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Annex 4:
《Good Manufacturing
Practice (2010 revision)
》
Annex1 to Annex5 Technical Reviewed by ISPE
Michael Lee, Zhao Chunhua
Zhao Yunxia, He Guoling, Ji Yiyun
Initial Translation from NNE Pharmaplan
附录4：
Annex 4:
血液制品
Blood Products
第一章 范围
Chapter 1
Scope
第一条
本附录中的血液制品特指人血浆蛋白类制品。本附录的规定适用于
人血液制品的生产、质量控制、贮存、发放和运输。
Article 1:
Blood products in this annex refer specifically to human plasma
protein
products. The provisions of this annex apply to the production, quality
control,
storage and transportation of blood products.
第二条
本附录中的血液制品生产包括从原料血浆接收、入库贮存、复检、
血浆分离、血液制品制备、检定到成品入库的全过程。
Article 2:
The production processes of blood products mentioned in this
annex
include receiving, storage, re-checking, and fractionation of plasma, the
preparation and testing of blood products, and storage of finished products.
第三条
生产血液制品用原料血浆的采集、检验、贮存和运输应当符合《中
华人民共和国药典》中“血液制品生产用人血浆”的规定和卫生部《单采血浆站质量
管理规范》。
Article 3:
The collection, testing, storage and transportation of plasma used
as source
material of blood production should comply with
“Procedure for
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Plasma in
Blood Products” listed in “Pharmacopoeia
of the People’s Republic of
China”
and the “Control Regulations for Plasmapheresis
Centres” enacted by
Ministry
of Health.
第四条
血液制品的管理还应当符合国家相关规定。
Article 4:
The management of blood products should also consist with any
relevant
regulations enacted by the State Council.
第二章 原则
Chapter 2 Principle
第五条
原料血浆可能含有经血液传播疾病的病原体（如HIV、HBV、HCV），
为确保产品的安全性，必须确保原料血浆的质量和来源的合法性，必须对生产过
程进行严格控制，特别是病毒的去除和/或灭活工序，必须对原辅料及产品进行严
格的质量控制。
Article 5:
Plasma used as raw material may have certain blood borne
pathogens
(e.g. HIV, HBV and HCV). The safety of these products therefore
relies on
the strictly control of plasma used as material and its origin as well as
on the
subsequent manufacturing procedures, including virus removal and
inactivation processes during which strict quality control on starting materials
and
products should be implemented.
第三章 人员
Chapter 3 Personnel
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第六条
企业负责人应当具有血液制品专业知识，并经过相关法律知识的培
训。
Article 6:
Legal representative and responsible person of manufacturers
should
have professional knowledge of blood products, and have been well
trained
with knowledge of relevant regulations.
第七条
生产管理负责人应当具有相应的专业知识（如微生物学、生物学、
免疫学、生物化学等），至少具有三年从事血液制品生产或质量管理的实践经验。
Article 7:
Persons who are responsible for production management should
have
relevant professional knowledge such as microbiology, biology,
immunology
and biochemistry etc; and have at least 3 years practical
experience
in the production or quality management of blood product production.
第八条
质量管理负责人和质量受权人应当具有相应的专业知识（如微生物
学、生物学、免疫学、生物化学等），至少具有五年血液制品生产、质量管理的实
践经验，从事过血液制品质量保证、质量控制等相关工作。
Article 8:
Persons who are responsible for quality management should have
relevant
professional knowledge such as microbiology, biology, immunology and
biochemistry etc; and have at least 5 years practical experience in the
production
or quality management of blood product production; and have been
engaged in
activities relating quality assurance and quality control of blood
products.
第九条
从事血液制品生产、质量保证、质量控制及其他相关人员（包括清
洁、维修人员）应当经过生物安全防护的培训，尤其是经过预防经血液传播疾病
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方面的知识培训。
Article 9:
Persons who are involved in the production, quality assurance and
quality
control of blood products and all related personnel including those
concerned
with cleaning or maintenance, should be given relevant information
and
training in bio-safety containment, especially in knowledge of the prevention
of blood
borne diseases.
第十条
从事血液制品生产、质量保证、质量控制及其他相关人员应当接种
预防经血液传播疾病的疫苗。
Article
10: Vaccines which can prevent from blood borne diseases should be
inoculated
for relevant persons who engage in the production, quality assurance
and
quality control of blood products.
第四章 厂房与设备
Chapter 4 Premises and Equipment
第十一条
血液制品的生产厂房应当为独立建筑物，不得与其它药品共用，
并使用专用的生产设施和设备。
Article
11: The premises used for the production of blood products should be
an
independent building that can not be shared with other products, and should
be
equipped with dedicated facilities and equipments.
第十二条
原料血浆、血液制品检验实验室应当符合国务院《病原微生物实
验室生物安全管理条例》、国家标准《实验室生物安全通用要求》的有关规定。
Article
12: The testing laboratory for plasma used as source materials and
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blood
products should comply with the
“Regulations of Administration of
Pathogenic
Microorganism Laboratories” enacted by State Council and National
Standards
of the
“General
Requirements of Biosafety in Laboratory”
第十三条
原料血浆检验实验室应当独立设置，使用专用检验设备，并应当
有原位灭活或消毒的设备。如有空调系统，应当独立设置。
Article
13: The testing laboratory for source plasma should be set up
independently, equipped with dedicated testing equipments, in place inactivation
and
disinfection equipments. The HVAC system should also be independent if
available.
第十四条
原料血浆破袋、合并、分离、提取、分装前的巴氏灭活等工序至
少在D
级洁净区内进行。
Article
14: The bag opening, combination, separation, extraction and
pasteurization before sub-packing of material plasma should be performed in a
grade D
clean area as a minimum.
第十五条
血浆融浆区域、组分分离区域以及病毒灭活后生产区域应当彼此
分开，生产设备应当专用，各区域应当有独立的空气净化系统。
Article
15: The areas for melting of plasma, separation of components and
production
after inactivation of virus should be independent from each other,
equipped
with dedicated equipments and separate HVAC system.
第十六条
血液制品生产中，应当采取措施防止病毒去除和/或灭活前、后制
品的交叉污染，病毒去除和/或灭活后的制品应当使用隔离的专用生产区域与设备，
并使用独立的空气净化系统。
Article
16: In the production process of blood products, protective measures
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should be
taken against cross-contamination to products before and after their
inactivation. Dedicated and isolated premises and equipments as well as HAVC
system
should be used for products which have been followed with viral
inactivation and/or removal procedures.
第五章 原料血浆
Chapter 5 Plasma Used As Source Materials
第十七条
企业对每批接收的原料血浆，应当检查以下各项内容：
（一）原料血浆采集单位与法定部门批准的单采血浆站一致；
（二）运输过程中的温度监控记录完整，温度符合要求；
（三）血浆袋的包装完整无破损；
（四）血浆袋上的标签内容完整，至少含有供血浆者姓名、卡号、血型、血
浆编号、采血浆日期、血浆重量及单采血浆站名称等信息；
（五）血浆的检测符合要求，并附检测报告。
Article
17: The following items should be checked for each received batch of
plasma
used as source materials:
1) The
collection units of raw material plasma should be confirmed with the
legal
plasma collecting stations approved by legal authorities.
2)
Complete monitoring records of temperature during transportation, the
temperature should meet the relevant requirements.
3)
Packaging of plasma bag should be in its integrity and with no damage.
4) Label
information on plasma packaging should be completed , and at least
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including
name of donor, donation code, blood type, reference number of
plasma,
date of collection, weight of plasma and collection stations.
5) Testing
of plasma should meet the relevant requirements and with test
reports.
第十八条
原料血浆接收后，企业应当对每一人份血浆进行全面复检，并有
复检记录。原料血浆的质量应当符合《中华人民共和国药典》相关要求。复检不
合格的原料血浆应当按照规定销毁，不得用于投料生产。
Article
18: Each plasma should be retested and recorded after receiving by
the
manufacture. The quality of plasma should be consistent with the relevant
requirements listed in Pharmacopoeia of the People’s Republic of China.
Unqualified plasma can not be used in production and should be destroyed
according
to relevant regulations.
第十九条
原料血浆检疫期应当符合相关规定。
Article
19: Quarantine time of plasma used as source material should
comply
with relevant regulations.
第二十条
投产使用前，应当对每批放行的原料血浆进行质量评价，内容应
当包括：
Article
20: Before put into production, the quality assessment should be
performed
on each batch of incoming plasma used as source materials in order,
including
:
（一）原料血浆采集单位与法定部门批准的单采血浆站一致。
1) The
collection units of raw material plasma should be confirmed with the legal
plasma
collecting stations approved by regulatory agencies.
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（二）运输、贮存过程中的温度监控记录完整，温度符合要求。运输、贮存
过程中出现的温度偏差，按照偏差处理规程进行处理，并有相关记录。
2) The
monitoring records temperature during transportation and storage are
complete,
and the temperature condition meets the requirements. Deviations
of
temperature during transportation and storage should be handled
according
to the procedures and the relevant records for this should be
available.
（三）采用经批准的体外诊断试剂对每袋血浆进行复检并符合要求。
3)
Retesting should be conducted on each bag of the plasma by using qualified
invitro
diagnostic reagents according to approved procedures and make sure
it comply
with the requirements.
（四）已达到检疫期所要求的贮存时限。
4) Storage
time limit has been reached according to the requirement of
quarantine.
（五）血浆袋破损或复检不合格的血浆已剔除并按规定处理。
5)
Package-broken plasma of off-retest plasma have been removed and
disposed
in accordance with the relevant provisions.
第二十一条
企业应当建立原料血浆的追溯系统，确保每份血浆可追溯至供
血浆者，并可向前追溯到供血浆者最后一次采集的血浆之前至少3
个月内所采集
的血浆。
Article
21: There must be a system in place which enables the path taken by
each
donation to be tracked forward from donor of each donation of plasma, and
also track
the plasma of each donor al least 3 months prior to the last donation of
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plasma.
第二十二条
企业应当与单采血浆站建立信息交换系统，出现下列情况应当
及时交换信息：
Article
22: A mutual information system between the plasma collecting
station
and the manufactures should be set up so that they can inform each
other if
the following events occur:
（一）发现供血浆者不符合相关的健康标准；
1) It is
found that the plasma donor does not meet the relevant donor health
criteria;
（二）以前病原体标记为阴性的供血浆者，在随后采集到的原料血浆中发现
任何一种病原体标记为阳性；
2) A
subsequent donation from a donor, who is previously found negative for
pathogeny,
is found positive for any of the pathogeny.
（三）原料血浆复验结果不符合要求；
3)
Retesting of plasma used as source material does not meet the requirements.
（四）发现未按规程要求对原料血浆进行病原体检测；
4) It is
found that testing for pathogens has not been carried out according to
procedures.
（五）供血浆者患有可经由血浆传播病原体（如HAV、HBV、HCV
和其他血
源性传播肝炎病毒、HIV
及目前所知的其它病原体）的疾病以及克-雅病或变异型
新克-雅病（CJD
或vCJD）。
5) The
plasma donor has developed an infectious disease caused by an agent
potentially transmissible by plasma-derived products (HAV/HBA/HCV and other
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hepatitis
viruses, HIV and other agents in the light of current knowledge) and
Creutzfeldt-Jakob disease (CJD or vCJD).
第二十三条
企业应当制定规程，明确规定出现第二十二条中的任何一种情
况的应对措施。应当根据涉及的病原体、投料量、检疫期、制品特性和生产工艺，
对使用相关原料血浆生产的血液制品的质量风险进行再评估，并重新审核批记录。
必要时应当召回已发放的成品。
Article
23: Relevant procedures should be established and specify the
responding
activities when any event stated in Article 22 occurs. Re-assessment
of quality
risks for the blood products manufactured using relevant source
plasma and
re-assessment of the batch record in production should be carried
out
according to athogeny, inventory rating, quarantine, the nature of the
products
and its production process. Recall the released finished products when
necessary.
第二十四条
发现已投料血浆中混有感染HIV、HBV、HCV
血浆的，应当停
止生产，用相应投料血浆所生产的组分、中间产品、待包装产品及成品均予销毁。
如成品已上市，应当立即召回，并向当地药品监督管理部门报告。
Article
24: Where there are indications that a donation contributing to a
plasma
pool was infected with HIV, HBV or HCV, the manufacture should be
stopped
immediately, and the relevant components, intermediates, bulk products
and
finished products using the same batch of plasma as source materials
should be
disposed as well. It should recall all the released products if any and
report to
the relevant pharmaceutical competent authorities.
第二十五条
质量管理部门应当定期对单采血浆站进行现场质量审计，至少
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每半年一次，并有质量审计报告。
Article
25: Quality audit for the plasma collection station should be regularly
performed
by Quality Management Department as least once every 6 months,
and
relevant reports should be made.
第六章 生产和质量控制
Chapter 6 Production and Quality Control
第二十六条
企业应当对原料血浆、血浆蛋白组分、中间产品、成品的贮存、
运输温度及条件进行验证。应当对贮存、运输温度及条件进行监控，并有记录。
Article
26: Validation and monitoring of the storage, temperature and
conditions
during transportation of plasma used as source materials, protein of
plasma,
intermediates and finished products should be carried out, and there
should be
relevant records.
第二十七条
用于特定病原体（HIV、HBV、HCV
及梅毒螺旋体）标记检查
的体外诊断试剂，应当获得药品监督管理部门批准并经生物制品批签发检定合格。
体外诊断试剂验收入库、贮存、发放和使用等应当与原辅料管理相同。
Article
27: In vitro diagnostic reagents used for marking specific pathogen
(e.g.,
HIV, HBV, HCV and Treponema pallidum) should be approved by SFDA
and
qualified by National Institute for the control of Pharmaceutical and
Biological
products. Their testing, stocking, storing, releasing and using should
be
regarded and managed the same as starting materials.
第二十八条
混合后血浆应当按《中国药典》规定进行取样、检验，并符合
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要求。如检验结果不符合要求，则混合血浆不得继续用于生产，应当予以销毁。
Article
28: After mixing, the plasma should be sampled and tested according
to Chinese
Pharmacopoeia and comply with the relevant requirements. If the
test
results does not meet the requirements, the mixed plasma should be
disposed
and should not be use in the manufacturing process.
第二十九条
原料血浆解冻、破袋、化浆的操作人员应当穿戴适当的防护服、
面罩和手套。
Article
29: Personnel engaged in the thawing, opening bags and pooling of
plasma
should wear appropriate protective clothing, masks and gloves.
第三十条
应当定期对破袋、融浆的生产过程进行环境监测，并对混合血浆
进行微生物限度检查，以尽可能降低操作过程中的微生物污染。
Article
30: Environment monitoring of opening bags and pooling of plasma
process
should be carried out periodically. Microorganism Limit Test should be
used for
mixed plasma in order to minimize the organism contamination during
the
operation process.
第三十一条
已经过病毒去除和/或灭活处理的产品与尚未处理的产品应当有
明显区分和标识，并应当采用适当的方法防止混淆。
Article
31: Methods for clearly distinguishing and marking between products
or
intermediates undergone a process of virus removal or inactivation and those
without
any treatments should be in place. Appropriate precautions should be
taken to
prevent from mixing up.
第三十二条
不得用生产设施和设备进行病毒去除或灭活方法的验证。
Article
32: The manufacturing facilities and equipments should not be used
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in the
validation of virus removal and inactivation methods.
第三十三条
血液制品的放行应当符合《生物制品批签发管理办法》的要求。
Article
33: The release of blood products should comply with the
requirements of
“Regulations
on Batch Release of Biological Products”.
第七章 不合格原料血浆、中间产品、成品的处理
Chapter 8 Handling of Rejected Plasma, Intermediates
or Finished
Products
第三十四条
应当建立安全和有效地处理不合格原料血浆、中间产品、成品
的操作规程，处理应当有记录。
Article
34: SOPs for safely and effectively handling rejected plasma,
intermediates and finished products should be established, and the records
should be
available.
Annex 4
reviewed by Michael Lee, Zhao Chunhua
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