CDER Head Looks to Improved Drug Safety Surveillance

CDER director Patrizia Cavazzoni says FDA’s recent increased funding request for fiscal year 2023 would, if enacted, help address a Center priority to improve drug postmarket surveillance and oversight of marketed products. The budget request calls for an almost 10% increase — a $356 million boost over current authorized spending levels (see earlier story).

Speaking at an online Alliance for a Stronger FDA 4/4 budget update, Cavazzoni said postmarket safety surveillance has been underfunded in previous budget requests. Over the years, she said, CDER has “undertaken a process to modernize our approach to safety surveillance, both from an operational aspect of how the teams work together and the sort of expertise that we bring to safety surveillance, as well as technology. All of this is really to keep up with the technological advances that we see in industry.”

Cavazzoni said CDER is reorganizing postmarketing surveillance along the lines of the “guiding principles used in the modernization of the new drug review program, which was anchored on cross-discipline work and developing integrated assessments of the application. We are also taking those principles to guide changes that we’re doing in postmarket surveillance.”

She said CDER has begun setting up multidisciplinary drug safety teams, which will work together from the get-go to identify new signals, validate the potential risks, and then determine how to mitigate them. “And so from day one, we have the clinicians coming together, the statisticians coming together, the toxicologists coming together in the same room …, rather than sending memos from each discipline once they have done the review,” she said.

Now when it comes to new surveillance technology, Cavazzoni said the agency is designing FAERS-2 [FDA Adverse Event Reporting System], a next-generation system based on newer technologies, including a cloud environment and new analytical tools that allow FDA scientists to evaluate and dissect the adverse event data as they come in. “It will also contain the product quality adverse events and last but not least it's our vehicle to implementing ICH R3 for transmission of adverse events…,” she said. “We’re really looking very carefully at what automation and artificial intelligence are doing, and the role that increasingly plays in the evaluation of safety data. Automation is important because we are reviewing and receiving increasing numbers of adverse events… And we also need to really understand how industry is automating their own surveillance systems including their transactional databases from which the send us their adverse events. We need to understand those operating characteristics because we need to inspect these systems too.”

Another overarching priority across the Center is the modernization of data analytics and technology platforms, according to Cavazzoni. Under the budget request, FDA is seeking $68 million for data modernization and enhanced technologies, such as artificial intelligence, and blockchain. Data modernization will also allow the agency to review large volumes of data more quickly to identify critical safety signals or emerging outbreaks. Cavazzoni is hopeful that CDER will get needed resources to modernize its technology systems if the agency-level funding request is approved.

Asked to explain further on the types of data modernization CDER hopes to advance, Cavazzoni pointed to CDER’s Office of Pharmaceutical Quality’s Knowledge-aided Assessment & Structured Application (KASA) tool for solid oral dosage forms, manufacturing, and biopharmaceutics regulatory assessments. KASA has been under development for years to improve efficiency, effectiveness, and quality assessment consistency by structuring quality-related data it receives, maintaining a collective knowledge base of the data, and enabling a more consistent scientific assessment of risk associated with applications, she said.

“The other very important area is data and analytics,” she said, adding that the Center is building a central data and analytic environment called CDER-1, which will improve the consistency of how the Center views data and its regulatory decision making. The platform will support the deployment of technologies, such as natural language processing and artificial intelligence, to help mine the data. “We have vast amounts of information that has come in through applications and there is so much knowledge that has been accumulated over the years that is difficult to capture and put to work because it's difficult to find, she said.

“Without having a unified approach to storing the data and analyzing it,” Cavazzoni continued, “you really don't know where the data are sitting.” For years industry has complained that decisions sometimes are not consistent and that is where knowledge management comes in, she explained, adding that CDER can more easily solve problems by making that knowledge base readily available. She said analytical tools will also be available to mine the knowledge base, manipulate it, and “learn from it so that we can sort of achieve also, among other things, a greater degree of consistency in our regulatory decision-making.”