Burger S R
Advanced Cell and Gene Therapy, LLC, Chapel Hill, NC 27516, USA.
Cytotherapy. 2003;5(4):289-98. doi: 10.1080/14653240310002324.
Cell-based therapies have grown dramatically in power and scope in recent years. Once limited to blood and BM transplantation, these therapies now encompass tissue repair and regeneration, metabolic support, gene replacement, and immune effector functions, with established and investigational clinical applications in disorders affecting nearly every tissue and organ system. The complexity and novel applications of human cells, tissues, and cellular and tissue-based products (HCT/Ps), however, present potential risks for adverse events. The US Food and Drug Administration, responding to these concerns, has established a tiered, risk-based regulatory structure, in which more rigorous controls and safeguards are required for products thought to pose increased risk. The proposed good tissue practices (GTP) rule and existing good manufacturing practices (GMP) requirements form the principal elements of this regulatory framework. The proposed GTPs are intended to prevent HCT/P contamination with infectious disease agents, and to ensure that these cells and tissues maintain their integrity and function. GMPs focus on production of safe, pure, and potent products, and entail a higher level of process control and product characterization. All HCT/Ps will be required to comply with GTPs. HCT/Ps considered to present greater risks of adverse events, however, will be subject to both GTPs and GMPs, and must obtain premarket approval using the Investigational New Drug (IND) mechanism established for biologics. Although these requirements will present significant challenges for clinician- investigators and laboratories producing HCT/Ps, the regulations fundamentally support good clinical care by increasing safety and control, and enable good science by improving the quality and reliability of data.
近年来，基于细胞的疗法在能力和范围上都有了显著增长。这些疗法曾经仅限于血液和骨髓移植，如今已涵盖组织修复与再生、代谢支持、基因替代以及免疫效应功能，在几乎影响每个组织和器官系统的疾病中都有既定的和正在研究的临床应用。然而，人类细胞、组织以及基于细胞和组织的产品（HCT/Ps）的复杂性和新颖应用带来了不良事件的潜在风险。美国食品药品监督管理局针对这些担忧，建立了一个分层的、基于风险的监管结构，对于被认为风险增加的产品需要更严格的控制和保障措施。拟议的良好组织规范（GTP）规则和现有的良好生产规范（GMP）要求构成了这一监管框架的主要要素。拟议的GTP旨在防止HCT/P被传染病原体污染，并确保这些细胞和组织保持其完整性和功能。GMP关注安全、纯净和有效的产品生产，需要更高水平的过程控制和产品特性描述。所有HCT/Ps都将被要求遵守GTP。然而，被认为具有更高不良事件风险的HCT/Ps将同时受制于GTP和GMP，并且必须使用为生物制品建立的研究性新药（IND）机制获得上市前批准。尽管这些要求会给生产HCT/Ps的临床研究人员和实验室带来重大挑战，但这些法规从根本上通过提高安全性和控制来支持良好的临床护理，并通过提高数据的质量和可靠性来促进良好的科学研究。
