US FDA Hoping To Solve Drug-Software Issues With Digital Health Working Group
Executive Summary
As more applications include software components, group wants assessors to apply best practices from CDRH to CDER whenever possible.
With software and drugs becoming increasingly intertwined, the US Food and Drug Administration is marshaling its expertise to make policy decisions and help application assessors.
The agency has established a working group on digital health that will address policy issues related to software that is used with drugs. The group includes representatives of the centers for devices and radiological health and drug evaluation and research, as well as the Office of Combination Products (OCP).
Kristina Lauritsen, CDER combination products regulatory policy advisor, said the group wants to take best practices from CDRH and apply them to CDER where possible.
"It's important that we're leveraging all of the really good work that CDRH has done," Lauritsen said on 30 October during the Drug Information Association Combination Products Conference. "We're not going to want to recreate anything in the digital health space. They own that. They know what they're doing with it, but we want to see how we can use that and leverage that in what we're doing with drugs."
In addition to assuring consistency in combination product assessment practices, the working group also will help assessors when questions arise.
"It's not a group that industry can come and interact with, but when an application comes across a reviewer's desk that has software, they have a resource," Lauritsen said.
The FDA is attempting to streamline its pathway for approving drugs that have companion apps or other related software. In 2018, the agency released a discussion proposal where the software output could be considered promotional labeling, which would allow sponsors to avoid pre-market approval as a device. Office of Prescription Drug Promotion or Advertising and Promotional Labeling Branch review may still be necessary. (Also see "Drug/Software Combos Likely Won't Require Pre-Market Review By US FDA" - Pink Sheet, 19 Nov, 2018.)
Agency officials also just published draft guidance allowing drug master files to be submitted for software envisioned for multiple products. A DMF allows the sponsor to avoid re-review of the software each time an application using it is filed. (Also see "CDER Permits Some Combo Product Software To Be Submitted As DMFs" - Pink Sheet, 28 Oct, 2019.)
Several questions remain unanswered, but OCP Director Thinh Nguyen said the agency is steadily working to resolve them.
"Some may be straight forward others are pretty much precedent-setting so we have to be sure we do the right thing," he said. "Have patience with us because those are not easy answers to give sometimes."
New Kind Of Product, Same Agency Strategy
Establishing a working group is a common strategy for the agency to ensure its policies for a new product type or application are followed. Drug and software pairs could be filed across multiple assessment divisions and sponsors will be looking for consistency, which could be a problem given that some divisions may be more experienced than others in handling them.
When the breakthrough designation program was established, requests were evaluated by the FDA's Medical Policy Council to ensure the standards were applied properly. (Also see "Inside FDA’s Debates On ‘Breakthrough’" - Pink Sheet, 11 May, 2015.) Often the council agreed with the assessment division's recommendation. (Also see "FDA Central Review Likely For Novel Surrogate Endpoints" - Pink Sheet, 17 Jun, 2015.)
A subcommittee of the Medical Policy Council also is helping assessors better understand how real-world evidence should be evaluated in applications, as well as ensure policies are followed. (Also see "US FDA Searches For Consistency On Assessment Of Real-World Evidence" - Pink Sheet, 29 Jul, 2019.)
In addition, rare disease expertise likely will be connected in order to assure consistent application of flexibility and other policies for those products. (Also see "US FDA Plans Rare Disease Center Of Excellence, But Not "That" Kind Of COE" - Pink Sheet, 25 Oct, 2019.)
Combo Product Check-Box Helps Connect Experts To Applications
Agency officials also are requiring sponsors to note at the top of their applications that it is a combination product, another streamlining and consistency effort.
Lauritsen said the FDA has long been identifying combination products when the application is submitted, but previously required a filing reviewer dig through the hundreds of pages to find the information. Now sponsors must check a box on their 356h forms indicating the product is a combination product, which is automatically transferred to FDA databases.
Lauritsen said the information helps FDA ensure the proper experts look at the application, which also can speed up the assessment process.
The agency similarly asks that sponsors indicate in their application cover letters that the package includes real-world evidence and its purpose, in part so they can be tracked. (Also see "Real-World Evidence Should Be Flagged In US Drug And Biologic Applications" - Pink Sheet, 8 May, 2019.)
Consult Requests, Collaboration Improving
Throughout the conference, agency officials touted the increase and openness for collaboration between the device, drug and biologics centers when it comes to combination products. Historically, conflicts between the various centers have slowed those assessments and approvals.
Nguyen said during the conference that inter-center consult requests increased nearly 2% from 1,419 in fiscal year 2017 to 1,445 in FY 2018, which is a sign of more collaboration between the centers. Nguyen also said staff across centers are working on guidances and standard operating procedures in addition to applications.
CDER requested the most consults in FY 2018, 867, followed by CDRH, 460, and CBER, 118, Nguyen said. CDER has made the most requests for several years, according to FY 2017 OCP performance report.
Overall, consult requests have jumped nearly 173% since FY 2011, when only 530 were reported. (See chart.)