From The Editor | December 4, 2018

The Status of Regulatory Framework For Cell And Gene Therapies


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

gene therapy

Jiwen Zhang, Executive Director, Regulatory Affairs at Tmunity Therapeutics Incorporated and Cell & Gene Editorial Advisory Board member explains the status of the cell and gene sector’s domestic and international regulatory framework. As President of the International Standards Coordinating Body (SCB), she also provides a synopsis of the most recent Stakeholder meeting.

Harris: Explain the status of the domestic regulatory framework for cell and gene therapies in comparison to other countries.

Zhang: Recent event of gene edited babies in China underscores the importance of regulations. Fortunately, there is a comprehensive regulatory framework in place in the U.S.

Jiwen Zhang, Executive Director, Regulatory Affairs at Tmunity Therapeutics Incorporated
In the U.S., cell and gene therapy products — together with tissue engineered products — are referred as advanced therapies. They are regulated as “biologics,” under the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration (FDA), and overseen by the Office of Tissues and Advanced Therapies (OTAT). CBER uses both the Public Health Service Act and the Federal Food Drug and Cosmetic Act as enabling statutes for oversight. 

Based on risks, advanced therapies are further categorized as “351” or “361” products subject to different sections of the Public Health Service Act. Like other biological drugs, “351” products require pre-market approval and licensure for product commercialization while “361” products do not require pre-market review and approval.

Over the years since the regulations have been established, FDA has issued a slew of guidance documents to help researchers and organizations interpret regulations and facilitate product development. OTAT’s cellular and gene therapy guidance webpage provide great resources.

Like the U.S., EU and Japan have also established specific regulatory frameworks for cell and gene therapy products, with some variations to reflect regional differences in developing and practicing these therapies. It is very important for stakeholders to fully understand and appreciate how these products are regulated, and regional or national regulatory differences to enable the most efficient product development to serve patients in need.

Harris: How close is the cell and gene sector to developing a similar international regulatory framework?

Zhang: Though U.S., EU, Japan have regulations in place, some countries are in the process of developing regulatory framework, and many others have yet to start. Regulations generally react to advancement of science and technologies to provide oversight to safe guard public health. Until there is a need, it is impractical for governments to implement laws and regulations. For example, regulations for medical devices are still being developed in some countries.

However, science and technologies are advancing faster, and cycles are becoming shorter. With cell and gene therapies promising curative potentials, development and adoption of cell and gene therapies will realize sooner than we would normally expect.

Recently, BioCentury analyzed the American Society of Hematology (ASH) annual meeting abstracts and found that cell therapy coverage rises dramatically this year, with an almost doubling over 2017 in both clinical and preclinical abstracts, suggesting cell therapies will continue to “flood clinical pipelines in the coming years” (BioCentury, November 28, 2018).

It is important for stakeholders to advocate the importance of regulations; to have patient’s safety and welfare as a high priority. The gene edited baby event clearly speaks to how critical this can be. Stakeholders should also actively participate in legislative discussions and provide input and feedback. In general, regulators are genuinely interested in stakeholders’ feedback and have mechanisms in place to engage stake holders nationally and globally. Both Singapore Agency and Taiwan Agency reached out to U.S. stakeholders this year (2018) to share their thoughts on cell and gene therapy regulations being developed and how to overcome unique hurdles in this space by developing a sensible regulatory framework.

While there are still major gaps in regulatory framework globally, and regulations in individual countries or regions will undoubted have their own unique components, stakeholders can leverage international standards to ensure quality research and products to be developed and practiced to treat patients.

Harris: You are President of the International Standards Coordinating Body. Please provide a detailed update about your Stakeholder meeting that was held two months ago.

Zhang: Like any nascent space, the need of standards is obvious. Recognizing such need, there have been various entities, organizations actively engaged in standard development. To ensure efficient standards development, avoid duplicate efforts, the FDA/CBER first called for coordination at a publica workshop in 2014. In response, after years of preparation, the Standards Coordinating Body (SCB) was finally launched in early 2017.

SCB has developed various mechanisms to engage stake holders to identify the need of standard projects, conduct prioritization and feasibility assessment, enlist experts to contribute to specific standard projects. Since its launch, particularly since funding by the FDA contract in September 2017, SCB has conducted, or presented at, 80 total sector meetings, conferences, and/or workshops, and engaged 200+ experts in online survey, 50+ stakeholders via individual interviews, and 300+ stakeholders via facilitated workshops. SCB is currently leading a list of standards projects and activities, and facilitating project discussion and expert recruitment for other organizations (

Mid-September, responding to the request from the Singapore’s Health and Sciences Agency (HAS), the SCB organized a stake holder meeting and provided feedback to the cell and gene therapy regulations Singapore is working on. Leveraging the knowledge and experiences of the participating experts, the meeting also focused discussions on challenges and next step actions in 3 key technical areas: viral vector manufacturing, cell characterization, and cell collection and logistics. Several post-meeting work streams were identified and SCB is following up on standards projects (

With completion of the 2017-2018 contract, the FDA has extended the contract for another 6 months with additional funding. One deliverable of the extended contract is to conduct a standards workshop scheduled on January 14 – 15, 2019: Realizing the Benefit of 21st Century Cures through Standards Development: A Workshop Convened by FDA, NIST, SCB, and Nexight Group. The workshop will feature updates from Standards Development Organization (SDO) representatives and industry organizations on the benefits of standards and participating in the standards development processes.

Harris: From SCB’s perspective, what is on the horizon for the cell and gene sector?

Zhang: If we look across the cell and gene sector, we see significant growth on the horizon, in terms of more development activities, application of innovative technologies, more patients will be treated with approved cell and gene therapies, potential new thinking of pricing and reimbursement scheme, and of course, continued evolution in regulatory frameworks. And all of these are happening in a global setting.

So, from SCB perspective, clearly there will be a continuous need for standards. In addition to standards to enable more efficient manufacturing, reducing cost, there will be an increased need for standards in clinical space, including medical practice of cell and gene products, evidentiary standards for pricing and reimbursement, logistics and supply chain management to ensure integrity and chain of custody. The standards developed also need to be applicable globally to enable international consistency and free trade.

Meanwhile, with science and technology fast advancing, there also needs to be a conscious balance of developing standards and not stifling innovations. Coordination of standard development efforts is not just to coordinate experts to engage in appropriate activities, but also on a strategic level, how to best utilize the resources and expertise to facilitate the sector growth. And last but not the least, all these activities require funding and participation. With support from all stake holders, including government agencies, research institutions, industry organizations, patient advocacy group, the SCB is striving to collaborate with stake holders closely to realize the mission to coordinate the accelerated advancement and improved awareness of standards and best practices that address the rapidly evolving needs of the global regenerative medicine advanced therapy community.