2022年出版——医药产品的无菌加工-Sterile Processing of Pharmaceutical Products

JimmyHE8888

比较热乎的出版物，2022年，由WILEY出版社发行的 ——
“Sterile Processing of Pharmaceutical Products - Engineering Practice, Validation, and Compliance in Regulated Environments”，即“医药产品的无菌加工 - 监管环境下的工程实践、验证和合规性”
by Sam A. Hout, Mission Viejo (CA, USA)

作者：Sam A. Hout，美国加利福尼亚州米逊维耶荷市(Mission Viejo)
（注：位于加州橙县南部的Saddleback Valley）



感觉有帮助的话，千万不要吝惜给个专业小红心，这将对我是极大的鼓励。
谢谢。

介绍部分的简要摘录——
This book is engineering driven to highlight basis of design, design criteria, and assumptions to coach and guide professionals involved in learning more about sterile manufacturing engineering and in pharmaceutical and biopharmaceutical manufacturing facilities, including operational requirements. The intent of this book is to present a simplified treatise with some very specific description of aseptic processing techniques and sterilization methods.
Sterile manufacturing engineering and process validation guides (USFDA, Guidance for Industry – Process Validation) are intended to manage risk, introduce Quality by Design (QbD), and ensure continued process reliability, consistency, and repeatability.
Sterile manufacturing guidelines are based on specific elements in the construction and installation of classified clean rooms, critical utility systems such as water for injection (WFI), solution transfer systems, powder transfer systems, and monitoring and controls, including automation of processes. Specialized technologies [1] in design of fill/finish lines of vials, cartridges, bottles for ophthalmic or otic purposes, prefilled syringes (PFSs), or ampoules, which might be filled and sealed aseptically or IV bags that are mostly terminally sterilized. In addition, considerations for personnel and material low to prevent cross contamination are usually very well defined to separate in and outmovements of sterile suites and cascading clean rooms through separate paths, including the use of path-through transfer systems for material low.
Overall, paying attention to the design, construction, and installation should focus on process flow and employ standardization of equipment and methodologies as much as possible. Building sustainable premises, equipment qualifications, cleaning validation, and sanitization requirements should be all in consideration as part of the design of pharma/biopharma processing. Similarly, process validation and periodic revalidation of manufacturing systems are all important stages and steps that need to be on well-defined schedules to ensure reliability of drug production [2].

本书以工程为导向，强调设计基础、设计标准和假设，以指导参与学习无菌生产工程和制药及生物制药生产设施的专业人士，包括操作要求。本书的目的是提出一个简化的论文，对无菌加工技术和灭菌方法进行一些非常具体的描述。
无菌生产工程和工艺验证指南（USFDA，工业指南-工艺验证）旨在管理风险，引入设计质量（QbD），并确保持续的工艺可靠性、一致性和可重复性。
无菌生产指南是基于分类洁净室、关键公用设施系统（如注射用水（WFI））、溶液传输系统、粉末传输系统以及监测和控制（包括过程的自动化）的建设和安装中的具体内容。眼科或耳科用的小瓶、药筒、瓶子、预装注射器（PFSs）或安瓿的灌装/完成线的设计方面的专业技术[1]，这些产品可能被灌装和密封 或静脉注射袋，它们可能是无菌灌装和密封的，大部分是终末灭菌的。此外，为防止交叉污染，对人员和材料低的考虑通常是非常明确的，通过单独的路径将无菌套间和层叠式洁净室的进出分开，包括使用材料低的路径传输系统。
总的来说，注意设计、建造和安装应注重工艺过程/流程，并尽可能采用设备和方法的标准化。作为制药/生物制药加工设计的一部分，建设可持续发展的场所、设备资格、清洁验证和消毒要求都应该被考虑在内。同样，生产系统的工艺验证和定期再验证都是重要的阶段和步骤，需要有明确的时间表，以确保药物生产的可靠性[2]。






本书序言写到——
There are two ways to manufacture sterile drug products: aseptic manufacturing and sterile fill-finish. First is a process in which the drug product, container, and closure are first subjected to sterilization methods separately, as appropriate, and then brought together (aseptic manufacturing). Second is ill and seal drug product in container and terminally sterilize.
Many complex drug products are not amenable to terminal sterilization,  leading to increased demand for aseptic manufacturing and sterile fill-finish capabilities. Aseptic processing is uniquely challenging because it requires careful planning, thoroughly trained personnel, and specialized facilities/equipment to properly execute. Cleanroom facilities and aseptic processes should be designed to minimize contamination risk from materials, equipment, and personnel. Sterile lyophilization requires investment into specialized equipment, facilities, and knowledge.
Drug products that are delivered via the parenteral, ophthalmic, inhaled, or otic route present an increased risk of infection or harm because they bypass many of the body’s natural defenses. To ensure patient safety, the FDA requires that drug products delivered via these routes be supplied as sterile products. This designation includes many complex drug products, including ophthalmic suspensions, sterile injectables, lyophilized powders for injection, and aqueous-based aerosols for inhalation.
“Sterile products” refer to products that are going to be administered using an enteral route of administration. The “products” are going to be infused directly into the bloodstream or body tissue, and it is extremely important they must be “sterile.” Consider that when a patient takes a tablet orally, their digestive system (acting as part of the immune system) could identify and kill any bacteria that may be present. With a parenteral route of administration, if any contaminants are present, they go right into the bloodstream, bypassing the digestive system.

Regulatory guidance is intended to help manufacturers meet the requirements in the FDA current good manufacturing practice (cGMP) regulations (2l CFR parts 210 and 211) when manufacturing sterile drug and biological products using aseptic processing.
Sterile injectables manufacturing involve the production of vaccines. A vaccine must be rigorously tested before the public gets it. We often think of vaccines as treatments for illness, rather they are preventative measures for specific targeted viruses such as the flu vaccines. People who are well are given vaccines to keep them from getting sick. herapeutic drugs are developed to cure diseases that already invaded the human body. They are tested and qualified for their efficacy in curing-specific disease indication and proven safety through extensive clinical trials that define their side effects.
Researchers will study the virus and attempt to determine which type of vaccine may work best. There are several kinds of vaccines. Some have a weakened live virus, which triggers a protective immune response but does not cause illness. Some vaccines contain inactive virus that creates an immune response in the body. Other types of vaccines utilize genetically engineered RNA or DNA, which triggers a protein that can prevent the virus from binding to our cells causing illness. The selection of which vaccine route to follow is dependent on experimental results that identify the best possible outcome. Following lab testing to ensure that a vaccine is working on the molecular cellular level, vaccines will undergo animal testing to predict safety for humans. This is followed by clinical trials targeting efficacy and safety for human use.

......"

参考译文（在线翻译）——
有两种制造无菌药物产品的方法：无菌制造和无菌灌装-完成。第一种是先将药物产品、容器和封口分别进行适当的灭菌方法，然后再一起进行灭菌（无菌生产）。第二种是在容器中涣散和密封药物产品，并进行终结性灭菌。
许多复杂的药物产品不适合终端灭菌，导致对无菌生产和无菌灌装-完成能力的需求增加。无菌加工具有独特的挑战性，因为它需要仔细的规划、经过全面培训的人员和专门的设施/设备来正确执行。洁净室设施和无菌工艺的设计应尽量减少材料、设备和人员的污染风险。无菌冻干需要投资于专业设备、设施和知识。
通过肠外、眼科、吸入或耳科途径给药的药物产品会增加感染或伤害的风险，因为它们绕过了身体的许多自然防御系统。为确保病人安全，FDA要求通过这些途径提供的药物产品必须是无菌产品。这种指定包括许多复杂的药物产品，包括眼科悬浮液、无菌注射剂、注射用冻干粉和吸入用水基气雾剂。吸入用的水基气雾剂。
"无菌产品 "是指使用肠道给药的产品。肠道给药途径的产品。这些 "产品 "将被直接注入 这些 "产品 "将直接注入血液或身体组织，因此它们必须是极其重要的 "无菌"。考虑到当病人口服药片时，他们的消化系统 (作为免疫系统的一部分）可以识别并杀死可能存在的任何细菌。可能存在的细菌。在肠外给药途径中，如果有任何污染物 它们会绕过消化系统，直接进入血液中。
法规指导旨在帮助制造商在使用无菌加工生产无菌药品和生物制品时满足FDA现行良好生产规范（cGMP）的要求（2l CFR第210和211部分）。
无菌注射剂生产涉及疫苗的生产。一种疫苗在公众获得之前必须经过严格的测试。我们经常认为疫苗是对疾病的治疗，相反，它们是对特定目标病毒的预防措施，如流感疫苗。身体健康的人被注射疫苗，以防止他们生病。治疗药物的开发是为了治疗已经侵入人体的疾病。它们通过广泛的临床试验确定其副作用，对其在治愈特定疾病指征方面的疗效进行测试和鉴定，并证明其安全性。
研究人员将研究病毒并试图确定哪种类型的疫苗可能效果最好。有几种类型的疫苗。一些疫苗含有弱化的活病毒，引发保护性免疫反应，但不会导致疾病。有些疫苗含有非活性病毒，在体内产生免疫反应。其他类型的疫苗利用基因工程的RNA或DNA，引发一种蛋白质，可以防止病毒与我们的细胞结合导致疾病。选择哪种疫苗途径，取决于确定最佳结果的实验结果。在实验室测试以确保疫苗在分子细胞水平上发挥作用后，疫苗将进行动物测试，以预测对人类的安全性。随后是针对人类使用的疗效和安全性的临床试验。
......（后续略）







补充内容 (2022-5-25 08:50):
介绍内容的中文机译有一定的错误，无菌产品应该是“非肠道给药”才对，现在才有空稍微看一下机译的内容。。。还有一些就不明说了，大家还是自己看英文原文吧

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