近日，欧洲药品管理局EMA更新了关于第三方审计的GMP问答，如下：

What are the expectations for the content of written final assessment ofthird-party audit reports? H+V New Apr 2025

对第三方审计报告的书面最终评估内容有何要求？

The QP has the ultimate responsibility to ensure that audit reports are properly evaluatedwhen the audit is performed by a third party. The written final assessment document should provide a comprehensible summary of this evaluation and should be readily available and shared with authorities, if requested.

QP 负有最终责任，确保在第三方执行审计时，审计报告得到适当评估。书面最终评估文件应提供该评估的易于理解的摘要，并应随时可用，并在需要时向当局提供。

The assessment should include all expected elements of the auditing process and auditreport(s) identified before, during and after the audit. In particular, this includes verification of contractual arrangements, scope and appropriate duration of audit, adequate competence of auditors considering the scope of the audit, planned audit frequency, and CAPAs whether adequate and how these are to be followed up. Any conflicts of interest identified should be discussed.

评估应包括审计过程的所有预期要素以及审计之前、期间和之后确定的审计报告。特别是，这包括确认合同安排、审计范围和适当的持续时间、审计人员考虑所审计范围的足够能力、计划的审计频率以及CAPA 是否足够以及如何跟进。应讨论发现的任何利益冲突。

Is an audit performed by a third party acceptable? H+V New Apr 2025

是否可以接受第三方进行的审计？

The document 'guidance on the occasions when it is appropriate for competent authorities to conduct inspections at the premises of manufacturers of active substances used as starting materials', published as part of the Union procedures, states that it is expected that manufacturing-authorisation holders will gain assurance that the active substances they use are manufactured in accordance with GMP through audit of the active-substance suppliers. Article 46 (f) of Directive 2001/83/EC states: "The holder of the manufacturing authorisation shall verify such compliance either by himself or, without prejudice to his responsibility as provided for in this Directive, through an entity acting on his behalf under a contract". Manufacturers may not have the necessary expertise or resources to conduct their own audits and therefore may contract with third parties to undertake relevant audits. MIA holders may rely on audits carried out by active substance manufacturers on their suppliers of active substance intermediates provided that there is an appropriate contractual arrangement in place between the MIA holder and the manufacturer of the active substance.

作为欧盟程序的一部分发布的文件“关于主管当局在用作起始材料的活性物质制造商的场所进行检查的适当情况指南”指出，要求生产许可持有人将通过对活性物质供应商的审计来确保他们所使用的活性物质是按照GMP 生产的。第 2001/83/EC 号指令第 46 （f） 条规定：“生产许可的持有人应自行确认此类合规性，或者在不影响其责任的情况下，通过委托代表其行事的实体进行确认”。制造商可能不具备必要的专业知识或资源来进行自己的审计，因此可能会与第三方签订合同进行相关审计。MIA 持有人可以依赖活性物质制造商对其活性物质中间体供应商进行的审计，前提是 MIA 持有人与活性物质制造商之间有适当的合同安排。

Section 5.27 of the GMP guideline requires that the selection, qualification, approval and maintenance of suppliers of starting materials, together with their purchase and acceptance, are performed by staff that have a current knowledge of the suppliers, the supply chain and the associated risks involved.

GMP 指南第 5.27 节要求起始材料供应商的选择、确认、批准和维护，以及起始物料的采购和验收，由对供应商、供应链和所涉及的相关风险有最新了解的人员进行。

An audit conducted by the manufacturing-authorisation holder itself should be integral to the manufacturer's quality-assurance system and subject to the basic GMP requirements, i.e. conducted by properly qualified and trained staff, in accordance with approved procedures. It should be properly documented. These aspects can be inspected as necessary by the competent authorities.

由生产许可持有人本身进行的审计应是制造商质量保证体系的组成部分，并受 GMP 基本要求的约束，即由具有适当资质和培训的人员按照批准的程序进行。它应该被适当地记录下来。主管当局可以根据需要检查这些方面。

If a third party is involved, the arrangements should be subject to chapter 7 of the GMP guideline. There should be evidence that the contract-giver has evaluated the contract-acceptor with respect to the aspects described above.

如果涉及第三方，则此类安排应符合 GMP 指南第 7 章的规定。应有证据表明合同提供方已经就上述方面对合同接受方进行了评估。

All parties involved should be aware that audit reports and other documentation relating to the audit will be made available for inspection by the competent authorities if requested. This should normally provide sufficient assurance that the results of an audit carried out by the third party are credible, thus waiving the need for an audit conducted by the manufacturing-authorisation holder itself. A third-party contractual arrangement may lead to a conflict of interest arising on the part of one or more of the parties involved. Conflicts of Interest should be regarded as any influencing factor that may affect the judgement of the auditor resulting in an audit report that may not provide a full and impartial assessment against EU GMP requirements.

所有相关方都应注意，如果主管当局要求，将提供审计报告和其他与审计相关的文件供其检查。这通常应提供足够的保证以证明第三方进行的审计结果是可信的，以免除由生产许可持有人自己进行审计的需要。第三方合同安排可能会导致相关一方或多方产生利益冲突。利益冲突应被视为可能影响审计人员判断的任何影响因素，从而导致审计报告可能无法根据GMP 要求提供全面和公正的评估。

Therefore, the MIA holder should ensure that there are arrangements in place to assure that any conflicts of interests are declared, and where declared, that they are assessed for their impact on the impartiality of the audit.

因此，MIA 持有人应确保有适当的安排来声明任何利益冲突，并评估其对审计公正性的影响。

Potential conflicts of interest may arise from diverse sources and may include for example:

潜在的利益冲突可能来自不同的来源，例如可能包括：

An auditor who declares that they have financial, family or social links to the company being audited.

声明与被审计公司有财务、家庭或社交联系的审计人员。

An auditor who declares that they have previously worked for the company being audited and who may be presented with documents during the audit that were issued, reviewed or approved by them.

声明以前曾为被审计公司工作的审计人员，并且在审计期间可能会收到曾经由他们签发、审查或批准的文件。

Contract auditors or companies who declare that they stand to make commercial gain from sale or supply of an audit report (particularly to sharing of audit reports between different manufacturing-authorisation holders using the same active substance supplier).

合同审计人员或公司，声称其可以通过销售或提供审计报告以获得商业利益（特别是在使用同一活性物质供应商的不同生产许可持有人之间共享审计报告）。

Auditors who declare that they stand to gain financially from a successful audit outcome, e.g. by payment of bonus or payment only on successful outcome or persons contracted as consultants (to advise) rather than specifically to conduct an impartial audit.

宣称其将从成功的审计结果中获得经济利益的审计人员，例如通过支付奖金或仅在成功的结果中付款，或签约担任顾问（提供建议）而不是专门进行公正审计的人员。

Definition of API starting materials, and hence which steps to perform under GMP, is a critical aspect where conflicts of interest may arise, especially in cases where an API intermediate is manufactured at a site different from the final API manufacturing site.

API 起始物料的定义，以及哪些步骤按照 GMP 执行，是可能产生利益冲突的一个关键方面，尤其是在 API 中间体的生产地点与最终API 生产地点不同的情况下。

In addition to the arrangements to assure that conflicts of interest are declared, each auditing body should have a quality system that supports the quality and integrity of audits.

除了确保声明利益冲突的安排外，每个审计机构还应有一个支持审计质量和完整性的质量体系。

Where a conflict of interest has been declared by a third-party auditor or contracting company, they should document the nature of the conflict of interest, the impact it may have on the conduction of the audit and how the overall assessment of the GMP compliance status of the auditee is assured.

如果第三方审计人员或公司声明存在利益冲突，他们应记录利益冲突的性质、它可能对审计实施产生的影响以及如何确保对受审计方的 GMP 合规状态进行总体评估。

This topic should be addressed in the technical contractual arrangements. Any measures taken by the contract-giver should be documented, e.g. signed undertakings by the auditors. The absence or presence of conflicts of interest on the part of auditors or contracting parties should be identified.

这一主题应在技术合同安排中解决。合同提供方采取的任何措施都应记录在案，例如由审计人员签署承诺书。应确定审计人员或受托方是否存在或不存在利益冲突。

QPs should ensure that the written final assessment and approval of third-party audit reports includes an evaluation of a declaration or absence of any conflicts of interest made by auditors and/or the contracting parties.

QP应确保第三方审计报告的书面最终评估和批准包括对审计人员和/或受托方所做的声明或不存在任何利益冲突的评估。

Conflicts of interest may come to light after the QP has relied upon a third-party audit report and it may be necessary for the QP to undertake a retrospective assessment.

利益冲突可能会在 QP 签署第三方审计报告后暴露出来，QP 可能需要进行回顾性评估。

The principles outlined above could be used in case of joint audits between different manufacturing authorisation holders or in those cases where the drug manufacturers have jointly contracted the third party auditor and have signed the contract before the audit took place, using the same active substance supplier, provided that the scope of the audits can be shown to be applicable to the active substances of mutual interest.

上述原则可用于不同生产许可持有人之间的联合审计，或者多个药品制造商与第三方审计人员共同签约并在审计前已经签约，使用同一活性物质供应商的情况，前提是审计的范围可以证明适用于共同关心的活性物质。