11 月 5 日，世界衛生組織（WHO）發布了“試驗用藥品GMP” 指南（Good manufacturing practices for investigational products）的征求意見稿。
該文件是對WHO GMP附錄7的修訂，目前正處于收集意見期，截止日期為2021年1月。此后，將于2021年2-3月份提交專家工作組，進行討論，完善后進行第2輪意見收集。最終修訂稿計劃于2021年10月份，提交第56藥物制劑專家委員會（ECSPP）批準。
本指南主體部分分為18個章節，內容如下：
1.背景
2.簡介
3.范圍
4.質量管理
5.質量風險管理
6.人員
7.文件
8.設施
9.設備和公用系統
10.物料
11.生產
12.質量控制
13.確認和驗證
14.投訴
15.召回
16.退貨
17.運輸
18.銷毀
PharmLink計劃進行翻譯連載，供參考。
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本次的內容為11-12章。
11. 生產
Production
11.1. Products intended for use in clinical trials (late Phase II and Phase III studies) should, as far as possible, be manufactured at a licensed facility. The batch size for investigational products manufactured in a pilot plant or small-scale facility, as opposed to the commercial batch size, may vary widely.
對于計劃用于臨床試驗（II期和III期后期）的產品，應盡可能在許可的工廠生產。在中試工廠或小型工廠中生產的試驗用藥品，在批量大小與商業批量大小不同。
11.2. The guidelines in this document are applicable to the following licensed facilities:
本文件中的準則適用于以下許可的設施：
• a pilot plant, primarily designed and used for process development; and
• a small-scale facility (sometimes called a "pharmacy"), separate both from the company's pilot plant and from routine production.
•中試工廠，主要設計用于工藝開發；
•小型工廠（有時稱為“藥房”），與公司的中試工廠和常規生產是分開的。
11.3. Facilities, as listed below, should be subject to all GMP requirements for pharmaceutical products;
下表列出的設施應符合藥品的所有GMP要求；
• a large-scale production line assembled to manufacture materials in larger batches (e.g. for late Phase III trials and first commercial batches); and
• the normal production line used for licensed commercial batches, and sometimes for the production of investigational products if the number of, for example, ordered ampoules, tablets or other dosage forms, is large enough.
•裝配了大規模生產線，以大批量生產物料（例如，用于III期后期試驗和第一批商業生產）；
•用于許可用于商業批次的正常生產線，如果訂購的安瓿、片劑或其它劑型的數量足夠大，有時用于生產試驗用藥品。
11.4. Where activities are outsourced to contract facilities, the contract must then clearly state, inter alia, the responsibilities of each party, compliance with GMP or of this guideline, and that the product(s) to be manufactured or controlled are intended for use in clinical trials. Close cooperation between the contracting parties is essential.
如果將活動外包給合同設施，則合同必須明確說明各方的責任，遵守GMP或本指南，保證生產或控制的產品可以用于臨床試驗目的。合同雙方之間的密切合作至關重要。
生產操作
Manufacturing operations
11.5. As process validation may not always be complete during the development phase of products, provisional quality attributes, process parameters and in-process controls should be identified, based on risk management principles and experience with analogous products.
由于在產品開發階段工藝驗證可能并不總是完整的，因此應基于風險管理原則和類似產品的經驗，來識別臨時質量屬性、工藝參數和過程控制。
11.6. The necessary instructions should be identified and may be adapted based on the experience gained in production.
應該確定必要的指導，并可以根據在生產中獲得的經驗進行調整。
11.7. Where processes such as mixing have not been validated, additional quality control testing may be necessary.
如果未驗證混合等過程，則可能需要進行其它QC檢驗。
11.8. For sterile investigational products, the assurance of sterility should be no less than for licensed products (see GMP for sterile products (6)).
對于無菌試驗用藥品，無菌保證應不低于許可產品的無菌水平（無菌產品參見GMP（6））。
包裝和貼標
Packaging and labelling
11.9. The packaging and labelling of investigational products are likely to be more complex and more liable to errors (which are also harder to detect) when "blinded" labels are used than for licensed products. Supervisory procedures such as label reconciliation, line clearance, and so on, and the independent checks by quality unit personnel, should be intensified accordingly.
與使用許可產品相比，使用“盲”標簽時，試驗用藥品的包裝和貼標可能會更復雜，并且更容易出錯（也更難以發現）。相應地應加強諸如標簽衡算、生產線清場等的監督程序，以及質量部門人員的獨立檢查。
11.10. The packaging must ensure that the investigational product remains in good condition during transport and storage. Any opening of, or tampering with, the outer packaging during transport should be readily discernible.
包裝必須確保試驗用藥品在運輸和儲存期間保持良好狀態。在運輸過程中任何打開或篡改外包裝的情況，都應易于辨認。
盲操作
Blinding operations
11.11. In the preparation of "blinded" products, the blind should be maintained until it is required to allow for the identification of the “blinded” product. In-process control should include a check on the similarity in appearance and any other required characteristics of the different products being compared.
在準備“盲”產品時，應保持盲狀態，直到需要識別“盲”產品為止。過程控制應包括檢查外觀的相似性，以及所比較的不同產品的任何其它所需特性。
11.12. A coding system should be introduced to permit the proper identification of "blinded" products. The code, together with the randomization list, must permit the proper identification of the product, including any necessary traceability to the codes and batch number of the product before the blinding operation.
應該引入編碼系統，以正確識別“盲”產品。該代碼以及隨機列表必須允許正確識別產品，包括在盲操作之前對代碼和產品批號的任何必要的可追溯性。
12. 質量控制
Quality control
12.1. Quality control should cover, for example, the sampling and testing of materials and products, ensuring that these are not released for use, sale or supply until their quality has been judged to be compliant with the specifications.
質量控制應包括，例如，物料和產品的取樣和檢驗，確保在判定其質量符合質量標準之前，不放行這些物料以供使用、銷售或供應。
12.2. Each batch of product should be tested in accordance with a Product Specification File and should meet its specification. Product release is often carried out in two stages; that is, before final packaging (bulk product testing) and after final packaging (finished product testing).
每批產品應按照產品質量標準文件進行檢驗，并應符合其質量標準。產品通常分為兩個階段：也就是說，在最終包裝之前（半產品檢驗）和最終包裝之后（成品檢驗）。
12.3. Bulk product testing should cover all relevant factors including production conditions, the results of in-process testing, a review of manufacturing documentation and compliance with the Product Specification File and the order. Finished product testing should cover, in addition to the bulk product assessment, all relevant factors including packaging conditions, the results of in-process testing, a review of packaging documentation and compliance with the Product Specification File and the order.
半產品檢驗應涵蓋所有相關因素，包括生產條件、過程檢驗結果、生產文件審查，以及對產品質量標準文件和訂單的符合情況。成品檢驗除對半成品的評估外，還應包括所有相關因素，包括包裝條件、過程檢驗結果、包裝文件審查，以及對產品質量標準文件和訂單的符合情況。
12.4. When necessary, quality control should also be used to verify the similarity in appearance and other physical characteristics such as the odour of "blinded" investigational products.
必要時，還應通過質量控制來驗證外觀和其它物理特性（例如“盲”試驗用藥品的氣味）是否相似。
12.5. End-product testing should be carried out in order to ensure that each batch meets its specification.
應當進行最終產品檢驗，以確保每個批次都符合其質量標準。
12.6 Reference and retention samples of each batch of product should be retained.
每批產品的參比樣品和留樣應保留。
12.7 Samples should be retained in the primary container used for the study or in a suitable bulk container for at least two years after the termination or completion of the relevant clinical trial. If the sample is not stored in the pack used for the study, stability data should be available to justify the shelf life in the pack used.
在相關臨床試驗終止或完成后，樣品應保存在用于研究的主要容器中或合適的散裝容器中，時間為至少兩年。如果樣品未保存在用于研究的包裝中，則應提供穩定性數據以證明所用包裝的有效期。
12.8 Retention samples should be kept until the clinical report has been prepared in order to enable the confirmation of product identity in the event of, and as part of an investigation into, inconsistent trial results.
留樣應一直保存，直到準備好臨床報告為止，以便在試驗結果不一致時，作為調查的一部分，能夠確認產品的鑒別。
12.9 The storage location of reference and retention samples should be defined in a technical agreement between the sponsor and manufacturer(s) and should allow for timely access by the competent authorities.
參比樣品和留樣的存放位置應在發起人與生產商之間的技術協議中規定，并應允許主管當局及時取用。
12.10The reference sample should be of sufficient size to permit the carrying out on, at least, two occasions of the full analytical controls on the batch in accordance with the Investigational Product dossier submitted for authorization in order to conduct the clinical trial.
參比樣品應有足夠的數量，以至少允許兩次對批次進行全面的分析控制，該分析控制基于為獲得臨床試驗許可而提交的試驗用藥品檔案。
12.11 In the case of retention samples, it is acceptable to store information related to the final packaging as written or electronic records if such records provide sufficient information. In the case of reference samples, the system should comply with the requirements of WHO guidelines for computerized systems (7).
對于留樣，如果能夠提供了足夠的信息，則可以書面或電子記錄形式儲存有關最終包裝的信息。對于參比樣品，系統應符合WHO對計算機系統指南的要求（7）。
12.12 The release of a batch of an investigational product should only occur after the designated responsible person has certified that the product meets the relevant requirements. These requirements include the assessment of, as appropriate:
僅在指定負責人證明產品符合相關要求后，才能放行該批試驗用藥品。這些要求包括對以下方面的評估：
• batch records, including control reports, in-process test reports, changes, deviations and release reports demonstrating compliance with the product specification file, the order, protocol and randomization code;
•批記錄，包括控制報告、過程檢驗報告、變更、偏差和放行報告，證明它們符合產品質量標準文件、訂單、草案和隨機編碼；
• production conditions;
•生產條件；
• the validation status of facilities, processes and methods, as appropriate;
•設施、工藝和方法的驗證狀態（如適用）；
• the examination of finished packs;
•成品包裝的檢查；
• where relevant, the results of any analyses or tests performed after importation;
•在相關的情況下，進口后進行的任何分析或檢驗的結果；
• stability reports;
•穩定性報告；
• the source and verification of conditions of storage and shipment;
•儲存和運輸條件的來源和確認；
• audit reports concerning the quality system of the manufacturer, where applicable;
•有關生產商質量體系的審計報告（如適用）；
• documents certifying that the manufacturer is authorized to manufacture investigational medicinal products or comparators for export by the appropriate authorities in the country of export; and
•就生產商已獲得出口國有關當局授權生產試驗用藥品或參比品，其出口相關的證明文件；
• where relevant, regulatory requirements for marketing authorization, GMP standards applicable and any official verification of GMP compliance.
•適當時，有關上市許可的法規要求，適用的GMP標準，以及對GMP合規性的任何官方確認。
Note: The relevance of the above elements is affected by the country of origin of the product, the manufacturer and the marketed status of the product
注意：以上要素的相關性受產品原產國、生產商和產品市場狀況的影響
Ref.: [WHO][2020-11-07]DRAFT WORKING DOCUMENT FOR COMMENTS: Good manufacturing practices for investigational products
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