Monthly Digest :: Blog Posts

FDA – Human Gene Therapy Products Incorporating Human Genome Editing; Draft Guidance for Industry
[Docket No. FDA-2021-D-0398];
In this guidance, we, FDA, are providing recommendations to sponsors developing human gene therapy  products incorporating genome editing (GE) of human somatic cells.  Specifically, this guidance provides recommendations regarding information that should be provided in an Investigational New Drug (IND) application in order to assess the safety and quality of the investigational GE product, as required in Title 21 of the Code of Federal Regulations 312.23 (21 CFR 312.23).  This includes information on product design, product manufacturing, product testing, preclinical safety assessment, and clinical trial design.

FDA – Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products; Draft Guidance for Industry.
Docket Number: FDA-2021-D-0404
Chimeric antigen receptor (CAR) T cell products are human gene therapy  products in which the T cell specificity is genetically modified to enable recognition of a desired target antigen for therapeutic purposes.  This guidance is intended to assist sponsors, including industry and academic sponsors, developing CAR T cell products.  In this guidance, we, FDA, provide CAR T cell specific recommendations regarding chemistry, manufacturing, and control (CMC), pharmacology and toxicology, and clinical study design.  Recommendations specific to autologous or allogeneic CAR T cell products are noted in this guidance.  This guidance also provides recommendations for analytical comparability studies for CAR T cell products.  While this guidance specifically focuses on CAR T cell products, much of the information and recommendations provided will also be applicable to other genetically modified lymphocyte products, such as CAR Natural Killer (NK) cells or T cell receptor (TCR) modified T cells.  These related product types can be highly specialized, and in many cases, considerations beyond those recommended in this guidance would depend on the specific product and manufacturing process.  To discuss considerations specific to these related products, we recommend sponsors communicate with the Office of Tissues and Advanced Therapies (OTAT) in the Center for Biologics Evaluation and Research (CBER) before submitting an Investigational New Drug Application (IND) (e.g., by requesting a pre-IND meeting (Ref. 1))..

New guideline will enhance oversight of research in frontier fields
Zhang Zhihao
China Daily   Updated: Mar 24,2022 10:20
[ENG.GOV.EN  The State Council – The People’s Republic of China]
[Editor’s Note: We have not identified a full English translation of this guideline as of 10 May 2022. We have added text bolding for emphasis.]

A new national guideline on research ethics and governance will enhance China’s oversight of projects in frontier fields, including life sciences, medicine and artificial intelligence, aiming to ensure that scientific and technological progress serves the greater good of humankind, officials and experts said.

The guideline also demands that international research projects abide by the regulations of the participants’ home countries and pass ethical reviews. Chinese authorities can organize experts to reevaluate international projects that have high ethical risks, it said.

On March 27, the general offices of the Communist Party of China Central Committee and the State Council, China’s Cabinet, issued the country’s first comprehensive guideline on enhancing governance over ethics in science and technology.

Xiang Libin, vice-minister of science and technology, said the current ethic governance system cannot keep up with China’s rapid sci-tech growth, given how some of the country’s cutting-edge scientific endeavors are exploring unchartered territories with many uncertainties. “Science and technology is a double-edged sword,” Xiang said. “Therefore, the guideline plays a key role in building consensus, improving public awareness on the importance of research ethics and governance, and mitigating ethical risks in scientific undertakings.”

A key requirement of the guideline is that research ethics should be emphasized and upheld throughout the entire process of scientific research and technological development, Xiang said. Managing sci-tech ethics in accordance with laws and regulations, swiftly and properly handling emerging ethical challenges, establishing a system of ethical standards based on Chinese characteristics, and enhancing international cooperation in sci-tech governance are also among the top objectives, he added.

Scientific activities should serve the greater good of humankind, respect human and animal rights, treat social groups from different backgrounds fairly and equally, properly prevent and manage ethical risks, and maintain openness and transparency during research, according to the guideline.

“No agency, organization or individual can conduct scientific activities that damage social, public, biological and ecological security, nor can they undermine the safety and well-being of people’s lives, health and dignity,” it said.

Universities are encouraged to bolster education about research ethics in undergraduate and graduate studies. Chinese authorities should guide universities, research institutions, medical agencies, social groups and companies to optimize their monitoring and early warning mechanisms to spot ethical risks.

Violators of research ethics will be investigated and punished in accordance with relevant laws and regulations, with measures ranging from revoking research grants and titles to banning offenders from conducting future studies.

In regard to ethical review of high-risk research, Dai Guoqing, director of the Department of Supervision and Scientific Integrity at the Ministry of Science and Technology, said there will be a multilayered review mechanism in which a proposal is not only required to pass a review by the ethical committee of the researchers’ institution, but also several rounds of reviews by local regulatory agencies.

Zhai Xiaomei, a member of the National Science and Technology Ethics Committee, said the profound respect for the right to life and personal dignity highlighted in the guideline is in the same spirit that led to the creation of China’s first Civil Code, which went into effect in January last year.

In the medical experiments, the rights of trial participants should be fully protected, including their right to privacy and the right to make informed decisions, Zhai said. “They should be treated fairly and justly, and not be forced to make a compromise due to their circumstances.”…

A major takeaway from the guideline for Zeng is the requirement for international projects to pass ethical reviews in the participants’ home countries. “This is a big deal because foreign researchers can no longer carry out studies in China that are deemed too ethically risky in their home countries,” he added.

The release of the new guideline, along with the country’s efforts to improve research ethics and governance in recent years, show that China has begun a systematic building of ethics in scientific activities, which will benefit the country’s sci-tech development and open new areas for international cooperation, Zeng said.