Navigating Regulatory Complexity In Cell And Gene Therapy

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

Cell and gene therapy continues to surge ahead as one of the most transformative areas in modern medicine, with groundbreaking science meeting the realities of complex regulation and manufacturing. For CGT developers, the ability to anticipate and adapt to evolving regulatory expectations is just as critical as scientific innovation. To explore these dynamics, I created a special four-part series as part of Cell & Gene: The Podcast called “FDA Fridays” that features insightful conversations with regulatory leaders Dr. Kaye Spratt, Monika Swietlicka, and Dr. Bambi Grilley. The fourth episode will feature regulatory expert Daniela Drago, and the recap of that episode is forthcoming. Together, these conversations shed light on the current challenges, best practices, and forward-looking strategies shaping the CGT regulatory environment.

Building Regulatory Strategy Early with Dr. Kaye Spratt

Kaye Spratt, Ph.D., Strategic and Non-Clinical Regulatory Consultant at Spratt Advanced Cell & Gene Therapy Regulatory Consulting, emphasized the importance of developing regulatory strategy as early as possible in the product lifecycle. Too often, she explained, CGT companies focus almost exclusively on science and preclinical promise without simultaneously building the framework needed to navigate regulatory review.

Dr. Spratt highlighted how early engagement with FDA and CBER can accelerate timelines, clarify expectations, and avoid costly missteps later in development. Sponsors should not approach regulatory agencies reactively but instead position them as strategic partners. This is especially critical for first-in-class therapies where precedent is limited, and the science often outpaces formal guidance.

She also underscored the increasing demand for robust CMC data. Regulators expect developers to demonstrate not only clinical potential but also a clear, reproducible path to manufacturing quality. By prioritizing process development and data collection early, companies can avoid painful delays when transitioning from early trials to pivotal studies.

Dr. Spratt’s message was clear: regulatory readiness is not a box-checking exercise but rather a fundamental pillar of successful CGT development.

Adapting to Global and U.S. Regulatory Trends with Monika Swietlicka

Monika Swietlicka, Principal, Regulatory Strategy at Halloran Consulting Group brought a broader lens to the discussion, focusing on both U.S. and international regulatory trends. She noted that while the U.S. FDA remains a gold standard for CGT approvals, harmonization with global regulators is increasingly important. For companies with international ambitions, aligning documentation and processes early can prevent major barriers when scaling into Europe, Asia, and beyond.

A central theme from Swietlicka’s discussion was regulatory agility. Policies and guidance in the CGT space are evolving rapidly with agencies frequently piloting new programs, such as expedited review mechanisms or adaptive clinical trial designs. Developers that can pivot quickly and build flexibility into their regulatory strategy will be better positioned to seize opportunities and mitigate risk.

Swietlicka also highlighted the critical role of real-world evidence (RWE) and digital health integration. Regulators are more open than ever to incorporating RWE into decision-making, particularly for rare diseases and small patient populations where traditional trials are limited. For CGT sponsors, this presents a chance to leverage novel data sources to strengthen submissions, but it also requires careful planning to meet evidentiary standards.

Ultimately, she advised CGT companies to maintain a proactive posture, tracking not only today’s regulations but also anticipating tomorrow’s shifts. The regulatory environment is dynamic, and success depends on foresight as much as compliance.

Bringing Patient and Clinical Perspectives Forward with Bambi Grilley

While Spratt and Swietlicka focused heavily on regulatory and strategic frameworks, Bambi Grilley, Ph.D., Professor of Pediatrics and the Director of Clinical Research and Early Product Development for the Center of Cell and Gene Therapy (CAGT) at Baylor College of Medicine and Chief Regulatory Officer for ISCT, highlighted the human dimension of CGT development. With deep experience spanning regulatory, clinical, and patient engagement, Grilley reminded listeners that regulations exist to protect patients and sponsors who center patient needs often find smoother regulatory pathways.

One key point Grilley raised was the importance of clear communication with patients and trial participants. For therapies that are first-in-class or highly complex, patients and caregivers must understand not only potential benefits but also risks and unknowns. Transparent communication builds trust and strengthens the ethical foundation of development.

Grilley also emphasized the role of academic-industry partnerships. Many cell and gene therapies originate in academic labs and ensuring that these early innovations are translated effectively into industry pipelines require collaboration and regulatory alignment. By fostering stronger partnerships, the field can move promising therapies from bench to bedside more efficiently.

Finally, she stressed the value of robust clinical trial design. Regulators are highly focused on safety and long-term follow-up in CGT trials. Sponsors who anticipate these needs and build them into early protocols are better positioned for success.

Key Themes Across All Three Conversations

While each guest brought unique insights, several unifying themes emerged across the series:

• Start Regulatory Planning Early – Whether building CMC data packages or planning clinical trial designs, early alignment with regulators reduces risk and accelerates timelines.
• Flexibility Is Essential – With regulations and science evolving rapidly, sponsors must build adaptable processes that can withstand change.
• Global and Long-Term Thinking Matters – Developers must anticipate not just U.S. regulatory requirements but also international expectations and the future evolution of policy.
• Patients Remain Central – Beyond technical compliance, patient trust, safety, and communication are the bedrock of sustainable CGT innovation.
• Data Will Drive the Future – From manufacturing analytics to real-world evidence, the ability to generate and leverage robust data is a differentiator.

Why the FDA Fridays Series Matters

The CGT sector is navigating unprecedented complexity. Scientific breakthroughs are opening new possibilities for patients, but regulatory and manufacturing challenges remain steep. The insights shared by Kaye Spratt, Monika Swietlicka, Bambi Grilley, and the soon-to-air episode featuring Daniela Drago provide practical guidance for developers who must balance innovation with compliance. Be sure to listen to all four episodes wherever you get your podcasts.