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Exclusive Life Science Feature agreement cannot be amended in the first two years of the GDUFA program. We are doing our best to get the whole program organized so it can operate on a much larger scale. OGD must work through all the backlog and start operating in a steady state as PDUFA does." QUALITY — CAN'T GET AROUND IT, SO GET ON BOARD If Woodcock has made any single issue the hallmark of her tenure at CDER, that issue would be quality in pharmaceutical and biopharmaceutical manufacturing. When we visited her in 2011, her group was working to develop an industry-wide consensus on defining quality above and beyond minimum GMP or product standards. Such a definition is still at the heart of current CDER initiatives, including OPQ. "I think you would do a great service if you could explain how we think about this," Woodcock says. "Actually, we defined the quality of a pharmaceutical product a long time ago: fitness for use. It delivers the properties described on the label and is not FDA'S FUTURE-INDUSTRY VISION: CONTINUOUS PRODUCTION As payers recognize the problem of reliability in the drug supply chain, they will gravitate toward the most reliable suppliers — and ultimately, perhaps, to an entirely different supply-chain model. That is the view of Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research (CDER). Are you ready for the concept of continuous drug production? Get ready, advises Woodcock: "A number of companies are on the verge of adopting continuous manufacturing and other advanced manufacturing techniques which are not susceptible to many of the problems of traditional manufacturing models. Continuous manufacturing can transpire in a single small room, starting with raw materials on one end and finishing with tablets on the other. We believe the new technologies are highly superior. They have a very small environmental footprint and they require high-tech workers experienced with advanced technologies. "Continuous drug manufacturing creates opportunities that haven't existed before. It will help personalized medicine, because it's very flexible, unlike traditional operations where everything has to be rigidly validated and so on. There are many new dosage forms that could be made with the new techniques. It is also perfect for clinical trials because you don't have to scale-up — you just run your machine longer. Bioprocessing also has some promising alternatives on the horizon. Plant-based protein production and single-use manufacturing equipment parallel the advancements with small-molecules. "In the United States, we lost our industrial base of drug manufacturing, and we ought to seize the day to bring it back. We ought to support academia in drug manufacturing innovation; states or other organizations could set up high-tech drug manufacturing centers; and the federal government should do its share of funding and incentives. It's a brave new world, and our nation would be welladvised to foster this new drug manufacturing paradigm. CDER will continue to take a progressive stance, doing our best to enable and actually stimulate the new methods of manufacturing." 22 LifeScienceLeader.com February 2014 contaminated. But the other piece is, what is quality in manufacturing? And that's really what we are focusing on. Right now, a lot of the industry delivers quality products by throwing away, by wasting, up to 35 percent of what's produced, and we don't believe that amounts to quality manufacturing. We've been exploring this question extensively with industry in a very open process: 'What metrics might we use that would measure the quality of your manufacturing processes?'" An April 2013 article in our web portal, Pharmaceutical Online, quoted Woodcock as saying that the FDA has no way of measuring drug-manufacturing quality, putting the agency in the same predicament as manufacturers. Here, she elaborates: "What is the inventory of facilities we regulate today? We are now conducting an extensive IT effort to create the inventory and then define the state of that inventory. How many API manufacturers earn a Six Sigma rating or have a very high level of defect-free products, no recalls, no problems? Which ones are in the bottom 10 percent?" Manufacturing quality — or a lack thereof — has received much of the blame for drug shortages, though some suppliers have faulted low-margin or below-cost reimbursement and puny contract prices for driving good manufacturers away from producing essential off-patent drugs. Claiming no expertise in economics, Woodcock seems to see some common sense in the argument. "You might pay $3.50 for a cup of coffee, but only 45¢ for a vial of propofol. Yet sterile injectables, in particular, are very hard to make right. They are very hard to make consistently sterile, without any particles or endotoxin in them, which they must be because they're given intravenously." Still, she stresses quality as the underlying issue, citing the inefficiencies built into manufacturers' legacy systems and technology. Besides coaxing industry to update and upgrade its facilities, she believes the FDA can also help widen payers' perspective. "We are trying to make quality of manufacturing more transparent to purchasers. Quality of manufacturing predicts reliability of supply." Internally, with no intent to impose or even publish the results, CDER is establishing a "framework" of quality metrics to help it characterize the variations among facilities in its database, she says. "Someday we might publish an annual report on the spread of performances, without identifying the companies. It would then be up to purchasers, in their due diligence, to go beyond the issue of cost. I don't think they've ever taken reliability of supply into account before now, because it has not been an issue. But shifts in the industry, probably including pricing structure, have consolidated suppliers and limited the sources for essential drugs." QUALITY ORGANIZING As the objective expression of a quality-promoting agenda, Woodcock has championed the creation of the new Office of Pharmaceutical Quality. Still in its infancy, the OPQ now consists of a "reorganization package," essentially a proposal that CDER must formally submit to all concerned parties for their review and sign-off. "We know how we want to work in the future, and this organization will reflect that, and it's going to