Pharmaceutical Quality affects every American. The Food and Drug Administration (FDA) regulates the quality of pharmaceuticals very carefully. The main regulatory standard for ensuring pharmaceutical quality is the Current Good Manufacturing Practice (CGMPs) regulation for human pharmaceuticals. Consumers expect that each batch of medicines they take will meet quality standards so that they will be safe and effective. Most people, however, are not aware of CGMPs, or how FDA assures that drug manufacturing processes meet these basic objectives. Recently, FDA has announced a number of regulatory actions taken against drug manufacturers based on the lack of CGMPs. This paper discusses some facts that may be helpful in understanding how CGMPs establish the foundation for drug product quality.
药品质量影响着每一个美国人。FDA对药品质量的监管非常严格。确保药品质量的主要监管标准是人用药品的现行药品生产质量管理规范(CGMP)。消费者希望他们服用的每一批药品都符合质量标准，从而保证安全有效。然而，大多数人不知道CGMP，也不知道FDA如何确保药品生产过程符合这些基本目标。最近，FDA宣布了一系列基于缺乏CGMP而对药品生产商采取的监管行动。本文讨论了一些可能有助于理解CGMP如何建立药品质量基础的事实。
What are CGMPs? 什么是cGMP？
CGMP refers to the Current Good Manufacturing Practice regulations enforced by theFDA. CGMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the CGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories. This formal system of controls at a pharmaceutical company, if adequately put into practice, helps to prevent instances of contamination, mix-ups, deviations, failures, and errors. This assures that drug products meet their quality standards.
CGMP是指由FDA执行的现行药品生产质量管理规范。CGMP规定了确保生产工艺和设施的适当设计、监控和控制的体系。遵守CGMP法规通过要求药品生产商充分控制生产操作来确保药品的鉴别、强度、质量和纯度。这包括建立强有力的质量管理体系，获得适当的优质原材料，建立健全的操作程序，检测和调查产品质量偏差，以及维护可靠的检测实验室。制药公司这种正式的控制体系，如果充分付诸实施，有助于防止污染、混淆、偏差、失败和错误的发生。这确保了药品符合其质量标准。
The CGMP requirements were established to be flexible in order to allow each manufacturer to decide individually how to best implement the necessary controls by using scientifically sound design, processing methods, and testing procedures. The flexibility in these regulations allows companies to use modern technologies and innovative approaches to achieve higher quality through continual improvement. Accordingly, the "C" in CGMP stands for "current," requiring companies to use technologies and systems that are up-to-date in order to comply with the regulations. Systems and equipment that may have been "top-of-the-line" to prevent contamination, mix-ups, and errors 10 or 20 years ago may be less than adequate by today's standards.
CGMP要求的建立是灵活的，以便允许每个生产商单独决定如何通过使用科学合理的设计、工艺方法和检测程序来最好地实施必要的控制。这些法规的灵活性允许公司使用现代技术和创新方法，通过持续改进来实现更高的质量。因此，CGMP中的“C”代表“现行”，要求公司使用最新的技术和系统以符合法规。在10年或20年前，防止污染、混淆和错误的“顶级”系统和设备可能在今天的标准下是不够的。
It is important to note that CGMPs are minimum requirements. Many pharmaceutical manufacturers are already implementing comprehensive, modern quality systems and risk management approaches that exceed these minimum standards.
值得注意的是，CGMP是最低要求。许多制药企业已经实施了全面的现代质量体系和风险管理方法，超出了这些最低标准。
Why are CGMPs so important? 为什么CGMP如此重要？
A consumer usually cannot detect (through smell, touch, or sight) that a drug product is safe or if it will work. While CGMPs require testing, testing alone is not adequate to ensure quality. In most instances testing is done on a small sample of a batch (for example, a drug manufacturer may test 100 tablets from a batch that contains 2 million tablets), so that most of the batch can be used for patients rather than destroyed by testing. Therefore, it is important that drugs are manufactured under conditions and practices required by the CGMP regulations to assure that quality is built into the design and manufacturing process at every step. Facilities that are in good condition, equipment that is properly maintained and calibrated, employees who are qualified and fully trained, and processes that are reliable and reproducible, are a few examples of how CGMP requirements help to assure the safety and efficacy of drug products.
消费者通常无法(通过嗅觉、触觉或视觉)检测到药品是否安全或是否有效。虽然CGMP要求检测，但单靠检测不足以确保质量。在大多数情况下，检测是在一个批次中的一个小样本上进行的(例如，药品生产商可能从一个包含200万片的批次中测试100片)，从而该批次绝大多数药品可以用于患者，而不是被检测破坏。因此，在CGMP法规要求的条件和实践下生产药品，以确保质量管理融入到了每一步的设计和生产工艺，这一点很重要。设施处于良好状态，设备得到适当维护和校准，员工经过合格和充分培训，工艺可靠和可重复，这些都是CGMP要求如何帮助确保药品安全性和有效性的几个例子。
How does FDA determine if a company is complying with CGMP regulations? FDA如何确定一家公司是否符合CGMP法规?
FDA inspects pharmaceutical manufacturing facilities worldwide, including facilities that manufacture active ingredients and the finished product.Inspections follow a standard approach and are conducted by highly trained FDA staff. FDA also relies upon reports of potentially defective drug products from the public and the industry. FDA will often use these reports to identify sites for which an inspection or investigation is needed. Most companies that are inspected are found to be fully compliant with the CGMP regulations.
FDA检查全球药品生产设施，包括生产活性成分（API）和制剂成品的设施。检查遵循标准方法，并由训练有素的FDA工作人员进行。FDA还依赖公众和行业对潜在缺陷药品的报告。FDA通常会使用这些报告来确定需要检查或调查的地点。大多数被检查的公司被发现完全符合CGMP法规。
If a manufacturer is not following CGMPs, are drug products safe for use? 如果生产商没有遵循CGMP，药品是否可以安全使用？
If a company is not complying with CGMP regulations, any drug it makes is considered “adulterated” under the law. This kind of adulteration means that the drug was not manufactured under conditions that comply with CGMP. It does not mean that there is necessarily something wrong with the drug.
如果一家公司不遵守CGMP规定，它生产的任何药物都被认为是“掺假”的。这种掺假意味着药品不是在符合CGMP的条件下生产的。这并不意味着这种药物一定有问题。
For consumers currently taking medicines from a company that was not following CGMPs, FDA usually advises these consumers not to interrupt their drug therapy, which could have serious implications for their health. Consumers should seek advice from their health care professionals before stopping or changing medications. Regulatory actions against companies with poor CGMPs are often intended to prevent the possibility of unsafe and/or ineffective drugs. In rare cases, FDA regulatory action is intended to stop the distribution or manufacturing of violative product. The impact of CGMP violations depends on the nature of those violations and on the specific drugs involved. A drug manufactured in violation of CGMP may still meet its labeled specifications, and the risk that the drug is unsafe or ineffective could be minimal. Thus, FDA’s advice will be specific to the circumstances, and health care professionals are best able to balance risks and benefits and make the right decision for their patients.
对于目前从未遵循CGMP的公司购买药品的消费者，FDA通常建议这些消费者不要中断药物治疗，这可能对他们的健康产生严重影响。在停止或更换药物之前，消费者应征求医疗保健专业人员的意见。针对CGMP差的公司的监管行动通常是为了防止不安全和/或无效药物的可能性。在极少数情况下，FDA的监管行动旨在停止违规产品的分销或生产。违反CGMP的影响取决于这些违反的性质和所涉及的具体药物。违反CGMP生产的药品可能仍然符合其标签规格，并且药品不安全或无效的风险可能很小。因此，FDA的建议将根据具体情况而定，医疗保健专业人员最能平衡风险和利益，并为患者做出正确的决定。
What can FDA do to protect the public when there are CGMP violations? 当存在CGMP违规时，FDA可以做些什么来保护公众?
If the failure to meet CGMPs results in the distribution of a drug that does not offer the benefit as labeled because, for example, it has too little active ingredient, the company may subsequently recall that product. This protects the public from further harm by removing these drugs from the market. While FDA cannot force a company to recall a drug, companies usually will recall voluntarily or at FDA’s request. If a company refuses to recall a drug, FDA can warn the public and can seize the drug.
如果不符合CGMP导致销售的药物不提供标签上的疗效，例如，它的活性成分太少，公司可能随后召回该产品。这可以通过将这些药物从市场上移除来保护公众免受进一步的伤害。虽然FDA不能强迫公司召回药品，但公司通常会自愿召回或应FDA的要求召回。如果一家公司拒绝召回一种药物，FDA可以警告公众并没收该药物。
FDA can also bring a seizure or injunction case in court to address CGMP violations even where there is no direct evidence of a defect affecting the drug’s performance. When FDA brings a seizure case, the agency asks the court for an order that allows federal officials to take possession of “adulterated” drugs. When FDA brings an injunction case, FDA asks the court to order a company to stop violating CGMPs. Both seizure and injunction cases often lead to court orders that require companies to take many steps to correct CGMP violations, which may include repairing facilities and equipment, improving sanitation and cleanliness, performing additional testing to verify quality, and improving employee training. FDA can also bring criminal cases because of CGMP violations, seeking fines and jail time.
即使没有直接证据表明存在影响药物性能的缺陷，FDA也可以在法庭上提起查封或禁令案件，以解决违反CGMP的问题。当FDA提起扣押案件时，会要求法院下达命令，允许联邦官员没收“掺假”药物。当FDA提起禁令案件时，FDA要求法院命令公司停止违反CGMP。查封和禁令案件通常都引发法院的命令，要求公司采取许多措施纠正违反CGMP的行为，其中可能包括修理设施和设备、改善卫生和清洁、进行额外的测试以确认质量以及改进员工培训。FDA还可以对违反CGMP的企业提起刑事诉讼，寻求罚款和监禁。
How would a new drug company learn about CGMPs and about FDA’s expectations on complying with them? 一家新的制药公司如何了解CGMP以及FDA对遵守CGMP的期望?
FDA publishes regulations and guidance documents for industry in theFederal Register. This is how the federal government notifies the public of what we are doing and why. FDA’s website, www.fda.gov also contains links to the CGMP regulations, guidance documents, and various resources to help drug companies comply with the law. FDA also conducts extensive public outreach through presentations at national and international meetings and conferences, to discuss and explain the CGMP requirements and the latest policy documents.
FDA在《联邦公报》上发布行业法规和指导文件。这是联邦政府告知公众我们正在做什么和为什么做的方式。FDA的网站www.fda.gov还包含CGMP法规、指导文件和各种资源的链接，以帮助制药公司遵守法律。FDA还通过在国内和国际会议和会议上的演讲进行广泛的公众宣传，讨论和解释CGMP要求和最新的政策文件。
内容来源：GMP干货
责任编辑：胡静 审核人：何发
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