Pharma Focus Asia


Key regulatory insights

Ghulam Moinuddin, A Scientific Regulatory Professional

The rapidly advancing field of cell and gene therapy (CGT) presents transformative solutions for a multitude of previously untreatable diseases. Over the last few years, numerous CGT products have successfully obtained clinical approval, with over 75 such therapies that are approved by Health Agencies now available for treatment worldwide. It underscores the immense potential of these modalities to treat or even cure otherwise intractable diseases. However, alongside its immense promise lies the critical need for a robust and adaptable regulatory framework to ensure patient safety and efficacy. Understanding the Regulatory landscape is paramount in the dynamic and groundbreaking field of Cell and Gene Therapy, where scientific innovation meets therapeutic potential.This article delves into the intricacies of CGT Regulations and hurdles surrounding Cell/Gene Therapy, exploring the challenges and opportunities that this transformative field presents for researchers, clinicians, Pharmaceutical/Bio Pharmaceutical industry professionals, and Health Agencies.

CGT stands at the forefront of personalised medicine, revolutionising healthcare by modifying patients' own cells or genes for therapeutic purposes. From tackling cancers and genetic disorders to potentially treating neurodegenerative conditions, CGT offers unprecedented avenues for medical intervention. However, this transformative potential is inextricably linked to the establishment of a robust and adaptable regulatory framework.

Matching up to the requirements and synchronising with technological advancements, the regulatory environment for Cell and Gene Therapy is rapidly evolving. Health authorities, including the FDA, EMA, and other global Regulatory bodies, are pivotal in creating a scientific and structured landscape.

Key Regulatory Insights

Some of the key and recent insights from the FDA include:

Expected Upsurge in CGT IND Filings

As per the statistics disclosed by the Director of the FDA’s Office of Tissues and Advanced Therapies (OTAT), there seems to be a drop in the number of Investigational New Drug (IND) filings for Cell and Gene Therapies (CGT) from 350 in 2020 to 299 in 2021. Despite this fact, these numbers are anticipated to rise again in the forthcoming years. Additionally, OTAT highlighted a noticeable rise in Breakthrough (BT) and Regenerative Medicine Advanced Therapy (RMAT) designation requests. These requests are typically submitted concurrently with IND filings or during an existing IND filing, with a simultaneous increase in accepted RMAT requests.

Bespoke Gene Therapy Consortium (BGTC)

It is well known that the FDA has launched a new initiative called the Bespoke Gene Therapy Consortium (BGTC) under its NIH Accelerating Medicines Partnership Program. The consortium is designed to simplify the development of small-batch gene therapies by addressing key therapeutic challenges. It will guide basic and clinical research, manufacturing, production, and Regulatory requirements for these therapies.


A relatively recent FDA initiative is the "INTERACT" informal meeting program initiated by CBER. The INTERACT program aims to address the questions and needs of the Cell and Gene Therapy (CGT) industry within existing clinical frameworks. It involves informal meetings between CBER staff and researchers or sponsors who are in the pre-Investigational New Drug (pre-IND) stage of development. The INTERACT meetings do not incur a Prescription Drug User Fee Act (PDUFA) fee, and their scheduling depends on CBER's availability and resources. It's important to note that these meetings do not replace other formal meetings. Therefore, it is advisable to request a pre-IND meeting before submitting an IND to initiate the first-in-human Phase I study, especially when seeking guidance on toxicology study designs.

Gene Therapy Pilot Program

The Gene Therapy Pilot Program, a recent initiative, includes the FDA giving sponsors immediate feedback during clinical development. This program works in conjunction with new Regulatory pathways like the Regenerative Medicine Advanced Therapy (RMAT) designation. The aim is to speed up the development process and reduce review times for submissions. Collectively, these initiatives provide sponsors and regulators with more opportunities for regular communication and discussion about technological advancements.

With ongoing rapid progress in this domain, plan sponsors can anticipate notable changes in the evolving landscape of the U.S. healthcare system. Emerging studies indicate a probable surge in the availability of gene therapies, with projections estimating that the count could surpass 60 by the year 2030.

Casgevy is the first FDA-approved therapy utilising CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/ Cas9 technology.

In addition to the FDA, EMA has also come up with key steps to accelerate Cell and Gene Therapy production. It includes:

Orphan Status to CGT Drugs

European authorities are eager to support novel treatments focusing on currently neglected disease areas. Consequently, the European Medicines Agency (EMA) has awarded orphan status to the majority of Cell and Gene Therapy (CGT) drugs in the developmental stage. Additionally, the agency has conducted expedited assessments for several therapies.

For e.g., The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended the authorisation of Glybera (alipogene tiparvovec) for marketing in the European Union. Glybera is a designated orphan medicine. The orphan designation was granted by the European Commission in March 2004. It is intended to treat lipoprotein lipase (LPL) deficiency in patients with severe or multiple pancreatitis attacks despite dietary fat restrictions.

Adhering to GMO Regulations

Within the EU, companies are obligated to adhere to an environmental risk assessment and comply with genetically modified organism (GMO) requirements. This is to ascertain whether their Cell and Gene Therapies (CGTs) contain any substances that may be harmful to patients, animals, plants, or micro-organisms and to evaluate their overall impact on the environment.

Despite the guidance provided by the EMA on GMO requirements, it is crucial for companies to comprehend the distinct requirements for clinical trials, as these may differ across EU countries.

Challenges and Hurdles

Global Health Authorities are taking a few key steps to streamline the production of CGTs. Alongside the initiatives, there exist a few challenges that have to be addressed at the forefront. These include the following.

Balancing Innovation and Safety

The core challenge lies in achieving a delicate balance between fostering innovation to swiftly bring life-altering therapies to patients and ensuring rigorous assessments that guarantee their long-term safety and efficacy. Expedited approval pathways, like the FDA's Breakthrough Therapy Designation, hold immense promise in accelerating access for patients in dire  need (US Food and Drug Administration, 2023). However, this must be counterbalanced by well-defined clinical trial designs and robust post-market surveillance mechanisms, such as the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) (European Medicines Agency, 2023).

Clinical Trial Design and Oversight

Initiating the regulatory pathway hinges on robust clinical trials that uphold the highest ethical standards. Regulatory agencies play a pivotal role in overseeing these trials, meticulously scrutinising protocols to ensure patient safety, informed consent, and scientific integrity. This oversight becomes even more crucial for CGT due to the inherent complexity of these interventions (Cantor et al., 2023).

Regulatory Challenges

Despite the immense promise, CGT faces a spectrum of Regulatory challenges. Understanding long-term safety and efficacy remains a significant hurdle. Post-market surveillance emerges as a cornerstone in addressing this, necessitating seamless collaboration between manufacturers, healthcare providers, and regulatory agencies (U.S. Food and Drug Administration, 2019). Additionally, logistical complexities surrounding manufacturing, storage, transport, and administration demand innovative solutions and harmonisation among industry stakeholders (Alliance for Regenerative Medicine, 2023).

Consistency in Global Regulations

Achieving harmonisation across global regulatory standards remains a hurdle. Divergent requirements and expectations among different regulatory bodies can complicate the development and approval process for multinational clinical trials and global market access.

Manufacturing Standards

Ensuring consistent and high-quality manufacturing processes for Cell and Gene Therapies is a critical challenge. Strict adherence to Good Manufacturing Practices (GMP) is essential, and any deviations may impact regulatory approval.

Long-Term Follow-Up

The durability of therapeutic effects and long-term safety of Cell/Gene Therapies require extensive follow-up data. Establishing and maintaining comprehensive post-marketing surveillance systems is a regulatory challenge that ensures continued patient safety.

Best Practices to Take Up

Amidst the burgeoning innovation in virology and genetic engineering, the future of gene therapies appears promising. To keep pace with the market trends, it is important for Regulatory bodies and manufacturers as well to keenly evaluate every aspect that they take up. Some of the proposed best practices can be:

Robust Communication

As these groundbreaking therapeutics explore new treatment areas and cater to broader patient populations, regulatory bodies must remain responsive to ongoing advancements. The key to ensuring the safety, efficacy, and quality of approved gene therapies lies in regulatory guidance that mirrors these transformative changes.

Achieving the ambitious approval goals necessitates not only adjustments on the part of Regulatory bodies to minimise delays but also adaptations from drug developers and manufacturers to align their processes with these evolving standards. Given the complexity of these dynamics, robust communication between gene therapy producers and regulatory bodies is anticipated to become increasingly vital.

Proposed Regulatory Strategies

Toward Collaboration and Efficiency: Embracing innovative strategies is crucial for navigating this evolving landscape. Risk-based assessments, as endorsed by the European Medicines Agency (European Medicines Agency, 2022), empower Regulatory agencies to tailor oversight based on individual therapies' specific risks. This allows for a more efficient and streamlined process without compromising robustness, particularly for therapies with lower risk profiles.

Real-World Evidence Integration

Integrating real-world evidence (RWE) into Regulatory decision-making represents a paradigm shift. RWE offers valuable insights into a therapy's performance in real-world settings beyond the controlled environment of clinical trials. Collaborative efforts between Regulatory bodies, healthcare providers, and data scientists are essential to harness the power of RWE effectively, allowing for continuous refinement of regulations based on real-world experiences.


The promise of CGT necessitates a collaborative and adaptable regulatory ecosystem. By bridging the gap between innovation and safety, fostering open communication, and leveraging RWE, we can pave the way for these transformative therapies to reach patients in need while upholding the highest ethical and scientific standards. This ongoing dialogue between researchers, clinicians, and Regulatory authorities is crucial to ensure that the future of medicine is shaped by both scientific advancement and responsible governance.

--Issue 54--

Author Bio

Ghulam Moinuddin

A Scientific Regulatory Professional with 17 years of extensive Regulatory Affairs and 5 years of academic experience, with a track record of providing leadership for Quality-CMC, Non-Clinical and Clinical Regulatory Projects at Amgen Inc., LG Life Sciences, Intas Bio-Pharmaceuticals, Dr. Reddy’s Biologics, Biocon and Recon. Demonstrated ability to strategise, author, compile, and review regulatory submissions to Health Authorities and customers. Actively participated in New Drug Development; Clinical Trial Approvals; Marketing Authorisations and Commercialisation of 14 Biologics, 1 NCE, 5 New Biologicals in India; SAARC; RoW; and 1 in Europe.

Extensive experience in CMC; with a strong background in Non-clinical Pharmacological and Toxicological studies; and Clinical Trials for small molecules and biologics. Efficiently managed Product Life Cycle, PAC, RTQ; Tech Transfer; Due-Diligence, Licensing. Participated in GMP audits by Benchmark HA and Global Pharmaceuticals.

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