape and the pressure of keeping costs low, the pharmaceutical industry is facing new challenges every day. Andersen recognized these challenges during his keynote, but the focus of his presentation was the same one he says he keeps in his daily role – with new challenges come new opportunities. “We have a full pipeline with a lot of products we’re trying to deliver for patients, and we’re trying to do so with fixed and limited resources,” he explains. “While we streamline activities where we can, we are also learning important new things about our processes and products that we need to investigate and explore in order to do things better. This allows us to not just prepare for the challenges today but also for what the next five to ten years will bring.”

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