APIC原料药协会《供应商审计》指南（原文翻译）

APIC原料药协会《供应商审计》指南（原文翻译）
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APIC发布了起始物料（RSM）供应商第三方审计问答文件，涵盖以下问题的解答：
•起始物料（RSM）供应商审计是否必须？
•是否只能由质量部门人员执行审计？
•如果一个供应商拒绝现场审计，而根据你们的程序和/或风险评估必须进行审计，将如何处理？
•是否需要审计经销商？
•如果供应商不提供生产工艺的信息，将如何处理？
•如果起始物料（RSM）供应商处并无质量部门，将如何处理？
•对合同员工的培训是否需要记录？
•是否允许在“开放式”或“部分开放式”环境中进行生产操作？
•如果政府部门（没有原始数据）做了校准是否可认为设备已校准？
•起始物料（RSM）供应商是否必须对所有进厂原料进行检测？
•是否需要执行ICH 稳定性试验以确定有效期或复验期？
•起始物料（RSM）供应商是否需要对起始物料（RSM）检验的分析方法进行验证？
•起始物料（RSM）是否可在待验期内发运？
该文件翻译如下：
APIC 3rd party audit sub team for RSM suppliers Q&A document
APIC：起始物料（RSM）供应商第三方审计问答
RSM=Registered Starting Materials（起始物料供应商）
Question & Answers
问答文件
Preamble
前言
Q: Is this guide mandatory /legally binding?
本指南是否强制/具有法规效力？
A: This guide is not mandatory neither legally binding, but it will support the user in evaluating the quality systems at the RSM supplier. If some of the requirements are not in place, a risk-based evaluation should be done to define the impact on the involved product.
本指南并非强制，也无法律效力，但它可以帮助使用方对起始物料（RSM）供应商质量体系的评估。

如果有些要求缺失，应执行基于风险的评估确定对所涉及产品的影响。

Q: Do we need to audit RSM suppliers?
是否需要对起始物料（RSM）供应商进行审计？
A: Auditingis not a legal requirement. However, it is important to evaluate the Quality System of the RSM supplier as part of the supplier qualification. There are different options to perform this (audit, questionnaire, …). The following criteria can be used (not limited):
审计并非法定要求。

然而，评估起始物料（RSM）供应商的质量体系作为供应商确认的一部分非常重要。

有多种方法可进行确认（审计、问卷……）。

可使用以下标准（不限于）：
•complexity of the molecule
•分子复杂程度
•number of manufacturing steps between RSM and API
•起始物料（RSM）与API之间生产步骤数量
•knowledge of the supplier (e.g. past experience)
•对供应商的了解（例如，过去的经验）
•worldwide available or custom made
•全球可及还是定制
•continuous process or single campaigns
•连续加工还是单批生产
•dedicated or multipurpose equipment
•专用还是共用设备
The decision not to audit can be overruled at a later stage in function of specific events such important quality related issues, regulatory actions against the supplier.
做出不审计决定之后，后期如果发生具体事件如严重的质量问题、该供应商被官方采取强制措施，可否定之前的不审计决定。

Q: Do audits have to be performed exclusively by members of the quality unit?
审计是否只能由质量部门人员执行？
A: Quality Auditing is the exclusive authority of members of the Quality Unit. In certain cases, other departments (e.g. Purchasing, Technical operations, R&D) can visit suppliers in support of supplier selection. These visits, when not attended by Quality unit persons cannot replace audits. Moreover, the final approval of a supplier is the responsibility of the Quality Unit.
质量审计是质量部门人员的专有权力。

在特殊情形下，其它部门（例如，采购、技术运营、R&D）亦可访问供应商，以支持供应商选择。

这些访问如果没有质量部门人员参与，则不能代替审计。

另外，对供应商进行最终批准是质量部门的职责。

Q: What if a supplier refuses an on-site audit, while the audit is mandatory according to your procedures and/or risk-assessment?
如果一个供应商拒绝现场审计，而根据你们的程序和/或风险评估必须进行审计，那要怎么办？
A: In case a supplier refuses it is very important to understand the reason for the refusal.A refusal can be due to several reasons
如果一个供应商拒绝审计，则了解拒绝原因很重要。

拒绝可能会源于几种理由：
•Confidentiality, e.g. in case the audited company is a
competitor
•保密原因，例如，受审计公司是竞争对手
•Business related, e.g. volume purchased is too low
•商业原因，例如，采购量太小
•Suppliers concerned they may not fulfil the expectations of the auditors
•供应商担忧不满足审计员要求
If, despite further discussion/ negotiation or alternative solutions (e.g. audit by third party) the refusal still remains, a documented risk evaluation should be performed in order to decide on further actions (additional questionnaires, additional testing/sampling upon receipt of the material, on-line interview/audit or change supplier).
如经过进一步讨论/谈判或替代方案（例如由第三方执行审计）之后，供应商仍拒绝审计，则应进行风险评估并记录，以决定后续措施（增加问卷、收到物料时增加检测/取样、在线访谈/审计或变更供应商）。

Q: Do we need to audit distributors instead of suppliers?
是否需要审计经销商而不是供应商？
A: You need to evaluate (audit or alternative) the manufacturing site. In addition, if the distributor has specific quality responsibilities that can impact the product (specific storage or transport conditions, dispensing/repacking/re-labelling of the product, testing of the product), they also need to be evaluated (audit or alternative depending on the risk assessment).
你们需要对生产现场进行评估（审计或其它）。

另外，如果经销商具有特定的质量义务，可能对产品产生影响（特定储存或运输条件，产品分装/重新包装-标签、产品检测），也需要对其进行评估（根据风险评估进行审计或其它）。

Q: What if the suppliers don’t want to provide information on the manufacturing process?
如果供应商不想提供生产工艺的信息，该怎么办？
A: A high-level ROS description of the RSM is needed from a regulatory perspective to complete your registration file and to evaluate the impact towards the quality of your API. If no information or too limited information is provided, another RSM supplier with a known ROS should be selected.
为了完成注册文件和评估对你们API质量的影响，需要获得起始物料（RSM）的详细ROS描述。

如果没有信息或所提交的信息非常有限，应选择已知ROS的另一起始物料（RSM）供应商。

Chapter 3:
第三章
<3.1>
Q: What ifthere is no quality unit at the RSM supplier?
如果起始物料（RSM）供应商处并无质量部门，要怎么办？
A: In the scope of this guide a person (or group of persons) that can take independent decisions related to quality can be considered as a quality unit.
Clear roles and responsibilities of this person (or group of persons) should be documented.
如果本指南内容中有一人（或一组人）可独立做出质量相关决策，则可视为具有质量部门。

该人（或该组人）的角色和职责应有文件明确规定。

Chapter 4:
第4章
<4.1>
Q: Should training of contractors be documented?
对合同员工的培训是否需要记录？
A: Yes, the level of the training and its documentation
depends on the criticality of the activities performed and it should not be based on the individual (permanent worker or contractor) who performs the activities.
需要，培训的水平及其文件取决于所执行活动的关键程度，而不是取决于由谁执行该活动（永久工人或是合同员工）。

Chapter 5:
第5章
<5.3>
Q: Are manufacturing operations in ‘open’ or ‘partly-open’ environment allowed?
是否允许在“开放式”或“部分开放式”环境中进行生产操作？
A: Yes, it can be acceptable under the condition that there is a control strategy in place, e.g. mobile protection devices, (dis)charging devices, filtration or distillation in downstream processes, …
允许，如果具备控制策略，如移动保护装置、投（放）料装置、后续工艺有过滤器或蒸馏，则可接受。

Chapter 6:
第6章
<6.3>
Q: Is a calibration certificated by the government (without raw data) enough to consider equipment as calibrated?
如果政府部门（没有原始数据）做了校准是否可认为设备已校准？
A: Yes, if the local governmental practices doesn’t allow to provide the raw data of the calibrations. However, the calibration certificates should always be internally reviewed and approved.
可以，如果当地政府规范并不允许提供校准原始数据。

但是，公司内部应对校准证书进行审核和批准。

Chapter 8:
第8章
<8.21>
Q: Does the RSM supplier has to test all incoming raw materials?
起始物料（RSM）供应商是否必须对所有进厂原料进行检测？
A: A process should be in place to evaluate if testing is appropriate or not.
应有流程评估是否需要进行检测。

For those raw materials evaluated not appropriate to be tested, other controls can be inplace. Examples are:
对于经过评估不适合进行检测的原料，可采取其它方式进行控制，例如：
•Review of certificate of conformity (e.g. for basic chemicals obtained from continuous manufacturing)
•审核合格证书（例如，连续生产出的基本化学物质）
•Review of CoA from the supplier against the internal specifications
•对供应商的COA进行审核，与内部标准进行比较
•Downstream testing (e.g. IPC testing, intermediates testing).
•下游检测（例如，IPC检测，中间体检测）
•…
•……
Chapter12:
第12章
<12.4>
Q: Do you need to perform ICH stability tests to define expiry or re-test dates?
是否需要执行ICH 稳定性试验以确定有效期或复验期？
A: No. Data to define expiry or re-test dates can also be based on literature, historical data, retest of retention
samples/stocks, …
不需要。

有效期或复验期亦可根据文献、历史数据、留样/库存复验数据进行规定。

<12.13>
Q: Does the RSM supplier need to validate the analytical methods for testing the RSM?
起始物料（RSM）供应商是否需要对起始物料（RSM）检验的分析方法进行验证？
A:Not necessarily. It is the user of the RSM that is responsible that the RSM is released based on test data obtained by validated test methods. Only in case the user is not generating own test data but relies on supplier COA data (i.e. reduced testing) it is necessary that these data are obtained by validated methods and that the supplier is qualified to run them.
不需要。

起始物料（RSM）的使用方有义务采用经验证的检验方法获得的检验数据对起始物料（RSM）放行。

只有当使用方不生成自己的检验数据，而依赖于供应商COA数据（即简化测试）时，才需要要求这些数据采用经验证的方法得到，且供应商经过确认可运行这些方法。

Chapter 11
第11章
<11.2>
Q: Can a RSM be distributed under quarantine?
起始物料（RSM）是否可在待验期内发运？
A: When evaluating (or auditing) a supplier it should be checked that RSM supplier’s procedures do not allow distribution under quarantine without customer’s approval. As an exception and under specific conditions, a RSM can be distributed under quarantine
在评估（或审计）供应商时，应检查起始物料（RSM）供应商的
程序，待检状态下没有客户批准时应不得发运。

特定的例外情形下，可在待验状态下发运起始物料（RSM）：
•if agreed in a documented manner by both parties (RSM supplier and the receiver)
•双方有文件协定（起始物料（RSM）供应商与接收方）
•and if the product is released by the RSM supplier before your internal use.
•起始物料（RSM）供应商放行之后方在你们内部使用。