Expedited programs usually shorten a US Food and Drug Administration new drug application assessment, but on average, maybe not as much as their reputation would suggest.
A Government Accountability Office (GAO) analysis found that expedited assessment programs generally are significant variables affecting assessment times, but less so than perhaps stakeholders might expect.
When all else is equal, the assessment for a new drug application qualifying for one expedited program will on average be only seven days shorter than an application not qualifying for any expedited program. The use of multiple programs did prove to be more timesaving. Applications qualifying for two or three of them on average were assessed 17 days faster than those not qualifying for any expedited programs.
Expedited programs included in the analysis were accelerated approval and the breakthrough and fast track designation programs.
GAO researchers interviewed FDA officials for the study, as well as representatives of two industry trade organizations, the Pharmaceutical Research and Manufacturers of America and Biotechnology Innovation Organization. No PhRMA or BIO comments were included in the report.
Danielle Friend, BIO senior director for science and regulatory affairs, said the trade group’s staff told GAO “how important both expedited approval pathways and innovative clinical trial designs are in accelerating the development of new therapies.”
“While it’s helpful to see how expedited pathways are used in different therapeutic areas, we would still like to see broader utilization across therapeutic areas, when the criteria is met,” Friend said. “Clear understanding by both biopharmaceutical companies and regulators about how these pathways can be utilized in different therapeutic areas could help spur investment and development where there is a critical need for innovation.”
The report was addressed to Sens. Michael Enzi (R-WY), Richard Burr (R-NC), and Pat Roberts (R-KS). Its results may help debunk misperceptions that expedited programs always result in a substantially quicker assessment.
The 6 April report stated that the goal dates set for an agency response to an NDA—and not the use of any special review approaches—created the majority of difference in assessment times.
The GAO review considered 637 NDAs initially submitted from fiscal year 2014 through FY 2018. Applications that were withdrawn or whose assessments were not completed by 31 March 2019 were excluded from the analysis. Only first-cycle assessments were considered.
Of the cohort, 32 percent had a priority review designation, 36 percent involved a new molecular entity, and 12 percent involved a major amendment, all factors associated with the setting of a goal date. Only one division, Gastroenterology and Inborn Errors, had a majority of applications associated with the key time features and also had a mean assessment time longer than the overall average, according to the report.
The FDA often is criticized because its expedited approval programs are perceived as allowing applications on the market too soon or with too little evidence. Payers have suggested that expedited programs allow for approval of applications with “less evidence,” which is not typically true. Agency officials also have argued against perceptions that the breakthrough therapy designation conveys a lower approval standard or amounts to a priority ratings system for drugs.
Several changes have been suggested, such as limiting exclusivity awards under accelerated approval until the necessary confirmatory studies have been completed.
MOST DIVISIONS AVERAGE TIMES WITHIN TWO WEEKS OF EACH OTHER
After controlling for the uneven distribution of applications qualifying for expedited assessment programs and differing goal dates, GAO found most divisions’ average assessment times were similar.
The average initial assessment times for 14 divisions, excluding oncology or hematology, were within two weeks of all the others and near the FDA-wide mean of less than 300 days. GAO found that times ranged from seven days less than the mean to five days more than the mean. None were statistically significant.
Those divisions at or above the agency-wide average included Anesthesia, Analgesia and Addiction Products, Gastroenterology and Inborn Errors, Pulmonary, Allergy and Rheumatology, and others. Without the controls, the Cardiovascular and Renal, Dermatology and Dental, Gastroenterology and Inborn Errors, and several others had mean assessment times above the overall average. (See table below.)
The GAO review was conducted before the Office of New Drugs completed its reorganization, which added several new offices and divisions and created a more disease-focused structure. The final phase of the reorganization began in March.
NOT SURPRISINGLY, ONCOLOGY, HEMATOLOGY ARE QUICKEST
Assessments in the hematology and oncology divisions usually were two or three weeks shorter. GAO said oncology assessments averaged 22 days less than the overall mean, and hematology assessments averaged 16 days less. Both were statistically significant.
FDA officials told GAO that the oncology and hematology assessment times can vary in part because they often handle products intended for life-threatening conditions and their risk-benefit analysis could differ from other divisions.
In general, the FDA oncology program is considered progressive in its approach to speeding assessments and often is where new ideas emerge. The breakthrough program was originally conceived for oncology but implemented for all applications.
The oncology staff also created the real-time review pilot program, which allows agency staff an early look at pivotal clinical trial data and potentially a much faster application decision. FDA assessors are expected to use the real-time review concept to speed decisions on potential coronavirus treatments.
In addition, Oncology Center of Excellence Director Richard Pazdur established Project Orbis, a program allowing simultaneous assessments of some oncology applications by multiple regulators, in order to increase global access to novel cancer drugs.