Pharmaceutical Technology - September 2019

Pharmaceutical Technology - Regulatory Sourcebook

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Page 24 of 54

Pharmaceutical Technology REGULATORY SOURCEBOOK SEPTEMBER 2019 25 Figure courtesy of the US Government Accountability Office. The GAO report focused on FDA's contribution to the prob- lem, but also noted a tendency for applicants to rush to file ap- plications despite gaps in process knowledge that translate into incomplete ANDAs. Focusing on this same tendency, but from the developer's side, was an anal- ysis of FDA data (2) by the Na- tional Institute for Pharmaceu- tical Technology and Education (NIPTE), which noted that this tendency to rush to file is having a serious impact on the generics pipeline. Over half of the generic drugs approved by FDA either never reach the market or are only commercialized after a delay. Of the 1600 generic pharmaceu- ticals that FDA approved in 2017 and 2018, about 43% were not on the market by the start of 2019. In addition, many potential generics never make it to the review stage. T he N I P T E a n a ly si s c on- cludes that scale-up issues, pro- cess validation, and repeatabil- ity can pose challenges. These challenges are then magnified by pressures to file first with- out incorporating adequate risk analysis and understanding of potential sources of variability, which NIPTE describes as gaps in prior k nowledge. To counter- act these problems, NIPTE has proposed a "New Prior Knowl- edge" concept that would make crucial process and product in- formation available. Its goal is to improve the quality of the first application and increase the likelihood of more ANDAs being approved during the first review cycle. Aja z Hu s s a i n, d i rec tor of NIPTE, discussed the concept with Pharmaceutical Technology. "The generics system works only when more than f ive generic companies can compete for the market," he said. Although sim- ple dosage form small-molecule generics may not pose a problem, generic pharmaceutical formula- tions are now more complex, he said, and mechanisms such as the technical citizen's petition to block approval or assessment of therapeutic equivalence re- quire additional work," he says. Need for new prior knowledge PharmTech: What is the New Prior Knowledge concept and what is its goal? Hussain: The 'time-cost-quality' constraint and the Hatch-Waxman incentive to 'file first' in the devel- opment of generic drugs can often be a cause for a 'file-first figure it out later' approach, in which a manufacturer receives multiple complete response letters, neces- sitating multiple review cycles. Furthermore, the available in- formation and prior knowledge about API and patient, product and process related failure modes are often not published in peer-re- viewed scientific literature. What Figure 1: Number and percentage of generic drug applications approved in the first review cycle, fiscal years 2015–2017 (1). First review cycle outcome Number (percentage) of applications 0 300 600 900 1,200 1,500 1,800 2,100 2,030 (100%) 1,790 (88%) 240 (12%) Approved Not approved Total number of applications reviewed Source: GAO analysis of Food and Drug Administration (FDA) data. |

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