FDA Advances New Approach to Drug Quality Assessment

As part of its ongoing efforts to ensure the availability of high-quality medicines, FDA’s Center for Drug Evaluation and Research (CDER) is rolling out a new system to enhance the evaluation of prescription drug attributes, risks, and control strategies. The Knowledge-aided Assessment and Structured Application (KASA) initiative aims to improve the efficiency, consistency, and objectivity of regulatory quality assessment by collecting structured data on drug substance, product design, and manufacturing process to better assess inherent risks and how they are controlled. CDER’s Office of Pharmaceutical Quality (OPQ) is piloting the program first for abbreviated new drug applications (ANDAs) for generics, with the aim of rolling out the system to generic solid oral dosage forms by year-end. Next will come generic liquids and injectables, followed by new drugs and biologics.

With more ANDAs and new drug applications (NDAs) filed each year, many involving complex therapies, and increasingly tight assessment time frames for approval set by user fee programs, CDER officials are looking for ways to evaluate submissions more expeditiously and effectively. This new approach asks manufacturers to file structured applications that present key data on product attributes, as opposed to lengthy, text-based narratives. The aim is for OPQ staffers to perform computer-aided analyses that support benefit/risk assessments for comparison across products and facilities. Under development for almost two years, the KASA initiative became more visible when it was discussed publicly and gained unanimous support at the September 2018 meeting of FDA’s Pharmaceutical Science & Clinical Pharmacology Advisory Committee.

CDER and OPQ leaders presented more detailed information on KASA at the April 2019 PQRI/FDA conference on Advancing Product Quality in Rockville, MD (1). KASA aims to provide a structured assessment of an application that summarizes key information and “minimizes text-based narratives,” explained OPQ Deputy Director Lawrence Yu. Advances in information technology not only generate more information on key quality attributes, Yu pointed out, but also allow for a faster, more complete assessment. He directed manufacturers to an article outlining the KASA program in the International Journal of Pharmaceutics: X for further information on the program and its approach (2).

Similarly, at the April 2019 CMC Workshop sponsored by the Drug Information Association (DIA), Geoffrey Wu, associate director of OPQ’s Office of Lifecycle Drug Products (OLDP), described how the KASA initiative will capture and manage knowledge of drug product quality to establish a product risk control strategy for lifecycle management. This approach will avoid inconsistent application of quality standards and help prevent shortages and quality failures of marketed drugs. KASA also will assess manufacturing risks and controls in order to “flag the potential need for a pre-approval inspection based on multiple factors and complexities using standardized risk thresholds,” Wu noted. This will involve examining the control strategy for the manufacturing facility, including site inspection history, based on a standardized assessment of risks compared across products and facilities.

More structured assessments

The modern drug assessment system under KASA will build on algorithms of risk and support computer-aided analysis for a structured assessment of an application. The process begins with an objective evaluation of risk that considers key critical quality attributes, enabling OPQ staff to then focus on more risky products. The analysis considers the severity of possible harms and the detectability of future failures to be able to compare risks across products and determine if attributes are within or outside acceptable ranges. With such information, CDER still may approve a risky product, but with a recognition of the need for greater oversight to control for possible future problems.

In making the case for KASA at the PQRI meeting, OLDP Director Susan Rosencrance observed that applications for new drugs and generics composed of unstructured text can be a hindrance to an efficient agency assessment of product quality. Too often, she said, the important information on how an applicant controls risk “is lost in hundreds of pages of text.” This may encourage a reviewer’s quality assessment to be more subjective, leading to inconsistent decisions by the agency.

Drug applications that present information in prose require reviewers to do “a lot of hunting and pecking” to pull out key data, added Mary Ann Slack, director of CDER’s Office of Strategic Programs. To move forward, FDA plans to develop and test electronic data standards for submitting product quality and chemistry, manufacturing, and controls (CMC) data to the agency, Slack explained. This will be described in draft guidance slated for publication by March 2020 to further explain how future applications should present data files that can be entered into FDA’s drug data system to check ranges and areas to review more closely.

KASA is part of broader CDER efforts to modernize its drug regulatory program. This includes reorganizing the Office of New Drugs, developing new IT platforms and applications, establishing quality metrics, and building the emerging technology program to promote new drug design and manufacturing strategies. More consistent and objective regulatory assessments under KASA fits these broader goals by helping FDA achieve more first-cycle approvals for manufacturers and more affordable and accessible medicines for patients.

References

1. PQRI, 4th FDA/PQRI Conference on Advancing Product Quality, April 2019. 

2. L. X. Yu et al.,International Journal of Pharmaceutics: X, 1 (December 2019).

Article Details

BioPharm International
Vol. 32, No 6
June 2019
Pages: 8–9

Citation

When referring to this article, please cite it as J. Wechsler, "FDA Advances New Approach to Drug Quality Assessment," BioPharm International 32 (6) 2019.