近日，歐洲藥品管理局EMA更新了關于第三方審計的GMP問答，如下：

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

對第三方審計報告的書面最終評估內容有何要求？

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 負有最終責任，確保在第三方執行審計時，審計報告得到適當評估。書面最終評估文件應提供該評估的易于理解的摘要，并應隨時可用，并在需要時向當局提供。

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.

評估應包括審計過程的所有預期要素以及審計之前、期間和之后確定的審計報告。特別是，這包括確認合同安排、審計范圍和適當的持續時間、審計人員考慮所審計范圍的足夠能力、計劃的審計頻率以及CAPA 是否足夠以及如何跟進。應討論發現的任何利益沖突。

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

是否可以接受第三方進行的審計？

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.

作為歐盟程序的一部分發布的文件“關于主管當局在用作起始材料的活性物質制造商的場所進行檢查的適當情況指南”指出，要求生產許可持有人將通過對活性物質供應商的審計來確保他們所使用的活性物質是按照GMP 生產的。第 2001/83/EC 號指令第 46 （f） 條規定：“生產許可的持有人應自行確認此類合規性，或者在不影響其責任的情況下，通過委托代表其行事的實體進行確認”。制造商可能不具備必要的專業知識或資源來進行自己的審計，因此可能會與第三方簽訂合同進行相關審計。MIA 持有人可以依賴活性物質制造商對其活性物質中間體供應商進行的審計，前提是 MIA 持有人與活性物質制造商之間有適當的合同安排。

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 節要求起始材料供應商的選擇、確認、批準和維護，以及起始物料的采購和驗收，由對供應商、供應鏈和所涉及的相關風險有最新了解的人員進行。

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.

由生產許可持有人本身進行的審計應是制造商質量保證體系的組成部分，并受 GMP 基本要求的約束，即由具有適當資質和培訓的人員按照批準的程序進行。它應該被適當地記錄下來。主管當局可以根據需要檢查這些方面。

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，則此類安排應符合 GMP 指南第 7 章的規定。應有證據表明合同提供方已經就上述方面對合同接受方進行了評估。

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.

所有相關方都應注意，如果主管當局要求，將提供審計報告和其他與審計相關的文件供其檢查。這通常應提供足夠的保證以證明第三方進行的審計結果是可信的，以免除由生產許可持有人自己進行審計的需要。第三方合同安排可能會導致相關一方或多方產生利益沖突。利益沖突應被視為可能影響審計人員判斷的任何影響因素，從而導致審計報告可能無法根據GMP 要求提供全面和公正的評估。

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 持有人應確保有適當的安排來聲明任何利益沖突，并評估其對審計公正性的影響。

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

潛在的利益沖突可能來自不同的來源，例如可能包括：

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

聲明與被審計公司有財務、家庭或社交聯系的審計人員。

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.

聲明以前曾為被審計公司工作的審計人員，并且在審計期間可能會收到曾經由他們簽發、審查或批準的文件。

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).

合同審計人員或公司，聲稱其可以通過銷售或提供審計報告以獲得商業利益（特別是在使用同一活性物質供應商的不同生產許可持有人之間共享審計報告）。

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.

宣稱其將從成功的審計結果中獲得經濟利益的審計人員，例如通過支付獎金或僅在成功的結果中付款，或簽約擔任顧問（提供建議）而不是專門進行公正審計的人員。

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 起始物料的定義，以及哪些步驟按照 GMP 執行，是可能產生利益沖突的一個關鍵方面，尤其是在 API 中間體的生產地點與最終API 生產地點不同的情況下。

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.

除了確保聲明利益沖突的安排外，每個審計機構還應有一個支持審計質量和完整性的質量體系。

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.

如果第三方審計人員或公司聲明存在利益沖突，他們應記錄利益沖突的性質、它可能對審計實施產生的影響以及如何確保對受審計方的 GMP 合規狀態進行總體評估。

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.

這一主題應在技術合同安排中解決。合同提供方采取的任何措施都應記錄在案，例如由審計人員簽署承諾書。應確定審計人員或受托方是否存在或不存在利益沖突。

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應確保第三方審計報告的書面最終評估和批準包括對審計人員和/或受托方所做的聲明或不存在任何利益沖突的評估。

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.

利益沖突可能會在 QP 簽署第三方審計報告后暴露出來，QP 可能需要進行回顧性評估。

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.

上述原則可用于不同生產許可持有人之間的聯合審計，或者多個藥品制造商與第三方審計人員共同簽約并在審計前已經簽約，使用同一活性物質供應商的情況，前提是審計的范圍可以證明適用于共同關心的活性物質。