10多个协会联合：欧盟GMP附录1应该这样...

9月24日，肠胃外药物协会（PDA）发布一项公告，表示在7月10日，PDA代表10多个行业协会组成的小组，向欧洲委员会和欧洲药品管理局（EMA）提交了一封沟通信函。就2020年2月对欧盟GMP附录1（无菌产品）的修订草案，该信函总结了制药行业的一致认可的评论意见。

PDA表示，虽然各协会提交了各自更为详细的意见，但这个协会联合信函指出了行业达成共识的地方，意义重大，因为它向监管机构表明，具有不同成员和目标的行业协会可以在需要时发出同一种声音，来解决共同关注的问题。

PDA认为，过去几年中，附录1修订版的发布是最令人期待的法规指南之一。预期修订后的附录1将在全球范围内使用（即不仅在欧洲使用），这是EMA-PIC/S联合工作组努力的结果。针对当前无菌产品的无菌工艺和最终灭菌，它解决了有关问题和疑虑。它应该适合于目前正在考虑的方法和创新技术，以及随着我们迈向未来而将要开发的方法和创新技术。

为了实现其目标，必须附录1的编写必须清楚，并能被世界许多国家/地区生产产品的众多公司所理解。它必须基于良好的科学和风险管理原则；它必须允许并在可能的情况下，鼓励追求和采用不断改进的工艺，以及过程控制技术和方法。它不应过于描述性，否则会给公司带来挑战，可能不适合现代生产工艺的现有方法，反而成为障碍。

PDA最后表示，对于签署这封信的10多个协会，这样做是为了强调努力的重要性，以及行业与监管机构合作的意愿，以使其成为更有效的指南，更好地促进其正确使用，并实现所有利益相关者的共同目标和利益，尤其是患者。

以下是该信函的主要内容：

RE: Second Consultation of the Draft Annex 1 Revision

RE：附录1修订草案的第二次征求意见

This Is a letter from the joint group of industry associations that is being sent separately from the submission of each associations individual comments.

这是来自行业协会联合小组的一封信，每个协会各自的意见已经单独提交。

On February 19, 2020, notice was sent by the European Commission to industry associations requesting a second targeted consultation of version 12 of the draft Annex 1 revision. In response, the undersigned industry associations will be submitting their comments, recommendations on changes, and the justification for changes to the Annex. Each association established and followed their own procedures far soliciting, considering, and submitting specific comments from their respective membership.

2020年2月19日，欧盟委员会向行业协会发送了通知，要求就附录1修订草案的第12版进行有针对性的第二次征求意见。作为回应，行业协会将提交其意见、有关更改建议以及更改理由。每个协会都建立并遵循各自的程序，以征求、考虑和提交各自成员的具体意见。

Although, each associations set of comments represents a different segment of the industry and geographic area, the association representatives see value in communicating some important common points uncovered during the Annex 1 revision process.

尽管每个协会的意见集代表了行业和地理区域的不同部分，但协会代表认为：交流附录1修订过程中发现的一些重要的共同点，是很有价值的。

应具有灵活性
1. The Annex should be flexible to support the use of appropriate alternative approaches.

1.附录应具有灵活性，以支持使用适当的替代方法。

It is important that where alternative approaches are supported by appropriate rationale and risk assessment and meet the intent of the Annex, that these alternative approaches be considered as acceptable. Regulators should allow flexibility to implement alternative process control strategies that effectively support product supply and patient (human and animal) needs, while meeting the underlying intent of the Annex for uncompromised product quality and safety principles. The importance of emphasizing in the Annex that adequate alternative approaches based on quality risk management (QRM) are acceptable and may even be indispensable to achieve the intent of the Annex cannot be overstated.

重要的是，在有适当论证和风险评估支持替代方法、并达到附录意图的情况下，这些替代方法应被视为可以接受。监管机构应允许灵活地实施替代过程控制策略，以有效地支持产品供应和患者（人类和动物）的需求，同时满足附录对于产品质量和安全原则要求的基本意图。在附录中强调基于质量风险管理（QRM）的适当替代方法是可以接受的，甚至对于实现附录意图是必不可少的，这一点很重要性。

This is the time for the industry and regulators to embrace contamination control strategies (CCS) based on QRM principles. The adoption of Quality by Design principles and risked based strategies for the attainment of quality and the prevention of failure is ever more important as an alternative to the traditional reliance on detection, monitoring and testing. Today the quantity and quality of scientific knowledge is much higher and widely spread than in the past. These control strategies must not only fit quality and supply needs, but as implied in EU Directives 2001/83/EC article 23 and Directive 2001/82/EC Article 27, be flexible enough to be of use today and to support the use of new technology, approaches, and therapies, both anticipated and unanticipated in the years that follow. If we fail to do this, then the increasing speed of learning and technology advancement will outpace our ability to take advantage of these advancements in # timely and effective manner.

现在是行业和监管机构采用基于QRM原理的污染控制策略（CCS）的时候了。传统上对检测、监视和测试过于依赖，作为替代方法，采用QbD原则和基于风险的策略，来达到质量和防止失效变得越来越重要。今天，科学知识在数量和质量都比过去更高，并且得到了广泛传播。这些控制策略不仅必须适合质量和供应需求，而且必须符合欧盟指令2001/83 / EC第23条和指令2001/82 / EC第27条的规定，必须足够灵活，可以在今天使用，也可以支持使用新的技术、方法和疗法——这些在接下来几年中是可预期、或者现在还不能预期的。如果我们不能做到这一点，那么不断提高的学习和技术进步速度将超过我们及时有效地利用这些进步的能力。


解释要清晰
2. There must be clear interpretation of the Annex.

对附录必须有清晰的解释。

It is essential that all who use and depend on this document have a clear and singleinterpretation of its meaning and intent. While the Annex is a European guidance, the Annex includes input from and will be used also by PIC/S and WHO. As such, it represents the latest scientific discussion of sterile product manufacturing and control and will be viewed as a global guide for the appropriate planning and design of such processes. To achieve the needed level of clarity, three important points should be considered:

所有使用和依赖本指南的人，都必须对其含义和意图进行清晰、单一的解释，这一点至关重要。尽管该附录是欧洲指南，但该附录包括PIC/S和WHO的输入，也将由PIC/S和WHO使用。因此，它代表了无菌产品生产和控制的最新科学讨论，将被视为此类工艺的适当计划和设计的全球指南。为了达到所需的清晰度，应该考虑三个要点：

-The use of specific examples should be avoided, because no matter how well they are defined as “examples”, they will be misinterpreted as rigid requirements by some in industry and some inspectorates. Without such clarity, there is a risk that companies will be discouraged from using innovative, alternative approaches.

-应避免使用特定示例，因为无论它们被定义为“示例”的程度如何，都会被某些行业和某些检查机构误解为严格的要求。如果没有这样的明确性，就有可能使公司不愿使用创新的替代方法。

- Clear distinctions between similar but different technologies and approaches, including isolators and RABS, form-fill-seal and blow-fill-seal, liquid and hard goods moist heat sterilization, and environmental qualification and classification are needed to understand the benefit and limitations of the respective technologies and promote their most effective use within the contamination control strategy. Without such clarity, there is a risk that companies will apply inappropriate control strategies.

-对于相似但不同的技术和方法之间区别，需要更为明显，包括隔离器和RABS、成型-灌-封-和吹-灌-封、液体和硬质物品湿热灭菌，以及环境确认和分类，以了解其优点和局限性，并在污染控制策略中促进其最有效的使用。没有这样的明确性，公司就有可能应用不合适的控制策略。

- An over-emphasis on process testing and monitoring (e.g. PUPSIT and APS) should be avoided, and instead, effective reliance on well-designed process and process control design and performance should be encouraged. Without such balanced approach, there is a risk that companies and regulators will apply a rigid Interpretation and miss the opportunity to use process design to prevent failures, relying instead on the testing and monitoring to detect failures.

-应避免过分强调过程测试和监视（例如PUPSIT和APS），而应鼓励有效地依赖精心设计的工艺、以及过程控制设计和性能。如果没有这种平衡的方法，则公司和监管机构可能会做出僵化的解释，而错过了使用工艺设计来预防故障的机会，而是依靠测试和监视来检测故障。

This should be a partnership between regulators and manufacturers. Ensuring and improving sterile healthcare product quality, safety and effectiveness as well as supply availability can only be attained and maintained through a partnership of the manufacturing sector and the health Authorities. History and recent events, including the challenges uncovered by the pandemic, have shown that this partnership is essential. Rapidly evolving technology and the importance to accelerate the development and availability of medicines to treat unmet medical needs of patients worldwide require the cooperation of experts from the industry, academia and regulatory agencies.

监管机构与生产商之间，应建立伙伴关系。确保和改善无菌医疗产品的质量、安全性和有效性以及供应可及性，只能通过生产企业和卫生当局的伙伴关系来实现和维持。历史和最近发生的事件，包括大流行中发现的挑战，都表明这种伙伴关系至关重要。技术在迅速发展，对于全世界患者未满足的医疗需求，也需要加速药物的开发和可及性，这些关键之处需要来自行业、学术界和监管机构的专家的合作。


需更多的工作
3. More work is needed.

需要做更多的工作。

We recognize that additional efforts will enhance the effectiveness of the Annex. These include the three key considerations: While much of the Annex covers topics where there is adequate scientific knowledge and consensus to clearly present positions, there are other topics which require additional scientific work to determine the most feasible and effective approaches. In these cases, a continued dialogue between regulators, industry, and academia to further develop guidance that is aligned with advances in knowledge and technology is of outmost importance. in addition, after Annex 1 has been finalized and made operational, there will inevitably be differences in the interpretation of specific sections of the Annex by regulators and/or industry, A mechanism to discuss and resolve such differences collaboratively in a joint regulator/industry forum or committee would be beneficial for everyone, with the outcomes published by the regulatory authorities as Interpretive guidance of Q&As. Finally, the effective implementation of this revised Annex will involve a significant effort to educate industry and regulators on proper intention and use the CCS and QRM principles that form its basis. The associations offer their assistance to help with that effort, through coordinated workshops, meetings, and training.

我们认识到，进一步的努力将提高附录的有效性。其中包括三个主要考虑因素：尽管，附录中的大部分内容涵盖了足够的科学知识和共识，以明确表述立场的主题，但其他主题还需要进行额外的科学工作，这样才能确定最可行和有效的方法。在这些情况下，监管机构、行业和学术界之间需要持续对话，以进一步制定与知识技术的进步相一致的指南，这点非常重要。此外，在附录1最终定稿并投入使用后，监管机构和/或行业对附录特定部分的解释将不可避免地会有差异，这时建立监管机构/行业联合论坛共同讨论和解决此类差异的机制，将对所有人都有益，监管机构发布的结果将作为解释性的问答指南。最后，有效实施此修订附录将需要付出巨大的努力，以对行业和监管机构进行适当意图的教育，从而使用构成其基础的CCS和QRM原则。协会可以通过协调的研讨班、会议和培训，为这些工作提供帮助。

合作精神
The undersigned associations have worked in a spirit of cooperation, continuing the efforts of the inter-association working groups to assisting the EMA and PIC/S with the gathering, analysis and communication of input from the sterile healthcare community and offer to work with the EMA to further the development of the guidance.

以下签名协会本着合作精神开展工作，继续协会间工作组的工作，以协助EMA和PIC/S收集，分析和交流无菌行业的意见，并愿意与EMA合作，进一步完善指南。

There is consensus among the associations that this Annex represents a great opportunity to improve the understanding of process control in our industry, As the EMA noted in its 2015 Annex 1 revision concept paper, a key objective of this revision is to “embrace the use of new technologies to prevent detrimental impact on product and to encourage the introduction of new technologies that are not currently covered.” The points noted in this letter, along with the individual comments of the associations are meant to help the EMA and PIC/S meet this common objective for clearly defined, modern guidance on contamination control strategies based on scientific evidence and quality risk management principles that promote technological and sterility assurance advancement for many years to come.

各协会之间达成共识，即本附录是增进我们行业对过程控制理解的绝佳机会。正如EMA在其2015年附录1修订版概念文件中指出的那样，该修订版的主要目标是“拥抱使用新技术，以防止对产品造成不利影响，并鼓励引入当前未涵盖的新技术。”这封信中指出的要点以及协会的各自意见，都是旨在帮助EMA和PIC/S达到这一共同目标，以科学的证据和质量风险管理原则为基础，对污染控制策略进行清晰定义，以促进技术和无菌保证的先进性可以将持续多年。

Yours sincerely,

on behalf of A3P, AnimalhealthEurope, AESGP, ECA, EFPIA, EIPG, FQPA, ISPE, Medicines for Europe, PDA, PHSS, and Vaccines Europe.

此致，

代表A3P，欧洲动物健康组织，AESGP，ECA，EFPIA，EIPG，FQPA，ISPE，欧洲药品，PDA，PHSS和欧洲疫苗组织。

Glenn E. Wright

Annex 1 - Associations Coordination Meeting Lead

Vice President of Scientific and Regulatory Affairs

PDA

格伦·赖特

附录1-协会协调会议负责人

科学与法规事务副总裁

PDA

       文章来源：PharmLink

       本网站刊载的所有内容，包括文字、图片、音频、视频、软件等，如非标注为“原创”，则相关版权归原作者所有，如原作者不愿意在本网站刊登相关内容，请及时通知本站，我们将第一时间予以删除。

曜分享

分享精彩资讯