ISPE 介绍新指南：RNA 生产工艺特点与基于风险的设施设计
RNA Manufacturing: Process Characteristics and Risk-Based Facility Design
ISPE 发布博客介绍其新的《RNA 治疗产品生产指南》，说明 IVT 无细胞工艺、封闭一次性系统等特点，以及基于风险的设施设计思路。指南称参考欧盟、FDA、WHO 与 PIC/S 等 GMP 框架及相关药典标准编写，不替代或解释具体监管要求。文中指出 mRNA 是当前最成熟的 RNA 模式，环状 RNA 与自扩增 RNA 仍在研究中。
iSpeak Blog
26 October 2026
The development and deployment of mRNA COVID-19 vaccines accelerated interest in RNA as a therapeutic platform. RNA-based approaches are now being investigated or developed for applications including vaccines, cancer immunotherapies, protein replacement, and gene editing.
Many mRNA products are manufactured using in vitro transcription (IVT), an enzymatic process in which RNA is generated from a DNA template in a cell-free reaction. Other RNA modalities may require different production approaches, so manufacturing requirements depend on the product and process.
For IVT-based processes, RNA production does not depend on propagation in a production cell line. This can reduce some risks associated with cell culture, including risks related to adventitious agents and the use of growth-promoting media, but it does not eliminate viral or microbial contamination risks. The process can be characterized and controlled through defined raw materials, process parameters, and analytical methods. High production yields and relatively low dose requirements for some products may also support smaller manufacturing footprints, although facility requirements remain product and process-specific.
These characteristics create opportunities for simpler facility designs and more streamlined operations. Rather than automatically applying legacy facility concepts developed for monoclonal antibodies or traditional vaccines, manufacturers can adopt approaches that align with the actual risks and process requirements of RNA production. According to Guide Lead David Estapé, PhD, Senior Fellow, CRB Group GmbH, “This new ISPE Guide: for RNA-Based Therapeutics Manufacturing will establish a new standard for RNA manufacturing.”
RNA processes may operate at smaller scales than some traditional biologics processes and can make extensive use of closed, single use systems. Where supported by contamination control and process risk assessments, these characteristics may enable more compact facilities, flexible manufacturing suites, modular concepts, and increased automation while maintaining applicable GMP requirements.
Regional manufacturing hubs, decentralized production networks, and point-of-care manufacturing are among the models being explored for some RNA products. Depending on the product, process, testing strategy, and regulatory framework, these approaches may offer options for supply resilience, transportation, access, or rapid capacity deployment. They also introduce technical, quality, logistical, and regulatory considerations that require case-specific evaluation.
The ISPE Guide: RNA-Based Therapeutics Manufacturing brings together considerations from manufacturing science, engineering, quality, regulatory, supply chain, and operational perspectives. Its multidisciplinary scope is intended to help readers evaluate RNA manufacturing approaches without prescribing a single technology, facility model, or regional regulatory interpretation.
Messenger RNA is the most established RNA modality in current clinical and commercial applications and can direct cells to produce therapeutic proteins or vaccine antigens. Other RNA formats are under investigation. Circular RNA is being studied for whether its closed structure can improve stability and extend expression, while self-amplifying RNA includes replication-related components intended to increase RNA amplification and protein expression, potentially permitting lower doses in some applications.
One of the most important lessons emerging from RNA manufacturing is the value of risk-based facility design. Rather than prescribing fixed solutions, modern RNA facilities should be developed around scientific understanding of the process, product, and associated risks. “By taking a risk-based approach, this Guide helps you prioritize resources where they are needed most, delivering greater efficiency and effectiveness,” said James Blackwell, PhD, President, Windshire Group, LLC.
This philosophy supports quality while avoiding unnecessary complexity, overspecification, and excessive operational costs. By focusing on actual risks such as RNA degradation, thermal stability, and nuclease sensitivity, manufacturers can create facilities that are both compliant and efficient. According to Guide Co-Lead Francesco Cicirello, PharmD, Senior Director, Quality Compliance BioNTainer, BioNTech US Inc., and a former TGA inspector and PIC/S contributor, “The Guide is not intended to replace or interpret specific regulatory requirements. Its principles were developed with reference to widely recognized global GMP expectations, including frameworks from the European Union, US Food and Drug Administration, WHO, and PIC/S, as well as relevant pharmacopeial standards. The international authorship team aimed to provide a practical baseline that can be considered across regulatory environments.”
The continuing challenge for RNA manufacturing is to translate product and process knowledge into appropriately controlled manufacturing systems. Science-based risk management, fit for purpose facility concepts, and suitable manufacturing technologies can support this objective. The resulting design will depend on the RNA modality, production scale, control strategy, supply model, and applicable regulatory requirements.
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来源：ISPE iSpeak 专家博客 · ispe.org