Unit - Granularity Technology Transfer - SVK

Granularity of Technology
Development and Transfer

BY
S HUBHA M KHOT
A S ST. P ROF, DE PA RTMENT OF P HA R M ACEU TI CS
WHO guidelines on transfer of technology in
pharmaceutical manufacturing
1. Introduction
2. Scope
3. Glossary
4. Organization and management
5. Production: transfer (processing, packaging and cleaning)
6. Quality control: analytical method transfer
7. Premises and equipment
8. Documentation
9. Qualification and validation
Introduction
• Transfer of processes to an alternative site occurs at some stage in the life-cycle of most products,
from development, scale-up, manufacturing, production and launch, to the post-approval phase
• Defined as “a logical procedure that controls the transfer of any process together with its
documentation and professional expertise between development and manufacture or between
manufacture sites”
• It is a systematic procedure that is followed in order to pass the documented knowledge and
experience gained during development and or commercialization to an appropriate, responsible
and authorized party
• The ever changing business strategies of pharmaceutical companies increasingly involve intra-
and intercompany transfers of technology for reasons such as the need for additional capacity,
relocation of operations or consolidations and mergers.
• Transfer of technology requires a documented, planned approach using trained and
knowledgeable personnel working within a quality system, with documentation of data covering
all aspects of development, production and quality control
Introduction
• It usually involves a SU (Sending Unit) and RU (Receiving Unit)
• [Receiving unit (RU) involves disciplines at an organization where a designated product, process or method
is expected to be transferred]
• [Sending unit (SU) involves disciplines at an organization from where a designated product, process or
method is expected to be transferred]
Introduction
• For the transfer to be successful, the following general principles and requirements should be met:
• The project plan should encompass the quality aspects of the project and be based upon the principles of quality
risk management
• The capabilities of the SU and at the RU should be similar, but not necessarily identical, and facilities and
equipment should operate according to similar operating principles
• A comprehensive technical gap analysis between the SU and RU including technical risk assessment and potential
regulatory gaps, should be performed as needed
• Adequately trained staff should be available or should be trained at the RU
• Regulatory requirements in the countries of the SU and the RU, and in any countries where the product is intended
to be supplied, should be taken into account and interpreted consistently throughout any transfer program project
• There should be effective process and product knowledge transfer
Introduction
• Technology transfer can be considered successful if there is documented evidence that the RU can routinely
reproduce the transferred product, process or method against a predefined set of specifications as agreed
with the SU
• In the event that the RU identifies particular problems with the process during the transfer, the RU should
communicate them back to the SU to ensure continuing knowledge management
• Technology transfer projects, particularly those between different companies, have legal and economic
implications
• If such issues, which may include intellectual property rights, royalties, pricing, conflict of interest and
confidentiality, should be addressed before and during planning and execution of the transfer
• Any lack of transparency may lead to ineffective transfer of technology
• Some of the principles outlined in this document may also be applicable to manufacturing investigational
pharmaceutical products for clinical trials as part of research and development
Scope
• Provides general recommendations on the activities necessary to conduct a successful intra or
inter-site transfer of technology as described in the Introduction to these guidelines
• Applicable to manufacturing active pharmaceutical ingredients (APIs), manufacturing and
packaging of bulk materials, manufacturing and packaging of finished pharmaceutical products
(FPPs) and/or performing analytical testing
• [Finished pharmaceutical product (FPP): A product that has undergone all stages of
production, including packaging in its final container and labelling. An FPP may contain one or
more APIs]
• Guidelines apply to all dosage forms but need to be adjusted on a case-by-case basis (e.g. by
using risk management principles). Particularly close control of certain aspects will be required
for certain formulations such as sterile products, and metered dose aerosols
Introduction
• The guidelines address the following areas at the SU and the RU:
• Transfer of development and production (processing, packaging and cleaning)
• Transfer of analytical methods for quality assurance and quality control
• Skills assessment and training
• Organization and management of the transfer
• Assessment of premises and equipment
• Documentation
• Qualification and validation
• Because each transfer project is unique, the provision of a comprehensive set of guidelines is
beyond the scope of this document
Organization and management
• Transfer comprises an SU and an RU. In some circumstances there may be an additional unit
which will be responsible for directing, managing and approving the transfer
• There is a formal agreement between the parties, which specifies the responsibilities before,
during and after transfer
• Organization and management of a successful technology transfer need to ensure that the main
steps have been executed and documented
• There should be a project management plan which identifies and controls all the necessary
activities identified at the start of the undertaking
• The transfer protocol should list the intended sequential stages of the transfer. The protocol
should include:
• Objective
• Scope
• Key personnel and their responsibilities
• A parallel comparison of materials, methods and equipment
• The transfer stages with documented evidence that each critical stage has been satisfactorily
accomplished before the next commences
• Identification of critical control points
• The transfer protocol should list the intended sequential stages of the transfer. The protocol should
include:
• Experimental design and acceptance criteria for analytical methods
• Information on trial production batches, qualification batches and process validation
• Change control for any process deviations encountered
• assessment of end-product
• Arrangements for keeping retention samples of active ingredients, Intermediates and finished
products, and information on reference substances where applicable
• Conclusion, including signed-off approval by project manager
• Change control: A formal system by which qualified representatives of appropriate disciplines review
proposed or actual changes that might affect a validated status. The intent is to determine the need
for action that would ensure that the system is maintained in a validated state]
• The SU should provide the necessary validation documentation for the process and its support
functions. Usually, an established process is transferred, and such documentation is already
available
• The SU should provide criteria and information on hazards and critical steps associated with the
product, process or method to be transferred, to serve as a basis for a quality risk management
(QRM) exercise at the RU
• The SU or third party should assess the suitability and degree of preparedness of the RU before
transfer, with regard to premises, equipment and support services (e.g. purchasing and
inventory control mechanisms, quality control (QC) procedures, documentation, computer
validation, site validation, equipment qualification, water for pharmaceutical production and
waste management)
• The SU and the RU should jointly verify that the following, satisfactorily completed, validation
protocols are available:
• Installation qualification (IQ) and operational qualification (OQ) 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
• The SU and the RU should jointly implement any training programmes that may be required specific
to the product, process or method to be transferred, e.g. on analytical methods or equipment usage,
and assess training outcomes
• The SU and the RU should jointly execute the transfer protocol according to a checklist and or flow
diagram showing the sequence of steps to be carried out to effect an efficient transfer
• Any changes and adaptations made during the course of the technology transfer should be fully
documented
•The SU and the RU should jointly document the execution of the transfer protocol in a transfer of
technology summary in a report
• Project team
• Any transfer project will be managed by a team comprising members with clearly defined key
responsibilities.
• The team should be drawn from members of relevant disciplines from both the SU and RU sites
• The team members should have the necessary qualifications and experience to manage their
particular aspect of the transfer
Production: transfer (processing,
packaging and cleaning)
• The RU should be able to accommodate the intended production capacity. If possible, it should
be established at the outset whether the intention is to perform single-batch manufacture,
continuous production or campaigns.
• 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.
• Consideration should be given to the technical expertise, site technology and site capabilities
for the RU. It should be identified upfront by the SU of any process robustness issues so that
plans may be put in place at the RU.
• The SU and the RU should jointly develop a protocol for the transfer of relevant information
related to the process under consideration from the SU to the RU, as well as the development of
a comparable process at the RU.
• Starting materials
• The specifications and relevant functional characteristics of the starting materials (APIs and
excipients) to be used at the RU should be consistent with materials used at the SU.
• Any properties which are likely to influence the process or product should be identified and
characterized.
• Active pharmaceutical ingredients (API)
• The SU should provide the RU with the open (applicant’s) part of the API master file (APIMF or
drug master file (DMF) or active substance master file (ASMF)), or equivalent information and
any relevant additional information on the API of importance for the manufacture of the
pharmaceutical product.
• [Drug master file (DMF): Detailed information concerning a specific facility, process or product
submitted to the medicines regulatory authority, intended for incorporation into the application
for marketing authorization]
• The following are examples of the information which may typically be provided; however the
information needed in each specific case should be assessed using the principles of QRM:
• Manufacturer and associated supply chain
• Step of the API to be transferred
• Flow chart of synthesis pathway, outlining the process, including entry points for raw materials,
critical steps, process controls and intermediates
• Where relevant, definitive physical form of the API (including photomicrographs and other
relevant data) and any polymorphic and solvate forms
• Solubility profile
• if relevant, pH in solution
• Partition coefficient, including the method of determination
• Intrinsic dissolution rate, including the method of determination
• The following are examples of the information which may typically be provided; however the
• Particle size and distribution, including the method of determination
• Bulk physical properties, including data on bulk and tap density, surface area and porosity as
appropriate
• Water content and determination of hygroscopicity, including water activity data and special
handling requirements
• Microbiological considerations (including sterility, bacterial endotoxins and bioburden levels
where the API supports microbiological growth) in accordance with national, regional or
international pharmacopoeial requirements
• Specifications and justification for release and end-of-life limits
• Summary of stability studies conducted in conformity with current guidelines, including
conclusions and recommendations on retest date
• List of potential and observed synthetic impurities, with data to support proposed specifications
and typically observed levels
• Information on degradants, with a list of potential and observed degradation products and data
to support proposed specifications and typically observed levels
• Potency factor, indicating observed purity and justification for any recommended adjustment to
the input quantity of API for product manufacturing, providing example calculations
• Special considerations with implications for storage and or handling, including but not limited to
safety and environmental factors (e.g. as specified in material safety data sheets) and sensitivity
to heat, light or moisture
• Excipients
• The excipients to be used have a potential impact on the final product.
• Their specifications and relevant functional characteristics should, therefore, be made available
by the SU for transfer to the RU site
• The following are examples of the information which may typically be provided; however, the
• Manufacturer and associated supply chain
• Description of functionality, with justification for inclusion of any antioxidant, preservative or
any excipient
• Definitive form (particularly for solid and inhaled dosage forms)
• Solubility profile (particularly for inhaled and transdermal dosage forms)
• Partition coefficient, including the method of determination (for transdermal dosage forms)
• Excipients
• Intrinsic dissolution rate, including the method of determination (for transdermal dosage forms)
• Particle size and distribution, including the method of determination (for solid, inhaled and
transdermal dosage forms)
• Bulk physical properties, including data on bulk and tap density, surface area and porosity as
appropriate (for solid and inhaled dosage forms)
• Compaction properties (for solid dosage forms)
• Melting point range (for semi-solid or topical dosage forms)
• pH range (for parenteral, semi-solid or topical, liquid and transdermal dosage forms)
• Ionic strength (for parenteral dosage forms)
• Excipients
• Specific density or gravity (for parenteral, semi-solid or topical, liquid and transdermal dosage
forms)
• Viscosity and or viscoelasticity (for parenteral, semi-solid or topical, liquid and transdermal
dosage forms)
• Osmolarity (for parenteral dosage forms)
• Water content and determination of hygroscopicity, including water activity data and special
handling requirements (for solid and inhaled dosage forms)
• Moisture content range (for parenteral, semisolid or topical, liquid and transdermal dosage
forms)
• Excipients
• Microbiological considerations (including sterility, bacterial endotoxins and bioburden levels
where the excipient supports microbiological growth) in accordance with national, regional or
international pharmacopoeial requirements, as applicable (for general and specific monographs)
• Specifications and justification for release and end-of-life limits
• Information on adhesives supporting compliance with peel, sheer and adhesion design criteria
(for transdermal dosage forms)
• Excipients
• Special considerations with implications for storage and or handling, including but not limited to
safety and environmental factors (e.g. as specified in material safety data sheets (MSDS)) and
sensitivity to heat, light or moisture
• Regulatory considerations, e.g. documentation to support compliance with transmissible animal
spongiform encephalopathy certification requirements (where applicable)
• Information on process and finished pharmaceutical products information
• The SU should provide a detailed characterization of the product, 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
• The SU should provide any information on the history of process development which may be
required to enable the RU to perform any further development and or process optimization
after successful transfer. Such information may include the following:
• Information on clinical development, e.g. information on the rationale for the synthesis, route
and form selection, technology selection, equipment, clinical tests, and product composition
• Information on scale-up activities: process optimization, statistical optimization of critical
process parameters, critical quality attributes, pilot report and or information on pilot-scale
development activities indicating the number and disposition of batches manufactured
• Information or report on full-scale development activities, indicating the number and
disposition of batches manufactured, and deviation and change control (sometimes referred to
as change management) reports which led to the current manufacturing process
• The change history and reasons, e.g. a change control log, indicating any changes to the process
or primary packaging or analytical methods as a part of process optimization or improvement
• Information on investigations of problems and the outcomes of the investigations
• 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, e.g. need
for gowning or protective clothings
• The SU should provide to the RU information on current processing and testing, including but
not limited to:
• A detailed description of facility requirements and equipment
• Information on starting materials, applicable MSDS and storage requirements for raw materials
and finished products
• Description of manufacturing steps (narrative and process maps or flow charts, and or master
batch records), including qualification of in processing hold times and conditions, order and
method of raw material addition and bulk transfers between processing steps
• Description of analytical methods
• Identification and justification of control strategy (e.g. identification of critical performance
aspects for specific dosage forms, identification of process control points, product quality
attributes and qualification of critical processing parameter ranges, statistical process control
(SPC) charts)
• [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 materials and components related to drug substances and
drug 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]
• Design space, in cases where this has been defined
• Validation information, e.g. validation plans and reports
• Annual product quality reviews
• Stability information
• An authorized set of protocols and work instructions for manufacturing
• Environmental conditions or any special requirement needed for the facility or equipment
depending on the nature of the product to be transferred
• During the transfer process, the RU should identify any differences in facilities, systems and
capabilities and communicate with the SU about these differences to understand the potential
impact on ability to run the process to deliver good product quality
• Differences should be understood and satisfactorily addressed 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 relevant plant
operating procedures and documentation before the start of production
• Process development at the RU should address the following tasks:
• 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 and or process maps or flow charts)
• Determination of critical steps in manufacture, including hold times, endpoints, sampling points
and sampling techniques
• Writing and approval of SOPs for all production operations (e.g. dispensing, granulation or
blending or solution preparation, tablet compression, tablet coating, encapsulation, liquid filling,
primary and secondary packaging and in-process quality control), packaging, cleaning, testing
and storage
• Evaluation of stability information, with generation of site-specific stability data if required
• Compliance with regulatory requirements for any changes made, e.g. in terms of batch size
• Packaging:
• The transfer of packaging operations should follow the same procedural patterns as those of
the production transfer
• Information on packaging to be transferred from the SU to the RU includes specifications for a
suitable container or closure system, as well as any relevant additional information on design,
packing, processing or labelling requirements and tamper-evident and anti-counterfeiting
measures needed for qualification of packaging components at the RU
• For QC testing of packaging components, specifications should be provided for drawings,
artwork and material (for example, glass, card or fibre board)
• Based on the information provided, the RU should perform a suitability study for initial
qualification of the packaging components. Packaging is considered suitable if it provides
adequate protection (preventing degradation of the medicine due to environmental influences),
safety (absence of undesirable substances released into the product), compatibility (absence of
interaction possibly affecting medicine quality) and performance (functionality in terms of drug
delivery)
• Cleaning:
• During the manufacturing process, pharmaceutical products and APIs can be contaminated by
other pharmaceutical products or APIs if the plant is processing different products
• To minimize the risk of contamination and cross-contamination, operator exposure and
environmental effects, adequate cleaning procedures are essential
• Cleaning procedures and their validation are site-specific. In order for the RU to defi ne 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 solubility of active ingredients, excipients and vehicles
• Minimum therapeutic doses of active ingredients
• Therapeutic category and toxicological assessment
• Existing cleaning procedures
• Cleaning:
• Additional information should be provided, as appropriate and where available, e.g.:
• Cleaning validation reports (chemical and microbiological)
• 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
• Before the transfer, the SU should provide information on limits for product residues, and the
rationale for limit selection
• Based on the information provided by the SU, cleaning procedures should be designed at the
RU, taking into account relevant characteristics of the starting materials (e.g. potency, toxicity,
solubility, corrosiveness and temperature sensitivity), manufacturing equipment design and
configuration, cleaning agent and products residue
• Implementation of processing, packaging and cleaning systems:
• Trial batch(es) (“demonstration batches”) are normally produced to confirm process capability
before initiating formal validation. Where trial batches are produced, at a minimum, all critical
processing parameters and finished product specifications should be assessed
• Once process capability has been established at the RU, assuring that the product, process or
method at the RU meets predefined and justified specifications, process validation and cleaning
validation can be carried out
Quality control: analytical method
transfer
• Transfer of analytical methods should accommodate all the analytical testing required to
demonstrate compliance of the product to be transferred with the registered specification
• Analytical methods used to test pharmaceutical products, starting materials, packaging
components and cleaning (residue) samples, if applicable, should be implemented at the testing
laboratory before testing of samples for process validation studies is performed by the RU.
Process validation samples may be tested at the RU, the SU or a third laboratory
• A protocol defining the steps should be prepared for transfer of analytical methods. The
analytical methods 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; references; signed approval; and details of reference samples (starting materials,
intermediates and finished products).
transfer
• The SU’s responsibilities for the transfer of analytical methods are to:
• Provide method-specific training for analysts and other quality control staff, if required
• Assist in analysis of QC testing results
• Define all methods 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 methods under transfer and demonstrate their robustness
• Provide details of the equipment used, as necessary (part of validation report, if available) and
any standard reference samples
• Provide approved procedures used in testing
• Review and approve transfer reports.
transfer
• The RU’s responsibilities are to:
• Review analytical methods provided by the SU, and formally agree on acceptance criteria before
execution of the transfer protocol
• Ensure that the necessary equipment for QC is available and qualified at the RU site. The equipment
used by the RU during the analytical transfer should meet appropriate specifications to ensure the
requirements of the method 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 methods, and of reporting, recording and collating data and
designation of status (approved, rejected, quarantine)
• Execute the transfer protocol
• Perform the appropriate level of validation to support the implementation of the methods
• Generate and obtain approval of transfer reports
transfer
• Appropriate training should be provided and all training activities and outcomes should be
documented.
• Reference to compendial monographs (e.g. The International Pharmacopoeia (15), European
Pharmacopoeia, British Pharmacopoeia and United States Pharmacopeia), where available, is
expected.
• Possible experimental designs and acceptance criteria for the main analytical testing methods
are shown in Table 1. Note that this table represents high-level guidance to apply the general
principle that method transfers should account for the variability and sensitivity of the method
and the specifications for the quality parameter. Alternative procedures and acceptance criteria
may be applied based on science and the characteristics of the analytical method and the
analyte.
transfer
Test Considerations of Replication of test Set-up Acceptance criteria
transfer
Identity Transfer should focus One determination - -
on sample usually sufficient to
preparation, demonstrate
instruments, data equivalence
interpretation.
Acceptable to include
in assay transfer
where relevant
Assay for potency –Non-specific assay At each site: 2 Different sets of -Comparison of mean
should not be used analysts × 3 lots, in instruments and and variability
for stability testing. triplicate (= 18 per columns Independent -Two one sided t-tests
–Bracketing may be site) solution preparation with intersite
appropriate for differences ≤ 2% ,
multiple strengths 95% CI
Bracketing: An experimental design to test only the extremes of, for example, dosage strength. The design assumes
that the extremes will be representative of all the samples between the extremes.
transfer
Bracketing: An experimental design to test only the extremes of, for example, dosage strength.
The design assumes that the extremes will be representative of all the samples between the
extremes.
Bracketing is a simplified direct calibration method used to compensate for the variation on
instrument response with time.
A validation scheme / protocol designed such that only batches on the extremes of certain
predetermined and justified design factors, e.g., strength, batch size, pack size are tested during
process validation.
transfer
transfer
Content Uniformity If method is At each site: 2 Different sets of -Mean at RU within ±
equivalent to assay analysts, × 1 lot (= 2 instruments and 3% of mean at SU;
method, separate per site) columns Independent comparison of
transfer is not usually solution preparation relative S.D.
required -Two one sided t-tests
with intersite
differences ≤ 3% ,
95% CI
Dissolution Bracketing may be 6 units (12 if not - -Mean at RU within ±

appropriate for routine at RU, and for 5% of mean at SU
multiple strengths extended release -Compare profile (e.g.
products) F2), or Compare data
at Q time points as
for assay
transfer
transfer
Cleaning verification Confirm that same - Use spiked samples, -All samples spiked
(recovery of residues swabbing material is with levels within 3× above specification
from surfaces) used at sending unit validated S.D. or should fail
(SU) and receiving within ± 10% of – 90% of samples
unit (RU) specification spiked below specifi
(whichever is the cation should pass
greater)
Spiking: The addition of a known amount of a compound to a standard, sample or placebo, typically for the purpose of
confirming the performance of an analytical procedure
Quality control: analytical method transfer
transfer
Microbiological -Execute common on- Triplicate Use different lots for – Qualitative:
testing (qualitative site validation each validation Demonstrate
and quantitative limit protocol: rationale; recovery of
tests) method identity; microorganisms
validation – Quantitative:
parameters; data Recovery levels
summary; acceptance within acceptance
criteria; methods of limits specified in
compiling and protocol
analysing data;
handling of out-of-
specification results;
follow-up
requirements
– Use same materials,
techniques, inoculum
preparation
transfer
transfer
Impurity, – Confirm response At each site: 2 – Different days, – (For low levels)
degradation, factors for analysts × 3 lots, in different sets of Values at RU within
residual solvents calculation relative duplicate (in instruments and ± 25% of values at
to drug peak; triplicate if done columns SU, or Mean at RU
– Confirm limit of together with – Use samples of within ± 0.05% of
quantitation at RU; assay) similar age, mean at SU (5%)
– Compare homogeneity, – (For moderately
chromatograms packaging, storage high levels) Two
– Compare – Use spiked one sided t-tests,
accuracy and samples if differences ≤10%,
precision for necessary 95% CI
spiking
experiments
Premises and equipment
• Premises:
• The SU should provide information to the RU on the layout, construction and finish of buildings
and services (heating, ventilation and air conditioning (HVAC), temperature, relative humidity,
water, power, and compressed air), which have an impact on the product, process or method to be
transferred
• The SU should provide information on relevant health, safety and environmental issues, including:
• Inherent risks of the manufacturing processes (e.g. reactive chemical hazards, exposure limits, fire
and explosion risks)
• Health and safety requirements to minimize operator exposure (e.g. atmospheric containment of
pharmaceutical dust)
• Emergency planning considerations (e.g. in case of gas or dust release, spillage, fire and firewater
run-off)
• Identification of waste streams and provisions for re-use, recycling and/or disposal
• Equipment:
• The SU should provide a list of equipment, makes and models involved in the manufacture, filling,
packing and or control of the product, process or method to be transferred, together with existing
qualification and validation documentation.
• Relevant documentation may include:
• Drawings
• Manuals
• Maintenance logs
• Calibration logs
• Procedures (e.g. regarding equipment set-up, operation, cleaning, maintenance, calibration and
storage)
• Equipment:
• The RU should review the information provided by the SU together with its own inventory list
including the qualification status (IQ, OQ, PQ) of all equipment and systems, and perform a side-by-
side comparison of equipment at the two sites in terms of their functionality, makes, models and
qualification status.
• The RU should perform a gap analysis to identify requirements for adaptation of existing
equipment, or acquisition of new equipment, or a change in the process, to enable the RU to
reproduce the process being transferred.
• Equipment:
• GMP requirements should be satisfied and intended production volumes and batch sizes (e.g.
same, scaled-up or campaign) should be considered. Factors to be compared include:
• Minimum and maximum capacity
• Material of construction
• Critical operating parameters
• Critical equipment components (e.g. filters, screens, and temperature/pressure sensors)
• Critical quality attribute
• Range of intended use
• Equipment:
• The facility- and building-specific location of all equipment at the RU should be considered at the
time of drawing up process maps or flow charts of the manufacturing process to be transferred,
including flows of personnel and material
• The impact of manufacturing new products on products currently manufactured with the same
equipment should be determined
• Any modification of existing equipment that needs to be adapted to become capable of
reproducing the process being transferred should be documented in the transfer project plan
Documentation
• The documentation required for the transfer project itself is wide ranging. Examples of
documentation commonly required are summarized in Table 2.
• The documented evidence that the transfer of technology has been considered successful should
be formalized and stated in a technology transfer summary report.
• That report should summarize the scope of the transfer, the critical parameters as obtained in the
SU and RU (preferably in a tabulated format) and the final conclusions of the transfer.
• Possible discrepancies should be listed and appropriate actions, where needed, taken to resolve
them.
Documentation (Table 2)
Key Task Documentation provided by SU Transfer documentation
Project definition Project plan and quality plan Project implementation plan TOT
(where separate documents), protocol
protocol, risk assessments, gap
analysis
Quality agreement
Facility assessment Plans and layout of facility, Side-by-side comparison with RU
buildings (construction, finish) facility and buildings; gap analysis
Qualification status (DQ, IQ, OQ) Qualification protocol and report
and reports
Health and safety assessment Product-specific waste
management plans Contingency
plans
Documentation
Skill set analysis and training SOPs and training documentation Training protocols, assessment results
(product-specific operations, analysis,
testing)
Analytical method transfer Analytical method specifications and Analytical methods transfer protocol
validation, including in-process quality and report
control
Starting material evaluation Specifications and additional
information on APIs, excipients
Equipment selection and transfer Inventory list of all equipment and Side-by-side comparison with RU
systems, including makes, models, equipment (makes, models,
qualification status (IQ, OQ, PQ) qualification status) Gap analysis
Drawings, manuals, logs, SOPs (e.g. Qualification and validation protocol
set-up, operation, cleaning, and report
maintenance, calibration, storage)
Documentation
Process transfer: manufacturing and Reference batches (clinical, dossier, History of process development at RU
packaging biobatches) Experiences at RU should be recorded for
Development report (manufacturing future reference Provisional batch
process rationale) manufacturing document (RU to develop)
History of critical analytical data Rationale Provisional batch packaging document (RU
for specifications to develop) Description of process at RU
Change control documentation (narrative, process map, flow chart)
Critical manufacturing process parameters Process validation protocol and report
Process validation reports Drug master file
API validation status and report(s)
Product stability data
Current master batch manufacturing and
packaging records
List of all batches produced Deviation
reports Investigations, complaints, recalls
Annual product review
Documentation
Cleaning Cleaning validation, including: Product- and site-specific
Solubility information; cleaning SOPs at RU
therapeutic doses; category Cleaning validation protocol and
(toxicology); existing cleaning report
SOPs; validation reports —
chemical and micro; agents used;
recovery study
Documentation
• The extent of qualification and or validation to be performed should be determined on the basis of
risk management principles
• Qualification and validation should be documented
Documentation
•FDA Guidance for Industry - Process Validation: General Principles and Practices: This document
provides guidance on the general principles and practices of process validation for pharmaceuticals,
biologics, and medical devices. It outlines a lifecycle approach to process validation, including
stages such as process design, qualification, and continued process verification.
• FDA Guidance for Industry - Analytical Procedures and Methods Validation for Drugs and
Biologics: This guidance focuses on the validation of analytical methods used for testing
pharmaceutical products. It outlines the expectations for method development, validation, and
transfer, emphasizing accuracy, reliability, and reproducibility.
Documentation
• EMA Guideline on Process Validation for Finished Products - Information and Data to Be Provided
in Regulatory Submissions: This guideline offers information on the data and documentation
required for process validation in regulatory submissions within the European Union. It covers
principles for process validation and considerations for data submission.
•EMA Guideline on Validation of Bioanalytical Methods: This document provides guidance on the
validation of bioanalytical methods used for quantifying pharmaceuticals in biological samples. It
outlines the validation parameters, acceptance criteria, and documentation requirements.
Documentation
• ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients: While not
solely focused on validation and qualification, this guideline emphasizes the importance of process
validation for active pharmaceutical ingredients (APIs). It provides guidance on GMP requirements
for API manufacturing, including aspects of validation.
•ICH Q2(R1) Validation of Analytical Procedures: Text and Methodology: This guideline provides a
comprehensive framework for the validation of analytical methods used in pharmaceutical quality
control. It covers parameters such as specificity, accuracy, precision, and linearity.
Documentation
1. Health Canada:
1. Guidance Document: Process Validation Requirements for Drug Products: This document outlines the
expectations for process validation in Canada. It covers topics such as process design, qualification, and
process validation stages. It emphasizes a risk-based approach to validation.
2.PIC/S (Pharmaceutical Inspection Co-operation Scheme):

1. PIC/S PE 009-14 Validation of Aseptic Processes: This document provides guidance on the validation of
aseptic processes used in the manufacture of sterile pharmaceutical products. It covers aspects like
design and operational qualification, media fill studies, and ongoing monitoring.
QUIZ
Question 1: What is the primary goal of pharmaceutical technology transfer?
a) Maximizing profits
b) Developing new patents
c) Ensuring patient safety and product quality
d) Reducing research and development costs
Question 2: What is the purpose of "Installation Qualification (IQ)" in technology transfer?
a) Testing the equipment under operational conditions
b) Ensuring that equipment is properly installed and meets specifications
c) Validating the entire manufacturing process
d) Assessing the effectiveness of cleaning procedures
QUIZ
Question 3: What is the key focus of "Analytical Method Validation" during technology transfer?
a) Training personnel on new equipment
b) Ensuring regulatory compliance for technology transfer
c) Transferring manufacturing processes to a new facility
d) Verifying the accuracy and reliability of testing methods
Question 4: Why is risk assessment important in pharmaceutical technology transfer?
a) To minimize the use of advanced technologies
b) To eliminate all potential challenges
c) To prioritize validation efforts and address potential issues
d) To ensure a quick and hasty transfer process
QUIZ
Question 5: Which stage of validation ensures that a manufacturing process consistently produces
products meeting quality specifications?
a) Process Qualification (PQ)
b) Operational Qualification (OQ)
c) Installation Qualification (IQ)
d) Performance Qualification (PQ)
Question 6: How can comparative testing be useful during pharmaceutical technology transfer?
a) It verifies the compliance with regulatory guidelines.
b) It ensures that personnel are properly trained.
c) It identifies discrepancies and differences between source and receiving sites.
d) It minimizes the need for validation.
QUIZ
Question 7: What is the purpose of "Operational Qualification (OQ)" in technology transfer?
a) Testing the equipment under operational conditions
b) Ensuring that equipment is properly installed and meets specifications
c) Validating the entire manufacturing process
d) Assessing the effectiveness of cleaning procedures
Question 8: What role does documentation play in technology transfer?
a) To create a record of all employees involved in the transfer
b) To provide instructions for the use of new equipment
c) To ensure that technology transfer is carried out quickly
d) To maintain a comprehensive record of all activities and decisions made
QUIZ
Question 9: Which aspect of technology transfer involves adapting a process to different
regulatory requirements?
a) Comparative testing
b) Risk assessment
c) Validation
d) Quality control
Question 10: What impact can successful technology transfer have on global health?
a) It can increase profits for pharmaceutical companies.
b) It can lead to rapid patent expiration.
c) It can improve patient outcomes by increasing access to essential medicines.
d) It can increase competition among pharmaceutical manufacturers.
Quality Risk Management – ICH Q9
• It is commonly understood that risk is defined as the combination of the probability of occurrence
of harm and the severity of that harm.
• The manufacturing and use of a drug substance and drug product, including its components,
necessarily entail some degree of risk.
• The risk to its quality is just one component of the overall risk.
• It is important to understand that product quality should be maintained throughout the product
lifecycle.
• An effective quality risk management approach can further ensure the high quality.
• Provides a proactive means to identify and control potential quality issues during development and
manufacturing.
• Also improves decision making and prediction of errors.
• Quality risk management that can be applied to different aspects of pharmaceutical quality.
• These aspects include development, manufacturing, distribution, and the inspection and
submission/review processes throughout the lifecycle of drug substances, drug (medicinal)
products, biological and biotechnological products (including the use of raw materials, solvents,
excipients, packaging and labeling materials in drug (medicinal) products, biological and
biotechnological products).
• Two primary principles of quality risk management are:
• The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to
the protection of the patient.
• The level of effort, formality and documentation of the quality risk management process should be
commensurate with the level of risk.
• Responsibilities:
• Quality risk management activities are usually, but not always, undertaken by interdisciplinary
teams.
• When teams are formed, they should include experts from the appropriate areas (e.g., quality unit,
business development, engineering, regulatory affairs, production operations, sales and marketing,
legal, statistics and clinical) in addition to individuals who are knowledgeable about the quality risk
management process.
• Decision makers should…
• Take responsibility for coordinating quality risk management across various functions and
departments of their organization
• Assure that a quality risk management process is defined, deployed and reviewed and that
adequate resources are available.
• Initiating a Quality Risk Management Process:
• Quality risk management should include systematic processes designed to coordinate, facilitate
and improve science-based decision making with respect to risk.
• Possible steps used to initiate and plan a quality risk management process might include the
following:
• Define the problem and/or risk question, including pertinent assumptions identifying the potential
for risk.
• Assemble background information and/ or data on the potential hazard, harm or human health
impact relevant to the risk assessment.
• Identify a leader and necessary resources.
• Specify a timeline, deliverables and appropriate level of decision making for the risk management
process.
• Risk assessment:
• It consists of the identification of hazards and the analysis and evaluation of risks associated with
exposure to those hazards (as defined below).
• Quality risk assessments begin with a well-defined problem description or risk question.
• When the risk in question is well defined, an appropriate risk management tool and the types of
information needed to address the risk question will be more readily identifiable.
• As an aid to clearly defining the risk(s) for risk assessment purposes, three fundamental questions
are often helpful:
• 1. What might go wrong?
• 2. What is the likelihood (probability) it will go wrong?
• 3. What are the consequences (severity)?
• Risk identification:
• It is a systematic use of information to identify hazards referring to the risk
question or problem description.
• Information can include historical data, theoretical analysis, informed opinions,
and the concerns of stakeholders.
• Risk identification addresses the “What might go wrong?” question, including
identifying the possible consequences.
• This provides the basis for further steps in the quality risk management process.
• Risk analysis is the estimation of the risk associated with the identified hazards.
• It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of
harms.
• In some risk management tools, the ability to detect the harm (detectability) also factors in the
estimation of risk.
• Risk evaluation compares the identified and analyzed risk against given risk criteria.
• Risk evaluations consider the strength of evidence for all three of the fundamental questions.
• Uncertainty is due to combination of incomplete knowledge about a process and its expected or
unexpected variability.
• Typical sources of uncertainty include gaps in knowledge gaps in pharmaceutical science and
process understanding, sources of harm (e.g., failure modes of a process, sources of variability),
and probability of detection of problems.
• The output of a risk assessment is either a quantitative estimate of risk or a qualitative description
of a range of risk.
• When risk is expressed quantitatively, a numerical probability is used.
• Alternatively, risk can be expressed using qualitative descriptors, such as “high”, “medium”, or
“low”, which should be defined in as much detail as possible.
• Sometimes a "risk score" is used to further define descriptors in risk ranking.
• In quantitative risk assessments, a risk estimate provides the likelihood of a
specific consequence, given a set of risk-generating circumstances.
• Thus, quantitative risk estimation is useful for one particular consequence at a
time.
• Alternatively, some risk management tools use a relative risk measure to combine
multiple levels of severity and probability into an overall estimate of relative risk.
• The intermediate steps within a scoring process can sometimes employ
quantitative risk estimation.
• Risk control includes decision making to reduce and/or accept risks. The purpose of risk control is
to reduce the risk to an acceptable level.
• The amount of effort used for risk control should be proportional to the significance of the risk.
• Decision makers might use different processes, including benefit-cost analysis, for understanding
the optimal level of risk control.
• Risk control might focus on the following questions:
• Is the risk above an acceptable level?
• What can be done to reduce or eliminate risks?
• What is the appropriate balance among benefits, risks and resources?
• Are new risks introduced as a result of the identified risks being controlled?
• Risk reduction focuses on processes for mitigation or avoidance of quality risk
when it exceeds a specified (acceptable) level.
• Risk reduction might include actions taken to mitigate the severity and probability
of harm.
• Processes that improve the detectability of hazards and quality risks might also be
used as part of a risk control strategy.
• The implementation of risk reduction measures can introduce new risks into the
system or increase the significance of other existing risks.
• Hence, it might be appropriate to revisit the risk assessment to identify and
evaluate any possible change in risk after implementing a risk reduction process.
• Risk acceptance is a decision to accept risk.
• Risk acceptance can be a formal decision to accept the residual risk or it can be a
passive decision in which residual risks are not specified.
• For some types of harms, even the best quality risk management practices might
not entirely eliminate risk.
• In these circumstances, it might be agreed that an appropriate quality risk
management strategy has been applied and that quality risk is reduced to a
specified (acceptable) level.
• This (specified) acceptable level will depend on many parameters and should be
decided on a case-by-case basis.
• Risk communication is the sharing of information about risk and risk management between the
decision makers and others.
• Parties can communicate at any stage of the risk management process. The output/result of the
quality risk management process should be appropriately communicated and documented.
• Communications might include those among interested parties; e.g., regulators and industry,
industry and the patient, within a company, industry or regulatory authority, etc.
• The included information might relate to the existence, nature, form, probability, severity,
acceptability, control, treatment, detectability or other aspects of risks to quality.
• Communication need not be carried out for each and every risk acceptance.
• Risk Review should be an ongoing part of the quality management process.
• A mechanism to review or monitor events should be implemented.
• The output/results of the risk management process should be reviewed to take into account new
knowledge and experience.
• Once a quality risk management process has been initiated, that process should continue to be
utilized for events that might impact the original quality risk management decision, whether these
events are planned (e.g., results of product review, inspections, audits, change control) or
unplanned (e.g., root cause from failure investigations, recall).
• The frequency of any review should be based upon the level of risk. Risk review might include
reconsideration of risk acceptance decisions.
Risk Management tools
• Quality risk management supports a scientific and practical approach to decision making.
• It provides documented, transparent and reproducible methods to accomplish steps of the quality risk
management process based on current knowledge about assessing the probability, severity and
sometimes detectability of the risk.
• Failure Mode Effects Analysis (FMEA)
• Failure Mode, Effects and Criticality Analysis (FMECA)
• Fault Tree Analysis (FTA)
• Hazard Analysis and Critical Control Points (HACCP)
• Hazard Operability Analysis (HAZOP)
• Preliminary Hazard Analysis (PHA)
• Risk ranking and filtering
• Supporting statistical tools.
• Basic risk management include some of the simple techniques that are commonly
used to structure risk management by organizing data and facilitating decision-
making are:
• Flowcharts
• Check Sheets
• Process Mapping
• Cause and Effect Diagrams (also called an Ishikawa diagram or fish bone diagram).
• FMEA provides for an evaluation of potential failure modes for processes and their likely effect on
outcomes and/or product performance.
• Once failure modes are established, risk reduction can be used to eliminate, contain, reduce or
control the potential failures.
• FMEA relies on product and process understanding.
• FMEA methodically breaks down the analysis of complex processes into manageable steps.
• It is a powerful tool for summarizing the important modes of failure, factors causing these failures
and the likely effects of these failures.
• Potential use
• FMEA can be used to prioritize risks and monitor the effectiveness of risk control activities.
• FMEA can be applied to equipment and facilities and might be used to analyze a manufacturing
operation and its effect on product or process.
• It identifies elements/operations within the system that render it vulnerable.
• The output/results of FMEA can be used as a basis for design or further analysis or to guide
resource deployment.
• The FTA tool is an approach that assumes failure of the functionality of a product
or process.
• This tool evaluates system (or sub-system) failures one at a time but can combine
multiple causes of failure by identifying causal chains.
• The results are represented pictorially in the form of a tree of fault modes. At each
level in the tree, combinations of fault modes are described with logical operators
(AND, OR, etc.).
• FTA relies on the experts’ process understanding to identify causal factors.
• Potential Areas of Use(s)
• FTA can be used to establish the pathway to the root cause of the failure.
• FTA can be used to investigate complaints or deviations in order to fully understand their root
cause and to ensure that intended improvements will fully resolve the issue and not lead to other
issues (i.e. solve one problem yet cause a different problem).
• Fault Tree Analysis is an effective tool for evaluating how multiple factors affect a given issue.
• The output of an FTA includes a visual representation of failure modes.
• It is useful both for risk assessment and in developing monitoring programs.
• HACCP is a systematic, proactive, and preventive tool for assuring product quality,
reliability, and safety.
• It is a structured approach that applies technical and scientific principles to
analyze, evaluate, prevent, and control the risk or adverse consequence(s) of
hazard(s) due to the design, development, production, and use of products.
• HACCP consists of the following seven steps:
• (1) conduct a hazard analysis and identify preventive measures for each step of the
process
• (2) determine the critical control points
• (3) establish critical limits
• (4) establish a system to monitor the critical control points
• (5) establish the corrective action to be taken when monitoring indicates that the critical
control points are not in a state of control
• (6) establish system to verify that the HACCP system is working effectively
• (7) establish a record-keeping system.
• HACCP might be used to identify and manage risks associated with physical, chemical and
biological hazards (including microbiological contamination).
• HACCP is most useful when product and process understanding is sufficiently comprehensive to
support identification of critical control points.
• The output of a HACCP analysis is risk management information that facilitates monitoring of
critical points not only in the manufacturing process but also in other life cycle phases.
• HAZOP is based on a theory that assumes that risk events are caused by deviations from the design
or operating intentions.
• It is a systematic brainstorming technique for identifying hazards using so-called “guide-words”.
• “Guide-words” (e.g., No, More, Other Than, Part of, etc.) are applied to relevant parameters (e.g.,
contamination, temperature) to help identify potential deviations from normal use or design
intentions.
• It often uses a team of people with expertise covering the design of the process or product and its
application.
• HAZOP can be applied to manufacturing processes, including outsourced production and
formulation as well as the upstream suppliers, equipment and facilities for drug substances and
drug (medicinal) products.
• It has also been used primarily in the pharmaceutical industry for evaluating process safety
hazards.
• As is the case with HACCP, the output of a HAZOP analysis is a list of critical operations for risk
management. This facilitates regular monitoring of critical points in the manufacturing process.
• PHA is a tool of analysis based on applying prior experience or knowledge of a hazard or failure to
identify future hazards, hazardous situations and events that might cause harm, as well as to
estimate their probability of occurrence for a given activity, facility, product or system.
• The tool consists of:
• 1) the identification of the possibilities that the risk event happens
• 2) the qualitative evaluation of the extent of possible injury or damage to health that could result
• 3) a relative ranking of the hazard using a combination of severity and likelihood of occurrence
• 4) the identification of possible remedial measures
• PHA might be useful when analyzing existing systems or prioritizing hazards where circumstances
prevent a more extensive technique from being used.
• It can be used for product, process and facility design as well as to evaluate the types of hazards for
the general product type, then the product class, and finally the specific product.
• PHA is most commonly used early in the development of a project when there is little information
on design details or operating procedures; thus, it will often be a precursor to further studies.
• Typically, hazards identified in the PHA are further assessed with other risk management tools such
as those in this section.
• Risk Ranking and Filtering
• Risk ranking and filtering is a tool for comparing and ranking risks.
• Risk ranking of complex systems typically requires evaluation of multiple diverse quantitative and
qualitative factors for each risk.
• The tool involves breaking down a basic risk question into as many components as needed to
capture factors involved in the risk.
• These factors are combined into a single relative risk score that can then be used for ranking risks.
• “Filters,” in the form of weighting factors or cut-offs for risk scores, can be used to scale or fit the
risk ranking to management or policy objectives.
• Risk ranking and filtering can be used to prioritize manufacturing sites for inspection/audit by
regulators or industry.
• Risk ranking methods are particularly helpful in situations in which the portfolio of risks and the
underlying consequences to be managed are diverse and difficult to compare using a single tool.
• Risk ranking is useful when management needs to evaluate both quantitatively-assessed and
qualitatively-assessed risks within the same organizational framework.
• Supporting Statistical Tools
• Statistical tools can support and facilitate quality risk management.
• They can enable effective data assessment, aid in determining the significance of the data set(s),
and facilitate more reliable decision making.
• A listing of some of the principal statistical tools commonly used in the pharmaceutical industry is
provided:
• Control Charts, for example: - Acceptance Control Charts, Control Charts with Arithmetic Average
and Warning Limits, Cumulative Sum Charts, Shewhart Control Charts, and Weighted Moving
Average.
• Design of Experiments (DOE); Histograms; Pareto Charts; Process Capability Analysis.
• Control Charts
• Design of Experiments (DOE)
• Histograms and Pareto Charts
• Histograms and Pareto Charts
• Process Capability Analysis
QUIZ
Question 1: What does ICH Q9 focus on?
A) Manufacturing techniques
B) Risk management in pharmaceuticals
C) Clinical trial design
D) Drug pricing
Question 2: Which step of risk management involves identifying potential sources of risk and
hazards?
A) Risk Assessment
B) Risk Identification
C) Risk Control
D) Risk Evaluation
QUIZ
Question 3: What is the main purpose of a HAZOP study?
A) Identifying critical control points
B) Analyzing process capability
C) Identifying and analyzing potential hazards
D) Conducting statistical analysis
Question 4: Which tool is commonly used to monitor and control a process over time?
A) Fault Tree Analysis
B) Pareto Chart
C) Control Chart
D) Preliminary Hazard Analysis
QUIZ
Question 5: What is the purpose of a Pareto Chart in risk management?
A) To identify potential hazards
B) To analyze process capability
C) To prioritize factors based on impact
D) To perform probability assessments
Question 6: Which element of risk management involves ranking risks based on their significance?
A) Risk Assessment
B) Risk Identification
C) Risk Evaluation
D) Risk Communication
QUIZ
Question 7: What does HACCP stand for?
A) Hazard Analysis and Critical Control Points
B) High Accuracy Control Chart Procedure
C) Hazard Assessment and Capability Control Plan
D) Health and Clinical Care Practices
Question 8: Which tool uses a graphical representation to analyze the causes of a specific event?
A) Histogram
B) Fault Tree Analysis
C) Pareto Chart
D) Control Chart
QUIZ
Question 9: What is the primary goal of risk communication?
A) To hide risks from stakeholders
B) To eliminate all risks from the process
C) To ensure regulatory compliance
D) To inform stakeholders about risks and risk management strategies
Question 10: Which step of risk management involves implementing measures to mitigate risks?
A) Risk Identification
B) Risk Assessment
C) Risk Control
D) Risk Evaluation
QUIZ
Question 11: What is the purpose of a Preliminary Hazard Analysis (PHA)?
A) To identify potential hazards early in the design phase
B) To analyze process capability
C) To rank risks based on impact
D) To conduct statistical analysis
Question 12: Which tool involves working backward from an undesired outcome to identify
contributing factors?
A) HAZOP
B) Fault Tree Analysis
C) Preliminary Hazard Analysis
D) Risk Ranking and Filtering
QUIZ
Question 13: What does the "Q" in ICH Q9 stand for?
A) Quality
B) Quantity
C) Quotient
D) Questionnaire
Question 14: What is the purpose of risk assessment in quality risk management?
A) To eliminate all risks from the process
B) To rank risks based on their significance
C) To identify and evaluate potential risks
D) To communicate risks to stakeholders
QUIZ
Question 15: Which step of risk management involves the iterative process of reviewing and
monitoring risks?
A) Risk Control
B) Risk Assessment
C) Risk Evaluation
D) Risk Review and Monitoring
Question 16: What is the purpose of process capability analysis in risk management?
A) To identify potential hazards
B) To evaluate the potential for defects and variations in the process
C) To analyze process capability
D) To rank risks based on impact
QUIZ
Question 17: Which tool is used to assess whether a process is capable of producing products within
specified limits?
A) Control Chart
B) HACCP
C) Fault Tree Analysis
D) Risk Ranking and Filtering
Question 18: What is the main purpose of risk ranking and filtering in risk management?
A) To eliminate all risks from the process
B) To communicate risks to stakeholders
C) To prioritize risks based on their significance
D) To conduct statistical analysis
QUIZ
Question 19: What does the term "iterative" mean in the context of risk management?
A) Following a fixed process without changes
B) Repeating a process with slight variations
C) Skipping steps in the process
D) Ignoring risks during the process
Question 20: Which element of risk management involves transparent and accurate sharing of risk
information?
A) Risk Assessment
B) Risk Control
C) Risk Communication
D) Risk Evaluation
TT Agencies in India
• APCTT
• NRDC
• TIFAC
• TBSE/SIDBI
• BCIL
• APCTT
• The Asian and Pacific Centre for Transfer of Technology (APCTT) is a regional institution under the
United Nations Economic and Social Commission for Asia and the Pacific (ESCAP).
• It is based in India and serves as a platform to promote the transfer of technology, innovation, and
knowledge among countries in the Asia-Pacific region.
• Objectives:
• Technology Transfer and Innovation:
• APCTT focuses on facilitating the transfer of technology and knowledge between countries in the
Asia-Pacific region.
• It aims to bridge the gap between technology-rich and technology-poor countries by promoting
collaboration, partnerships, and technology sharing.
• APCTT
• Objectives:
• Capacity Building:
• APCTT offers capacity-building programs, training workshops, and seminars to enhance the skills
and capabilities of professionals, researchers, and policymakers in the field of technology transfer
and innovation.
• APCT provide capacity-building support to policymakers and other stakeholders to design effective
polices to facilitate sound development of the technology-based entrepreneurs, start-ups, and
SMEs.
• The programme covers key aspects as technology business incubation, technology transfer and
commercialization, start-up internationalization, financing tools and mechanisms, among others.
• APCTT
• Objectives:
• Policy Support: APCTT provides policy advice, research, and analysis to member countries to help
them create conducive environments for technology transfer, innovation, and the development of a
vibrant technology ecosystem.
•Technology Information and Networking:
• APCTT serves as a hub for technology-related information, resources, and best practices.
• It creates networks and platforms for sharing knowledge, experiences, and successful technology
transfer stories.
• Innovation and Entrepreneurship:
• APCTT supports initiatives related to innovation and entrepreneurship by providing guidance,
mentorship, and resources to startups, small enterprises, and innovators.
• APCTT
• Objectives:
• International Collaboration:
• APCTT collaborates with international organizations, institutions, and agencies to foster global
cooperation in the field of technology transfer and innovation.
• Sustainable Development:
• APCTT promotes the use of technology and innovation to address sustainable development
challenges, such as climate change, poverty alleviation, and inclusive growth.
• APCTT
• Technology Bureau for Small Enterprises (TBSE) is a joint venture between Small Industries
Development Bank of India (SIDBI) and Asian and Pacific Centre for Technology Transfer (APCTT) to
assist Small and Medium Enterprises (SME) in finance and technology.
• The Technology Bureau for Small Enterprises (TBSE) is a platform for MSMEs to tap opportunities
at the global level for the acquisition of technology or establishing business collaboration.
• APCTT – TBSE/SIDBI
• Features of Technology Bureau for Small Enterprises (TBSE)
• Offering a professionally managed system for the reasons of technology and collaboration
exploration.
• Helping in the building up of confidence between potential partners.
• Lending a friendly hand in the complex task of negotiations and matching of perceptions.
• Providing an opportunity to global technology market through the process of networking.
• Exclusive mechanism for the arrangement of technology and finance.
• Taking up project appraisal and the preparation of a business plan.
• Services offered:
• Technology Information:
• The TBSE has a huge computerized data base related to technology options obtainable from
different countries.
• It provides the user updated information on the sources of technologies and means of accessing
them.
• In addition background information on technology-seeking enterprises is maintained and ready
available to interested technology suppliers as well as collaborators.
• Match Making:
• The TBSE recognizes business partners who are willing to work in partnership, brings them face-to-
face and offers support to tie up financial assistance and other necessities for transfer of
technology and joint ventures.
• Collaborating partners are further helped in drafting agreements, obtaining a range of approvals
and preparation of business plans.
•The TBSE also renders support to small enterprises for the reason of export of technologies and the
products created by them by means of business tie-ups as a part of the package.
• To encourage international cooperation amid SMEs the Bureau organizes overseas visits of
business delegations.
• Finance Syndication
• It is dependent on the cost of project, nature and quantum of assistance necessary,
• the TBSE undertakes financial syndication through SIDBI –
• Covering term loans, foreign currency, venture capital, lines of credit, equity assistance and on a
selective basis offering interest-free loan to meet preliminary expenditure in the pre-technology
absorption stage.
•Support Services
•The Technology Bureau for Small Enterprises offers consultancy services, visits of overseas experts
for the purpose of in-plant counseling, organizes buyer-seller meets for precise product process
technologies and represents the business interests of small enterprises in the domain of
international events.
• APCTT – SIDBI
• The Small Industries Development Bank of India (SIDBI) is a financial institution based in India that
primarily focuses on providing financial and developmental support to the micro, small, and
medium-sized enterprises (MSMEs) sector.
• It was established on April 2, 1990, through an Act of Parliament as a wholly-owned subsidiary of
the Industrial Development Bank of India (IDBI).
• However, in April 2000, it became an independent entity under the ownership of the Indian
Government.
• Objectives:
• Financial Assistance: SIDBI offers various financial products and services to MSMEs, such as term
loans, working capital loans, venture capital, and direct and indirect refinance facilities through
partner financial institutions.
• APCTT – SIDBI
• Objectives:
• Developmental Initiatives:
• The bank is involved in various developmental activities aimed at fostering the growth and
development of MSMEs.
• These initiatives include promoting innovation, technology adoption, and skill development within
the sector.
• Credit Guarantee: SIDBI operates credit guarantee schemes to provide collateral-free credit to
MSMEs, enabling them to access finance even if they lack sufficient collateral.
• Risk Capital: The bank provides risk capital to startups and early-stage enterprises through its
venture capital arm, SIDBI Venture Capital Limited (SVCL).
• APCTT – SIDBI
• Objectives:
• Capacity Building: SIDBI conducts training programs, workshops, and seminars to enhance the
business management skills and technical knowledge of MSME entrepreneurs.
• International Cooperation: SIDBI collaborates with international organizations and institutions to
promote best practices, knowledge exchange, and international partnerships for the benefit of
Indian MSMEs.
• Sustainable Development: SIDBI also focuses on promoting environmentally sustainable practices
among MSMEs through initiatives related to energy efficiency, clean technologies, and green
financing.
• NRDC
• The National Research Development Corporation (NRDC) is an enterprise under the Department of
Scientific and Industrial Research (DSIR) of the Ministry of Science and Technology, Government of
India.
• NRDC was established in 1953 with the aim of promoting, developing, and commercializing
technologies, innovations, and intellectual property emerging from research and development
activities in India.
• To promote, develop, nurture and commercialize innovative, reliable and competitive technologies
from RnD institutes through values addition and partnership.
• To install and work pilot, proto-type, or semi-scale unit, or full commercial plants to develop a
innovation or invention and ensure production for sale.
• NRDC
• NRDC
• NRDC
• Objectives:
• Technology Transfer and Commercialization:
• NRDC facilitates the transfer of technologies and innovations developed in research institutions,
universities, and laboratories to the commercial sector.
• This involves licensing technologies to industries and entrepreneurs for further development and
commercialization.
• NRDC
• Objectives:
• Intellectual Property Management:
• NRDC helps in managing and protecting intellectual property rights (IPR) arising from research
activities.
• This includes filing patents and copyrights to safeguard the innovative work of researchers.
• Promoting Innovation and Entrepreneurship:
• NRDC plays a role in fostering innovation and entrepreneurship by supporting startups and small
enterprises that are working on innovative technologies.
• They provide guidance, resources, and financial assistance to these entities.
• NRDC
• Objectives:
• Consultancy and Project Services:
• NRDC offers consultancy and project management services to organizations looking to develop,
commercialize, or implement technology-related projects.
• Collaborations and Partnerships:
• NRDC collaborates with industries, research institutions, universities, and other stakeholders to
promote technology transfer, research, and development partnerships.
• NRDC
• Objectives:
• Technology Awareness and Training:
• NRDC conducts workshops, seminars, and training programs to raise awareness about technology
transfer and commercialization among researchers, entrepreneurs, and industries.
• International Collaborations:
• NRDC fosters international collaborations and partnerships to promote knowledge exchange,
technology transfer, and joint research efforts with organizations outside of India.
• Technology Valuation: NRDC assists in assessing the value of technologies and innovations, helping
researchers and inventors understand the potential commercial viability of their work.
• NRDC
• Achievements:
• Over 4800 Technology license agreements signed
• Over 2000 technologies available for commercialization in various sectors
• 890 Innovations awarded
• Promoted 350 IP awareness programmes
• Filed 1700 patents
• Over 50,000 scientists/employees
• International contacts and promotions; Ghana, Japan, Argentina etc.
• TIFAC
• The Technology Information, Forecasting and Assessment Council (TIFAC) is an autonomous
organization in India under the Department of Science and Technology (DST).
• TIFAC was established in 1988 with the aim of promoting technological advancements, innovation,
and technology forecasting and assessment in various sectors.
• Objectives:
• Technology Forecasting and Assessment:
• TIFAC conducts studies and assessments to forecast emerging technology trends and their
potential impact on various sectors of the economy.
• This information helps policymakers, industries, and researchers make informed decisions about
technology adoption and development.
• TIFAC
• Objectives:
• Technology Development and Innovation:
• TIFAC supports technology development and innovation by providing funding, resources, and
guidance to research and development projects.
• It aims to bridge the gap between academia and industry, facilitating the transfer of technology
from the lab to practical applications.
• Promoting Industry-Academia Collaboration:
• TIFAC encourages collaboration between industries and academic institutions to foster research,
innovation, and knowledge exchange.
• This collaboration is crucial for addressing real-world challenges and developing solutions with
practical applications.
• TIFAC
• Objectives:
• Technology Networking and Dissemination:
• TIFAC creates networks and platforms for sharing technology-related information, best practices,
and experiences.
• This helps in creating a collaborative ecosystem that benefits both researchers and industries.
• Technology Policy Advocacy:
• TIFAC contributes to the formulation of technology policies by providing insights, data, and
recommendations to government bodies.
• It plays a role in shaping policies that promote technology-driven growth and development.
• TIFAC
• Objectives:
• Entrepreneurship and Startups:
• TIFAC supports entrepreneurship and startup initiatives by providing mentoring, guidance, and
resources to aspiring entrepreneurs who are working on innovative technologies.
• Skill Development and Capacity Building:
• TIFAC organizes training programs, workshops, and seminars to enhance the skills and capabilities
of professionals in various technology domains.
• BCIL
• Biotechnology Consortium India Limited (BCIL) is a government-owned company in India that
operates under the Department of Biotechnology, Ministry of Science and Technology, Government
of India.
• BCIL primarily focuses on promoting and supporting biotechnology-related activities and projects
in the country.
• Objectives:
• Commercialization of Technologies:
• BCIL helps in transferring biotechnology innovations from research institutions and laboratories to
the commercial sector by facilitating technology transfer and licensing agreements.
• BCIL
• Objectives:
• Entrepreneurship Development:
• BCIL assists in nurturing biotechnology startups and entrepreneurs by providing them with
guidance, mentorship, and access to resources.
• They often organize workshops, training programs, and events to foster entrepreneurship in the
biotech sector.
• International Collaborations:
• BCIL works to establish collaborations and partnerships between Indian biotech companies,
research institutions, and their counterparts in other countries.
• This helps in knowledge exchange and the development of new technologies.
• BCIL
• Objectives:
• Project Management and Consultancy: BCIL provides project management services and
consultancy to various biotechnology projects, helping them navigate regulatory, technical, and
business challenges.
• Capacity Building: The organization is involved in training and skill development activities for
professionals in the biotech sector. This is done through workshops, seminars, and training
programs.
Confidentiality agreement
• A confidentiality agreement, also known as a non-disclosure agreement (NDA), is a legal contract
between two or more parties that outlines the terms and conditions under which sensitive and
confidential information will be shared and protected.
• The main purpose of a confidentiality agreement is to prevent the unauthorized disclosure or use
of confidential information by the parties involved.
• This type of agreement is commonly used in business and professional settings to safeguard trade
secrets, proprietary information, and other sensitive data.
• Key elements:
• Parties Involved: The agreement identifies the parties entering into the contract, such as
individuals, companies, or organizations.
• Definition of Confidential Information: The agreement defines what constitutes confidential
information. This can include trade secrets, proprietary technology, business strategies, customer
lists, financial data, and more.
• Obligations of the Parties:
• The agreement outlines the responsibilities and obligations of both the disclosing party (the one
sharing the confidential information) and the receiving party (the one receiving the information).
• The receiving party is typically bound not to disclose, use, or exploit the confidential information
for any purpose other than what is outlined in the agreement.
• Key elements:
• Duration of Confidentiality: The agreement specifies the duration for which the confidentiality
obligations will apply. This could be a fixed period or for as long as the information remains
confidential.
• Permitted Disclosures: The agreement may outline situations where the receiving party is allowed
to disclose the confidential information, such as to employees or contractors who have a need to
know for a specific purpose.
• Consequences of Breach: The agreement usually details the consequences of a breach of
confidentiality, which can include legal action, financial penalties, or other remedies.
• Legal Jurisdiction: The agreement may specify the jurisdiction where legal disputes related to the
agreement will be resolved.
Confidentiality agreements can be bilateral (two-way) or unilateral (one-way):
• Bilateral Agreement:
• Both parties agree to keep each other's information confidential. This is often used when both
parties are sharing sensitive information with each other.
• Unilateral Agreement:
• One party agrees to keep the other party's information confidential. This is used when one party is
sharing sensitive information with another party, such as a company sharing its trade secrets with a
potential investor.
• Confidentiality agreements play a crucial role in maintaining trust, protecting valuable information,
and preventing unauthorized use or disclosure of sensitive data.
Licensing
• Licensing in the context of technology transfer refers to a legal arrangement in which the owner of
a technology, intellectual property (IP), or innovation grants permission to another party to use,
produce, or sell the technology in exchange for certain terms, often including financial
compensation.
• This arrangement allows the technology owner (licensor) to leverage their intellectual property
while enabling the licensee to benefit from the technology without having to develop it themselves
from scratch.
• Technology licensing can encompass a wide range of scenarios, including software, patents,
trademarks, copyrights, and other forms of intellectual property.
Licensing
• Key Components:
• Licensor: The party that owns the technology or intellectual property and grants permission to
another party to use it.
• Licensee: The party that receives the rights to use the technology in accordance with the terms of
the license.
• Intellectual Property: This includes patents, trademarks, copyrights, trade secrets, and other forms
of proprietary knowledge and inventions.
• License Agreement: A legal contract that outlines the terms and conditions under which the
technology is being licensed. It includes details about the scope of the license, duration, royalties,
and any restrictions.
Licensing
• Key Components:
• Scope of License: The license agreement defines how the technology can be used by the licensee.
This could involve restrictions on geography, industry, or specific applications.
• Royalties and Fees: The licensee typically pays royalties or fees to the licensor in exchange for
using the technology. These payments can be a lump sum, ongoing royalties based on sales or
usage, or a combination of both.
• Duration: The license agreement specifies the duration for which the licensee is allowed to use the
technology. This can be for a specific period or perpetually.
• Exclusivity: The license can be exclusive or non-exclusive. An exclusive license grants the licensee
the sole right to use the technology within a certain context, while a non-exclusive license allows
the licensor to grant the same rights to other parties.
Licensing
• Considerations:
• Negotiations: Both parties negotiate the terms of the license agreement, including scope,
royalties, duration, and any other relevant factors.
• Value Proposition: The licensee evaluates whether the licensed technology aligns with their
business objectives and offers a competitive advantage.
• Technical Support: Depending on the complexity of the technology, the licensor might offer
technical support or training to the licensee to ensure effective use.
• Intellectual Property Protection: The license agreement should address how the licensed
technology will be protected from infringement or unauthorized use.
• Compliance: The licensee must adhere to the terms outlined in the license agreement, including
any usage restrictions or quality standards.
Licensing
• Considerations:
• Termination: The license agreement should outline conditions under which the license can be
terminated, such as breach of terms or expiration of the agreement.
• Dispute Resolution: The agreement may specify procedures for resolving disputes that might arise
during the course of the licensing relationship.
• Technology licensing is a strategic way for companies to monetize their innovations, expand their
market reach, and collaborate with other businesses to bring valuable products and services to
market.
MoUs
• In the context of technology transfer, a Memorandum of Understanding (MoU) is a formal
document that outlines the preliminary terms and intentions of collaboration between two or more
parties.
• An MoU is not a legally binding contract, but it serves as a framework for discussions and
negotiations that may lead to more formal agreements, such as licensing agreements, joint
ventures, or research collaborations.
• An MoU establishes the intention of the parties involved to work together toward a common goal
related to technology transfer.
• It clarifies the areas of collaboration and sets the stage for further negotiations.
MoUs
• Key Elements:
• Parties Involved: Identifies the parties entering into the MoU.
• Purpose: Clearly states the objective and scope of the collaboration, often highlighting the
technology or innovation being transferred.
• Scope of Collaboration: Outlines the specific areas of cooperation, such as joint research,
technology development, knowledge sharing, and commercialization efforts.
• Duration: Specifies the period during which the MoU is valid.
• Responsibilities: Describes the roles and responsibilities of each party, including any contributions
or resources they commit to the collaboration.
• Confidentiality: Addresses how sensitive information shared during the collaboration will be
treated.
MoUs
• Key Elements:
• Intellectual Property: Sets out initial understandings about ownership and rights related to any
intellectual property created during the collaboration.
• Financial Terms: Specifies how costs, funding, and revenue sharing will be handled, if applicable.
• Dispute Resolution: Outlines the procedures to be followed in case disputes arise.
• Termination: Describes the conditions under which the MoU can be terminated.
• Future Agreements: States that the MoU is not legally binding and that future formal agreements
will be negotiated to govern specific aspects of the collaboration.
MoUs
• Flexibility and Framework:
• Since an MoU is not legally binding, it offers flexibility for parties to explore collaboration without
committing to the detailed terms of a contract.
• It allows parties to establish a framework and continue discussions to refine their collaboration
goals.
• Transition to Formal Agreements:
• Once the parties have agreed on the preliminary terms outlined in the MoU, they can move
forward with negotiating more formal agreements, such as licensing agreements, joint venture
contracts, or research partnership contracts.
• These agreements will incorporate more detailed legal and financial terms.
MoUs
• Importance of Legal Review:
• While an MoU is not legally binding, it's essential to ensure that the language used is clear and
accurately reflects the parties' intentions.
• Consulting legal experts can help draft an MoU that lays a solid foundation for successful
collaboration and minimizes misunderstandings.
• Overall, an MoU is a useful tool in technology transfer to initiate collaboration, set expectations,
and facilitate discussions between parties interested in working together.
• It provides a starting point for exploring the potential benefits of technology transfer without
immediately committing to the complexities of a legally binding agreement.

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