建议：
首先明确GMP等级缺陷有哪些：
根据《药品检查管理办法（试行）》第二十五条：缺陷分为严重缺陷、主要缺陷和一般缺陷，其风险等级依次降低。
其次找出每种缺陷定义，根据《药品生产现场检查风险评定指导原则》：
缺陷分为“严重缺陷”、“主要缺陷”和“一般缺陷”，其风险等级依次降低，相关定义为
（一）严重缺陷
严重缺陷是指与药品GMP要求有严重偏离，产品可能对使用者造成危害的缺陷。属于下列情形之一的为严重缺陷：
1．对使用者造成危害或存在健康风险；
2．与药品GMP要求有严重偏离，给产品质量带来严重风险；
3．有文件、数据、记录等不真实的欺骗行为；
4．存在多项关联主要缺陷，经综合分析表明质量管理体系中某一系统不能有效运行。
（二）主要缺陷
主要缺陷是指与药品GMP要求有较大偏离的缺陷。属于下列情形之一的为主要缺陷：
1．与药品GMP要求有较大偏离，给产品质量带来较大风险；
2．不能按要求放行产品，或质量受权人不能有效履行其放行职责；
3．存在多项关联一般缺陷，经综合分析表明质量管理体系中某一系统不完善。
（三）一般缺陷
一般缺陷是指偏离药品GMP要求，但尚未达到严重缺陷和主要缺陷程度的缺陷
等级分类还可以借鉴PIC/S 的GMP缺陷分类的新指南（PI 040-1），里面有提到以下情况可以对缺陷进行升级或者降级：
1.Risk Increasing Factors – Upgrading Initial Classification
A “Major” and “Other” deficiency may be upgraded by one level to either a “Critical” or “Major” deficiency respectively when conditions may exist to satisfy the intent of the definition for the upgraded risk classification. This is considered to be achieved when defined risk increasing factors are present. Risk increasing factors include:
Repeat or recurring deficiencies (Appendix 2 Step 3)
Grouping or combination of deficiencies (Appendix 2 Step 4) Product risk (Appendix 2 Step 5)
Failure of a manufacturer’s management to identify and take prudent measures to reduce the patient risk to an acceptable level for a product distributed and future production from a deficient practice or process.
2.Risk Reducing Factors – Downgrading Initial Classification
A “Critical” or “Major” deficiency may be downgraded by one level to either a “Major” or “Other” deficiency respectively when conditions may exist to satisfy the intent of the definition for the downgraded risk classification. This is considered to be achieved when defined risk reducing factors are present. When considering risk reducing factors, it is important to ensure that these factors are both consistent and effective. Risk reducing factors include:
Minimising product risk (Appendix 2 Step 5)
Minimising risk of patient harm Other risk reducing factors (Appendix 2 Step 6)
Actions taken by the manufacturer eg CAPA plan to reduce the risk of the deficiency The impact of product already distributed to market should be considered when downgrading a critical deficiency.
3. Repeat or Recurring Deficiencies – Upgrading Initial Classification
Repeat or recurring deficiencies are deficiencies that were also identified at a previous inspection where appropriate corrections or corrective actions have not been implemented In certain cases, recurring deficiencies may be considered to be subject to a risk enhancing effect to permit upgrading the initial risk classification, particularly if it is apparent that there is wilful or unsatisfactory effort to resolve the deficiency. A risk increasing effect should only be considered when:
There is a serious failure in the Quality System that fails to satisfactorily identify the potential root causes for the deficiency or fails to adequately address these causes without other risk reducing factors being present, or
There are other factors for consideration such that the definition of the upgraded risk classification is achieved, for example, unreasonably protracted implementation of corrective actions. Note: It is expected that the upgrading of risk for a recurring deficiency will require understanding of potential factors that may have led to the reoccurrence.
4. Grouping or Combining of Deficiencies - Upgrading Initial Classification
Different issues identified during an inspection may be grouped or combined into one deficiency, if each issue supports or relates to the core deficiency that is stated. A risk increasing effect can be applied to upgrade an initial risk classification by one level when the definition of the upgraded risk classification has been achieved. Examples of several “Other” deficiencies, none of which on its own may be “Major” but which may together represent a “Major” deficiency should be explained and reported as such.
5. Product Risk – Upgrading or Downgrading Initial Classification
Some manufacturing sites have product and processes that involve much higher risks than others. Product Risk Classification definitions: High risk- products that are highly susceptible to contamination through the manufacturing process including shelf life, e.g. microbial or chemical. Low Risk- products that have a lower chance of contamination through the manufacturing process including shelf life. Both risk increasing and risk reducing factors may be applied after considering product risks as follows:
High risk products may have certain “Major” deficiency or “Other” deficiency classifications respectively upgraded to a “Critical” deficiency or “Major” deficiency. This can be applied when circumstances of a deficiency under consideration meets the interpretation of the definition for a “Critical” deficiency. Low risk products may have certain “Critical” deficiency or “Major” deficiency classifications downgraded to a “Major” deficiency or “Other” deficiency respectively. For low risk products, a “Critical” deficiency may be downgraded to a “Major” deficiency unless the definition of “Critical” deficiency is achieved.
6. Other Risk Reducing Factors When other risk reducing factors are evident to mitigate the risk associated with a deficiency then the risk rating may be downgraded. Other risk reducing factors can typically be considered only when a secondary system has been established that can mitigate risks associated with a deficiency. For example, a validated packaging system vision system that provides 100% verification of every packaged product may be considered as a risk reducing factor for a deficiency associated with printed primarily packaging materials stored in a disordered manner that could cause mix-up. If there are a number of risk increasing and risk reducing factors, consider all risk factors at the same time and then determine an overall risk assessment to upgrade or downgrade initial risk.
Note: the list is an illustrative list to help position the tool and is not an exhaustive and binding list. Examples are provided of deficiencies that are classified as “Critical”, “Major” and “Other”. In some examples, classification is also based on the type of manufacturer or product risk. These examples also assist the user in providing a quick reference for the classification of the deficiency or can verify the classification that has been determined using the management tool. The classification may be in the context of the physical inspection performed, information provided at the time and its associated risk. For complex deficiencies refer to Appendix 1 for more information on classification.
以上说的是GMP审计中对于已列出的各缺陷等级的再判定条件。
依据：药品检查管理办法（试行）
思考：
应明确问题的指向，从法规中找出相对应的依据
补充一下：不知道提问者只是问“缺陷等级(类别)的判断依据是什么，还是问在实际GMP审计中，官方给出的审计报告deficiency等...
不过关于这块可以借鉴PIC/S 的GMP缺陷分类的新指南（PI 040-1），里面有提到以下情况可以对缺陷进行升级或者降级：
1.Risk Increasing Factors – Upgrading Initial Classification
A “Major” and “Other” deficiency may be upgraded by one level to either a “Critical” or “Major” deficiency respectively when conditions may exist to satisfy the intent of the definition for the upgraded risk classification. This is considered to be achieved when defined risk increasing factors are present. Risk increasing factors include:
Repeat or recurring deficiencies (Appendix 2 Step 3)
Grouping or combination of deficiencies (Appendix 2 Step 4) Product risk (Appendix 2 Step 5)
Failure of a manufacturer’s management to identify and take prudent
measures to reduce the patient risk to an acceptable level for a
product distributed and future production from a deficient practice or
process.
2.Risk Reducing Factors – Downgrading Initial Classification
A “Critical” or “Major” deficiency may be downgraded by one level to either a “Major” or “Other” deficiency respectively when conditions may exist to satisfy the intent of the definition for the downgraded risk classification. This is considered to be achieved when defined risk reducing factors are present. When considering risk reducing factors, it is important to ensure that these factors are both consistent and effective. Risk reducing factors include:
Minimising product risk (Appendix 2 Step 5)
Minimising risk of patient harm Other risk reducing factors (Appendix 2 Step 6)
Actions taken by the manufacturer eg CAPA plan to reduce the risk of the deficiency The impact of product already distributed to market should be considered when downgrading a critical deficiency.
3. Repeat or Recurring Deficiencies – Upgrading Initial Classification
Repeat or recurring deficiencies are deficiencies that were also identified at a previous inspection where appropriate corrections or corrective actions have not been implemented In certain cases, recurring deficiencies may be considered to be subject to a risk enhancing effect to permit upgrading the initial risk classification, particularly if it is apparent that there is wilful or unsatisfactory effort to resolve the deficiency. A risk increasing effect should only be considered when:
There is a serious failure in the Quality System that fails to satisfactorily identify the potential root causes for the deficiency or fails to adequately address these causes without other risk reducing factors being present, or
There are other factors for consideration such that the definition of the
upgraded risk classification is achieved, for example, unreasonably
protracted implementation of corrective actions.
Note: It is expected that the upgrading of risk for a recurring deficiency will
require understanding of potential factors that may have led to the
reoccurrence.
4. Grouping or Combining of Deficiencies - Upgrading Initial Classification
Different issues identified during an inspection may be grouped or combined
into one deficiency, if each issue supports or relates to the core deficiency that
is stated.
A risk increasing effect can be applied to upgrade an initial risk classification
by one level when the definition of the upgraded risk classification has been
achieved.
Examples of several “Other” deficiencies, none of which on its own may be
“Major” but which may together represent a “Major” deficiency should be
explained and reported as such.
5. Product Risk – Upgrading or Downgrading Initial Classification
Some manufacturing sites have product and processes that involve much higher risks than others. Product Risk Classification definitions: High risk- products that are highly susceptible to contamination through the manufacturing process including shelf life, e.g. microbial or chemical. Low Risk- products that have a lower chance of contamination through the manufacturing process including shelf life. Both risk increasing and risk reducing factors may be applied after considering product risks as follows:
High risk products may have certain “Major” deficiency or “Other”
deficiency classifications respectively upgraded to a “Critical”
deficiency or “Major” deficiency. This can be applied when
circumstances of a deficiency under consideration meets the
interpretation of the definition for a “Critical” deficiency.
Low risk products may have certain “Critical” deficiency or “Major”
deficiency classifications downgraded to a “Major” deficiency or
“Other” deficiency respectively. For low risk products, a “Critical”
deficiency may be downgraded to a “Major” deficiency unless the
definition of “Critical” deficiency is achieved.
6. Other Risk Reducing Factors
When other risk reducing factors are evident to mitigate the risk associated
with a deficiency then the risk rating may be downgraded.
Other risk reducing factors can typically be considered only when a secondary
system has been established that can mitigate risks associated with a
deficiency. For example, a validated packaging system vision system that
provides 100% verification of every packaged product may be considered as
a risk reducing factor for a deficiency associated with printed primarily
packaging materials stored in a disordered manner that could cause mix-up.
If there are a number of risk increasing and risk reducing factors, consider all
risk factors at the same time and then determine an overall risk assessment
to upgrade or downgrade initial risk.
Note: the list is an illustrative list to help position the tool and is not an
exhaustive and binding list.
Examples are provided of deficiencies that are classified as “Critical”, “Major”
and “Other”. In some examples, classification is also based on the type of
manufacturer or product risk. These examples also assist the user in providing
a quick reference for the classification of the deficiency or can verify the
classification that has been determined using the management tool.
The classification may be in the context of the physical inspection performed,
information provided at the time and its associated risk.
For complex deficiencies refer to Appendix 1 for more information on
classification.
以上说的是GMP审计中对于已列出的各缺陷等级的再判定条件。
1.FDA检查员指导手册CP 7356.002：
2.药品检查管理办法（试行）2021年5月24日
第二十六条 现场检查结论和综合评定结论分为符合要求、基本符合要求、不符合要求。
第二十七条 药品生产企业现场检查结论和综合评定结论的评定标准：
（三）发现缺陷为严重质量安全风险，质量体系不能有效运行，检查结论为不符合要求，包含但不限于以下情形：
（1）对使用者造成危害或者存在健康风险；
（2）与GMP要求有严重偏离，给产品质量带来严重风险；
（3）有编造生产、检验记录，药品生产过程控制、质量控制的记录和数据不真实；
（4）发现严重缺陷或者多项关联主要缺陷，经综合分析表明质量管理体系中某一系统不能有效运行。
（该系列问答来自课程《GMP迎检工作分析及注意事项》）
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