Regulatory challenges have been even more top of mind than usual given recent upheaval at the FDA. BioSpace spoke to three industry experts about key issues, which include applying new artificial intelligence guidance. The experts also shared advice for working with regulators.
Amidst a backdrop of change at the FDA, including substantial layoffs, leadership switches and guidance reversals, regulatory professionals are tackling a variety of issues these days. To explore three of those challenges—two of which involve artificial intelligence (AI)—as well as how to best work with regulators, BioSpace interviewed three regulatory experts.
Interpreting and Applying New AI Guidance
In January, the FDA and European Medicines Agency issued new guidance for using AI in drug development. The two-page document lists 10 guiding principles meant to “inform, enhance, and promote the use of AI for generating evidence across all phases of the drug product life cycle.” However, there’s no depth to that guidance, according to Gurpreet Gill-Sangha, a former supervisory pharmaceutical scientist at the FDA who is now a regulatory pharmaceutical consultant with her own business, GS Consulting MD.
As an example of the principles’ brevity, the explanatory text for the first one, “human-centric by design,” simply says, “The development and use of AI technologies align with ethical and human-centric values.”
Given its broadness, the document therefore serves as a first step in helping companies use AI to present data, Gill-Sangha told BioSpace. Until more guidance arrives, she advised, industry members must ensure that applications they submit to the FDA are fundamentally sound.
“The fundamentals cannot go away,” Gill-Sangha said. “AI can support the data, but if you submit an application that’s weak on fundamentals, but it’s strong on AI, that’s not a good way to take a step forward.”
Gill-Sangha stressed the importance of having a dialogue with the FDA prior to submissions to ensure that applications have deep foundations that will help them receive approval. Many times, she noted, that dialogue doesn’t happen, even at large pharmas, resulting in complete response letters or outright rejections.
Applying Fast-Moving AI to Regulatory Frameworks
Another challenge facing regulatory professionals in AI-driven drug discovery is translating fast-learning systems into slow-moving regulatory frameworks, according to Rahul Gupta, president of GATC Health. The Irvine, California–based biotech applies artificial intelligence and multiomics to accelerate drug discovery and development.
“FDA frameworks were built to evaluate fixed products and static datasets, while AI systems learn and update constantly,” Gupta told BioSpace via written interview responses.
The resulting regulatory tension, he noted, is that if an AI model changes, is it the same “validated” system it was before?
The best way to tackle AI regulatory challenges doesn’t involve adjusting speed, according to Gupta.
“The practical path forward isn’t to slow innovation, but to make it governable by freezing models for regulatory use, being candid about data limits, treating AI outputs as supportive rather than decisive evidence, and engaging FDA early to align expectations before precedents harden,” he wrote.
Having a Great Supply Chain
Regulatory challenges go beyond implementing fast-moving technology. They also include the FDA’s expectation that biopharmas have multiple suppliers, which isn’t always easy, according to Ayda Delpassand, director of business development and project management at Houston-based RadioMedix. The biotech, which develops targeted radiopharmaceuticals for cancer diagnosis, monitoring and therapy, works with isotopes, and there aren’t many isotope suppliers in the industry, Delpassand told BioSpace. In addition, she said, there are certain regulatory and radiation requirements for supplying isotopes.
A shortage of manufacturing sites in the radiopharma field is another supply-chain challenge Delpassand noted.
“It’s very challenging to get a manufacturing site authorized by the FDA, because for them to come and inspect you, you have to have a drug already at the stage of being commercially available, and that would mean filing an ANDA or an NDA,” she said. “FDA does not have all the resources in the world to just have inspectors out for INDs.”
To address the supplier issue in radiopharma, Delpassand said regulatory professionals should lock up supply early and make sure suppliers have a good understanding of—and comply with—regulations that apply to them. Regarding finding a contract development and manufacturing organization, she advised that it may be best to use a company that already has FDA authorization or an approved product.
Working With Regulators
Whatever challenges regulatory professionals face, working with regulators is a critical part of bringing drugs to patients. Gill-Sangha and Delpassand shared advice for how to best do that.
When it comes to submissions, Gill-Sangha said it’s important to have clarity in the documents, as regulators are extremely overwhelmed and have a lot on their plates.
“So, the applications that are extremely clear, concise—they tell you that this is their conclusion, and it’s based on XYZ, whether it’s per a regulation, per this guidance or some other data—fly through for approval,” Gill-Sangha said.
Delpassand noted that at RadioMedix, their mindset is to view the FDA as an ally, not a gatekeeper.
“I never really look at regulatory as being this entity that’s trying to keep me from getting a drug across the finish line,” she said. “I always look at them as a partner in this.”
Delpassand also recommended regulatory professionals be proactive.
“You essentially want to interact so you don’t have to react, and I think that’s the best path forward when it comes to working with the regulatory body and having regulatory challenges up front,” she said.
