Annex 4

WHO guidelines on technology transfer in pharmaceutical

manufacturing
Background
During the fifty-fifth meeting of the World Health Organization Expert Committee
on Specifications for Pharmaceutical Preparations, Expert Committee members
were updated on the annual consultation on good practices for health products
manufacture and inspection, which took place in July 2020 over a series of
virtual meetings due to the COVID-19 pandemic. During these virtual meetings,
a group of experts made a series of proposals for future activities, including a
possible update of the WHO guidelines on transfer of technology in pharmaceutical
manufacturing (1). This original document was published in 2011, since when
numerous regulatory changes have been made. Transfer of technology is
considered an integral part of the product life cycle management and is subject to
regulatory expectations, including in the areas of a risk-based and science-based
process and method design (such as a quality by design approach), achieving a
state of control, and data governance. The original document therefore requires
updating, not least to support the consistent supply of therapies for critical needs,
including public health emergencies.
The Expert Committee asked the WHO Secretariat to explore this
proposal.

Contents
Background 197
Abbreviations 199
1. Introduction 199
2. Scope 200
3. Glossary 202
4. Due diligence and gap analysis 206
5. Organization and management 207
6. Quality management and quality risk management 209
7. Documentation 210
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8. Premises 211
9. Equipment and instruments 211
10. Qualification and validation 212
11. Life cycle approach 213
12. Phases of a technology transfer project 213
Phase I: Project initiation 213
Phase II: Project planning 214
Phase III: Project transfer execution 216
Production (example: finished pharmaceutical product) 216
Quality control: analytical procedure transfer 217
Cleaning 219
Phase IV: Project review and close-out 220
References 220
Appendix 1 Documentation commonly required for technology transfer 223
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Abbreviations
ALCOA attributable, legible, contemporaneous, original and accurate
API active pharmaceutical ingredient
ICH International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use
RU receiving unit
SU sending unit

1. Introduction
1.1 Technology transfer is a logical procedure involving the transfer of
products, processes and knowledge, supported by relevant documentation
and professional expertise. Technology transfer may include development,
manufacturing and testing sites.
1.2 The transfer of production and control procedures of pharmaceutical
products from one site to another may take place before or after obtaining
regulatory marketing authorization. Product transfer may therefore occur
during development, full-scale commercialization and commercial batch
manufacturing. The level of rigour applied in the technology transfer should
be commensurate with the respective product life cycle phase.
1.3 Technology transfer, particularly between different companies, has legal
and economic implications that may include intellectual property rights,
royalties, pricing, conflict of interest and confidentiality agreements. Such
matters should therefore be addressed in undertaking the transfer.
1.4 Technology transfer requires a planned approach by trained, knowledgeable
personnel working within a quality system with the appropriate
documentation, data and information covering all aspects of development,
production and quality control, as applicable, and considering the stage of
the product life cycle and the regulatory requirements.
1.5 Technology transfer takes place between a sending unit (SU) and a receiving
unit (RU). In some cases, it may be advantageous to establish a separate unit
to manage the project.
1.6 The technology transfer project should fulfil the following general principles
and requirements. There should be:
■■ a documented project plan covering the relevant aspects of the
project;
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■■ a detailed quality risk management plan;

■■ a comprehensive gap analysis, including due diligence performed
covering technical, quality and regulatory aspects;
■■ similar capabilities between the SU and RU, including facilities and
equipment, where appropriate;
■■ knowledge of the differences in process ability between the SU and
RU, including the impact, risk and control strategies to overcome
any differences;
■■ a sufficient number of adequately trained personnel with suitable
qualifications and experience;
■■ effective process and product knowledge management;
■■ effective communication and transparency between the SU and RU.
1.7 Technology transfer should include relevant documentation, data,
information and knowledge from the SU in order to enable the RU to
effectively execute the specified process or procedure in, for example,
production and quality control. A successful technology transfer project
should result in documented evidence that the RU can routinely reproduce
the transferred product, process or procedure against a predefined set of
specifications, as agreed between the SU and RU.
1.8 This document should be read in conjunction with other WHO guidelines,
as referenced below (2–15), as well as other regulatory guidelines, including
the International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use (ICH) guidelines Q7, Q8, Q9, Q10, Q11
and Q12. This guideline does not intend to replace any of those guidelines.
1.9 Product, process and procedure knowledge should be an essential part of
the transfer process from the SU to the RU.
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1.10 The critical quality attributes, critical process parameters, material

attributes, control strategy and any other elements potentially impacting
the quality of the product should be available (see also ICH guidelines).
1.11 This version of the document provides guiding principles reflecting current
good practices in technology transfer and replaces the previous version
published by the World Health Organization (WHO) (1).

2. Scope
2.1 This document provides guiding principles on technology transfer,
including transfer from research and development to production sites,
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and between two production sites. The principles therefore apply to newly
commercialized products as well as to marketed products. The principles
may also be applied to investigational products.
2.2 Throughout life cycle stages, transfers should be appropriate and
proportionate to the phase of the product life cycle in order to ensure that
product knowledge is maintained and that processes are appropriately
controlled. This guideline should be applied when transferring the
technology of manufacturing processes and analytical procedures relating to
active pharmaceutical ingredients (APIs), isolated API intermediates, bulk
drug products and finished pharmaceutical products. While medical devices
as part of the finished pharmaceutical product of a combination medicinal
product would be considered under this guidance, the specific regulatory
and quality requirements for medical device manufacturing are covered
under separate medical device regulations and quality management systems.
2.3 The guideline applies to all pharmaceutical dosage forms and may be
adapted on a case-by-case basis by using risk management principles.
Particular attention should be given to certain complex formulations, such
as sterile products and metered dose inhalers.
2.4 Although this document focuses on pharmaceutical products, the principles
can also be applied to the transfer of production, related processes and
controls for other products, such as vaccines, biotherapeutic products,
advanced therapy medicinal products, cell and gene therapy products,
medical devices and vector control products.
2.5 Because each transfer project is unique, the provision of a comprehensive
set of guidelines specific to a product or process is beyond the scope of this
document.
2.6 This document does not provide guidance on any intellectual property,
legal, financial or commercial considerations associated with technology
transfer projects. These are prerequisites for a successful transfer that need
to be defined and controlled prior to the transfer in the course of due
diligence. Examples include health, safety and environmental aspects and
the availability of confidentiality disclosure agreements, which should be
in place prior to the start of the transfer.
2.7 This document addresses the following principal areas:
■■ organization and management of the transfer;
■■ transfer of relevant information in production, including processing,
packaging and analytical procedures;
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■■ documentation, premises and equipment;

■■ personnel qualification and training;
■■ quality management and risk management;
■■ change management and life cycle approach;
■■ control strategy;
■■ qualification and validation.

3. Glossary
The definitions given below apply to the terms used in these guidelines. They
have been aligned as much as possible with the terminology in related WHO
guidelines and good practices and included in the WHO Quality Assurance of
Medicines Terminology Database: list of terms and related guideline,1 but may have
different meanings in other contexts.
acceptance criteria. Measurable terms under which a test result will be considered
acceptable.
active pharmaceutical ingredient (API). Any substance or mixture of substances
intended to be used in the manufacture of a pharmaceutical dosage form and
that, when so used, becomes an active ingredient of that pharmaceutical dosage
form. Such substances are intended to furnish pharmacological activity or other
direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease,
or to affect the structure and function of the body.
ALCOA+. A commonly used acronym for “attributable, legible, contemporaneous,
original and accurate” that puts additional emphasis on the attributes of being
complete, consistent, enduring and available – implicit basic ALCOA principles.
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bracketing. An experimental design to test the extremes of, for example, dosage
strength. The design assumes that the extremes will be representative of all the
samples between the extremes.
change control. A formal system by which qualified representatives of
appropriate disciplines review proposed or actual changes that might affect the
registration and validated status. The intent is to determine the need for action
that would ensure that the system is maintained in a regulatory compliant and
validated state.

1
[Link]
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confirmation testing. An execution of tests that confirm and validate the results
obtained by another test.
control strategy. A planned set of controls, derived from current product and
process understanding, that assures process performance and product quality.
The controls can include parameters and attributes related to API and finished
pharmaceutical product materials and components, facility and equipment
operating conditions, in-process controls, finished product specifications, and
the associated methods and frequency of monitoring and control.
corrective action. Any action to be taken when the results of monitoring at a
critical control point indicate a loss of control.
critical. Having the potential to impact product quality or performance in a
significant way.
critical process parameter. A process parameter whose variability has an impact
on a critical quality attribute and therefore should be monitored and controlled
to ensure the process produces the desired quality.
critical quality attribute. A physical, chemical, biological or microbiological
property or characteristic that should be within an appropriate limit, range or
distribution to ensure the desired product quality.
design space. The multidimensional combination and interaction of input
variables (such as material attributes) and process parameters that have been
demonstrated to provide assurance of quality.
drug master file. Detailed information concerning a specific facility, process,
packaging material or product submitted to the medicines regulatory authority,
intended for incorporation into the application for marketing authorization.
finished pharmaceutical product. A product that has undergone all stages of
production, including packaging in its final container and labelling. A finished
pharmaceutical product may contain one or more APIs. In some cases, it may be
in combination with a medical device.
gap analysis. The identification of the critical elements of a process that are
available at the sending unit (SU) but are missing from the receiving unit (RU)
with the objective of assessing which gaps have a potential impact on the process
or method and to mitigate those gaps, as appropriate.
good manufacturing practices. That part of quality assurance that ensures that
pharmaceutical products are consistently produced and controlled to the quality
standards appropriate to their intended use and as required by the marketing
authorization.
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good practices. A collection of quality guidelines and regulations in order

to ensure that products are safe, effective, and of required quality; meet their
intended use; and adhere to quality processes during production, control,
storage and distribution.
in-process control. Checks performed during production in order to monitor
and, if necessary, adjust the process to ensure that the product conforms to
its specifications. The control of the environment or equipment may also be
regarded as a part of in-process control.
installation qualification. Documented verification that the installations
(such as machines, equipment and instruments, computer system components,
measuring devices, utilities and manufacturing) used in a processor system are
appropriately selected and correctly installed, in accordance with established
specifications.
intercompany transfer. A transfer of technology between the sites of different
companies.
intracompany transfer. A transfer of technology between sites of the same
group of companies.
marketing authorization holder. An individual or a corporate entity being in
possession of a marketing authorization of a pharmaceutical product.
operational qualification. Documented verification that the system or subsystem
performs as intended over all anticipated operating ranges.
process validation. The collection and evaluation of data, from the process
design stage through to commercial production, that establish scientific
evidence that a process is capable of consistently delivering the API or finished
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pharmaceutical product meeting its predetermined specifications and quality

attributes.
qualification. Documented evidence that premises, systems or equipment are
able to achieve the predetermined specifications when properly installed and
working correctly, and lead to the expected results.
quality assurance. Quality assurance is a wide-ranging concept covering all
matters that individually or collectively influence the quality of a product.
It is the totality of the arrangements made with the objective of ensuring that
pharmaceutical products are of the quality required for their intended use.
quality control. All measures taken, including the setting of specifications,
sampling, testing and analytical clearance, to ensure that starting materials,
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intermediates, packaging materials and finished pharmaceutical products

conform with established specifications for identity, strength, purity and other
characteristics.
quality planning. Part of quality management, quality planning entails setting
quality objectives and specifying necessary operational processes and related
resources to fulfil the quality objectives.
quality policy. A brief statement that describes the organization’s purpose, overall
intentions and strategic direction; provides a framework for quality objectives;
and includes a commitment to meet applicable requirements.
quality risk management. A systematic process for the assessment, control,
communication and review of risks to the quality of the pharmaceutical product
throughout the product’s life cycle.
receiving unit (RU). The involved disciplines at an organization where a
designated product, process or method is expected to be transferred.
sending unit (SU). The involved disciplines at an organization from where a
designated product, process or method is expected to be transferred.
standard operating procedure. An authorized written procedure giving
instructions for performing operations, not necessarily specific to a given
product or material, but of a more general nature (for example, operation of
equipment, maintenance and cleaning, validation, cleaning of premises, and
environmental control, sampling and inspection). Certain standard operating
procedures may be used to supplement product-specific master and batch
production documentation.
starting material. Any substance of a defined quality used in the production of
a pharmaceutical product, but excluding packaging materials.
technology transfer, transfer of technology. A logical procedure that controls
the transfer of any product or process, including product or process knowledge,
together with its documentation and professional expertise. Technology transfer
may involve development, manufacturing or testing sites.
technology transfer protocol (master plan). A document that describes the
intended sequential phases and activities of the transfer, and serves as a plan for
the execution and management of the transfer.
technology transfer report. A documented summary of a specific technology
transfer project listing procedures, acceptance criteria, results achieved and
conclusions.
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validation. Action of proving and documenting that any process, procedure or

method actually and consistently leads to the expected results.
validation batches. Those batches produced by the receiving unit (RU) to
demonstrate its ability to manufacture the transferred product in compliance
with its predetermined specifications, or as part of process performance
qualification.
validation master plan. A high-level document that summarizes the
manufacturer’s overall philosophy and approach, to be used for establishing
performance adequacy. It provides information on the manufacturer’s
qualification and validation work programme and defines details of and timelines
for the work to be performed, including a statement of the responsibilities of
those implementing the plan.
validation protocol. A document describing the activities to be performed
during validation, including the acceptance criteria.
validation report. A document in which the records, results and evaluation of
validation are documented and summarized. It should also contain a conclusion
of the outcome of the validation.

4. Due diligence and gap analysis

4.1 When considering a technology transfer project, the first steps should
include a process of due diligence and gap analysis through visits to the SU
and RU.
4.2 The suitability and degree of preparedness of the RU should be assessed
prior to the start of the transfer. The procedure to be followed and the
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results and conclusions should thereafter be documented.

4.3 The gap analysis should be performed by a team of appropriately qualified
persons with knowledge and experience in the field of good practices and
the activity to be transferred. It is recommended that the quality units of
the SU and RU participate in this activity. The team should be involved
throughout each phase of the project, as appropriate (see section 12 on
phases of a technology transfer project).
4.4 The gap analysis should further cover the capabilities and resources related to
personnel, premises, equipment and instruments, utilities, cleaning, quality
control, documentation, computerized systems, qualification, validation,
and further health, safety and environment-related considerations, including
waste management.
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4.5 The gap analysis to determine the feasibility for technology transfer may
include technical, engineering, business, quality, regulatory, supply and
legal aspects.

5. Organization and management

5.1 All technology transfer activities should be organized and planned.
5.2 There should be formal written agreements, signed between the parties
involved in technology transfer, that specify the responsibilities of each
party before, during and after transfer. The agreements should cover, for
example, data management, data integrity, documentation and validation.
5.3 All the necessary activities to be executed during the technology transfer
project should be identified, organized and documented at the start of
the project. The responsibilities of the SU, RU, sponsor and marketing
authorization holder should be defined in writing.
5.4 Where applicable, the marketing authorization holder should coordinate
the transfer of the necessary documentation related to the technology
transfer from the SU to the RU, including the relevant regulatory
documents. The product dossier, production and control documentation
should be assessed for compliance with regulatory requirements before the
transfer of the documentation.
5.5 The SU should provide criteria and information on the inherent risks,
hazards and critical steps associated with the process, product or procedure
to be transferred. These may serve as a basis for the gap analysis and risk
assessment exercises.
5.6 The technology transfer should be managed by responsible persons from
each site (the SU and RU) and any other units with the appropriate technical
and quality oversight. A technology transfer team may be appointed with
identified and documented responsibilities.
5.7 The team members should have the necessary qualifications and experience
to manage the particular aspects of the transfer.
5.8 The SU should make available in relevant documents all the necessary
information and knowledge with regard to the product, process or procedure
in order to ensure a successful transfer.
5.9 The RU should be able to accommodate the intended production capacity. If
possible, it should be established at the outset whether or not the intention is
to perform single-batch manufacture, continuous production or campaigns.
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5.10 Consideration should be given to the level and depth of detail to be

transferred to support production and any further process development
and optimization at the RU, as intended under the transfer project plan.

5.11 Consideration should be given to the technical expertise, site technology

and site capabilities of the RU. Any product and process robustness issues
should be identified at the outset by the SU so that plans may be put in
place at the RU.

5.12 The SU should assess the suitability and degree of preparedness of the RU
before transfer with regard to personnel, premises, equipment, materials,
suppliers and support services (specifically, purchasing and inventory
control mechanisms and the pharmaceutical quality system – quality
control procedures, documentation, computer validation, site validation,
equipment qualification, water for pharmaceutical production and waste
management).

5.13 The SU and the RU should jointly verify that the following, satisfactorily
completed, qualification and validation protocols and reports are available:
■■ installation qualification and operational qualification data for
manufacturing and packaging equipment at the RU site and
analytical equipment;
■■ qualification of the rooms for both manufacture and packaging at
the RU site;
■■ cleaning validation.

5.14 A training programme should be implemented covering various topics,

including those specific to the process, product or procedure to be
transferred. The effectiveness of training should be evaluated. Records
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should be maintained.

5.15 Changes and adaptations made during the course of the project should be
done in accordance with a standard procedure. Risk assessment, where
appropriate, should cover technical, quality, regulatory and other aspects.
The project manager should evaluate the impact to the project cost,
schedule, and resourcing based on an updated risk assessment.

5.16 The execution of the technology transfer project should be documented,

for example in a report, supported by the relevant data. The overall
technology transfer strategy and acceptance criteria to confirm a successful
transfer should be documented a priori in the technology transfer protocol.
These should consider the stage of development – both clinical and
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commercial stages (including the fulfilment of relevant regulatory country

requirements).
5.17 Whenever possible, targeted on-site or virtual visits between the SU and
RU at critical phases of the project should be allowed to assist with the
transfer of knowledge.
5.18 Data should be in accordance with ALCOA+ principles.

6. Quality management and quality risk management

6.1 The SU and RU should each have an appropriately designed, clearly defined
and documented quality management system.
6.2 The quality management system should be adequately resourced,
implemented and maintained.
6.3 The quality management system should incorporate good practices that
should be applied to the life cycle stages of the products and processes,
including technology transfers.
6.4 The quality management system should ensure that:
■■ responsibilities are clearly specified in writing
■■ operations are clearly defined in writing
■■ there is a system for change management
■■ there is a system for quality risk management
■■ arrangements are made for the documented technology transfer.
6.5 Quality risk management should be implemented as a systematic process
for the assessment, control, communication and review of risks.
6.6 The system for quality risk management should be described in writing and
cover appropriate areas, including premises, equipment, materials, products,
production, processes, quality control and microbiology, qualification,
validation and the process of technology transfer.
6.7 The evaluation of the risk should be based on scientific knowledge and
experience, including that of the process and product.
6.8 The level of effort, formality and documentation of the quality risk
management process should be commensurate with the level of risk.
6.9 The procedures and records for quality risk management should be retained.
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7. Documentation
7.1 An authorized technology transfer document – for example, a master plan
or technology transfer protocol – should list the intended sequential phases
and activities of the transfer, where appropriate. The document should
include the following:
■■ title;
■■ objective;
■■ scope;
■■ names and addresses of the SU and RU;
■■ technology transfer team, including key personnel and their
responsibilities, from SU and RU;
■■ phases of the project, including key activities, deliverables and
associated accountabilities;
■■ approximate timing of key activities and deliverables, including the
timing of trial production batches and validation batches;
■■ reference to other transfer plan documents relevant to the process
being transferred;
■■ reference to validation master plans relevant to the process being
transferred, including equipment, facilities and utilities qualification
project plan, site-independent or site-dependent process validation
master plan, method validation master plan;
■■ reference to gap analysis and risk assessments;
■■ acceptance criteria for a successful transfer;
■■ a parallel comparison of premises, equipment, instruments, materials,
procedures, and methods for the transfer under consideration.
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Note: A list with examples of documents commonly required in

technology transfer is presented in Appendix 1.
7.2 Standard operating procedures should be followed, describing the actions
to be taken during the technology transfer process.
7.3 Records should be maintained of the activities performed during the
technology transfer process (such as a technology transfer report).
The report content should reflect the protocol and standard operating
procedures that were followed. The report should summarize the scope of
the transfer, the critical parameters as obtained in the SU and RU, and the
final conclusions of the transfer. Changes, deviations, investigations and
the relevant appropriate actions taken should be recorded. The SU should
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provide all the relevant supportive documents with data, results and other
relevant information in order to facilitate a successful technology transfer.

8. Premises
8.1 The RU should have appropriate premises with a layout, construction and
finishing suitable for the intended operations. Utilities such as heating,
ventilation and air-conditioning, as well as gas and water systems, should
have sufficient capacity and should be appropriate for the intended process,
product or procedure to be transferred.
8.2 The SU should provide the RU with information on relevant health, safety
and environmental issues, including:
■■ the inherent risks of the manufacturing processes (for example,
reactive chemical hazards, exposure limits, fire and explosion risks,
microbiological contamination risks);
■■ health and safety requirements to minimize operator exposure to
and ensure containment and management of pharmaceutical waste;
■■ emergency planning considerations (for example, in case of gas or
dust release, spillage, fire or firewater run-off);
■■ identification of waste streams and provisions for reuse, recycling or
disposal, including antimicrobial substances.

9. Equipment and instruments

9.1 The SU should provide a list (or similar document) of equipment and
instruments involved in production, filling, packing, quality control and
microbiological testing. It should include the makes and models of the
relevant equipment and instruments, including automated systems and
those of single use, in order to ensure the evaluation of similar principles
of operation.
9.2 A review and side-by-side comparison of the equipment and instruments,
as well as process steps and parameters of the SU and RU, should be carried
out in terms of their working principle, capacity, make and model to ensure
that they are capable of appropriately performing the required processes
and methods.
9.3 The facility- and building-specific location of all equipment at the RU
should be considered at the time of drawing up process maps or flowcharts
of the manufacturing process to be transferred, including the flow of
personnel and the flow and intermediate storage of materials.
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9.4 Where the review and comparison identify any gaps or differences, the
appropriate action should be taken. This may include the adaptation of
existing equipment or the acquisition of new equipment. Any modification
or adaptation of existing equipment to become capable of reproducing the
process being transferred should be documented.
9.5 Production volumes and batch sizes at the SU and RU should be compared.
Where batch sizes are different, the impact should be assessed as part
of risk assessment and the appropriate action planned and taken. Other
factors relating to equipment to be reviewed may include:
■■ minimum and maximum capacity
■■ material of construction of contact surfaces
■■ critical operating parameters
■■ components (such as filters, screens, and temperature or pressure
sensors)
■■ range of intended use.
9.6 The impact of the potential product to be transferred on existing products
manufactured on site (and vice versa) should be assessed.

10. Qualification and validation

10.1 The extent of qualification and validation to be performed should be
determined on the basis of risk management principles, taking into
account the product’s life cycle phase.
10.2 Equipment and instruments should be qualified and calibrated before
using them to support the technology transfer activities.
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10.3 Process validation should be done according to guidelines, as published in

the WHO Technical Report Series (3).
10.4 Production processes and analytical procedures should be appropriately
transferred to the RU following documented procedures. Where validation
data exist, these should be included in the transfer.
10.5 For cleaning procedures, development and validation should be done in
accordance with the guidelines published in the WHO Technical Report
Series (6). Points to consider when including health-based exposure
limits in cleaning validation (14) should be taken into account in
establishing cleaning procedures, undertaking cleanability studies and
setting acceptance limits.
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10.6 Analytical procedures should be validated or verified according to the

guidelines published in the WHO Technical Report Series (7).
10.7 Qualification and validation procedures, protocols, data and results should
be appropriately recorded. The documents should be retained as defined
in procedures.

11. Life cycle approach

11.1 The relevant stage of the life cycle of the facility, equipment, instrument,
utility, product, process or procedure to be transferred should be taken
into consideration when the transfer is planned and executed. This also
applies to the control strategy and process validation.
11.2 The responsible entities should monitor the progress of the project at each
applicable stage of the life cycle aspect of the transfer to ensure successful
completion of the transfer.

12. Phases of a technology transfer project

12.1 The technology transfer project plan may be divided into different phases.
These may include:
■■ Phase I: Project initiation
■■ Phase II: Project planning
■■ Phase III: Project transfer execution
■■ Phase IV: Project review and closeout.

Phase I: Project initiation

12.2 During the initiation phase of the project, a unit normally identifies the
need for the technology transfer. This may be due to a lack of capacity,
a transfer from development to commercial site or a transfer from one
company to another.
12.3 During an initial discussion, it should be identified whether or not an RU
has any interest in such a project (see also the section on due diligence
above).
12.4 The RU should be able to accommodate the intended activity.
12.5 The RU should have the necessary technical expertise, technology and
capability.
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12.6 A sufficient level and depth of detail to support the activity, and any
further development and optimization at the RU, should be transferred.

Phase II: Project planning

12.7 The marketing authorization holder, SU and RU should jointly establish
a team that will coordinate activities and execute the technology transfer
exercise. Where the technology transfer involves a site that has limited
manufacturing experience or the process being transferred is complex,
the SU should consider providing extensive training and on-site support
before the project execution phase begins.
12.8 The team should perform a gap analysis and risk assessment based on the
available data, information and knowledge of the premises, equipment,
materials, products, procedures and other related information.
12.9 The team should prepare the technology transfer document, such as the
master plan or technology transfer protocol.
12.10 The team should develop a control strategy that includes:
■■ risks
■■ raw, starting and packaging material attributes
■■ analytical and microbiological test procedures
■■ sampling plans and release and stability specifications
■■ critical quality attributes, critical process parameters and in-process
controls
■■ acceptance criteria and limits.
12.11 The specifications and critical material attributes of the starting materials
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(APIs and excipients) to be used at the RU should be consistent with

those materials used at the SU unless there is a planned change associated
with these materials as part of the transfer and regulatory approval
is obtained, as applicable. Documentation to support compliance
with transmissible animal spongiform encephalopathy certification
requirements, or other regulatory requirements, should be present at the
RU, where applicable.
12.12 The SU should provide the RU with the open part of the drug master
file or API master file, as applicable, or equivalent information, as well
as any relevant additional information on the API of importance to the
manufacture of the pharmaceutical product.

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12.13 The SU should provide to the RU product information, including its

qualitative and quantitative composition, physical description, method
of manufacture, in-process controls, control method and specifications,
packaging components and configurations, and any safety and handling
considerations.
12.14 The marketing authorization holder or SU should provide any information
on the history of process development as well as any historical process
changes that may be required to enable the RU to perform any further
development or process optimization after successful transfer.
12.15 The SU should provide to the RU information on any health, safety and
environmental issues associated with the manufacturing processes to be
transferred and the implications thereof (for example, need for gowning
or protective clothing).
12.16 The SU should provide to the RU information on current processing and
testing, including:
■■ a detailed description of facility requirements and equipment;
■■ information on starting materials, applicable material safety data
sheet where required, and storage and distribution requirements for
raw materials, intermediates and finished products;
■■ description of manufacturing steps (narrative and process maps
or flowcharts and master batch records), including the qualification
of in-processing hold times and conditions, and the order and
method of raw material addition and bulk transfers between
processing steps;
■■ description of analytical procedures;
■■ identification and justification of control strategy (for example,
identification of critical performance aspects for specific dosage
forms, identification of process control points, product quality
attributes and qualification of critical processing parameter ranges,
sampling plans, and statistical process control charts);
■■ design space, in cases where this has been defined;
■■ validation information (such as validation plans and reports);
■■ annual product quality reviews;
■■ stability information;
■■ an authorized set of protocols and work instructions for
manufacturing;

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■■ environmental conditions or any special requirement needed for

the facility or equipment, depending on the nature of the product to
be transferred.

12.17 Information on packaging to be transferred from the SU to the RU should

include specifications for a suitable container and closure system, as well
as any relevant additional information on design, packing, processing or
labelling requirements and tamper-evident and anticounterfeit measures.

12.18 For quality control and microbiological testing of packaging components,

specifications should be provided, including drawings, artwork and
material and reference to relevant pharmacopoeias, where applicable.

Phase III: Project transfer execution

12.19 The team should execute the project in accordance with the procedures
and agreed plan.

Production (example: finished pharmaceutical product)

12.20 During the transfer process, the RU should identify any differences in
facilities, systems and capabilities and discuss these with the SU. The SU
should cooperate with the RU to understand the potential impact and
satisfactorily address this in order to assure equivalent product quality.
Based on the information received from the SU, the RU should consider
its own capability to manufacture and pack the product to the required
standards and should develop the relevant site operating procedures and
documentation before the start of routine production.

12.21 The RU should address the following tasks:

WHO Technical Report Series, No. 1044, 2022

■■ comparison and assessment of suitability and qualification of facility

and equipment;
■■ description of manufacturing process and flow of personnel and of
materials at the RU (narrative or process maps or flowcharts);
■■ determination of critical steps in manufacture, including hold times,
end-points, sampling points and sampling techniques;
■■ writing and approval of a training plan and standard operating
procedures for all production operations (for example, dispensing,
granulation or blending or solution preparation, tablet compression,
tablet coating, encapsulation, liquid filling, primary and secondary
packaging and in-process quality control and microbiology),
packaging, cleaning, testing and storage;
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■■ evaluation of stability information, with generation of site-specific

stability data if required;
■■ compliance with regulatory requirements for any changes made that
may impact the quality and efficacy of the product.
12.22 The transfer of packaging operations should follow the same procedural
principles as those of the product processing.
12.23 The RU should determine the need for qualification and validation for
the packaging process.

Quality control: analytical procedure transfer

12.24 Analytical procedures used to test pharmaceutical products, starting
materials, packaging components and cleaning (residue) samples, if
applicable, should be implemented at the testing laboratory before the
testing of samples for process validation studies is performed by the RU.
The transfer of the analytical procedure may be accomplished by several
approaches, such as confirmation testing, comparability testing between
SU and RU results, co-validation between laboratories, or through paper-
based knowledge transfer. The strategy chosen should be risk based and
scientifically justifiable.
12.25 A protocol and test transfer plan defining the steps should be prepared for
the transfer of analytical procedures. The analytical procedures transfer
protocol should include:
■■ a description of the objective, scope and responsibilities of the SU
and the RU;
■■ a specification of materials and methods;
■■ the experimental design and acceptance criteria;
■■ documentation (including information to be supplied with the
results and report forms to be used, if any);
■■ procedure for the handling of deviations;
■■ details of test samples (starting materials, intermediates and finished
products).
12.26 The SU’s responsibilities for the transfer of analytical procedures typically
are to:
■■ provide method-specific training for analysts and other quality
control and microbiology staff, if required;
■■ assist in analysis of quality control and microbiology testing results;
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■■ define all procedures to be transferred for testing a given product,

starting material or cleaning sample;
■■ define experimental design, sampling methods and acceptance
criteria;
■■ provide any validation reports for procedures under transfer,
including proof of their robustness;
■■ provide details of the equipment used, as necessary (part of the
validation report, if available) and any standard test samples;
■■ provide approved procedures used in testing;
■■ review and approve transfer reports.
12.27 The RU should exercise its responsibility to:
■■ review analytical procedures provided by the SU, and formally agree
on acceptance criteria before execution of the transfer protocol;
■■ ensure that the necessary equipment for quality control is available
and qualified at the RU site, and that the equipment used by the RU
during the analytical transfer meets the appropriate specifications
in order to ensure the requirements of the procedure or specification
are met;
■■ ensure that adequately trained and experienced personnel are in
place for analytical testing;
■■ provide a documentation system capable of recording receipt and
testing of samples to the required specification using approved
test procedures, and of reporting, recording and collating data and
designation of status (approved, rejected, quarantine);
■■ execute the transfer protocol;
■■ perform the appropriate level of validation or verification to support
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the implementation of the procedures;

■■ generate and obtain approval of transfer reports.
12.28 The appropriate training should be provided and all training activities and
outcomes should be documented.
12.29 Reference should be made to recognized compendial monographs, where
these are relevant.
12.30 An experimental design should be prepared that includes acceptance
criteria for the analytical testing procedures.
12.31 Where products are transferred from one unit to another, the applicable
analytical procedures should also be transferred.
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12.32 Relevant analytical procedure development and validation documentation

should be made available by the SU to the RU, if required.
12.33 The appropriate transfer protocols and procedures should be followed
when analytical procedures are transferred.
12.34 The number of analysts involved in the transfer, from both SU and RU,
should be defined and justified.
12.35 The parameters to be included in the experimental evaluation of the
transfer of the analytical procedure should be defined and justified.
12.36 Acceptance criteria should be set to determine the success of the transfer
and capability of the process and procedures; where appropriate, statistical
trending of results should be undertaken in order to demonstrate this.

Cleaning
12.37 To minimize the risk of contamination and cross-contamination, adequate
cleaning procedures should be followed.
12.38 Cleaning procedures and their validation should normally be site specific.
In order for the RU to define its cleaning strategy, the SU should provide
information on cleaning at the SU to minimize cross-contamination due
to residues from previous manufacturing steps, operator exposure and
environmental impact, including:
■■ information on cleanability;
■■ information on solubility of active ingredients, excipients and
vehicles;
■■ toxicological assessment, including health-based exposure limits;
■■ existing cleaning procedures.
12.39 Additional applicable information should be provided, such as:
■■ cleaning validation reports (chemical and microbiological);
■■ potential degradation products and impurities;
■■ risks of antimicrobial resistance;
■■ information on cleaning agents used (efficacy, evidence that they do
not interfere with analytical testing for residues of APIs, removal of
residual cleaning agents);
■■ recovery studies to validate the sampling methodology.

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12.40 Before the transfer, the SU should provide information on limits for
product residues and the rationale for limit selection.
12.41 Based on the information provided by the SU, cleaning procedures should
be designed at the RU, considering relevant characteristics of the residues
to be cleaned (such as potency, toxicity and solubility), manufacturing
equipment design and configuration, and cleaning agent.

Phase IV: Project review and close-out

12.42 The progress and success of the technology transfer should be monitored
and reviewed during and after completion of the project. The review
should further ensure that, as appropriate, stability studies are started
and continued; post-marketing commitments are monitored; and new
material suppliers are integrated into the quality management system.
12.43 Compliance with the procedures and protocols should be verified.
Deviations and changes should be documented and investigated, where
appropriate.
12.44 Where possible, data and results should be subjected to appropriate
statistical calculation and evaluation to determine trends and compliance
with control limits and capability studies.
12.45 A document such as a technology transfer report should be prepared,
based on the data and information obtained during the project. The
supportive data should be stored and should be accessible.
12.46 The document, which should include an assessment of the data and
information and a conclusion, should be authorized by the appropriate
responsible person or persons. It should further state whether or not
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the team has achieved the completion of the technical transfer. Any
deviations and changes from the master plan should additionally be
assessed and evaluated before close-out of the project.

References
1. WHO guidelines on transfer of technology in pharmaceutical manufacturing. In: WHO Expert
Committee on Specifications for Pharmaceutical Preparations: forty-fifth report. WHO Technical
Report Series No. 961, Annex 7. Geneva: World Health Organization; 2011.
2. WHO good manufacturing practices for pharmaceutical products: main principles. In: WHO Expert
Committee on Specifications for Pharmaceutical Preparations: forty-eight report. WHO Technical
Report Series No. 986, Annex 2. Geneva: World Health Organization; 2014.

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3. WHO good manufacturing practices: guidelines on validation. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations: fifty-third report. WHO Technical Report Series
No. 1019, Annex 3. Geneva: World Health Organization; 2019.
4. Guidelines on heating, ventilation and air-conditioning systems for non-sterile pharmaceutical
products. Part 2: interpretation of guidelines. In: WHO Expert Committee on Specifications for
Pharmaceutical Preparations: fifty-third report. WHO Technical Report Series No. 1019, Annex 2.
Geneva: World Health Organization; 2019.
5. Good manufacturing practices: guidelines on validation. Appendix 2: Validation of water
systems for pharmaceutical use. In: WHO Expert Committee on Specifications for Pharmaceutical
Preparations: fifty-third report. WHO Technical Report Series No. 1019, Annex 3. Geneva: World
Health Organization; 2019.
6. Good manufacturing practices: guidelines on validation. Appendix 3: Cleaning validation. In:
WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-third report. WHO
Technical Report Series No. 1019, Annex 3. Geneva: World Health Organization; 2019.
7. Good manufacturing practices: guidelines on validation. Appendix 4: Analytical procedure
validation. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-
third report. WHO Technical Report Series No. 1019, Annex 3. Geneva: World Health Organization;
2019.
8. Good manufacturing practices: guidelines on validation. Appendix 5: Validation of computerized
systems. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-third
report. WHO Technical Report Series No. 1019, Annex 3. Geneva: World Health Organization; 2019.
9. Good manufacturing practices: guidelines on validation. Appendix 6: Guidelines on qualification.
In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-third report.
WHO Technical Report Series No. 1019, Annex 3. Geneva: World Health Organization; 2019.
10. Guidelines on good manufacturing practices: validation. Appendix 7: Non-sterile process
validation. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations: forty-
ninth report. WHO Technical Report Series No. 992, Annex 3. Geneva: World Health Organization;
2015.
11. WHO guidelines on quality risk management. In: WHO Expert Committee on Specifications for
Pharmaceutical Preparations: forty-seventh report. WHO Technical Report Series No. 981, Annex 2.
Geneva: World Health Organization; 2013.
12. Guidance on good data and record management practices. In: WHO Expert Committee on
Specifications for Pharmaceutical Preparations: fiftieth report. WHO Technical Report Series No.
996, Annex 5. Geneva: World Health Organization; 2016.
13. Guideline on data integrity. In: WHO Expert Committee on Specifications for Pharmaceutical
Preparations: fifty-fifth report. WHO Technical Report Series No. 1033, Annex 4. Geneva: World
Health Organization; 2021.
14. Points to consider when including health-based exposure limits (HBELs) in cleaning validation. In:
WHO Expert Committee on Specifications for Pharmaceutical Preparations: fifty-fifth report. WHO
Technical Report Series No. 1033, Annex 2. Geneva: World Health Organization; 2021.
15. A risk-based identification of essential medicines for local manufacturing in low- and middle-
income countries: draft for comments. Working document QAS/16.682. Geneva: World Health
Organization; 2016.

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Further reading
■■ European Medicines Agency. 2014. Guideline on setting health-based exposure limits for use in
risk identification in the manufacture of different medicinal products in shared facilities. EMA/
CHMP/CVMP/ SWP/169430/2012.
■■ European Medicines Agency. 2018. Questions and answers on implementation of risk-based
prevention of cross-contamination in production.
■■ European Medicines Agency. 2020. Reflection paper on good manufacturing practice and
marketing authorisation holders. EMA/457570/2019.
■■ International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use. 2005. Quality risk management. ICH harmonised guideline Q9,
current step 4 version, 9 November 2005.
■■ International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use. 2009. Pharmaceutical development. ICH harmonised guideline
Q8(R2), current step 4 version, August 2009.
■■ International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use. 2012. Development and manufacture of drug substances
(chemical entities and biotechnological/biological entities). ICH harmonised guideline Q11,
current step 4 version, 1 May 2012.
■■ International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use. 2019. Technical and regulatory considerations for pharmaceutical
product life cycle management. ICH harmonised guideline Q12, final version, 20 November 2019.
■■ International Medical Device Regulators Forum. 2018. Essential principles of safety and
performance of medical devices and IVD medical devices.
■■ International Society for Pharmaceutical Engineering. 2018. Good practice guide: technology
transfer, third edition.
■■ Parental Drug Association. 2014. Technical report No. 65: technology transfer.
WHO Technical Report Series, No. 1044, 2022

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Appendix 1
Documentation commonly required for technology
transfer
Table 1 provides examples of the documentation commonly required for
technology transfer. Note that these are examples: all the required documents
should be identified for the different tasks.

Table 1
Documentation commonly required for technology transfer

Aspect Related documentation

Regulatory Regulatory process description
Applicable regulatory documentation
Starting materials (active Drug master file, API master file, active substance
pharmaceutical ingredients master file
(APIs) and excipients) Material safety data sheets
Product development report
Storage conditions
Stability data
Forced stability data
Specifications
Supplier qualification
References
Formulation Formulation development reports
Master formula
Material compatibility and interaction studies
Specifications for delivery devices
Batch manufacturing Master of executed batch record
Scale-up information
Risk assessment
Critical process parameters
In-process control specification
Scale-up protocol and report
Process validation

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Table 1 continued
Aspect Related documentation
Packaging Packaging material specification
Master of executed packaging record
Validation
Sampling plan
Acceptance quality level for products and defects
Packaging validation
Finished product Specification
Product dossier
Analytical procedures Analytical test procedures
Analytical procedure development
Analytical procedure validation
Standard test procedures
Instrument specifications
Quality control Sampling procedures (e.g. in-process control)
Stability testing protocol and procedures
Release test analytical procedure validation
Equipment and instruments List of equipment and instruments
Preventive maintenance information
Overview of qualification
Cleaning Cleaning validation master plan
Cleaning procedure development and cleanability
Cleaning procedures
Health-based exposure level (permitted daily
WHO Technical Report Series, No. 1044, 2022

exposure) information reports

Analytical procedures validation for cleaning
Cleaning validation reports and recovery study
reports
Other documents Recalls and complaint reports
Bio-batch information
Pilot batch information
History of changes and change management
Hold time protocols and reports

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