WHO 发布技术报告系列第 1067 号附录 10，提出医用氧全生命周期监管考量
TRS 1067 - Annex 10: Regulatory considerations for the life cycle of medicinal oxygen
WHO 发布技术报告系列第 1067 号（TRS 1067）附录 10，就医用氧从生产、质量控制、贮存、流通到上市后监测的全生命周期提出监管考量，供国家监管机构（NRA）参考。文件建议将医用氧按药品监管，内容涵盖市场授权要求及豁免情形、生产与流通企业许可与检查、质量控制检测、上市后监督及医疗机构现场制氧。文中援引的 WHO 案头审查显示，194 个成员国中仅 80 个目前将医用氧作为药品监管。
文件把医用氧从生产到患者使用的各环节监管职责逐项列出，便于对照本国市场授权、检查与上市后监测的缺口。
WHO 正式技術報告附錄：TRS 1067 - Annex 10: Regulatory considerations for the life cycle of medicinal oxygen
官方目錄發布日：2026-06-09（原文 9 June 2026）；報告年份、會議日期及適用範圍請以文件正文為準。
官方出版頁：https://www.who.int/publications/m/item/trs-1067---annex-10--regulatory-considerations-for-the-life-cycle-of-medicinal-oxygen
PDF 文字版；图形和原始排版请参阅官方 PDF。
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Annex 10
Regulatory considerations for the life cycle of medicinal
oxygen
For any further information or request, please send an email to the Norms and
Standards for Pharmaceuticals (NSP) Team at WHO, at email [email protected].
Contents
Abbreviations 477
1. Introduction 477
2. Purposes 479
3. Scope 479
4. Glossary 480
5. Life cycle of medicinal oxygen from production to patient 482
6. Legal and regulatory considerations for medicinal oxygen 485
6.1 Role and responsibilities of the national regulatory authority 487
6.1.1 Requirements for market authorization 489
6.1.2 Medicinal oxygen to be placed on the market 492
6.1.3 Medicinal oxygen exempted from market authorization 492
6.1.4 Documentation requirements relating to distribution 492
7. Considerations for assuring quality of medicinal oxygen 493
7.1 Large-scale production of medicinal oxygen 494
7.2 Licensing and inspection of establishments for medicinal oxygen 494
7.3 Post-licensing inspection of medicinal oxygen establishments 495
7.4 Storage and distribution of medicinal oxygen 495
7.4.1 Medicinal oxygen cylinder storage 496
7.5 Regulatory inspections 497
7.5.1 Inspection of medicinal oxygen manufacturers 497
7.5.2 Inspection of distributors 497
7.6 Importation of medicinal oxygen 498
7.7 Quality control testing 498
7.7.1 Important factors for quality control testing 499
7.7.2 Quality control processes 500
7.7.3 Risk analysis and control 502
7.7.4 Control of the finished product 502
7.7.5 Stability testing and expiry considerations 502
7.7.6 Cylinders and pressure regulators 503
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8. Post-authorization requirements 503
8.1 Quality monitoring 503
8.2 Vigilance system for medicinal oxygen 503
8.3 Post-approval changes or variations 503
8.4 Renewal of licence to manufacture medicinal oxygen 504
8.5 Withdrawal or suspension of approval or licence to manufacture medicinal
oxygen 504
9. On-site production of medicinal oxygen 504
9.1 Regulatory framework for the on-site production and oversight of medicinal
oxygen: roles, activities and compliance 506
9.2 Responsibilities of the qualified personnel designated by the health care facility 508
References 509
Appendix 1 Manufacturing of medicinal oxygen 512
Appendix 2 Requirements for medicinal oxygen authorization 518
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Abbreviations
GMP good manufacturing practices
GSDP good storage and distribution practices
NRA national regulatory authority
PSA pressure swing adsorption
QMS quality management system
VPSA vacuum pressure swing adsorption
VSA vacuum swing adsorption
WHO World Health Organization
1. Introduction
Medicinal oxygen is a lifesaving and critical therapeutic gas, with no substitutions
in the treatment and prevention of hypoxaemia and hypoxia. It plays a vital role
in a wide range of clinical settings, from intensive care and emergency medicine
to home-based therapy. Its use is especially important in the care of newborns,
children with pneumonia, surgical and trauma patients, and vulnerable
populations, such as elderly people and pregnant women. Recognizing its
essential role, the World Health Organization (WHO) includes medicinal oxygen
in its Model List of Essential Medicines (1), emphasizing that it has no effective
substitute in the treatment of respiratory failure (2).
Oxygen for use in health care facilities40 can be obtained in several forms:
medical liquid oxygen, produced through cryogenic distillation and stored in
cryogenic tanks before being vaporized for use; compressed medicinal oxygen,
filled into high-pressure cylinders and connected to manifold systems; and on-
site oxygen production using generator plants, such as pressure swing adsorption
(PSA), vacuum swing adsorption (VSA), or vacuum pressure swing adsorption
(VPSA), which extract oxygen from ambient air (3). Each source requires
suitable infrastructure, reliable power and trained personnel to ensure safe and
continuous delivery of oxygen to patients.
When intended for therapeutic, prophylactic (prevention of hypoxia
during and after surgery by maintaining oxygen saturation and prevention of
altitude sickness above 3000 meters), diagnostic, or other medical purposes,
medicinal oxygen is regulated as a medicinal product. As such, it must meet the
40
Includes hospitals, clinics or similar facilities that provide patients with their health care needs.
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same minimum standards for quality, safety and efficacy as other pharmaceutical
products. Medicinal oxygen achieves its therapeutic effect primarily through
a pharmacological mechanism – by increasing the partial pressure of oxygen
in blood and tissues. To ensure patient safety, its production, handling and
distribution must comply with good manufacturing practices (GMP) and be free
from contaminants such as water, carbon monoxide, sulfur dioxide, hydrocarbons
and particulates.
Oxygen is available in the market for industrial and medical uses, but these
are not interchangeable. Medicinal oxygen is different from industrial oxygen in
purity and quality, which is influenced by a robust manufacturing process and
testing controls. Medicinal oxygen must be manufactured under GMP conditions
and tested for compliance with pharmacopoeial specifications, including identity,
purity and assay. In contrast, Industrial oxygen is not subject to the same purity,
testing or contamination controls, and may contain harmful substances such
as hydrocarbons, particulates or other industrial residues, making it unsafe for
medical use. Regulatory systems must enforce strict segregation in production,
sourcing, labelling and distribution to prevent the inadvertent or inappropriate
use of industrial-grade oxygen for medical purposes.
Medicinal oxygen can be produced through two main methods: large-
scale industrial manufacturing and on-site generation. Large-scale production
often employs cryogenic distillation of ambient air to achieve high-purity liquid
oxygen, which is then stored and distributed via cylinders or cryogenic tanks,
and compressed medicinal oxygen, produced by compressing liquid oxygen
and vaporizing it to produce a high-pressure gas, which is then filled into high-
pressure gas cylinders. On-site generation, typically via oxygen generator plants
such as PSA technology, produces the gas by removing the nitrogen from ambient
air using molecular sieves. It provides a reliable source of oxygen directly at health
care facilities. While PSA systems are predominantly used for immediate patient
WHO Technical Report Series, No. 1067, 2026
care, they can also be employed for cylinder filling, provided that appropriate
quality and safety standards are met. National regulatory frameworks should not
unduly restrict such practices when adequate oversight is in place.
Despite its classification as an essential medicine, regulatory oversight of
medicinal oxygen remains inconsistent globally. A WHO desk review revealed
that only 80 out of 194 Member States currently regulate medicinal oxygen
as a medicinal product. In many low- and middle-income countries, national
regulatory authorities (NRAs) either lack legal frameworks for oxygen or do not
actively enforce them. This regulatory gap poses serious risks to patient safety
and contributes to unreliable oxygen access in critical settings.
To address these gaps, WHO has developed a regulatory consideration
document covering the production, distribution, storage and delivery of medicinal
oxygen. This document complements existing guidance, including WHO
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publications, The International Pharmacopoeia (4), and other relevant resources,
to support the development of robust regulatory systems for medicinal oxygen.
A structured approach is essential for effective regulation. NRAs are
encouraged to carry out gap analyses in collaboration with relevant stakeholders,
integrating best practices from established regulatory systems and adapting them
to their local context. This will help identify key priorities and requirements.
Developing detailed implementation plans, which include clear transition
periods, action roadmaps, timelines and deliverables, will be critical for ensuring
regulatory compliance and securing a consistent and reliable supply of medicinal
oxygen. Whereas medicinal oxygen intended for administration to a patient is
regulated as a medicinal product, the associated administration equipment may
be regulated as a medical device, depending on the equipment.
2. Purposes
This regulatory consideration document provides recommendations for NRAs on
the oversight of medicinal oxygen throughout its life cycle, covering production,
quality control, storage, distribution and post-market activities. It also aims to
support manufacturers, importers and distributors in understanding the regulatory
requirements needed to ensure that medicinal oxygen consistently meets established
quality and safety standards and is effectively delivered to patients.
3. Scope
The document outlines a regulatory framework for the entire life cycle of
medicinal oxygen, including pre-market activities such as production and
quality control, as well as post-market activities such as market surveillance and
vigilance. It focuses on medicinal oxygen and its primary packaging, including
container closures and valves. Permanently affixed valves or integrated pressure
regulator assemblies that are not intended for removal are considered part of the
authorized medicinal product and fall within the scope of this guidance.
Also, the document outlines recommendations for medicinal oxygen
produced on a large scale for commercial distribution and for oxygen
manufactured or handled at health care facilities for use with their patients.
It does not cover regulatory requirements for medicinal oxygen produced
at home for personal use. Nonetheless, the principles outlined here may be applied
in such contexts to ensure that home-generated oxygen is suitable for its intended
use and meets appropriate quality standards. In addition, the recommendations
in this document exclude oxygen manufactured for industrial purposes.
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4. Glossary
active substance gas. Any gas intended to be an active substance for a medical
product or medicinal gas (5).
authorized person. The person recognized by the national regulatory authority
as having the responsibility for ensuring that medicinal oxygen made available
to the end user has been manufactured, tested and approved for release in
compliance with the laws and regulations in force in that country (6).
distribution. Procuring, purchasing, holding, storing, selling, supplying,
importing, exporting or movement of pharmaceutical products, with the
exception of dispensing or providing pharmaceutical products directly to a
patient or their agent (7).
distributor. Any natural or legal person in the supply chain who, on their own
behalf, furthers the availability of medicinal oxygen to the end user (8).
importation. The act of bringing or causing to be brought any goods into a
customs territory (national territory, excluding any free zone) (7).
importer. An individual or company or similar legal entity importing or seeking
to import a medical product. A “licensed” or “registered” importer is one who has
been granted a licence for the purpose (9).
manifold. Equipment or apparatus designed to enable one or more gas containers
to be emptied or filled at the same time (10).
manufacturer. A company that carries out operations such as production,
packaging, repackaging, labelling and relabelling of pharmaceuticals (5).
manufacturing. Manufacture consists of the operations of division or distribution
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and filling into dedicated pharmaceutical and medicinal packaging. Packaging is
often automated and may include prior modification of the physical state of the
gas (vaporization by heating of liquefied gas and compression) (7).
market surveillance. The activity carried out by authorities to ensure that
products on the market conform to the applicable laws and regulations and
comply with existing requirements. Market surveillance covers a full range of
actions, including the monitoring and control of the market and, where necessary,
the imposition of corrective measures and penalties. It involves close contact of
authorities with stakeholders, consumers and consumer organizations (11).
medical device. Any instrument, apparatus, implement, machine, appliance,
implant, reagent for in vitro use, software, material or other similar or related
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article intended by the manufacturer to be used, alone or in combination, for
human beings for one or more of the specific medical purposes of:
■ diagnosis, prevention, monitoring, treatment, or alleviation of
disease;
■ diagnosis, monitoring, treatment, alleviation of, or compensation
for an injury;
■ investigation, replacement, modification or support of the anatomy
or physiological process;
■ supporting or sustaining life;
■ control of conception;
■ cleaning, disinfection, or sterilization of medical devices;
■ providing information by means of in vitro examination of
specimens derived from the human body;
■ that which does not achieve its primary intended action by
pharmacological, immunological or metabolic means, in or on the
human body, but which may be assisted in its intended function by
such means (8).
medicinal oxygen.41 Medicinal oxygen is an essential medicine used for
therapeutic purposes. It is defined as oxygen that meets the purity standards set
forth by a pharmacopoeia (for example, The International Pharmacopoeia, United
States Pharmacopeia, or European Pharmacopoeia) and is intended for human
use in medical applications. Medicinal oxygen gas is a finished product that has
undergone all stages of production and quality control, including packaging
in its final container and labelling. Medicinal oxygen gas product is released
to the market by an authorized person and can be used directly by health care
professionals or by the patients themselves. Medicinal oxygen can be presented
as a medicine, but also as an active substance and as a service product from an
oxygen concentrator.
national regulatory authority. A government body or other entity that exercises
a legal right to control the use or sale of medical products within its jurisdiction,
and that may take enforcement action to ensure that medical products marketed
within its jurisdiction comply with legal requirements (8).
post-market surveillance for medicines. The science and activities related to
the detection, assessment, understanding, and prevention of adverse effects
41
In some jurisdictions, medicinal oxygen is used interchangeably with medical oxygen. For the purpose of
this document, both terms refer to the same product.
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or any other medicine- or vaccine-related problem. Essentially, post-market
surveillance ensures the safe use of medicines by monitoring their effects
throughout their life cycle (12).
production. All operations involved in the preparation of a pharmaceutical
product, from receipt of materials, through processing, testing, packaging, and
repackaging, labelling, and relabelling, to completion of the finished product (13).
purity standard. Medicinal oxygen must meet the purity requirements specified
by the relevant pharmacopoeia. For example, at least 99.5% by cryogenic
distillation or oxygen 93% by oxygen generator plants (which contains not
less than 90% and not more than 96% volume in volume (v/v) of oxygen, the
remainder consisting mainly of argon and nitrogen) (4).
5. Life cycle of medicinal oxygen from
production to patient
Regulatory considerations include understanding the linked processes and
responsibilities that underpin the effective management of medicinal oxygen
throughout its life cycle.
Table A10.1 provides an overview of the key stages in the life cycle of
medicinal oxygen, from production to patient administration. It highlights the
critical activities, stakeholders involved, and relevant considerations at each stage
to ensure the quality and purity of medicinal oxygen.
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Table A10.1
Stages in the medicinal oxygen life cycle: from production to patient administration
Life cycle Who? Legislation Responsibility How Examples of Role of the
standards and regulator
norms
Manufacturing
Active Manufacturer Medicine law Manufacturer Cryogenic GMP for ✓ Inspection
substance gas distillation medicinal
supplier gases (5, 6)
Manufacturing Manufacturer Medicine law Manufacturer QMS, GMP ✓ Manufacture authorization
site ✓ Licensing
✓ Inspection
(1, 2, 10)
Health care Designated Health policy Pharmacist Production via GMP (1, 2) ✓ Licensing
facility personnel Medicine law oxygen generator GSDP (13) ✓ Inspection
plants: PSA, VSA,
VPSA
Oxygen distribution
Distribution, Manufacturer, Medicine law Manufacturer, Tanks and tankers, GSDP (13) ✓ Market
import distributor importer or cylinders ISO authorization
distributor ✓ Inspection
✓ Licensing
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Table A10.1 continued
WHO Expert Committee on Specifications for Pharmaceutical Preparations Fifty-ninth report
Life cycle Who? Legislation Responsibility How Examples of Role of the
standards and regulator
norms
Health care facility
Oxygen Pharmacist Medicine law Pharmacist, Cylinders, medical WHO guidance ✓ Inspection
delivery Medical devices engineer, gas pipeline (14, 15) ✓ Surveillance
regulation nurses system, pressure ISO
valves, nozzles
Receiving and Pharmacist Medicines law Pharmacist Tanks, cylinder WHO guidance ✓ Inspection
storage (15)
ISO
Oxygen Clinicians, Medicine law Prescriber and Administered via WHO guidance ✓ Inspection of
administration nurses, Health policy health care nasal cannula, (14, 15) clinical practices
to patient anaesthetists, provider face mask, non- ISO ✓ Pharmacovigilance
Clinical practice
respiratory rebreather mask,
standards ✓ Clinical
therapists or ventilator
surveillance
GMP = good manufacturing practices; GSDP = good storage and distribution practices; ISO = International Organization for Standardization; QMS = quality management system.
Note: Examples of applicable ISO standards for medicinal oxygen regulation and use include the following.
• ISO 15001:2010. Anaesthetic and respiratory equipment – Compatibility with oxygen.
• ISO 8573-1:2010. Compressed air – Part 1: Contaminants and purity classes.
• ISO 7396-1:2016. Medical gas pipeline systems – Part 1: Pipeline systems for compressed medical gases and vacuum.
• ISO 10156:2017. Gas mixtures – Determination of fire potential and oxidizing ability for the selection of cylinder valve outlets.
• ISO 20421-1:2018. Cryogenic vessels – Large transportable vacuum-insulated vessels – Part 1: Design, fabrication, inspection and testing.
• ISO 10524-1:2018. Pressure regulators for use with medical gases – Part 1: Pressure regulators and pressure regulators integrated with flow-metering devices.
• ISO/TR 24971:2020. Medical devices – Guidance on the application of ISO 14971.
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6. Legal and regulatory considerations
for medicinal oxygen
The regulatory framework for medicinal oxygen should follow a similar approach
to that of medicines, ensuring comprehensive regulation of the entire life cycle of the
product from development and approval to market entry and patient availability.
Although medicinal oxygen shares many characteristics with medicines, it also
presents unique considerations (such as its physical form, production process and
delivery systems) that may require adaptations within regulatory frameworks.
National law should guide regulation of medicinal oxygen and, in this context,
national medicines legislation should form the basis for regulation. Where not
already established, national frameworks may consider explicitly classifying
medicinal oxygen as a medicinal product under pharmaceutical legislation to
ensure appropriate regulatory oversight. The law should empower the NRA to
license establishments and oversee all aspects of medicinal oxygen, including
initial authorization, renewal, and ongoing compliance monitoring through
inspections and reporting mechanisms. The NRA should have the legal power
and resources to ensure that all medicinal oxygen produced meets minimum
quality assurance standards and complies with pharmacopoeial requirements
(for example, The International Pharmacopoeia, United States Pharmacopeia, or
European Pharmacopoeia) for quality and purity. The ministry of health must
prioritize investing in and strengthening NRA capacity, rather than substituting
its role in regulating medicinal oxygen. It is important that medicinal oxygen
be clearly defined within law or regulations to establish its regulatory status and
ensure appropriate application of pharmaceutical oversight mechanisms. The
definition should differentiate between industrial or non-medicinal oxygen and
the oxygen intended for medical purposes, emphasizing the intended use of the
latter. It should also encompass aspects such as purity, quality, delivery systems to
health care facilities, and proper storage conditions. The legal definition may also
refer to specifications outlined in relevant pharmacopoeias and WHO guidance
to ensure alignment with internationally recognized standards.
High-level requirements should be included within the laws and
regulations, ensuring they align with the guiding principles of applicable
legislation. The law should prioritize safety, quality, purity and oversight, treating
medicinal oxygen with the same level of care and compliance with specifications
as medicines. Given its critical role in patient care, regulation of medicinal
oxygen should address its unique characteristics, including its associated risk of
fire, specific handling requirements, and the risks posed by impurities, through a
structured risk-based regulatory approach that informs oversight, inspection and
mitigation measures. Additionally, because medicinal oxygen is often delivered
through specialized equipment such as oxygen concentrators and delivery systems,
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which are regulated as medical devices, and through pressure equipment such as
cylinders, the regulatory framework should include requirements to ensure these
components meet applicable safety standards, undergo regular inspections, and
function properly to prevent failures and adverse events (Fig. A10.1).
Medicinal oxygen regulations should address, at a minimum, the
following:
■ regulatory requirements for production facilities and equipment;
■ quality control processes, including testing for purity and
contamination;
■ proper labelling and packaging to guarantee safe handling and use;
■ regulatory oversight procedures, including inspection and approval
mechanisms;
■ post-market surveillance.
Fig. A10.1
Legal and regulatory framework for medicinal oxygen
National medicines law to guide
Product-related requirements
regulation of medicinal oxygen
• State legal definition and scope of Examples of regulatory requirements
regulation include:
• Full life cycle regulatory oversight • compliance with required
• Incorporate into law risk-based standards
requirements to address the • special storage and transportation
uniqueness of oxygen conditions
• Define roles and responsibilities • packaging and labelling
of medicinal oxygen stakeholders • batch release testing requirements
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Regulatory documentation System-related requirements
• The law should mandate the NRA • GMP/QMS-based quality system
to develop and enforce medicinal for consistent safety and purity in
oxygen regulations, guidelines, manufacturing, importation and
standard operating procedures, distribution
and technical standards (WHO • Defined roles for market
and relevant pharmacopoeia) authorization holder,
• Enforce compliance with manufacturers, distributors, other
regulatory requirements on stakeholders
medicinal oxygen • Strong market surveillance and
vigilance for post-market safety
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The law should require the licensing of manufacturers, importers and
distributors interested in engaging in production, importation, exportation or
distribution of medicinal oxygen. The legal framework should also define the
roles and responsibilities of all stakeholders, including NRAs, manufacturers,
importers, distributors and health care facilities when medicinal oxygen is
manufactured on site. It should establish a structure that facilitates collaboration
across multiple agencies, ensuring that various aspects of medicinal oxygen
regulation, such as purity, safety and quality, are effectively managed and
monitored by relevant authorities. These guidelines should be regularly
reviewed and updated to align with WHO and other international standards, as
applicable. In addition, detailed guidelines should be provided to stakeholders to
clarify aspects of medicinal oxygen, such as production, storage, handling and
monitoring. The guidelines should address the regulatory components of both
pre-market and post-market authorization and logistical aspects. They should be
reviewed regularly and aligned with international best practices, as applicable.
It is recommended that the NRA oversee and conduct post-market
surveillance activities, thus ensuring that manufacturers adhere to the necessary
regulations and that proper mechanisms for monitoring, sampling and testing,
reporting, and addressing adverse events are in place. Additionally, the legal
framework should include provisions to authorize the NRA to adopt the principles
of reliance and recognition pathways and leverage decisions, including regulatory
decisions on medicinal oxygen made by competent authorities or institutions in
other jurisdictions, where appropriate. While reliance can facilitate faster access
to medicinal oxygen and support efficient use of resources, the NRA should
nonetheless retain full accountability for all final regulatory decisions.
Note: The regulatory authority is expected to carry out all core functions to ensure
the effective regulation of medicinal oxygen, including issuance of licences;
issuance of marketing authorization; regulatory inspections defining the roles and
responsibilities of relevant stakeholders; strengthening interagency collaboration;
providing clear regulatory guidelines to guide regulation of the entire life cycle of
medicinal oxygen; implementing post-market surveillance activities; and adopting
principles of reliance and recognition to streamline regulatory processes.
6.1 Role and responsibilities of the national regulatory authority
The NRA should have functions and powers to implement, enforce and regulate
all matters relating to medicinal oxygen in compliance with good regulatory
practices (16). The NRA shall ensure the safety, quality and efficacy of the
medicinal oxygen through authorization and inspection activities. This should be
achieved through evaluation of scientific data, on-site inspections, and laboratory
testing on medicinal oxygen prior to market authorization. Table A10.2 outlines
the key roles and responsibilities of NRAs in regulating medicinal oxygen.
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Table A10.2
Roles and responsibilities of the NRA in medicinal oxygen regulation
Regulatory function Key responsibilities and activities
Market authorization • Define medicinal oxygen as a medicinal product, detailing
its specific characteristics, such as form, purity, production
process, distribution pathways and appropriate storage.
• Outline the regulatory principles applicable to medicinal
oxygen within the broader context of medicine regulation.
• Align national regulatory requirements, such as those
recommended by WHO, to ensure consistency, facilitate
global market access, and promote reliance and
recognition of regulatory decisions across countries and
regions.
• Publish the decision on medicinal oxygen as a medicinal
product.
• Publish technical dossier requirements for medicinal
oxygen.
• Establish or adopt internationally harmonized
specifications for medicinal oxygen.
• Establish requirements for market authorization
of medicinal oxygen applications and licensing of
establishments.
• Establish requirements for medicinal oxygen labels,
labelling and packaging.
• Develop guidance and guidelines to assist the industry to
comply with the regulatory requirements.
Inspection and • Describe the key steps involved in the production, quality
enforcement control and distribution of medicinal oxygen, highlighting
the associated regulatory requirements at each stage.
• Establish or adapt internationally harmonized
WHO Technical Report Series, No. 1067, 2026
specifications for GMP and good storage and distribution
practices (GSDP) for medicinal oxygen.
• Establish requirements for storage and transportation and
ensure cylinders and piping in storage and distribution of
medicinal oxygen meet the applicable standards.
• Conduct regular inspections to ensure ongoing regulatory
compliance.
• Conduct on-site inspection of manufacturing sites and of
importers and distributors.
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Table A10.2 continued
Regulatory function Key responsibilities and activities
Post-market • Ensure robust mechanisms for post-market surveillance to
surveillance monitor the product’s safety, quality and efficacy.
• Designate testing laboratories and set regulatory
requirements to ensure their effective functioning.
• Establish systems for tracking and reporting post-market
surveillance and vigilance.
• Establish requirements for reporting and documentation of
adverse events.
• Establish requirements for handling complaints, including
reporting compliance status and any deviations to NRAs,
and recalls.
6.1.1 Requirements for market authorization
Due to its peculiarity, medicinal oxygen may be presented either as a finished
medicinal product or as an active substance. It is recommended that the NRA
grant marketing authorization to manufacturers of medicinal oxygen to ensure
their legal accountability for the product’s quality, safety and efficacy throughout
its entire life cycle. The regulatory framework should set out clear requirements
that manufacturers must comply with before bringing medicinal oxygen to
market. The market authorization process should include requirements related
to registration of medicinal oxygen.
Applications submitted for market authorization of medicinal oxygen
should contain, at a minimum, information describing the manufacturing
process, its control, packaging, the specification of medicinal oxygen to be
authorized, the name and address of the applicant, the name and address of
the facility or facilities where the medicinal oxygen is or will be manufactured,
and any other information as prescribed by the NRA. It is the responsibility of
applicants to provide necessary information in accordance with the regulatory
requirements to allow the NRA to make regulatory decisions concerning
market authorization. The NRA should establish clear guidelines for the types
of authorizations required for medicinal oxygen, ensuring the quality, safety
and efficacy of the product.
Documents required for market authorization
Documentation requirements for market authorization should contain the
following (10).
■ Information and description of physical chemical characteristics of
the active substance gas.
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■ Description of the product, including the name of the gas, physical
form, name and address of the manufacturer, pressure and
concentration, packaging (for example, cylinder, mobile cryogenic
container or fixed cryogenic container).
■ Data demonstrating the stability of medicinal oxygen during the
various stages of the product life cycle as a function of its conditions
of storage, transport, and handling (may be bibliographic data), or
justification for not performing new studies, supported by literature
references or pharmacopoeial standards.
■ Description of the containers or cylinders, specifying the capacity,
filling pressure of the container or cylinder, type of material used
for the container, and the reference code for the manufacturer and
suppliers of the containers.
■ Capacity and working pressure, valves and valve assembly, including
regulators, tubing and the type of valves, their reference codes,
the suppliers and the type of valve outlet connection should be
stated. The quality of the valve, regulators and tubing may impact
the quality of medicinal oxygen being delivered, and therefore
regulatory oversight is recommended for these products.
■ The principle of the manufacturing method chosen by the
manufacturer should be explained and justified.
■ Information to support the compatibility and suitability of
medicinal oxygen gas with packaging materials and delivery
mechanisms. The following considerations should be made:
– known compatibility of the materials of the cylinders, including
information from literature, standards and long-term use of such
materials;
WHO Technical Report Series, No. 1067, 2026
– use of new materials and their gas compatibility (for example,
alloys for container shells, plastic materials for valves);
– choice of new packaging components, especially the valve
connections, the most fragile part of the cylinder, especially in
terms of airtightness;
– container filling at a pressure not previously used in the
medicinal field for this type of container, with justification
required to demonstrate safety, suitability and compliance with
regulatory standards;
– suitability of the container capacity;
– diversity of cylinders used, if they have quite different capacities
and dimensions and are of different materials.
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■ Information and reports of process validation and evaluation of
manufacturing process.
■ Control of quality:
– specifications;
– details and information on analytical methods or procedures;
– batch analyses.
■ Labels and labelling requirements: the NRA must provide the
labelling requirements for a medicinal oxygen on its final use
containers, including a warning statement concerning the use of
the medicinal oxygen and appropriate directions and warnings
concerning storage and handling. The label should include at least
the following:
– product name;
– dosage form: medicinal oxygen;
– name of active substances;
– purity, pressure, temperature (for liquid oxygen);
– batch or lot number;
– manufacturing date;
– shelf-life, where applicable (for example, oxygen filled in
cylinders for commercial supply);
– storage conditions;
– name and address of manufacturer;
– safety label: precaution or warning;
– pack size (unit, volume).
■ Transportable pressure equipment (cylinders), including pressure
rating, cylinder material, valve type, fill volume and safety markings.
■ Fixed pressure equipment (cryogenic tanks), including tank
capacity, maximum allowable working pressure, insulation type and
operational safety instructions.
■ Post-market surveillance: as part of the application for market
authorization, the manufacturer of medicinal oxygen should
include a comprehensive post-market surveillance plan. This plan
should outline the approach for monitoring product performance
and identifying any adverse events once the product is on the
market. It should also detail mechanisms for incident reporting
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and provide clear guidance on managing any issues related to the
use of medicinal oxygen, in line with practices for other medicinal
products.
■ In the case of cylinder bundles, the material and dimensions, for
example, internal diameter used for the loop, should be provided.
The outlet valves and the suppliers should be provided.
■ For therapeutic claims of medicinal oxygen that go beyond
conventional oxygen therapy, clinical trial documentation should be
submitted, and, where applicable, prior clinical trial documentation
should be provided.
6.1.2 Medicinal oxygen to be placed on the market
Medicinal oxygen intended to be placed on the market must undergo an
assessment process to ensure compliance with regulatory requirements. This
process can only apply to medicinal oxygen manufactured on a large scale42 for
commercial distribution. Liquid oxygen supplied in bulk, as well as cylinders
filled commercially from liquid oxygen sources or by operators of medium- and
small-sized standalone PSA, VSA or VPSA plants, fall into this category. The
NRA should be responsible for granting market authorization after verifying that
the manufacturer has met all regulatory requirements. The authorization process
should ensure that the product complies with established quality, efficacy and
safety standards before it reaches health care facilities or patients.
6.1.3 Medicinal oxygen exempted from market authorization
Medicinal oxygen produced and distributed solely for use within a health care
facility and its related satellite facilities, and not intended for external market
distribution, may be exempt from the formal market authorization process.
However, such oxygen must still meet specific regulatory requirements set by the
WHO Technical Report Series, No. 1067, 2026
NRA. These requirements should ensure that oxygen produced within the health
care facility maintains consistent quality, efficacy and safety standards, in line
with the needs of patients within the facility. The NRA should clearly define these
criteria and enforce compliance to safeguard patient health and safety.
6.1.4 Documentation requirements relating to distribution
The delivery of bulk gases in mobile delivery tanks or stationary storage tanks
to hospitals should be clearly detailed in the authorization dossier submitted by
the manufacturer. Additionally, individually filled oxygen cylinders distributed
42
Large-scale manufacturing of medicinal oxygen refers to the industrial production of oxygen in high
volumes using specialized technologies to supply health care facilities and distributors.
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from production sites must include proper documentation and labelling to
ensure traceability, safety and compliance. It is important to avail written
instructions, procedures and records that document all activities relating to the
distribution of medicinal oxygen from the point of production to the point of use.
Documentation should be provided to demonstrate that there will be no mixing
between the bulk oxygen gas and any gases originating from other manufacturers
in the storage tanks intended for the bulk gas.
NRAs should ensure that manufacturers comply with regulatory
requirements for transporting, handling and storing bulk medicinal oxygen. This
includes validating storage systems, using proper equipment and implementing
measures to prevent cross-contamination.
The subsequent distribution or dispensing of medicinal oxygen by third
parties is not typically part of the dossier to be assessed and authorized by the
NRA, as the dossier focuses primarily on product quality, safety and efficacy at
the time of market authorization. However, it is recommended that the NRA
maintain oversight of the distribution process through regular inspections, audits
and reporting requirements. This ensures that third-party distributors adhere to
the necessary quality standards and regulations, safeguarding the integrity of the
medicinal oxygen up to the point of use.
7. Considerations for assuring quality of medicinal oxygen
Regardless of its source, whether produced by large-scale manufacturing facilities,
packaged in different facilities, delivered in various formats, or produced on-site
at health facilities, the quality and purity or concentration of medicinal oxygen
must remain consistent and fulfil the regulatory requirements. This consistency is
vital to ensure that all oxygen delivered to patients meets the necessary therapeutic
specifications, minimizing the risk of adverse events or inefficacy. The NRA
should establish regulatory standards to ensure that medicinal oxygen remains
free from contaminants and maintains the required purity levels throughout its
delivery and use. It is recommended that the NRA ensure that medicinal oxygen
complies with the specification for the assay of the gas as well as the limits for
impurities, as specified in the monograph of The International Pharmacopoeia
(4) and other recognized pharmacopoeias, or national specifications as specified
from time to time where harmonized monographs are unavailable. The NRA
should ensure that manufacturers comply with all regulatory requirements,
including the implementation of rigorous quality assurance measures.
The NRA should carry out an evaluation of scientific evidence, quality
control and quality assurance documentation, and manufacturing practices,
storage, inventory management and distribution, to confirm the conformance
with requirements of safety and quality of medicinal oxygen.
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7.1 Large-scale production of medicinal oxygen
The NRA should oversee production of medicinal oxygen at large-scale
manufacturing facilities to ensure compliance with GMP principles throughout
production activities, including processing, filling, transfilling, purifying,
separating, transferring, packaging and distribution. The specification of medicinal
oxygen should adhere to stringent regulatory requirements, with appropriate
quality control verifications. The WHO guidelines on good manufacturing
practices for medicinal gases serve as a key reference in this context (5).
Facilities intending to manufacture, store, supply or distribute medicinal
oxygen must hold a valid manufacturing licence issued by the NRA. Additionally,
the product should meet all applicable medicine registration requirements, as
prescribed by the NRA.
Continuous production and delivery of oxygen to patient bedsides or
points of use, whether from cryogenic or PSA processes, do not require batch-to-
batch analysis. This exemption is based on the real-time monitoring of process
parameters and online quality controls that ensure the consistency of the delivered
product. NRAs should establish requirements for hospitals to ensure compliance
with safety and quality standards of oxygen distributed in piping networks. These
requirements should include routine testing and monitoring of oxygen at regular
intervals based on perceived risk. Documentation of testing results, maintenance
logs, flow rates and corrective actions should be maintained.
7.2 Licensing and inspection of establishments
for medicinal oxygen
NRAs should establish and enforce requirements for licensing and conducting
risk-based inspection of establishments involved in the production, import and
wholesale of medicinal oxygen. Such requirements should enhance compliance
with best practices in GMP and GSDP as essential components of the medicine
WHO Technical Report Series, No. 1067, 2026
regulatory framework.
Manufacturing licence. A manufacturing licence for medicinal oxygen
should be mandatory, irrespective of:
■ the method of oxygen production (for example, cryogenic
distillation or PSA);
■ the production scale (for example, small, medium, large);
■ the mode of distribution (for example, cylinders);
■ the end users (for example, patients).
Inspection and oversight. The NRA should conduct an inspection
before issuance of the licence and should continue with regular inspections
of establishments to verify their compliance with GMP and GSDP standards.
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This includes ensuring that manufacturing processes, storage, and distribution
systems meet the required quality and safety standards.
Licensing of importers, wholesalers and transporters. Importers,
wholesalers and transporters involved in the distribution of medicinal oxygen
should also be licensed by the NRA. Their operations should be in full compliance
with GSDP before distribution to end users.
7.3 Post-licensing inspection of medicinal oxygen establishments
The NRA should ensure that licensed establishments undergo regular risk-based
inspections to evaluate their continued compliance with QMS, GMP, GSDP and
other regulatory requirements. Post-licensing inspections should be periodically
conducted by the NRA and when significant changes are proposed to the licensed
operations. Significant changes may include alterations to production methods,
site changes, new delivery formats or major equipment replacements. These
inspections should take place before approval to ensure that any modifications to
the production process, storage conditions or distribution practices comply with
regulatory standards. The NRA should establish requirements for any production
changes and specific notification requirements.
7.4 Storage and distribution of medicinal oxygen
Manufacturing facilities where medicinal oxygen is produced should be equipped
with suitable storage areas that meet the necessary security provisions. These
facilities must comply with the essential principles of GSDP. The WHO Good
storage and distribution practices for medical products (13) should be referenced
to ensure adherence to best practices for the safe storage and distribution of
medicinal products.
The NRA should enforce implementation of GSDP guidelines in all licensed
establishments through regular inspections and other enforcement activities. The
NRA should ensure that personnel responsible for handling, moving or using
medicinal oxygen should be adequately trained and deemed competent to perform
these tasks under proper supervision. It is essential that written policies and standard
operating procedures for the storage and supply of medicinal oxygen are developed
and followed, and that their implementation is subject to regulatory oversight.
In cases where medicinal oxygen is supplied into bulk storage tanks, it
should be transferred from the tanks to the facility through a medical gas pipeline
system (17).43 This pipeline system may include vacuum systems, anaesthetic
gas scavenging systems, medical air, and nitrous oxide. The NRA should ensure
43
When the medical gas pipeline system is defined as a medical device, it should comply with the requirements
for its design in accordance with the ISO standard (ISO 7396-1:2016. Medical gas pipeline systems – Part 1:
Pipeline systems for compressed medical gases and vacuum) or the equivalent national standard.
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that all pipeline systems comply with the required standards and regulations
to guarantee the safety and integrity of the oxygen supply. The NRA should
ensure that all manual or automatic filling systems, including equipment used
to transport and transfill, comply with the required standards and regulations
to guarantee the safety of the oxygen supply. These systems must comply with
standards for design, installation, validation, verification and ongoing operational
management to ensure safe and efficient distribution of medicinal oxygen (18).
While medicinal oxygen itself is chemically stable and may not degrade over
time, the storage vessels (for example, cylinders) are subject to requalification
and certification expiry, which must be clearly indicated on the label.
7.4.1 Medicinal oxygen cylinder storage
Regulatory requirements should be established for the handling and storage
of medical gas cylinders, whether used as a primary or secondary source of
medicinal oxygen, for example when serving as an alternative to a medical gas
pipeline system. When not in immediate use, all gas cylinders should be stored
under the conditions highlighted in Table A10.3.
Table A10.3
Storage conditions for medicinal oxygen cylinders
Category Storage conditions
Designated Medicinal oxygen cylinders should be kept in a designated storage
storage area area appropriately marked with status labels, safety signs and
warning notices indicating the gas and any potential hazards. There
should be segregated areas for full, empty and quarantined cylinders
indicating the gas and any potential hazards, in accordance with ISO
7396-1 or equivalent local standards.
WHO Technical Report Series, No. 1067, 2026
Ventilated The storage area should be clean, well ventilated, and away from any
and safe sources of ignition, excessive temperatures, flammable materials, or
environment incompatible products (such as food), to minimize safety risks.
Security and The storage location should be secure, with access strictly controlled to
access control prevent unauthorized handling and to ensure the safety of personnel.
Clean and Cylinders should be stored under cover, ensuring that the
protected environment is clean, dry and suitable for use in a medical setting,
storage while still maintaining proper ventilation. They should be kept
secured with racks or chains and fitted with valve protective devices
such as valve caps or valve guards. Cylinders should be inspected
regularly for damage, corrosion and valve integrity, and requalified
as per the manufacturer’s and regulatory requirements.
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7.5 Regulatory inspections
Regulatory inspections are essential to verify that medicinal oxygen establishments
comply with applicable standards, thereby ensuring that patients receive safe and
high-quality medicinal oxygen. The NRA should establish a risk-based inspection
system, including development of guidelines and standard operating procedures
for internal and external stakeholders. The system should ensure that all entities
involved in manufacturing, distribution or importation adhere to regulatory
requirements and maintain the integrity of the medicinal oxygen supply chain.
7.5.1 Inspection of medicinal oxygen manufacturers
The NRA should carry out risk-based inspections of medicinal oxygen
manufacturers at various stages of the product life cycle to ensure consistency
in quality and purity. Additionally, the NRA should require manufacturers to
implement strong quality control systems to ensure that medicinal oxygen
consistently meets established regulatory requirements. For domestic
manufacturers, this encompasses a comprehensive site inspection, including
assessment of the QMS and verification of compliance with GMP standards. For
overseas manufacturers, the NRA should ensure that a valid GMP compliance
certificate is issued and recognized, in accordance with international standards.
Where necessary, the NRA should conduct its own inspection of foreign
manufacturing sites. Where possible, the NRA may rely on certificates issued
by regulatory authorities recognized under mutual recognition or reliance
agreements, provided appropriate verification is conducted.
Inspection outcomes should inform decisions related to market
authorization, licensing of manufacturing and storage sites, and ongoing
regulatory monitoring. The NRA may reference the Pharmaceutical Inspection
Co-operation Scheme aide-memoire on inspection of medicinal gases (19) and
the WHO good manufacturing practices for medicinal gases (5) for inspections to
guide this process.
7.5.2 Inspection of distributors
The NRA should ensure that every importer and wholesaler responsible for
placing medicinal oxygen on the market follows GSDP (13). This includes
ensuring that medicinal oxygen is stored, distributed and handled appropriately
under controlled conditions (for example, adequate ventilation, temperature
management, and segregation of empty and full cylinders). The NRA should
carry out inspections of distributors to verify their adherence to GSDP standards
and to ensure that the integrity of the product is maintained throughout the
distribution process, and should carry out spot checks for quality of the product.
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7.6 Importation of medicinal oxygen
When medicinal oxygen is imported, the manufacturer in the country of origin is
responsible for holding the market authorization or may authorize a representative
to act on their behalf. The authorized party should also ensure that post-market
surveillance obligations are fulfilled in the importing country. The importer is
required to apply for market authorization to the NRA, which then evaluates the
application to determine whether it complies with national regulations. The NRA
should prescribe the designated ports of entry for importation or exportation of
medicinal oxygen.
The NRA should follow the standard process applicable to imported
medicinal products, which includes the following:
■ assess documents for market authorization and, where appropriate,
rely on or recognize approvals issued by trusted regulatory
authorities or WHO-listed authorities;
■ conduct a site inspection to assess and license the premises of the
importer, ensuring that the facility meets the required regulatory
and safety requirements for handling and distribution of medicinal
oxygen;
■ verification of importation documents to ensure compliance with
applicable regulations and issuance of import authorization;
■ Inspection and sampling44 of medicinal oxygen consignments at the
designated ports of entry.
7.7 Quality control testing
The NRA should ensure that manufacturers are conducting batch-specific quality
control tests or continuous online analysis for each batch of medicinal oxygen
before release for distribution or consumption (including assay and impurity
WHO Technical Report Series, No. 1067, 2026
analysis) and follow internationally recognized laboratory control requirements.
Any deviations from written specifications, standards, sampling plans, test
procedures or other quality control mechanisms should be appropriately recorded
and justified. The NRA should ensure that medicinal oxygen, which is derived
from ambient air using various oxygen production technologies including PSA
and cryogenic processes, is subject to stringent quality control testing to meet
national and international standards. These standards should encompass quality,
safety, specification, purity, packaging, labelling and identification of the product.
44
NRAs should develop guidelines and standard operating procedures to guide inspection activities at ports
of entry. Sampling and testing may include verification of identity, purity, and compliance with recognized
pharmacopoeia standards .
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Internationally recognized pharmacopoeias, such as The International
Pharmacopoeia, the United States Pharmacopeia and the European Pharmacopoeia,
provide specific monographs for medicinal oxygen. The NRA should ensure that
manufacturers refer to and comply with any of those standards and perform
batch-specific quality control testing before release for medical use, including
testing for purity, contaminants, and compliance with monograph standards.
7.7.1 Important factors for quality control testing
To ensure the quality and safety of medicinal oxygen, the NRA should adopt the
following roles and responsibilities to guide manufacturers in meeting quality
control standards.
1. Medicinal oxygen purity levels
■ The NRA should provide clear guidance on the required oxygen
specifications based on the production method used – whether
cryogenic or PSA systems or other methods. The NRA should ensure
that medicinal oxygen purity levels or oxygen concentration (% O2)45
meet internationally recognized pharmacopoeia requirements. This
purity can vary depending on the production method, using either
cryogenic technology or PSA plants. Medicinal oxygen must meet
extremely high purity standards, with specified minimum oxygen
content and maximum allowable levels of contaminants, such as
moisture, oil, carbon dioxide and carbon monoxide.
■ For oxygen produced via cryogenic distillation process, the NRA
should ensure alignment with the requirement of The International
Pharmacopoeia of a minimum of 99.5% v/v O2.
■ For PSA-produced oxygen, the NRA should adopt and promote
WHO’s interim guidance of 93% ± 3%46 v/v O2 purity as the
minimum acceptable standard (20).
■ Regulatory oversight should include validation of production
methods and regular testing to confirm that oxygen meets the
required specifications.
2. Trace contaminants
The NRA should require manufacturers to implement comprehensive quality
control systems to detect and limit trace contaminants, such as hydrocarbons,
45
Oxygen purity or concentration (% O2) refers to the amount of oxygen present in the final product.
46
The ± 3% tolerance for PSA applies only under validated production and monitoring conditions.
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volatile organic compounds and particulate matter, based on a risk assessment.
The quality and safety of medicinal oxygen can be compromised by even trace
amounts of impurities. Therefore, robust quality control measures should be
implemented to monitor and reduce the levels of potential gas contaminants
to acceptable limits. Regulatory guidelines should emphasize routine testing
for contaminants associated with PSA, VSA or VPSA and cryogenic oxygen
production, including carbon monoxide, carbon dioxide, humidity, sulfur
dioxide, nitrogen oxides and oil. The NRA should establish or adopt detailed
monographs for PSA-produced oxygen to ensure all relevant contaminants are
identified and controlled.
3. Microbial contamination
The NRA should ensure that manufacturers maintain appropriate design and
hygiene standards for oxygen supply and storage systems to prevent microbial
contamination. The NRA should issue guidance requiring manufacturers to
implement practices such as regular cleaning, sanitization and microbiological
monitoring.
Regulatory inspections should include assessment of manufacturers’
compliance with microbial control procedures.
7.7.2 Quality control processes
NRAs are encouraged to enforce national and internationally recognized quality
standards, such as those outlined in The International Pharmacopoeia, the United
States Pharmacopeia and the European Pharmacopoeia, or WHO guidelines
on medicinal oxygen production. The manufacture of medicinal oxygen
should involve procedures to test, monitor and verify quality and consistency
of production operations. This may include in-process control by continuous
monitoring of critical factors such as oxygen purity, flow rates and pressure
WHO Technical Report Series, No. 1067, 2026
levels. The NRA should ensure that in-process control tests are defined and
followed and that manufacturers maintain regular calibration in accordance with
manufacturer instructions and relevant calibration standards (such as ISO 10012)
and maintenance for equipment and instruments. The NRA should also require
manufacturers to maintain control charts or logs for continuous monitoring and
maintain procedures for handling and documenting deviations.
The NRA should set provisions for final product testing to confirm
that the medicinal oxygen meets established purity standards and regulatory
requirements. The testing should ensure that all necessary specifications are met
before each batch or lot of the product is released for distribution.
The NRA should verify availability of written procedures that clearly
outline:
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■ sampling and testing plans that include the number of units per
batch that will be sampled and tested;
■ test methods and acceptance criteria for sampling and testing;
■ corrective actions to be taken if test results fall outside the
specifications.
Note: On-site oxygen generation that continuously feeds a directly connected
piping distribution system by nature may not be batch tested. However, it should
be continuously monitored to ensure that only medicinal oxygen that meets the
required quality and purity standards is administered to patients. The sampling
and testing should be carried out by continuous on-line monitoring.
On-site oxygen is produced continuously and supplied via a medical
gas pipeline system without prior control or release by a responsible person
or releasing officer, which is then administered directly to patients; therefore,
continuous monitoring of quality and purity is mandatory. This ensures that
any out-of-specification product is detected, and the supply can be switched to a
backup source.
Quality control at points of use
The NRA should prescribe the requirements for health care facilities to conduct
quality control analyses on the medicinal oxygen they receive and distribute
within the health care facility supply system. This also includes prescribing the
requirements for distribution devices, such as manifolds, which can affect the
oxygen’s quality and purity. Extensive regulatory oversight should be considered,
since even in pressurized systems, leaks may allow contaminants from the
environment to enter the system, potentially affecting the purity of the oxygen, as
per Graham’s laws of diffusion and effusion (21).
The WHO monograph on medicinal oxygen (4), pharmacopoeias
and other internationally recognized tests provide simple testing methods
for detecting contaminants in oxygen, whether it is produced through PSA
technology or other means. The NRA should recommend that hospitals perform
these tests at the point of use to ensure that the oxygen supplied to patients is free
of harmful impurities.
The NRA should emphasize that these tests, as an additional quality
assurance measure, are essential to ensure the quality of medicinal oxygen provided
to patients. The responsibility for conducting these tests lies with the pharmacist
at the health care facility. If no pharmacist is available, this responsibility may
be assigned to another qualified professional, such as a biomedical engineer, as
specified by the hospital.
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7.7.3 Risk analysis and control
The NRA should enforce the implementation of a comprehensive risk management
strategy to identify potential risks and vulnerabilities in the production, storage
and distribution systems of medicinal oxygen. Manufacturers must ensure that
any evaluation of risks to oxygen quality is based on sound scientific principles,
with risk assessments being documented. To identify potential failure modes,
their causes, and associated risks in the oxygen generation process, the NRA
should encourage the use of risk analysis methods such as failure mode and
effects analysis. The NRA should follow up and verify adequacy of risk mitigation
measures implemented.
7.7.4 Control of the finished product
For finished medicinal oxygen, the product specifications should comply with the
requirements set out in the relevant pharmacopoeial monographs. The control of
the finished product should consist of the control according to the monograph or
using validated methods if shown to be equivalent (identity, assay and impurities).
Specifications should at least include tests for identity, assay and impurities
according to the monograph in the relevant pharmacopoeia, the appearance of
the packages, the labelling, and the content (for cylinders and cylinder bundles).
The control of the filling batch can be performed during packaging (for example,
weight and volume checks) and the control of leak tightness after filling. Controls
should also ensure there is no cross-contamination between different gas types
during filling operations, especially in multigas facilities.
7.7.5 Stability testing and expiry considerations
Medicinal oxygen has unique stability characteristics. Unless explicitly specified
during market authorization, medicinal oxygen does not require a designated
shelf-life, meaning manufacturers may not need to maintain an ongoing stability
WHO Technical Report Series, No. 1067, 2026
programme. Thus, bibliographic data may be sufficient to demonstrate stability.
However, it is essential that containers and closures are verified to be capable
of maintaining the gas at the appropriate pressure before being released for
distribution (22–24). Even in the absence of an expiry date, the condition and
safety of storage vessels must be verified periodically, including hydrostatic
testing for cylinders and pressure monitoring for bulk tanks.
In cases where a manufacturer assigns an expiration date to medicinal
oxygen, this must be supported by stability studies. If an expiration date is
provided for a batch, manufacturers should establish, document and implement
a stability testing programme. Conversely, if no expiration date is assigned to the
medicinal oxygen, supporting stability studies are not required (10).
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7.7.6 Cylinders and pressure regulators
The cylinder or containers and pressure regulators should comply with the
specifications outlined in the existing national or international (ISO) standards
concerning equipment intended to contain and deliver gases. The certificates of
compliance with the applicable standards should be provided by the manufacturer.
The NRA may verify that the cylinders, manifolds and regulators have undergone
appropriate testing, inspection and certification prior to use or distribution. NRAs
should also require that cylinders be evacuated or purged (25) to a specified
pressure before refilling to prevent post-process contamination. NRAs should
require documentation of periodic inspection, pressure testing and recertification
of cylinders in accordance with ISO 9809 (22) or applicable local standards.
8. Post-authorization requirements
8.1 Quality monitoring
The NRA should ensure that manufacturers conduct continuous monitoring
of registered or listed medicinal oxygen through post-market surveillance
activities. Manufacturers, importers and distributors are required to implement
a systematic product complaint handling procedure and maintain appropriate
records. Any quality or safety concerns related to medicinal oxygen should
be promptly reported to the NRA. Furthermore, the NRA should ensure that
these stakeholders have a robust procedure in place to address identified issues,
including corrective and preventive actions.
8.2 Vigilance system for medicinal oxygen
The NRA shall be responsible for ensuring that an appropriate vigilance system
is established to monitor medicinal oxygen, and appropriate action is taken
when necessary. The system and procedures in place should be adequate for
monitoring, handling, evaluating and providing feedback to reporters or health
care providers regarding adverse events. The NRA should ensure that adverse
events are reported within the stipulated timelines, and the minimum required
information for reporting adverse events includes an identifiable reporter, an
identifiable patient, the adverse reaction, and a suspect product (26).
Note: Medicinal oxygen-related adverse events are rare but can be serious
(examples: contamination, pressure failure, equipment interface issues).
8.3 Post-approval changes or variations
The NRA should be alerted to any changes to the approved medicinal oxygen
establishment or product. Such variations may be classified as major, minor or
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notifications (27), with criteria for each category defined according to national
requirements. The NRA must establish clear requirements for handling variations
or changes, consistent with provisions outlined in the national medicinal law and
relevant regulatory guidelines. Provisions should be put in place to ensure that
the approval process for variations does not disrupt the supply chain of medicinal
oxygen, particularly in health facilities. For instance, production should be
allowed to continue while the NRA reviews minor variations.
8.4 Renewal of licence to manufacture medicinal oxygen
The renewal of registration by the NRA should align with the applicable
requirements for the renewal of medicinal products. This process provides an
opportunity to assess whether the manufacturer has fulfilled all commitments
and to ensure the consistency of the approved product, including verification of all
approved variations and ongoing compliance with GMP and QMS requirements.
8.5 Withdrawal or suspension of approval or
licence to manufacture medicinal oxygen
In situations where a manufacturer wishes to withdraw an approved medicinal
oxygen product, the NRA may deregister or delist the product or suspend its
approval or manufacturing licence. This action may also apply to any medicinal
oxygen product deemed approved under medicinal law, if deemed necessary by
the NRA.
Any withdrawal or suspension for reasons other than commercial
considerations should be well documented and appropriately justified, where
applicable.
9. On-site production of medicinal oxygen
WHO Technical Report Series, No. 1067, 2026
Oxygen generator plants within health care facilities may produce medicinal
oxygen for direct delivery through the hospital’s piping system, supported by
a backup manifold. These systems should be subject to regulatory oversight to
ensure compliance with safety, quality and performance standards. The piped
oxygen will reach an area valve service unit and be delivered to the patients’
bedside outlets. Oxygen produced from on-site generation plants can also be
compressed to fill high-pressure medical gas cylinders. Extreme care should be
taken due to risks of fire and contamination.
Production facilities and equipment for on-site oxygen generation
should be designed to meet logistical and environmental needs, especially where
conventional oxygen supply chains are unreliable. Oxygen-generating plants
rely on molecular sieve technology (zeolites) to selectively adsorb and discharge
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nitrogen, allowing oxygen to concentrate for downstream use. While there are
diverse types of oxygen generator plants (for example, PSA, VSA, VPSA) they
operate on the principle of pushing pressurized air through a molecular sieve bed
for nitrogen removal. NRAs should ensure that health care facilities operating
oxygen generator plants possess adequate technical knowledge of their operation
and comply with applicable safety standards and regulatory requirements.
The NRA should verify that timely servicing of PSA technology is
carried out according to the manufacturer’s instructions. Regular maintenance
and timely replacement of components, including valves and filters, are crucial
for ensuring the optimal performance and safety of the oxygen production and
distribution systems.
Additionally, the NRA should enforce requirements for specialized storage
and transport systems, such as cylinders and cryogenic tanks for compressed or
liquid oxygen, made available for use in health care facilities. The NRA should
verify that medicinal oxygen produced by these plants contain no less than 93%
± 3% oxygen derived from ambient air (28).
Specific considerations for on-site oxygen production are as follows.
■ Production may be exempted from formal market authorization
procedures under the medicines law, but still subject to technical
authorization and NRA oversight.
■ Risk-based QMS and GMP are required, tailored to a different scale
compared to industrial manufacturing. The NRA should establish
the requirements for a quality management system for on-site
production of medicinal oxygen, selecting applicable elements from
GMP standards.
■ The responsibility for oversight lies with the (hospital) pharmacist.
■ Production is not intended for commercial scale or placement on
the market.
■ Production is demand driven, dependent on the specific need of
the health care facility. The health care facility involved should
define the quantity of medicinal oxygen to be supplied from on-site
production for the facility.
■ The NRA should oversee production of medicinal oxygen within
health care facilities, including the issuance of manufacturing
authorization. On-site production premises should be subject to
inspection prior to granting authorization, in accordance with
applicable regulatory requirements.
■ Where PSA, VSA or VPSA supply sources are used, each plant must
be provided with a reliable source of electricity that can maintain
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supplies even under single fault conditions. A backup electricity
generator may be required to maintain supplies.
■ Where supply sources are installed at remote locations, a reliable
independent electricity supply source is required for each plant
location.
■ Inadequate sizing of oxygen generator plants can result in reduced
medicinal oxygen purity when the demand exceeds the plant’s
designed flow rate.
■ Continuous analysis: as the medicinal oxygen produced by the
oxygen generator plants is not batched and released prior to it
being fed to the medicinal gas pipeline system, the product must
be continuously analysed for assay and for any contaminant
specified by the relevant pharmacopoeia monograph or potential
contaminant identified during the initial risk assessment.
9.1 Regulatory framework for the on-site
production and oversight of medicinal oxygen:
roles, activities and compliance
The NRA should establish the framework and activities to be regulated within the
supply chain for medicinal oxygen produced on site, outlining the activities that
require regulation at each stage (Fig. A10.2):
■ pre-authorization activities: manufacturing processes, quality
control measures, testing protocols, labelling, packaging and storage;
■ inspection and enforcement: GMP and GSDP requirements for on-
site production;
■ post-authorization activities: monitoring, reporting of adverse
WHO Technical Report Series, No. 1067, 2026
events and surveillance.
Furthermore, the NRA should establish compliance teams within
the NRA, including regulatory, quality assurance and other technical experts
responsible for overseeing these activities. These teams should also coordinate
closely with technical teams within hospitals to ensure effective implementation.
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Fig. A10.2
Overview of activities in the regulation of medicinal oxygen across pre-, during, and
post-authorization stages
NRA
1 Pre-authorization 3 Post-authorization
• Draft and implement GMP 2 Inspection and • Set up systems for adverse
specific to on-site production enforcement event reporting and market
of medicinal oxygen at surveillance
health care facilities • Develop requirements for • Conduct regular audits and
• Establish protocols for storage conditions and inspections of manufacturing
product testing and quality distribution channels within and distribution at health
assurance the health care premises facilities
• Define labelling and • Establish or adapt • Monitor compliance with
packaging requirements to internationally harmonized regulations and take
ensure safety and requirements for GMP and corrective actions as
compliance GSDP of medical oxygen necessary
• Conduct inspections of
on-site production facilities,
importers and distributors
Training and awareness
The NRA should organize training sessions for health care and hospital staff
involved in the medicinal oxygen life cycle to ensure they are informed about and
comply with the regulatory framework. Training should be competency-based
and include simulations or mock inspections. Training programmes should be
regularly updated to reflect regulatory changes and integrate best practices.
Quality control and testing
While the NRA should retain oversight of quality control practices, the
responsibility for establishing and managing testing laboratories should rest with
health care facilities. Each health care facility should be required to implement
a reliable real-time testing system to verify the purity, identity and impurities of
medicinal oxygen.
Documentation and reporting
The NRA should develop comprehensive documentation requirements for all
regulated activities related to on-site production. Systems for regular reporting and
record keeping should be put in place to ensure transparency and accountability
in the production process.
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Monitoring and auditing
The NRA should encourage health care facilities to conduct regular internal
audits to ensure ongoing compliance with regulatory requirements. Health
care facilities should establish procedures for implementing external audits and
inspections conducted by the NRA to verify compliance across the supply chain.
Implementation plan
To ensure seamless and efficient regulation of the on-site production of
medicinal oxygen, the NRA should take a proactive role in establishing an
implementation plan of actions to be undertaken as part of the implementation
to ensure the successful oversight and management of this process. As part of the
implementation plan, the NRA should:
■ identify and compile a list of health care facilities involved in
manufacturing of medicinal oxygen;
■ establish a transition period to ensure a smooth implementation of
regulations;
■ develop specific guidance for QMS (based on GMP) for on-site
production of medicinal oxygen;
■ create requirements and a simplified procedure for assessing the on-
site production of medicinal oxygen (see Appendix 2);
■ develop an inspection strategy for both manufacturing and
distribution sites of medicinal oxygen;
■ develop an enforcement strategy.
9.2 Responsibilities of the qualified personnel
designated by the health care facility
WHO Technical Report Series, No. 1067, 2026
In health care facilities where medicinal oxygen is produced, the NRA should
recommend that the qualified personnel (as determined by the facility’s
management) are accountable for the quality and safety of the oxygen administered
to patients. The NRA should oversee the responsibilities of these qualified
personnel. The designated qualified on-site personnel are responsible for:
■ maintaining the quality management system and ensuring
adherence to GMP for on-site medicinal oxygen production;
■ supervising production operations at the health care facility and
ensuring compliance with the minimum recommended principles
outlined in the WHO good manufacturing practices for medicinal
gases (5);
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■ ensuring that the supply of medicinal oxygen from the on-site PSA
plant complies with GSDP;
■ overseeing quality control requirements to ensure compliance with
the relevant pharmacopoeia and national standards;
■ establishing testing frequency and quality control procedures to
confirm that the oxygen administered to patients meets required
quality and purity standards;
■ defining appropriate testing frequency to prevent and detect gas
contamination;
■ ensuring the suitability of oxygen supplied via the medical
gas pipeline system by conducting routine inspections of the
piping system and performing online testing prior to patient
administration;
■ maintaining full traceability of oxygen produced on site and
administered to patients;
■ investigating any reported adverse events related to on-site
medicinal oxygen.
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Geneva: World Health Organization; 2020 (https://iris.who.int/handle/10665/331746). Licence: CC
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specifications and guidance for oxygen therapy devices. Geneva: World Health Organization; 2019
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21. Graham’s laws of diffusion and effusion. LibreTexts: Chemistry, section 2.9 (https://chem.
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Health Organization; 2024 (https://iris.who.int/handle/10665/380072).
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Appendix 1. Manufacturing of medicinal oxygen
Large- scale and on-site manufacturing and
distribution of medicinal oxygen
Medicinal oxygen, like all medical gases, is a distinct product. It differs from
medicinal products in several aspects, including its starting material, physical form,
primary packaging, physical properties, dosage form, distribution and method
of administration. Managing medicinal oxygen can take place on site in health
facilities or off site at manufacturing sites. Although different standards may apply
depending on the production method and location, both production methods
must adhere to strict regulations for quality assurance and undergo quality control
verification, which should be conducted by certified, specialized laboratories.
A detailed diagram of the manufacturing process should be presented,
together with the controls carried out at the different stages. The production station
should be indicated, and the automated packaging system and specifications of the
equipment (for example, pumps and balances) should be described and validated.
Validation and revalidation of the cylinder-filling process should be performed.
Manufacture of medicinal oxygen involves a series of operations, including the
division or distribution and filling into dedicated medicinal packaging. Packaging
is often automated and may include prior modification to the physical state of the
gas, such as vaporization by heating of liquefied gas or compression.
The concentration of medicinal oxygen is possible using multiple methods
as described below, which separate nitrogen and oxygen, and sometimes argon
and other rare inert gases, from atmospheric air. The different separation methods
to obtain concentrated oxygen are as follows.
1. Cryogenic distillation of ambient air using an air separation unit to
generate liquid oxygen, which liquefies at –183 °C and contains the
purity of not less than 99.5% v/v of O2.47 Facilities can be equipped
WHO Technical Report Series, No. 1067, 2026
with large bulk liquid oxygen tanks that are refilled periodically
by a liquid oxygen tanker from a supplier. The liquid oxygen tank
supplies a centrally piped system throughout the health facility by
self-vaporization, meaning that a power supply is not required.
Note: This process is conducted off-site, away from the health facility.
2. Medical ceramic oxygen generator system developed by the
United States National Aeronautics and Space Administration:
oxygen is separated through ionization and electrochemical
processes. The output is approximately 99.995% oxygen. It uses
47
Oxygen 99.5% is produced from ambient air by cryogenic distillation, as defined in The International
Pharmacopoeia.
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ceramic membranes with the unique ability to ionize oxygen atoms
from ambient air, transport the ions through the solid membrane
wall, and recombine them into oxygen molecules on the other side.
3. Oxygen generator plants (PSA, VSA, VPSA). Oxygen generator
plants may be used as an alternative source of supply for the
medical gas pipeline system for medicinal oxygen, using a plant
that is installed and run on the health care site. Since these plants
may be the only medicinal oxygen source of supply available to
the hospital, their operations must be strictly controlled due to the
fact that the oxygen produced is supplied directly to the medical
gas pipeline system without being batched and tested before use.
Depending on the design of the plant, it produces the medicinal
oxygen to the appropriate grade, using zeolites and molecular
sieves in adsorption beds to remove the nitrogen and argon from
ambient air, producing oxygen at concentrations varying between
90% and close to 100%.
When produced by means of oxygen generator plants through molecular
sieves (that is, no liquification), then the minimum standard for medical grade
oxygen should be 93% ± 3% (90–96%) purity v/v from ambient air.
There are a few variations of oxygen generator plants involving different
separation technologies to obtain concentrated oxygen, as follows.
– Pressure swing adsorption (PSA). This technology separates
gases from a mixture under pressure based on their molecular
properties and affinity for an adsorbent such as zeolite. Nitrogen
is trapped from the air at high pressure and then released when
the pressure inside the generator decreases. The process alternates
between high and low pressure to regenerate the adsorbent.
– Vacuum swing adsorption (VSA). Similar to PSA, this method
also uses a zeolite sieve to separate oxygen from nitrogen. Instead
of an air compressor, a vacuum blower is employed, with fewer
adsorption vessels and valves. It leverages the adsorbent’s higher
selectivity under negative pressure.
– Vacuum pressure swing adsorption (VPSA). This is a mixed
technology that combines engineering systems of pressure
variations from positive (PSA) to negative (VSA) at different
stages of the overall process to concentrate oxygen.
Oxygen generator plants can be used to generate oxygen in
health facilities, which is then piped directly to patient bedsides,
or can be further compressed to fill high-pressure gas cylinders.
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– Home or bedside oxygen concentrators. These are types of
medical devices that use the same technology as PSA plants but
on a much smaller scale to meet individual patient needs. The
typical oxygen concentration is greater than 82%. The flow rate
can be adjusted based on patients’ needs. These products are not
covered in this document.
Large-scale production of liquid oxygen
Bulk liquid oxygen is typically produced on a large scale at manufacturing facilities.
This is the most common method for industrial-scale production of oxygen. The
process involves separating atmospheric air – composed of approximately 78%
nitrogen, 21% oxygen, and 0.9 % argon, with trace amounts (0.1%) of other gases
such as carbon dioxide, moisture, carbon monoxide, and inert gases such as
neon, helium, krypton and xenon. The gases are separated into their individual
components through cryogenic distillation, whereby air is cooled to a very low
temperature until it becomes a liquid. Once in a liquid state, the air is separated
into its components by taking advantage of their different boiling points. Since
nitrogen has a lower boiling point than oxygen, it vaporizes first, leaving behind
high-purity liquid oxygen. Bulk liquid oxygen is then stored and distributed for
medical use in health care settings.
Additionally, compressed medicinal oxygen is produced by taking bulk
liquid oxygen, vaporizing it under pressure, and then filling high-pressure
cylinders. The gas can be filled into cylinders or bundles (manifolded cylinders)
or delivered through the medical gas pipeline system.
Storage and distribution of medicinal oxygen
Oxygen can be supplied from the production or distribution site to health facilities,
either in liquid or in gas form. Liquid oxygen can be stored at the manufacturing
WHO Technical Report Series, No. 1067, 2026
facility in vacuum-insulated pressure vessels. The transportation of liquid oxygen
must comply with strict national and international regulations prescribed by the
NRA for handling of cryogenic pressure vessels.
Oxygen gas can be compressed and stored in cylinders, which are filled
at gas manufacturing plants using methods such as cryogenic distillation, PSA,
VSA or VPSA. These cylinders are then transported to health care facilities,
where they are connected to manifold systems that distribute the oxygen through
medical gas piping to bedside terminal outlets. Alternatively, cylinders can be
used directly in patient care areas by connecting with a flow meter to control
pressure from the cylinder and measure the flow rate of the gas. The use of
cylinders often involves transporting them both within facilities and to and from
bulk supply depots for regular refilling, which can present logistical challenges
and ongoing cost implications.
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Cylinders are durable and refillable containers designed to store
compressed gases, such as medicinal oxygen, at high pressures. They can store
medicinal oxygen pressurized up to 200 bar (2900 psi) but are more typically
used at 150 bar (2175 psi) for standard valve cylinders.
Transportation of packaged medicinal oxygen
The NRA should establish requirements for the transportation of medicinal
oxygen to ensure that the finished product is delivered in a manner that provides
sufficient protection during transit. Transportation activities should comply
with GSDP requirements. If medicinal oxygen cylinders are transported in open
vehicles, they must be transported in an upright position and be equipped with
appropriate plugs and dust covers to safeguard the valves.
Small-scale PSA oxygen production in health care facilities
NRAs should oversee on-site production systems to ensure compliance with
applicable regulations. Continuous monitoring is essential to guarantee that the
produced oxygen consistently meets safety and quality standards for patient care.
On-site PSA systems typically provide oxygen directly to the hospital pipeline
system via manifold systems or fill cylinders for later use. All systems operate by
passing pressurized ambient air through molecular sieves (for example, zeolites)
to selectively remove nitrogen, resulting in concentrated oxygen for medical use.
Storage and distribution of on-site medicinal oxygen in a health care facility
The NRA should be responsible for oversight to ensure that the oxygen produced
on site through PSA, VSA or VPSA plants in health care facilities is stored and
distributed safely and efficiently. The concentrated oxygen, in gas form, may be
delivered directly to the medical gas pipeline system or stored in high-pressure
cylinders filled at designated cylinder filling stations. These high-pressure
cylinders serve as a storage method for the oxygen, which is then transported to
patient bedside outlets or connected to a distribution manifold for further use.
The NRA must oversee and regulate these processes to ensure compliance with
safety and quality standards.
Regulatory oversight of categories of medical devices for medicinal oxygen production
and delivery
Delivery equipment and medical devices serve as an interface to administer
oxygen to the patient. Devices intended to support delivery of medicinal
oxygen directly to integrated hospital supply systems through either oxygen
concentrators or bedside medical gas outlets of a central piped system should
be regulated as medical devices according to the applicable law. Also, some
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equipment, such as medical gas regulators, demand valves, medical gas flow
meters and patient monitoring equipment (such as pulse oximeters), must be
appropriately classified and regulated as medical devices. NRAs should oversee
all types of devices that are integral to the regulation and conditioning of oxygen
gas and patient monitoring, ensuring that they meet the required technical
specifications to guarantee their safety and performance. The devices fall into two
broad categories: non-invasive, which support the patient without penetrating
the airway; and invasive, which require internal access to the airway (for example,
endotracheal tubes or tracheostomy). The NRA, or any institution responsible for
ensuring the safety and performance of these devices, should ensure that medical
devices meet the minimum technical specifications required for their safe use in
health care settings.48
Medical devices must comply with medical device regulations. A facility
that wishes to manufacture medical devices (including medicinal oxygen
classified as medical device gases) should be registered with the NRA.
Non-invasive delivery devices
Non-invasive medical devices are mostly intended for single-patient use,
connected to patient ventilators, and may be reusable – following reutilization
measures and lifespan recommended by the manufacturer. Table 1 lists
representative examples of such devices.
Table 1
Examples of non-invasive medicinal oxygen delivery devices
Device Examples
Oxygen source devices • Concentrator
WHO Technical Report Series, No. 1067, 2026
Oxygen delivery devices • High-flow nasal oxygen cannula
• Face mask
• Mask with reservoir bag
• Venturi mask
Conditioning, regulation • Flowmeters – Thorpe tube
and testing devices
• Valves
48
WHO technical specifications for health facility based medicinal oxygen systems. Geneva: World Health
Organization; 2024 (https://iris.who.int/handle/10665/380072).
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Table 1 continued
Device Examples
Conditioning, regulation • Pressure regulators
and testing devices
continued • Heated, humidified high flow
• Oxygen analysers
• Flow splitter
• Non-heated bubble humidifier
• Tubing (for medical gases)
Ventilator devices • Ventilators
• High-flow nasal oxygen
• Continuous positive airway pressure machine
• Bilevel positive airway pressure device
Manual ventilator device • Self-inflating resuscitation bag with mask
• Heat and moisture exchange filter
• Colorimetric end-tidal CO2 detector
Patient monitoring • Pulse oximeter (handheld, tabletop and fingertip)
devices
• Patient monitoring multiparametric (basic,
intermediate and advanced)
Invasive medical devices (invasive ventilators)
Invasive ventilators provide long-term respiratory support in intensive care
settings. These devices require trained health care personnel and are capable of
delivering up to 99.5% oxygen based on prescribed clinical needs. Proper operation
includes setting parameters such as volume, pressure and alarm systems.
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Appendix 2. Requirements for medicinal oxygen
authorization
Submission components Medicinal oxygen
Manufacturing large Manufacturing:
scale: off site on site
Application form yes yes
Quality assurance statement yes yes
Label and insert yes yes (where applicable)
Premise licence yes covered under
hospital licence
GMP certificate yes adapted GMP
requirements
Technical dossier yes not applicable
Testing results yes yes
Risk management plan yes adapted to scope
Location plan yes adapted to hospital
infrastructure
Stability testing yes not applicable
Credentials of the pharmacist in yes yes
charge
Credentials of other qualified yes adapted to country’s
personnel requirements
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Other procedures, protocols, yes as per prescribed
records, and reports required by GMP requirements
WHO or Pharmaceutical Inspection
Co-operation Scheme GMP
Source: Adapted from: Regulations for registration of medicinal products In: Laws and regulations database of
the Republic of China (Taiwan)
(https://law.moj.gov.tw/ENG/LawClass/LawParaDeatil.aspx?pcode=L0030057&bp=4).
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来源：WHO 药品质量技术报告与指南 · cdn.who.int