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FDA confirmed quality focus while Congress moved to bolster biomedical innovation.
In the past year, the biopharmaceutical industry faced numerous challenges on the regulatory, political, and legislative fronts. Congress approved legislation seeking to encourage the development of “21st Century Cures” by incentivizing and streamlining manufacturer regulation. FDA revised its operations for overseeing drug production and quality, with an eye to reducing shortages and facilitating the development and approval of more new therapies. Patient groups gained more visibility as advisors on drug development and advocates for more effective R&D programs. In recent months, however, the uproar over escalating drug prices raised questions about the value of new pharmaceuticals, threatening support for innovation policies.
More new drugs, biologics
There was good news for important, life-saving therapies coming to market, including additional cures for hepatitis C, new treatments for seriously high cholesterol, and new therapies for cancer and rare diseases. In 2014, FDA approved a near record 41 new drugs and 10 biologics, many designated as “breakthrough” to treat serious and rare conditions. This year appears headed for similarly noteworthy achievements: the agency had approved 35 new therapies as of early November, with a number of applications scheduled for final assessment by year-end.
FDA’s breakthrough drugs program continued to prove valuable, as the agency approved 10 new therapeutics in that category. That rate is likely to continue, as FDA received nearly 100 sponsor requests for the breakthrough designation, as of October 2015, and had granted 25. While there’s strong support for the program, its continued growth may require more resources to support the additional meetings and advisories FDA provides manufacturers of promising treatments.
An important milestone in 2015 was FDA’s approval of the first biosimilar therapy, Zarxio from Sandoz. This unofficially launched biosimilars in the United States, which have been anxiously awaited by patients and payers eager for access to less costly biotech therapies since authorized by Congress in 2010. FDA has invested considerable resources in developing guidance for manufacturers on how best to analyze and document comparability of new biosimilars to reference products, a process that relies on advanced assessment of product structure and production methods to ensure comparable quality, safety, efficacy, purity, and potency. FDA has received six biosimilar applications to reference products, and 57 biosimilar products for 16 reference drugs were enrolled in FDA’s Biosimilar Product Development program as of mid-September; sponsors were seeking preliminary advice on another 27 projects.
The biopharmaceutical industry further demonstrated its R&D capabilities by responding quickly to the need for new vaccines and treatments to combat the Ebola virus. While the National Institutes of Health and other public health agencies played critical roles in paving the way for animal and clinical testing of promising new therapies, accelerated product formulation and manufacturing proved valuable to this and other international efforts to produce and distribute treatments for lethal diseases around the world.
Emphasis on quality
FDA’s campaign to reduce drug shortages and to improve oversight of growing foreign production and import of drugs and active ingredients was bolstered by the official establishment of the new Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER). The new organization aims to provide a more coordinated and effective process for ensuring the consistent production of high-quality medicines, both brands and generics. This effort involves establishing a more predictable and timely application approval process, with possibly fewer inspections of those facilities able to document low risk and adherence to GMPs. FDA also collaborated with industry on devising a set of quality metrics designed to indicate a facility’s quality status, but that program ran into objections from manufacturers, and further guidance is not expected for several months. The ultimate goal is for OPQ programs and policies to encourage industry adoption of modern manufacturing systems able to detect quality problems before they occur, and to limit routine oversight in the process.
OPQ was officially established in January 2015 after two years of planning for the extensive organizational changes in staff and functions involved. The program makes notable changes in the review of drug chemistry, manufacturing, and controls (CMC) submissions from pre-clinical and clinical testing, through application review, to postapproval changes and generic-drug development. While the Office of Biotechnology Products continues to oversee innovator and biosimilar therapies, an Office of New Drug Products now evaluates the quality aspects of new drugs during development and approval. After a year on the market, those products shift to the Office of Lifecycle Drug Products, which handles postmarketing changes and generic-drug development. An Office of Process and Facilities brings together oversight of manufacturing operations, microbiology reviews, and preapproval inspections, in coordination with CDER’s Office of Compliance and the FDA field force.
These changes facilitate team reviews by staffers from a range of CDER functions and field offices to coordinate evaluations, inspections, and compliance actions. There is an emphasis on adopting risk-based models to target oversight to facilities, processes, and products where quality failures are most likely to harm patients. A central project management staff oversees whether OPQ operations meet timelines and objectives, and a new policy office manages the development and publication of quality-related guidance documents and rules. Important for all these programs is a new unit establishing a comprehensive data system that lists the location and operations of all facilities around the world producing drugs and their ingredients for the US market. In September 2015, CDER director Janet Woodcock signaled that the new super office was firmly established by stepping down as OPQ acting director and handing over the reins to former Novartis Vice-President Mike Kopcha.
Delays in bringing new generic drugs to market, which had created an immense backlog in abbreviated new drug applications (ANDAs) awaiting approval, also prompted reorganization of CDER’s Office of Generic Drugs (OGD). Woodcock had formed a new OGD super office to manage the ANDA review process, while also shifting to OPQ the review of generic-drug CMCs and manufacturing processes. Although generic-drug makers have complained about CDER’s slow progress in whittling down the backlog and speeding up ANDA approvals, the agency appeared to be making progress on both fronts by year’s end.
Changes at the top
Industry comments on FDA regulations and lobbying on legislation to bolster biopharma innovation are coming from different voices following the appointment this year of new executives to lead both the Pharmaceutical Research and Manufacturers of America and the Generic Pharmaceutical Association. Even more notable is change at the top of FDA since the departure in March 2015 of commissioner Margaret Hamburg. Duke University cardiologist Rob Califf came to FDA early in the year as Hamburg’s unofficial replacement, but his formal nomination as commissioner did not come until this fall and only began to move forward in the Senate last month.
FDA chief scientist Steven Ostroff has been a capable placeholder for Califf much of the year and has kept agency programs on track. But a confirmed commissioner is important for initiating any important innovations in agency policies, especially at a time when Congress is weighing major revisions in agency programs, and negotiations are moving forward for renewal of user fees in 2017. All these developments will continue to shape pharmaceutical and biotech operations in the coming year.
Article DetailsPharmaceutical Technology
Vol. 39, No. 12
Citation: When referring to this article, please cite it as J. Wechsler, “New Drugs and New Initiatives Shaped 2015,” Pharmaceutical Technology39 (12) 2015.