Pilot project allows FDA conclusions about a drug’s efficacy and safety to be integrated with, but distinguished from, a sponsor’s own analysis; though currently used for reviews of oncology applications, template could become the basis for a consolidated advisory committee briefing document.
The US FDA’s Assessment Aid (AAid) pilot project resulted from a desire to reduce the amount of word processing oncology reviewers do as they analyze drug applications, but it also could spur a change in how FDA and sponsors put together briefing documents for advisory committee meetings.
The AAid is a voluntary submission by an applicant to facilitate FDA’s assessment of a new drug application (NDA) or biologics license application (BLA), including supplements. It is intended to focus the agency reviewers’ time on critical thinking rather than simply repeating the applicant’s analysis, with the goal of improving review efficiency and quality, agency officials said.
The AAid initiative was one of two Oncology Center of Excellence (OCE) pilot projects discussed by representatives from FDA, industry and the patient community at the recent Friends of Cancer Research (FOCR) meeting. It has been used in conjunction with two of the first four approvals under OCE’s Real-Time Oncology Review (RTOR) pilot program. (See sidebar.)
FDA Commissioner Scott Gottlieb announced the launch of the two pilot projects at the American Society of Clinical Oncology annual meeting in June. (Also see “Gottlieb Uses ASCO Platform To Unveil Two Pilot Programs To Speed Drug Review” – Pink Sheet, 3 Jun, 2018.)
Clear Delineation Of Sponsor, FDA Views
Under the AAid pilot, participating sponsors receive a form that is modeled after FDA’s multidisciplinary review template. It covers the critical regulatory elements of a drug or biologic application that need to be evaluated for approval decisions and labeling recommendations.
Most sections of the template are divided into two parts to clearly delineate the applicant’s position and FDA’s conclusions. The form is sent to the applicant during the investigational new drug phase, such as around the time of the pre-NDA/BLA meeting. The applicant fills in its portion of the template and submits it with the NDA/BLA.
“The applicant portion should be concise and only include critical information (e.g., should generally be no longer than 75 pages),” OCE’s web page states.
After conducting their scientific analyses, FDA reviewers add their assessment into the same document, highlighting areas of agreement or disagreement with the sponsor as well as additional findings by the agency.
Once completed, this document will serve as the FDA review, while also incorporating the applicant’s voice, said Qiu Lu, a team leader in the Office of Clinical Pharmacology and a member of the OCE team that developed the AAid pilot program.
What Is the AAid Pilot?
- Intended to focus the FDA review of a new drug application or biologics license application (and supplements) on critical thinking, and increase review efficiency and consistency while decreasing review time spent on administrative tasks such as formatting.
- A voluntary submission from the applicant to facilitate FDA’s assessment of the NDA/BLA application that is based on the FDA Multidisciplinary Review template. For most portions of the template, the sections are divided into two parts, clearly delineating the applicant’s position and FDA’s assessment.
- Open to all oncology drug applications, including new molecular entities and supplemental applications. Can be used alone or as part of the Real-Time Oncology Review pilot program.
‘Wasting Time As Word Processors’
OCE Director Richard Pazdur, who also serves as acting director of the Office of Hematology and Oncology Products, said the initiative grew out of a desire to reduce the amount of cutting and pasting that FDA reviewers do between an application and their own review memos.
“It really, I felt, was a waste of people’s time just to be word processors basically,” Pazdur said. “We really wanted this to be looking at the reviewers spending time to critically evaluate what was going on, rather than just documenting this thing, this table, that table, this table. It allows people to put in their own analysis if they want to, that’s for sure. It does not truncate or prevent people from expressing differences of opinion.”
Pazdur said FDA is considering whether the AAid could serve as a joint briefing document for Oncologic Drugs Advisory Committee meetings, replacing the separate briefing packages that FDA and a sponsor currently prepare for such meetings.
A single, consolidated advisory committee briefing document could reduce the confusion inherent with separate briefing packages from the FDA and sponsor and eliminate the need for corrections, FDA’s Pazdur said.
“One of the problems that we’ve had at advisory committees … you have two different documents and it’s very confusing what the positions are,” he said.
In addition, there may be disagreements between FDA and a sponsor as to the accuracy of information in each other’s briefing document. “We have to go through corrections, for example, our documents versus the company’s assessment of what might be said wrong on those documents,” Pazdur said. “This way you won’t have that situation.”
The single briefing document would clearly delineate what’s in the application and the points of contention between FDA and the sponsor, Pazdur said.
The idea of a consolidated advisory committee briefing document drew support from industry representatives on the panel at the FOCR meeting.
A multi-stakeholder white paper proposes other potential uses for the AAid.
“The AAid could be expanded to incorporate additional analyses of patient-reported outcomes to inform benefit-risk assessments of NDAs/BLAs,” the paper states. “Future considerations for the AAid will be how [information requests] and updates to the company position will be addressed and how the completed AAid will be communicated to the sponsor after regulatory action has been taken.”
Ribociclib Review Reflects New Template
An early case study of the AAid template’s use can be found in FDA’s July 18 multi-disciplinary review and evaluation of an expanded breast cancer indication for Novartis AG’s Kisqali (ribociclib), which was also the first supplement approved under RTOR.
“The applicant’s position” and “the FDA’s assessment” are reflected throughout the review, with FDA’s findings distinguished by bold lettering and gray shading.
Jennifer Gao, the Division of Oncology Products 1 clinical reviewer for the ribociclib supplement, said the AAid template aided communications with the sponsor during the review and the clarity of the final decision.
“It’s not meant to be an iterative, back and forth document, but when we initially got the submission we said maybe here [are] a couple of areas where it would be an opportunity to ask Novartis to make some changes,” Gao said. “It also helped us to learn how the company thinks about our instructions in the assessment aid so that we can modify it and make it clearer going forward.”