FprEN ISO 18362

SLOVENSKI STANDARD
01-december-2018
Proizvodnja izdelkov za zdravstveno nego na osnovi celic - Kontrola mikrobnega
tveganja med obdelavo (ISO 18362:2016)
Manufacture of cell-based health care products - Control of microbial risks during
processing (ISO 18362:2016)
Herstellung von zellbasierten Gesundheitsprodukten - Kontrolle der mikrobiellen Risiken
während der Verarbeitung (ISO 18362:2016)
Fabrication de produits de santé à base de cellules - Contrôle des risques
microbiologiques durant le procédé (ISO 18362:2016)
Ta slovenski standard je istoveten z: prEN ISO 18362
ICS:
11.080.01 Sterilizacija in dezinfekcija na Sterilization and disinfection
splošno in general
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

INTERNATIONAL ISO
STANDARD 18362
First edition
2016-02-01
Manufacture of cell-based health care
products — Control of microbial risks
during processing
Manufacture de produits de soins de santé fondés sur les cellules —
Contrôle des risques microbiaux durant le processus
Reference number
ISO 18362:2016(E)
©
ISO 2016
ISO 18362:2016(E)
© ISO 2016, Published in Switzerland
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ii © ISO 2016 – All rights reserved

ISO 18362:2016(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Quality system elements . 5
5 Process definition . 5
5.1 General . 5
5.2 Risk management . 6
5.2.1 General considerations . 6
5.2.2 Cell-based starting material risk assessment . 7
5.2.3 CBHP process risk assessment . 7
5.2.4 Use of risk assessment methods and tools for supply of CBHPs for use in
clinical trials . . 8
6 Manufacturing environment . 8
6.1 General . 8
6.2 Alternative processes . 8
6.3 Manufacturing environment design . 8
6.3.1 Containment area . 8
6.3.2 Construction containment features . 8
6.4 Layout . 9
6.5 Material and personnel flow . 9
6.5.1 General. 9
6.5.2 Equipment . 9
6.5.3 Handling of waste material . 9
6.6 HVAC system .10
6.7 Utility services and ancillary equipment .10
6.8 Environmental and personnel monitoring programmes .10
7 Equipment .10
7.1 General .10
7.2 Additional requirements .10
8 Personnel .11
8.1 General .11
8.2 Personnel procedures .11
8.3 Gowning procedures .11
8.4 General employee health .11
9 Manufacture of product .12
9.1 General .12
9.2 Control of starting material .12
9.2.1 Cell-based starting material .12
9.2.2 Other starting materials .12
9.3 Manufacturing procedures .13
9.4 In-process controls and process monitoring .13
9.5 Virus elimination and inactivation .13
10 Process simulation and process confirmation .13
10.1 General .13
10.2 Process simulation .14
10.3 Process confirmation studies .14
10.4 Media selection and growth support .14
11 Finished product release: test for sterility .15
ISO 18362:2016(E)
11.1 General .15
11.2 Additional requirements .15
12 Finished product release: testing for biological contamination that cannot be
detected by the test for sterility .16
12.1 General .16
12.2 Extrinsic biological contamination .16
12.3 Intrinsic biological contamination .16
Annex A (informative) Examples of microbial risks for CBHP .17
Annex B (normative) Decision trees for application of risk assessment for cell-based
starting materials .18
Annex C (informative) Containment facilities .20
Annex D (normative) CBHP starting material .27
Annex E (normative) Containment requirements for procured, non-sterile starting
materials before entering the manufacturing area.29
Annex F (informative) Typical elements of a process definition .30
Bibliography .31
iv © ISO 2016 – All rights reserved

ISO 18362:2016(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity
assessment, as well as information about ISO’s adherence to the WTO principles in the Technical
Barriers to Trade (TBT) see the following URL: Foreword - Supplementary information
The committee responsible for this document is ISO/TC 198, Sterilization of health care products.
ISO 18362:2016(E)
Introduction
0.1 General
A cell-based health care product (CBHP) comprises prokaryotic or eukaryotic cells or cell derived
biological entities as an essential ingredient. Cell-based or cell derived starting material used in the
manufacture of a CBHP can be viable or non-viable and of human, animal, microbial or plant origin. A
common feature of CBHPs is that their efficacy is based on their biological properties. They are classified
as medicines, medical devices, biologics or combination products depending on the international,
national and/or regional regulations that govern supply of these products.
CBHPs might be limited in their ability to withstand sterilization and purification methods. This
International Standard focuses on process rather than product. It describes the minimum elements
necessary for a risk-based approach to the processing of a CBHP in order to reduce the potential for
an increase in intrinsic contamination of product and to avoid extrinsic contamination of product. The
design of the processes, equipment, facilities, utilities, the conditions of preparation and addition of
buffers and reagents, and training of the operators are key considerations to minimize contamination.
0.2 CBHPs labelled as ‘sterile’
A CBHP that is labelled as ‘sterile’ is sterilized by a terminal sterilization process or is aseptically
processed.
Examples of CBHPs that are terminally sterilized include, but are not restricted to, cancellous bone,
demineralized bone matrix, catgut sutures, biological heart valves and tissue patches. Sterility
assurance for these CBHPs is achieved through suitable design and control of the environment, controls
on starting materials and packaging, suitable design and qualification of manufacturing processes
including the terminal sterilization process, and the application of appropriate in-process controls and
testing. Requirements and guidance for terminal sterilization of CBHPs are contained in ISO 17665-1,
ISO/TS 17665-2, ISO 11137-1, ISO 11137-2, ISO 11137-3, ISO 11135, ISO 14160, ISO 20857, ISO 14937 and
ISO 25424, as applicable.
Controls for some infectious agents, e.g. viruses and protozoa, might require a multifaceted approach to
ensure product quality and safety. Such agents are not specifically considered in the existing standards
for terminal sterilization or aseptic processing.
A CBHP that is labelled ‘sterile’ and which cannot be terminally sterilized is aseptically processed.
Sterility assurance for these CBHPs is achieved through suitable design and control of the environment,
controls on starting materials and packaging, suitable design and qualification of manufacturing
processes, process simulation (in accordance with the requirements of the ISO 13408-series), the
application of appropriate in-process controls during manufacture, and testing to demonstrate
achievement of aseptic processing conditions. As a prerequisite, starting materials and packaging
materials are sterilized by validated processes. In this regard this International Standard does
not reiterate requirements for specific processes that are used during processing of a CBHP that is
labelled ‘sterile’. In cases where a CBHP is aseptically processed and labelled as ‘sterile’ refer to the
ISO 13408-series.
0.3 CBHPs supplied without a label claim for sterility
For a CBHP that is supplied without a label claim for sterility, e.g. corneal tissue or viable skin grafts,
processing involves the use of appropriate aseptic techniques at all stages during the process.
Components might be subject to bioburden reduction during preparation prior to their assembly
or combining to form finished product. This is necessary to minimize the potential for intrinsic
contamination of product to increase during processing and to avoid extrinsic contamination of
product. The controls and techniques to maintain product quality during processing of these CBHPs
might be different from those used for processing of a CBHP that is labelled ‘sterile’.
Controls for some infectious agents, e.g. viruses and protozoa, can require a multifaceted approach to
ensure product quality and safety.
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ISO 18362:2016(E)
Microbiological quality assurance for a CBHP that is supplied without a label claim for sterility is
achieved through control of the environment, controls on starting materials and packaging, suitable
design and qualification of manufacturing processes, process confirmation and process simulation
studies and the application of appropriate in-process controls and testing. Risk assessment underpins
selection of suitable microbiological quality criteria for a CBHP that is supplied without a label claim
for sterility. These criteria define the acceptability of product based on the absence or presence, or
number of microorganisms, per defined quantity of product, to ensure finished product does not pose a
microbiological risk to the patient.
INTERNATIONAL STANDARD ISO 18362:2016(E)
Manufacture of cell-based health care products — Control
of microbial risks during processing
1 Scope
This International Standard specifies the minimum requirements for, and provides guidance on, a
risk-based approach for the processing of cell-based health care products (CBHPs) requiring control of
viable and non-viable microbial contamination. It is applicable both to CBHPs labelled ‘sterile’ and to
CBHPs not labelled ‘sterile’.
This International Standard is not applicable to:
— procurement and transport of cell-based starting material used in processing of a CBHP,
— cell banking,
— control of genetic material,
— control of non-microbial product contamination,
— in vitro diagnostics (IVDs), or
— natural medicines.
EXAMPLE Vitamins and minerals, herbal remedies, homoeopathic medicines, traditional medicines such as
traditional Chinese medicines, probiotics, other products such as amino acids and essential fatty acids.
This International Standard does not define biosafety containment requirements.
This International Standard does not replace national or regional regulations that apply to the
manufacture and quality control of a CBHP.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated
references, the latest edition of the referenced document (including any amendments) applies.
ISO 11135, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 11137 (all parts), Sterilization of health-care products — Radiation
ISO 13022:2012, Medical products containing viable human cells — Application of risk management and
requirements for processing practices
ISO 13408-1:2008, Aseptic processing of health care products — Part 1: General requirements
ISO 13408-1:2008/Amd.1:2013, Aseptic processing of health care products — Part 1: General
requirements / Amendment 1
ISO 13408-7:2012, Aseptic processing of health care products — Part 7: Alternative processes for medical
devices and combination products
ISO 14160, Sterilization of health care products — Liquid chemical sterilizing agents for single-use medical
devices utilizing animal tissues and their derivatives — Requirements for characterization, development,
validation and routine control of a sterilization process for medical devices
ISO 18362:2016(E)
ISO 14644-4, Cleanrooms and associated controlled environments — Part 4: Design, construction and
start-up
ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizing
agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 17665-1, Sterilization of health care products — Moist heat — Part 1: Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 20857, Sterilization of health care products — Dry heat — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 22442 (all parts), Medical devices utilizing animal tissues and their derivatives
ISO 25424, Sterilization of medical devices — Low temperature steam and formaldehyde — Requirements
for development, validation and routine control of a sterilization process for medical devices
ICH Q7, Good manufacturing practice guide for active pharmaceutical ingredients, International
Conference for Harmonization; identical to Annex 18 of the EU-GMP-Guideline
ICH Q9, Quality Risk Management
European GMP Part II — Good Manufacturing Practice — Medicinal Products for Human and Veterinary
Use — Part II: Basic Requirements for Active Substances used as Starting Materials
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 13408-1 and the following apply.
3.1
active ingredient
any chemical or biological component that is included in the formulation of a cell-based health care
product in sufficient concentration to achieve the intended therapeutic purpose of the specific product
3.2
animal
any vertebrate or invertebrate [including amphibian, arthropod (e.g. crustacean), bird, coral, fish,
reptile, mollusc and mammal] excluding humans (Homo sapiens)
[SOURCE: ISO 22442-1:2007, 3.1]
3.3
aseptic technique
conditions and procedures used to exclude the introduction of microbial contamination
[SOURCE: ISO 14161:2009, 3.2]
3.4
biological contamination
presence of cells or biological entities other than the intended components
Note 1 to entry: This can include extrinsic and/or intrinsic contamination.
EXAMPLE Viruses, bacteria, fungi, protozoa, multicellular parasites, contaminating eukaryotic cells,
aberrant proteins known as prions, endotoxins or active DNA/RNA.
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ISO 18362:2016(E)
3.5
biological entity
functional assembly of biological molecules or structures
Note 1 to entry: A biological entity can be an enzyme complex, a membranous structure, ribosomes, etc., or a
combination thereof that is kept assembled to maintain its biological functionality.
3.6
CBHP
cell-based health care product
health care product that contains or consists of pro- or eukaryotic cells or cell derived biological entities
as an essential ingredient
3.7
cell-based starting material
any cell-based or cell derived material, ingredient, component or reagent that is used in the production
of cell-based health care products
Note 1 to entry: Cell derived materials are procured cells, tissues, biological entity, intermediates.
Note 2 to entry: This can include tissue samples and/or biological fluids without a well-defined structure. This
exceeds the scope of the definition of active pharmaceutical ingredients (API) starting material as given in ICH Q7.
3.8
CPA
cell-processing area
area for processing cell-based materials consisting of different zones for processing and, where
applicable, for containment
Note 1 to entry: The zones can include zones for aseptic processing areas (APA) (for a definition for APA see
ISO 13408-1:2008, 3.5) and/or other zones where the processing environment is controlled to minimize extrinsic
contamination of the product.
3.9
closed system
system preventing egress of hazardous agents and ingress of extrinsic contamination
3.10
containment
combination of buildings, engineering functions, equipment and work practices to allow safe handling
of hazardous biological or chemical agents to prevent accidental release of these agents to the
environment outside of the facility
3.11
containment area
designated area that comprises cell processing area and associated degowning room
Note 1 to entry: Isolators are considered to be a containment area.
3.12
containment facility
combination of manufacturing rooms including the containment area and associated rooms within a
physical containment barrier
Note 1 to entry: This can include airlocks, access and support rooms, laboratories and interconnecting corridors.
Note 2 to entry: A containment facility uses a series of barriers (primary, secondary and tertiary) to minimize
the escape of hazardous agents to facility workers, the general population and the environment, e.g. isolators (if
necessary, negative pressure type); biological safety cabinets (Class I, II or III); negative air pressure cleanroom;
personnel protective clothing; appropriate work practices; appropriate disposal of hazardous waste; restriction
of access to the facility.
ISO 18362:2016(E)
3.13
extrinsic contamination
ingress of extraneous material (viable and non-viable) during the manufacturing process
3.14
health care product(s)
medical device(s), including in vitro diagnostic medical device(s), or medicinal product(s), including
biopharmaceutical(s)
[SOURCE: ISO/TS 11139:2006, 2.20]
3.15
inactive ingredient
any chemical or biological component other than an active ingredient that is included in the formulation
Note 1 to entry: An inactive ingredient is also known as an excipient.
EXAMPLE Buffer agents, scaffolds, water.
3.16
intrinsic contamination
foreign matter (viable and non-viable) present in cell-based starting material
3.17
microbial contamination
presence of unintended bacteria, fungi, protozoa, viruses
Note 1 to entry: This can include extrinsic and/or intrinsic contamination.
3.18
microorganism
entity of microscopic size, encompassing bacteria, fungi, protozoa and viruses
[SOURCE: ISO/TS 11139:2006, 2.26]
3.19
negative air pressure room
room where the ventilation system has been designed in such a way that the pressure in the room is
below that of the surrounding areas
Note 1 to entry: The design of the room and the ventilation system for the room ensures that airborne
contamination generated in the room does not disperse to other parts of the facility.
3.20
process confirmation studies
exercise designed to verify the specified state of intrinsic microbial control of manufacturing processes
for cell-based health care products
3.21
process simulation
exercise that simulates the manufacturing process or portions of the process in order to demonstrate
the capability of the aseptic process to prevent microbial contamination
Note 1 to entry: Process simulation using sterile surrogate can be used to demonstrate the absence of ingress
of extrinsic microbial contamination in processes using non-sterile starting materials that are processed using
aseptic techniques.
Note 2 to entry: Viruses are excluded from process simulation.
[SOURCE: ISO 13408-7:2012, 3.2, modified – The phrase “microbial contamination” has replaced
“biological contamination”.]
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ISO 18362:2016(E)
3.22
processing of cell-based health care products
handling of cell-based health care products in a controlled environment, in which the air supply,
materials, equipment and personnel are regulated to avoid extrinsic biological contamination of the
product and to minimise the potential for intrinsic biological contamination of the product to increase
3.23
reagent
material used for cellular growth, differentiation, selection, purification or other critical manufacturing
steps but that is not intended to be part of the final product
EXAMPLE Fetal bovine sera, culture media.
4 Quality system elements
A quality management system, appropriate to the nature of the operations, shall be implemented to
ensure control over all activities affecting CBHP processing. Unless a superseding national, regional,
or international Good Manufacturing Practice (GMP) is employed (e.g. the World Health Organization
GMPs), a quality management system shall be applied, e.g. ISO 13485, Good Tissue Practice (GTP), Good
Clinical Practice (GCP).
NOTE Guidance on selecting a suitable model is given in ISO 9004 and ISO/TR 14969.
5 Process definition
5.1 General
5.1.1 Depending on the end product specifications processing of CBHPs can involve many individual
operations that need to be effectively combined and controlled to:
a) minimize potential for intrinsic biological contamination in the starting material,
b) limit proliferation of intrinsic biological contamination in the process,
c) avoid extrinsic biological contamination of the product, and
d) ensure finished product with defined biological characteristics.
The purpose of the process definition is to obtain a comprehensive understanding of the integration of
all the different elements required to successfully and safely manufacture the CBHP. Typical elements
are given in Annex F.
5.1.2 The process definition for a CBHP shall be conducted after the starting material specification
and CBHP finished product specification have been established. Acceptance criteria defined in these
documents shall be used as input requirements.
5.1.3 When a CBHP is sterilized by a terminal sterilization process, ISO 14937, the ISO 11137-series,
ISO 17665-1, ISO 20857, ISO 14160, ISO 11135 and ISO 25424 (as applicable), shall be followed.
Specific consideration shall be given to the
a) systematic analysis of cell-based starting materials to identify the risk of microbial contamination
in the course of processing (see examples listed in Table A.1),
b) systematic analysis of the potential for introduction of extrinsic microbial contamination in
the process, and
c) development of process confirmation studies (e.g. pre-sterilization bioburden treatment).
ISO 18362:2016(E)
5.1.4 When a CBHP is intended to be sterile, and cannot be terminally sterilized, it shall be aseptically
processed. ISO 13408-1 and ISO 13408-7 (as applicable) shall be followed.
Specific consideration shall be given to systematic analysis of cell-based starting materials to identify
the risk of microbial contamination in the course of processing (see examples listed in Table A.1).
5.1.5 When a CBHP cannot be terminally sterilized or aseptically processed, the following shall apply:
a) systematic analysis of cell-based starting materials to identify the risk of intrinsic microbial
contamination in the course of processing (see examples listed in Table A.1);
b) systematic analysis of the potential for introduction of extrinsic microbial contamination in the
process;
c) development of process confirmation studies.
5.1.6 Based on the CBHP process definition an assessment of processing risks shall be conducted.
Methods and/or procedures to minimize and control these risks shall be described and implemented
(see 5.2). Residual risks shall be justified.
NOTE 1 Examples of specific process risks associated with CBHP include: use of starting material with
intrinsic biological contamination, insufficient inactivation (or selective enhancement) of intrinsic biological
contamination, ingress of extrinsic contamination, inactivation of biological activity and accidental release of
hazardous material from a containment facility.
NOTE 2 Examples of specific contamination risks for CBHP are given in Annex A.
5.1.7 The process definition shall consider the complete process and give a rationale describing how
each element involved in processing contributes to the attainment of product specification. The process
definition shall be documented and approved by designated personnel.
5.1.8 The process definition shall be reviewed whenever a change occurs.
NOTE Guidance on identifying critical quality attributes, process parameters and material attributes, which
are necessary in the development of a process definition, is given in ICH Q8.
5.2 Risk management
5.2.1 General considerations
For materials used during processing of CBHPs, consideration shall be given to the prevention, removal
or inactivation of contaminants during the risk assessment process.
a) A risk management process shall be established and implemented according to ISO 14971 and ICH Q9.
b) Risk assessment shall be conducted to identify and evaluate risks associated with the processing
and risks associated with the specific CBHP, and to understand interaction of these risks. The
results of risk assessment shall be used as input for risk mitigation measures and to design process
simulation and process confirmation studies.
NOTE 1 Intrinsic biological contamination risks caused by cell-based starting materials and their
contribution to inter-batch cross contamination risks are of major importance in the processing of CBHP.
NOTE 2 Risk management tools can be selected and employed throughout the life cycle of the product, for
example, in the product and process design, development and validation stages.
c) Measures to control process risks for the manufacture of CBHP shall be defined and implemented.
Residual risks deemed to be acceptable shall be documented and justified.
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ISO 18362:2016(E)
d) The output/results of the risk management process shall be reviewed to take into account new
knowledge and experience. Once a quality risk management process has been initiated, that process
shall continue to be utilized for events that might affect the original quality risk management decision.
5.2.2 Cell-based starting material risk assessment
a) A cell-based starting material risk assessment process shall be established and implemented (see
also Figure B.1).
b) For risk assessment of viable materials of human origin, ISO 13022 shall apply. For risk
assessment of materials of animal origin, ISO 22442 (all parts) shall apply. For materials of plant
origin, infectious agents (e.g. mycoplasma, bacteria, fungi, yeasts, protozoa and viruses) shall be
considered according to local regulatory requirements.
c) It is recognized that intrinsic biological contamination can exist in starting materials. Acceptance
criteria associated with such contamination in starting materials shall be established and
confirmed in the risk assessment, documented in the starting material specification and addressed
in process validation and release criteria.
5.2.3 CBHP process risk assessment
a) During the design and development of a CBHP process, risk assessment shall be used to identify
and quantify biological contamination hazards for each step in the process in order to avoid cross-
contamination. This includes ingress of extrinsic biological contamination and dissemination of
intrinsic biological contamination. Mitigating procedures shall be implemented where identified as
being necessary.
b) Both the quantification of contamination risk and the verification of the effectiveness of mitigating
procedures shall be determined and controlled. This shall include but is not limited to:
1) intrinsic biological contamination control of product including specified microorganisms,
2) extrinsic biological contamination of the product or the manufacturing environment, and
3) particulate monitoring of the environment (viable and non-viable) depending on the level
of cleanliness.
c) Risk assessment shall be used to design the process simulation for aseptically processed products
as in ISO 13408-1 and ISO 13408-7.
NOTE 1 Process simulation is employed to verify that the overall residual risk of extrinsic microbial
contamination of the entire process is acceptable.
NOTE 2 The CBHP process can be simulated in one continuous process or can be divided into two or more
stages for the purposes of process simulation, e.g. employing two or more different approaches for process
simulation based on the process steps, provided that the entire process is simulated.
d) For non-sterile product or product where biological contamination control steps are required (see
Clause 10), starting material risk assessment shall be used to design process simulation and/or
process confirmation studies.
NOTE 3 The results of the risk assessment can be used in the design of process simulation and/or process
confirmation studies (where applicable) to demonstrate that the process prevents extrinsic contamination
and that intrinsic contamination is controlled.
e) The application of risk assessment and biological testing is usually an iterative process. As the
process develops and is further enhanced, the CBHP process simulation shall be modified, where
necessary, to ensure that it reflects the entire process.
f) The original risk assessment shall be reviewed, and where necessary modified, to ensure that all
risks associated with the entire process are identified, assessed and controlled.
ISO 18362:2016(E)
g) The container closure integrity of primary packaging shall be assessed.
5.2.4 Use of risk assessment methods and tools for supply of CBHPs for use in clinical trials
Development and qualification of the process for production of CBHPs for clinical trials shall follow
national or regional regulatory requirements.
6 Manufacturing environment
6.1 General
ISO 13408-1:2008, Clause 6 applies to aseptically processed CBHP. The principles contained therein
apply to all CBHPs. If there are cogent reasons for not applying ISO 13408-1:2008 the rationale for this
decision shall be documented.
Additional requirements, see 6.2 to 6.8, shall apply if they are applicable based on process definition
and risk assessment.
6.2 Alternative processes
The nature of the product and the source of starting materials might require additional or alternative
precautions with respect to facilities and equipment. Alternative processes might be acceptable for starting
materials, intermediates and final products that are unsuitable for processing under the conditions
required by ISO 13408-1. These alternative processes shall be justified, validated and documented.
The following requirements shall be considered:
a) quarantine of potentially contaminated material;
b) use of air locks for equipment, material and personnel;
c) suitability of containers and packaging;
d) need for protective equipment for employees;
e) need for specialized disposal and management of potentially hazardous and hazardous waste;
f) need for specialized hygiene measures;
g) need for containment, including where applicable, negative air pressure rooms;
h) level of environmental control based on the processing step and level of contamination risk (e.g.
cell processing areas);
i) need for use of single use/ disposable components;
j) need for the control of potentially contaminated documents covering their entry, exit and archiving.
6.3 Manufacturing environment design
6.3.1 Containment area
Consideration shall be given to the requirement for containment.
The containment area shall be designed in agreement with process definition and risk assessment. The
design review shall be documented.
6.3.2 Construction containment features
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ISO 18362:2016(E)
a) Facilities shall be constructed to prevent escape of contaminated air and discharges from the
containment facility to other parts of the facility and to the ext
...