TECHNOLOGY

TRANSFER
Basics, Role of QA & Best Practices

Vaishali Yardi
 Contents
• Technology Transfer Process and
• Overview
Oversight
• Types of Technology Transfers • Six stages of TT
• Pharmaceutical Product life cycle • Cross Functional Roles and Responsibilities
• Clinical to Clinical TTs • TT Project Structure
• Development to Commercial TT
• Stagewise Role of Quality in TT & Best
• Commercial to Commercial TT
Practices
• • Role of Quality
Types of Sites
• Internal-Internal TT • Best Practices
• Internal-External TT • Summary
• External-External TT
• References
Overview
• TT or Technology Transfer plays an important role in regulated pharmaceutical and
biopharmaceutical industries
• Expanded use of contract development and manufacturing organizations,
advances in manufacturing flexibility, increase in corporate mergers and
acquisitions, and enhanced regulatory complexity all contribute to the need for
technology transfers to maintain the continuity of drug supply
• In order to replicate systems safely, maintain high quality standards and meet
regulatory requirements, manufacturers have established approaches to
successfully transfer manufacturing and analytical technology and knowledge
from one site to another.
Overview
• TT uses a systematic approach to ensure the knowledge required to execute the
manufacturing process and product testing performed at one site can be incorporated
at a new site while maintaining understanding and product characteristics.
• This results in same, safe effective and consistent product being manufactured at both
the locations.
• Technology transfer can happen at all stages of product life cycle i.e., from drug
development through clinical trials to commercial release.
• PDA TR 65 on Technology Transfer covers the following:
• New product introductions
• Transfer of products being manufactured for phase III clinical trials
• Commercial release

• For TTs happening at an earlier stage of development, where process and product
knowledge is less understood, certain processes may not be required
Overview
• Involved parties in the technology transfer process should have established
systems for commercial manufacturing. Thus, standard requirements given below
are expected to be established:
• Equipment and Facility Maintenance
• Annual Product reports
• Lifecycle validation
• Complaint handling
• Continued process verification (CPV) programs
 Types of Technology Transfers
• ICH Q10 describes TTs as new product transfers during development through
manufacturing and transfers within or between manufacturing and testing sites for
marketed products. This broadly includes the following:
• Analytical method transfers to an alternate laboratory
• Transfer to scale up a developmental product
• Transfer from a laboratory to a cGMP production environment

• When establishing a TT program, it is important to understand the impact of

product lifecycle phase, types of sites involved and the associated CMC
requirements.
Pharmaceutical Product Life Cycle
• During its lifecycle, a product typically progresses through discovery and
development, culminating in commercial readiness and regulatory approval as
depicted below
• TT is the key part of product life cycle as a new drug product and its corresponding
drug substances move from clinical phase 1 through to commercial
manufacturing, often at different production scales and different manufacturing
sites.
• While TT can occur at any part of the product lifecycle, each TT should have its
own purpose and will have a discrete beginning and end.
Pharmaceutical Product Lifecycle
Product Design & Development

Continuous Improvement

Technology Transfer

Commercial Manufacturing

Product Discontinuation

Phase
Clinical Clinical Clinical Product
Phase 1 Phase 2 Phase 3 Approval
Pharmaceutical Product Lifecycle
• For driving reproducibility, elements of TT are performed at each phase of product
life cycle as knowledge of the process, product and testing increases.
• TTs can be described based on product life cycle phase like:
• Within clinical phases (Clinical to clinical)
• Transfers from Development phase (Developmental to commercial)
• Transfers within Commercial phase ( Commercial to commercial)
Clinical –Clinical Technology Transfers
• TTs at clinical stages should be developed, reviewed, and executed with
thoughtful consideration and should be phase appropriate from CMC perspective.
• TTs during these phases should address clinical patient safety and should start
building a foundation of future commercial production.
• During early clinical phases, involved sites should constantly consider future needs
related to scaling up and validating the manufacturing process, determining the
type of facility required, and defining the product, process and analytical
characteristics necessary to ensure Quality, Safety and Efficacy of product being
transferred
• Making knowledge management through early clinical phases is very important
especially because of complication arising in small material demands and possible
extended pauses for site inspections and regulatory approvals as clinical data is
being collected.
Development –Commercial Technology Transfers
• These TTs which begin when the product is in clinical phase III, involve transfer of full scope of
CMC requirements.
• By Phase III, the product, process and analytical development should progress in parallel with the
TT program to define the final CMC requirements for commercial readiness and process and
analytical validation. For example:
• Final dosage form and dosage should be known
• Drug substance manufacturing process should be established such that there are minimal changes in
impurity profile from clinical phase III to process validation
• Process validation and Critical Quality Attributes (CQAs) should be defined including characterization of
critical components and materials
• Initial stability for both drug substance and drug product should have been evaluated
• Risk assessments should be performed throughout the final development to determine the impact areas
for commercial manufacture.
• The objective of TT activity is to establish comparability between the Sending unit (SU) and the
Receiving unit (RU) processes or methods, and, as result, provide the regulatory authorities an
assurance to allow the use of the RU to supply clinical material or commercial inventory into the market
Commercial –Commercial Technology Transfers
• In these TTs, product is already being marketed and produced at an existing facility, yet
business needs might need it to be produced in another site
• This may need an operational scale-up or a scale-down
• Addition of a new market may require addition of an alternate packaging facility, which
world require TT of packaging operations.
• Alternate laboratories may also be used, requiring transfer of the analytical methods to a
new location.
• In TTs involving a marketed product, the original or current manufacturing location should
provide full CMC requirements with historic product and process knowledge, that
demonstrates manufacturing robustness.
• These types of TT may be an opportunity to implement process improvements at the
receiving unit, provided that those improvements align with business and regulatory
strategies for the TT.
Types of Sites
• Typically, 2 sites are involved in TT process
• Sending Unit: Location with current knowledge of product, process and analytical
methods
• Receiving Unit: location where the product will be manufactured or tested in the future.
• The use of contract manufacturing organizations (CMOs) and contract
development and manufacturing organizations (CDMOs) have introduced
variations in defining SU and RU sites during TT.
• Both SU and RU sites can be classified as external or internal. The type of site and
its relationship to the marketing authorization holder (MAH) impacts effectiveness
of knowledge transfer as well as overall TT team and governance framework.
• Internal –Internal Technology Transfers:
• Internal –External Technology Transfers
• External-External Technology Transfers
Types of Sites
Internal- Internal Technology Transfers
• A TT performed between locations of the same company or facility is considered as most
manageable in terms of knowledge transfer between the SU and RU sites because of the
following reasons:
• Most likely that both SU and RU sites are governed by the same Quality Management System
(QMS), have integrated document management systems and employ a standardized TT
procedure.
• If the company is transferring technology for an existing commercial product, historical data on
process or test performance should be readily available.
• If the internal SU and RU sites are in different geographical locations, an initial evaluation
will be needed to determine the potential impact of language, local implementation of
global QMS, import and export requirements and regulatory requirements.
• This TT may require additional budget for site-to-site interactions that allow SU to share
knowledge with RU and participate in initial manufacturing activities and SU
Types of Sites
Internal- External or External –Internal Technology Transfers
• The Marketing Authorization Holder may choose to work with an external company in
many different scenarios like,
• Product developed internally will be manufactured at commercial scale at an external
company, such as a CMO or CDMO, for cost or time-to-market purposes or due to limited
capability in internal facilities.
• Products developed by a CDMO will be manufactured at an internal site
• Commercialization was performed internally and transferred to an external company after
receiving regulatory approval or vice versa.
• Use of multiple manufacturing facilities will better meet demand and/or provide risk
mitigation for supply
• Expansion of product to a new market requires alternate global manufacturing capability
• A corporate acquisition or merger results in manufacturing consolidation
In these types of scenarios, the TT project manager has the additional challenge of managing
the TT activities across different sites, organizations and cultures.
Types of Sites
Internal- External or External –Internal Technology Transfers
• Unlike internal-internal transfers, any transfer to or from an external site may
involve difference in organization, Quality systems, and specific procedures.
• In some cases, the external organization may have competing priorities, which can
be difficult to discern
• Defining the differences in organizational structure, quality systems and business
priorities early can facilitate alignment on the TT boundaries and success factors.
• Agreement on the presence of SU SME (subject matter expert) at the external site
during the TT process to ensure successful knowledge transfer is an important
point that cannot be overlooked and should be documented in the appropriate
agreements.
Types of Sites
External- External Technology Transfers
• Often a Marketing Authorization Holder must manage a transfer between 2
external sites, which may also involve two different companies.
• This type of TT presents the highest challenge particularly if the two locations are
unfamiliar to each other (e.g., part of business strategy)
• If the external parties cannot interact, the MAH will need to act as SU for the TT
and facilitate the knowledge transfer to the RU
• Agreements on the presence of MAH and SU SMEs at the external site during the
TT process to ensure a successful knowledge transfer is an important point that
cannot be overlooked and should be documented in the appropriate agreements.
 Technology Transfer Process and Oversight
Six Stage Technology Transfer Process

Stage Gate
Stage Gate

Stage Gate
Stage Gate
Stage Gate

Stage Gate
Initiation Planning Knowledge Readiness Execution Handover
Transfer

6
5
3

4
1

2
• Regulatory authorities expect companies to have a documented TT process that describes the steps to be
taken and the compliance requirements for each step.
• TT process used six stages and six gates
• Each stage 0f a TT serves a purpose and has identifiable outcomes. At each stage gates allow a steering
committee to determine whether those outcomes have been met and to decide if the TT should proceed.
• Stage gates at each of the six stages allow the steering committee to determine whether a TT is ready to
proceed to next stage.
• Often TT activities are performed in parallel than sequential in interest of business needs. Any information
during a stage indicating change in TT boundaries and/or assumptions should be immediately
communicated to steering committee.
 Technology Transfer Process and Oversight

Stage Gate

Stage Gate

Stage Gate
Stage Gate
Stage Gate

Stage Gate
Initiation Planning Knowledge Readiness Execution Handover
Transfer

6
5
3

4
1

2
Once knowledge RU This stage
Potential RUs TT team The formal demonstrates
transfer of transfer closes the TT
are evaluated assesses the elements are and qualifies with
to identify TT risks and the detailed obtained, the TT the process at
requirements regulatory
sites with risk identifies team works in scale,
specific to TT approvals and
profile elements the readiness culminating in
begins allows normal
meeting critical to the stage to perform Regulatory
business the activities and operations to
knowledge submission begin
objective achieve
transfer and deliverables
TT team is overall required to
formed at RU timings achieve full
site operational
readiness
Cross Functional Roles & Responsibilities
TT Agreement
• All involved sites should document expectations, roles and responsibilities in a
formal TT Agreement
• Should specify the measuring units to be used in TT
• In case of internal-internal TT, shared procedure may be developed in place of TT
agreement
• This TT agreement or shared procedure provides information about the level of
involvement of each functional role at the SU and RU that will allow each site to
resource a TT team
Each site involved in TT should develop a cross functional team to execute the TT.
Each team should include a lead person who is an SME for respective functional
role.
Cross Functional Roles & Responsibilities
Function / Role Responsibilities
Business Strategy, marketing, Finance, legal and Sales
TT Project Manager Leads the overall TT process. There should be a project manager at each
involved site to support TT
Process Process chemistry and engineering, process performance qualification and
validation
Analytical Raw material, in-process controls, product, stability (development and QC)
Engineering Installation and qualification, equipment maintenance
Manufacturing Plant operations and EHS
Regulatory Health authority strategy and filing
Quality QMS Requirements, inspection readiness
Sourcing / Supply Chain Material sourcing, production planning and logistics
TT Project Manager (TTPM)
• Each site involved in TT should assign a Project manager for respective sites.
• This role requires technical knowledge across the functional areas as well as
knowledge of CMC requirements
• Serves as a potential point of contact and facilitates communication, knowledge
transfer and task completion
• In internal-internal TTs, a single project manager may serve for both SU and RU
functions.
• Wherever TT PM is located, this role is critical in facilitating constant
communication and should be the primary contact point for changes, decision and
team alignment.
TT Project Structure

TT Project Sponsor Regulatory

Process
SU Analytical
TTPM Engineering
SU Management Manufacturing
Oversight Quality
TT Project Manager

Sourcing / Supply

TT Steering Committee
Marketing Authorization Holder (MAH)

Regulatory
Process
RU Management
Analytical
Oversight RU Engineering
TTPM Manufacturing
Quality
Sourcing / Supply
Stagewise Role of Quality in TT & Best Practices
 Initiation Stage

Role of Quality

• The Quality function at the Marketing Authorization Holder (MAH)

performs the quality assessment as part of due diligence on the
potential RU, that includes RU Site Assessment.
Role of • Quality function typically ask the potential RU to complete a
questionnaire and conducts a search of compliance history records.
Quality in • The purpose of the quality due diligence is to determine the maturity
TT & Best of the RU quality system, the RUs organizational mindset regarding
GMPs, and its adherence to applicable regulatory requirements.
Practices • Quality will provide a compliance risk evaluation of the potential RUs
 Initiation
Best Practices
Topic Practice
Establishing a Ensure that such a committee, primary escalation channel, is
Steering committee established early so that the committee, site leadership and
executive leadership understand the project scope and
requirements.
Develop a project A simplified document summarizing the project’s key
Role of charter requirements and scope that can be further defined as the
project progresses

Quality in Document
Agreement &
• Ensure documented plan is in place that specifies who is
responsible and accountable for specific activities
TT & Best Contracts • Describe strategies in the charter that represent the full
scope of the project and avoid documenting only short-
Practices term needs
• Some aspects of charter may be included in contractual
agreement for clarity
• Draft an initial regulatory strategy, including expected
timeline for the submission.
 Initiation
Topic Practice
Involve key functions • Involve key functions and personnel early to review the
early project requirements. This can help avoid missed
requirements or changes to the scope later in the project.
• Leverage expertise and lessons learned from involved
personnel
Ensure adequate • Ensure that the TT team includes all key functions and
Role of talent, expertise, and
focus on TT team
expertise pertinent to the project and the team members
have appropriate experience with transferring the product
Quality in • Ensure that the TT team personnel are either dedicated or
are made accountable to prevent inattention
TT & Best • Develop a backup plan to mitigate any potential loss of key
personnel
Practices Utilize Risk
Management
• Use risk management tools to assess and document risks
related to process requirements, facility selection (e.g., gap
assessment with process requirements) safety and quality
requirements
 Initiation
Topic Practice
Utilize Risk • Document formally the assessment of the project and
Management company requirements for the product being transferred,
record identified risks, classification of findings, mitigation
strategies or actions required
Identify and plan for • Consider use of PAT as a component of process control
long led items strategy
• Identify long lead equipment
Role of • Critical workstreams have a clear plan from beginning to
Quality in end
• Identify and develop a plan for filling key project positions
TT & Best Develop Checklists
to ensure that personnel are in place and are trained in time
• Prepare a checklist to assist in leveraging lessons learned
Practices from previous TTs
• Use checklists for 1) Capability, Equipment, Material,
Quality, Safety, Personnel and 2) Documentation of
procedural , physical, automation and process
requirements
 Planning
Role of Quality

• The MAH Quality function will work with the RU process function to
document in the product file and product specification, the
requirement that will ensure the quality, safety and efficacy of the
product.
Role of • In this stage, quality agreements must be developed concurrently and
Quality in executed, as required between the MAH and RU and vice versa and
additional GMP providers and external laboratories.
TT & Best • Based on target market, current stability requirements and
Practices commitments made to regulatory authorities, Quality will work with
the Process, Analytical, and Regulatory functions to prepare the
stability requirements
• Regulatory uses the stability plan to further develop the overall
regulatory time-line to ensure that all conditions of commitment are
met.
 Planning
Role of Quality

• Using regulatory strategy, Quality begins GMP audit readiness

activities at the RU to ensure full inspection readiness when needed in
the execution stage.
• Initially, MAH Quality function performs an audit of the chosen RU so
Role of that all compliance gaps impacting the TT can be addressed prior to
Quality in physical implementation of the cross functional requirements.
• When significant quality changes are required, a quality improvement
TT & Best plan will be developed to address and remediate the compliance gaps
Practices • Quality also performs a gap assessment of the SU, RU and MAH
quality systems and negotiates an aligned QMS for the technology
transfer.
• This alignment should be performed even when the SU and RU are
both internal sites.
 Best Practices Planning
Topic Practice
Hold a well-organized • Kick off meeting should be well organized and cover all relevant
project kick off activities and functions
• TT team should discuss and align with the project plan and key
milestones.
• Establish online repository of document sharing

Understand • Identify and share with the RU the existing manufacturing

Established process conditions at the SU, including material, people and
Role of Conditions process flows.
• Determine and communicate the changes that might be needed
Quality in at the RU

TT & Best Define pre-requisites

for introduction of
• Ensure that the proposed process, development data and
control strategy meet all expectations and requirements
Practices product to a new site • Ensure requirements for SU and RU are well understood for all
processes, analytical methods, documents and forms required
to initiate activities related to project start, e.g., change control
or material set up.
• Ensure key timelines / actions necessary to meet each
requirements are understood.
 Best Practices Planning
Topic Practice
Perform risk • Conduct or update detailed process and analytical risk
assessments assessments so the TT team will be well informed about the
primary areas of risk in this transfer allowing them to create risk
mitigation steps.
Ensure project • Assign one person from both the RU and SU as team leads or
oversight and team project managers to be accountable for the project throughout
Role of engagement its lifecycle
• Ensure that the team members are participating, engaged as
Quality in per their assigned actions and respective time-lines

TT & Best Engage vendors • Engage all vendors (equipment, excipients) early to identify
tentative lead times and begin drafting project timelines
• Ensure that the RU understands the quality requirements for
Practices raw materials and drug substances to ensure that selected
vendors will meet the quality requirements outlined in
marketing authorization
• Identify and process alternate vendors
 Best Practices Planning
Topic Practice
Engage regulatory • Further define the regulatory strategy with project requirements
function • Discuss strategy with the TT team to ensure alignment
• Engage TT team to define variations that may cause deviation
• Proactively engage regulatory agency to support / advice on the
strategy

Create timeline that • Ensure that project timeline includes key milestones related to
Role of ensures sufficient time
for drafting and review
drafting, review and submission of filling and allows for regulatory
agency approval
Quality in of regulatory filing • Develop stability plan, making sure that all potential areas where
product needs to be marketed are considered
TT & Best • Coordinate activities and documents required for submission to
avoid extensive loss of finished product due to shelf-life
Practices restrictions while awaiting submission approval
• When developing timeline, anticipate that additional questions
that may need to be addressed after initial submission

Documentation • Quality documentation is critical to ensure that the regulatory

quality filing will be approved within the expected timeline
 Knowledge Transfer
Role of Quality
• At the KT stage , the RU Quality function performs a risk assessment
to evaluate the ability of the RU’s quality system
• In conducting this risk assessment, the Quality function will use the
knowledge and information that has been shared by the SU
Role of • The QRA will rely on the findings from audits, outcomes from Quality
improvement plan, SU quality metrics and market actions.
Quality in • For a product already manufactured under a marketing authorization,
TT & Best the quality risk assessment also can examine deviations and corrective
actions at the SU as well as process trends, product complaint history,
Practices and annual product reports as available.
• Quality function should also perform compliance training and address
any gaps identified by the quality risk assessment
• Quality also finalizes the stability plan based on the requirements in
the specifications and ensures alignment with the regulatory strategy
for the TT.
 Knowledge Transfer
Role of Quality
• RU Quality function works with the supply chain function to identify,
schedule, and perform supplier qualification audits for all material
being procured for the TT.
• These functions will document the findings and recommendations in a
Role of supplier qualification report. They will also define expiry / retest dating
requirements for both materials and products.
Quality in • Quality also plays a key role in assessing the compliance of the
TT & Best analytical validation plan, change controls, project plan, and process,
cleaning and capital VMPs.
Practices
 Best Practices Knowledge Transfer
Topic Practice
Prepare package of • Ensure a clear, well organized TT package is accessible to the RU
materials for the RU team. Essure that the regulatory function confirms the version of
site before KT kicks off key documents provided
• Ensure that RU has access to key documents of SU
Establish a • Avoid sending lengthy, very large number or complex documents
communication plan to RU.
for effective • Arrange for the SU/MAH to provide training sessions to orient the
Role of collaboration RU and personnel to explain documents and to share expertise
during the review process
Quality in • Review and incorporate knowledge from similar projects
• Ensure that SU provides key personnel to and train support RU
TT & Best staff. Capture tacit knowledge

Practices Provide RU with • SU should provide RU with historical data not already included un
historical data and the TT package. For an existing commercial process, for instance,
performance of this may include several years of commercial data such as release
product manufactured testing, CPV reports, annual product reports (APRs), deviations,
complaints etc.
 Best Practices Knowledge Transfer
Topic Practice
Process comparability • Depending on project scope, the TT team may perform a
assessment and define comparability assessment and review learnings from the SU and
strategy MAH to define overall project strategy (i.e., scaling up, creating a
new process or proving equivalency)
• Develop a decision tree to consider whether process data is
sufficiently equivalent between SU and RU
• Plan for engineering batches or appropriate analyses to
Role of demonstrate comparability or equivalence.
Use Quality by design • A quality –by –design approach might be used to fully understand
Quality in approach the process design space before starting engineering batches

TT & Best Leveraging Risk

assessment to define
• Prepare a clear, well-organized plan documenting the process
requirements against all site, company and industry requirements,
KT requirements identifying gaps that will need to be addressed in the next stage
Practices • Use risk assessment throughout the TT project to identify any gaps
in process, methods, materials and people
 Best Practices Knowledge Transfer
Topic Practice
Formulate an • Prepare a plan for how process data will be recorded
adequate process data • Consider data integrity requirements, as well as any requirements
monitoring plan for inclusion in a data repository
• Determine if the RU requires additional software capabilities to
match SU
• Ensure appropriate data are collected to support project execution
• Ensure data monitoring requirements are supported by RUs IT
Role of infrastructure
Plan adequately for • Leveraging learning as those from cleaning validation, equipment
Quality in validation needs or
leveraging existing •
validation and plan for sufficient equipment.
Identify and leverage SMEs with knowledge on existing or similar
TT & Best knowledge
•
equipment at both SU and RU
Leveraging support from vendors for new equipment and
Practices Hire/train RU
technology, which may include on site visits during next stage
Ensure that needed personnel are hired/trained at RU to avoid
•
personnel errors and repeat work throughout the TT
 Readiness Stage
Role of Quality
• During the readiness stage, the Quality function is extensively
involved with all cross-functional areas, performing compliance
reviews and approving documentation involved in preparing for PPQ,
including quality elements of the control strategy
Role of • Quality ensures closure of all deviations, corrective and preventive
actions and change controls prior to PPQ.
Quality in • The Quality function should develop a procedure for PPQ batch
TT & Best release with the input from SU.
• Collaborating with SU on the PPQ batch release procedures ensures
Practices alignment on the data to be reviewed and ensures clarity for any
unique aspects associated with the TT process and RU site
• In this stage, the Quality function also should establish role
requirement for product release to determine if a qualified person or a
responsible person with specific knowledge base will be needed
 Readiness Stage
Role of Quality
• Working with Regulatory, the Quality function also develops a
Preapproval Inspection readiness plan, which may be revised as
additional relevant information becomes available during the
execution stage.
Role of • PAI readiness plan should include a strategy to respond to any
observations found during mock inspections
Quality in • Quality function qualifies new vendors and audit high risk and critical
TT & Best material suppliers in preparation for PPQ

Practices
 Best Practices Readiness Stage
Topic Practice
Use of risk • Use a risk register to ensure all potential risks are addressed and /
management plan for or a mitigation plan is in place before proceeding for ‘Execution’
risk mitigation • Systematically address process risks based on lab or
manufacturing data

Use a checklist • Use a checklist detailing all key requirements to ensure overall
process readiness
Role of • Create and share a regulatory submission tracker
Ensure all documents • Plan adequate time to draft, review, resolve comments on, and
Quality in are ready and approve the documents within the project timeline
approved • Consider all plant level documentation and regulatory submission
TT & Best documentation such as SOPs, Batch records, protocols, process
description, specifications for product release and stability
Practices documents
• Use templates where possible for consistency and make sure
authors and approvers are aware of timelines.
 Best Practices Readiness Stage
Topic Practice
Ensure all materials • Ensure that material shipment lead times, site system setups,
are ready and tests and release timelines meet project needs
approved • Identify lead times early and share RU personnel aware of
timelines to test, receive, release and set up ahead of “Execution’
activities.
• Check in with the vendors to avoid last minute surprises

Role of Ensure all equipment • Ensure that equipment shipment lead times , installation and
is ready and validated validation timelines meets project needs
Quality in for qualification in next • If facility modifications or equipment installations are needed, plan
stage and coordinate use of shared resources (personnel and equipment)
TT & Best and estimate potential impact on the process
• Identify lead times early and make receiving parties aware of
Practices timeline, with an adequate buffer included, before activities will be
executed
• Check in with the vendors to avoid last minute surprises
 Best Practices Readiness Stage
Topic Practice
Identify all parameters • Ensure that the final process is ready for the ‘Execution’ stage
of final recommended including all batch record instructions, SOPs, training needs, and
process for verification parameters for primary, secondary and support manufacturing
during next stage systems
• Ensure that process development studies are adequate and that
testing, and equipment qualification meet the requirements of
intended process, risk assessment and procedures
Role of • Produce data map for process data that shows all parameters
requiring control , the means of control e.g., batch record,
Quality in automated controls, in process controls etc. and means of
recording
TT & Best • Use the data map to enable process monitoring and to assess
whether access to data in a timely manner will present challenges
Practices during the next stage.
Perform engineering • If any final changes are made to the process, or development was
run on the final not performed on the final intent commercial equipment, perform
commercial process an engineering batch to verify the final intended process prior to
proceeding to next stage
 Best Practices Readiness Stage
Topic Practice
Establish a plan for • Plan to draft, review and approve filing for on time submission
successful regulatory within the project’s timeline and launch requirements. This plan
filing should be detailed in the submission tracker and regulatory strategy
documents

Minimize handoffs • Ensure that personnel are adequate to proceed to the next stage
between functions and and that loss of personnel does not impact the overall process
Role of keep personnel on the • Avoid reliance on contractors for all project activities. If contractors
project throughout are necessary, use a mix of fulltime employees and contractors to
Quality in ensure sufficient internalization of key process information
• Maintain key staffing throughout the project. Use same set of
TT & Best personnel throughout development, process verification and
commercial stage
Practices Take sufficient time at • Use stage gate, risk management tools or gap analysis, and
each stage to identify checklists to plan for all requirement are ensure that tasks are
key requirements completed prior to proceeding to next stage
• Formally assess risks of any open or incomplete action to
understand potential impact on next stage if not closed
 Best Practices Readiness Stage
Topic Practice
Take sufficient time at • Fully investigate any process failures or results operating on the
each stage to identify edge of process design and, as a team, identify if development
key requirements needs to revisited prior to proceeding

Ensure supporting • Trouble shoot, test and qualify key equipment for readiness to
systems are ready for begin executing activities to ensure that software, change
new process management, spare parts, cleaning, maintenance, calibration,
Role of supporting functions, and resources ready for new process
• Test batch reports, release process, validated electronic systems
Quality in (SAP, ERP etc.) during engineering batches to avoid PPQ surprises
• Ensure that testing facilities have qualified or validated analytical
TT & Best methods as required and will be able to test according to the agreed
upon schedule
Practices Hire personnel soon • Ensure that functional managers and steering committees follows
enough to train before up in time for resource approvals, hiring and training in advance
they are needed • Involve manufacturing operators in automation-testing, SOP
preparation, batch record and automation development to promote
learning
 Best Practices Readiness Stage
Topic Practice
Conduct Operations • Finalize work instructions for the start of the batch manufacturing
Training • Ensure that the operators have sufficient time to train on the work
instructions.

Establish batch release • Ensure alignment among Process, Quality and Manufacturing
process functions on the batch release process. Address such questions as
• What batch reports will be reviewed?
Role of • Will the intermediates be released or processed straight through
• Will the batch records be reviewed on the floor as completed
Quality in • Which forms will need to be approved and how are all requirements
of change control satisfied?
TT & Best • Are trucks scheduled if outside the normal hours?

Practices
 Role of Quality Execution Stage
• The Quality function is integral throughout the Execution stage as it
releases material for use
• Quality is responsible for product release, including batch record
review and overall batch disposition in accordance with site quality
procedures
• Quality is also responsible for supporting the review and approval of
Role of all documentation for the PPQ, including protocols, reports, batch
Quality in records, forms, results, change controls and deviation and
investigation close-outs
TT & Best • Quality function is expected to close out the QRM associated with the
TT at the end of the PPQ
Practices • At this stage, Quality performs final inspection readiness activities in
anticipation of the regulatory filing activities which depending on TT
type, may trigger a Pre-Approval Inspection (PAI).
• A mock inspection (in depth audit) of RU to identify issues to be
addressed before filing a submission
• Completion of PAI may be marked as end of execution stage
 Best Practices Execution Stage
Topic Practice
Create technical • Ensure that the SMEs are on the floor prior to execution, to provide
support plan for training and trouble shoot if needed
qualification • To ensure knowledge transfer from SU to RU and to resolve any
issues or escalate in timely manner to avoid delays
• Involve technical personnel during qualification for technical support
of new equipment if issues arise and to monitor future improvements

Role of Ensure team

involved in
• Ensure that technical representatives and SMEs from the TT team
provide formal training on any new equipment and process to the
qualification is production personnel who will execute qualification batches.
Quality in trained adequately
prior to the first
• Ensure sufficient time to train personnel if technology or process
steps are new or otherwise present a high risk of human error.
TT & Best engineering run.

Practices Perform a trial run • Conduct a mock or a trial run with a water batch or rejected material
to ensure equipment readiness and adequacy of operations training
• Ensure the production team has sufficient time to practice using new
equipment, parameters, batch record and process steps beforehand
 Best Practices Execution Stage
Topic Practice
Call a readiness • Ensure the production team is clear on process requirements prior to
meeting before execution
running qualification • Review and /or update the control strategy
batches • Avoid introducing new variables not challenged in previous stages
• Plan ahead and reference best practices on engineering run, in pre
batch readiness meetings and during operators training
• Use risk assessment to address any new variables that cannot be
Role of avoided
Prepare filing and • Provide regulatory authorities with documents that support the filing
Quality in plan for questions
from regulatory
as they become available, in alignment with the submission tracker
• Identify and prepare SME to address questions received from
TT & Best authorities regulatory authorities after initial submission

Practices Ensure adequate

development testing
• Provide robust supporting data and rationale from the previous stage
through adequate testing to support recommended parameters,
from previous stage process and instructions
• Ensure a repeatable process that is controlled within its
recommended operating parameters.
 Best Practices Execution Stage
Topic Practice
Provide adequate • Ensure all requirements and expectations are clearly defined in the
batch record batch record and that training is documented and documented
instructions • Use the engineering batch to help identify any missing instruction that
can be incorporated prior to the start of qualification

Ensure adequate • Ensure hands-on training of personnel on the post–transfer operations

training of team. Operator qualification is recommended over read only training
Role of production operator

Quality in Ensure process

performs as
• Ensure no changes are made to the final process prior to qualification
without first revisiting the Readiness stage or performing an
TT & Best expected within
requirements and
engineering run.
• Reference best practices for risk management and use of stage gate to
Practices control strategy review any uncertainties in final intended process to determine if
process is ready for qualification
• Review the control strategy and ensure all the variables are adequately
controlled with sufficient monitoring, sampling and other mechanisms
• Monitor data from engineering and PPQ batches and access against
the control strategy
 Best Practices Execution Stage
Topic Practice
Hold stage gates • Hold a stage gate meeting with the TT team upon completion of
before proceeding qualification to verify the execution stage meets all requirements and
to next phase expectations, and to verify readiness to proceed to next stage
(handover to post-transfer operations team)
• Ensure that all functions are aligned and that the process meets all
requirements, is well controlled and repeatable and ready for
Role of handover
• Review any process improvements / learnings from qualification
before handover
Quality in • Review risk management plan and appropriateness of mitigations

TT & Best
Practices
 Handover stage
Role of Quality
• As a part of Handover stage, the MAH Quality function establishes the
quality management review process which should involve both the RU
and the SU.
• The quality agreement may need to be updated to address everything
associated with commercial manufacture
Role of • Quality will ensure the closure of all documentation from the TT,
Quality in including change controls, validation reports, deviation and CAPAs.
• It may also play a role in identifying lessons learned from the
TT & Best Execution stage that should be incorporated in future training
operations team to improve process quality
Practices
 Best Practices Handover Stage
Topic Practice
Host a formal • Hold a formal meeting between the TT team and the post transfer
handover meeting operations team to ensure overall readiness of the process
• Handover key documents, process understanding and learnings
• Provide a regulatory dossier and communicate any post marketing
commitments made to regulatory authorities
• Have the TT team provide an overview of new equipment, launch
timeline, commercial forecast, manpower requirement,
Role of procurement requirements, open actions from risk assessment,
process improvement and lessons learned
Quality in
TT & Best Create a long-term
training plan for
• Prior to handover, assess whether the production team needs
additional training on the process and equipment
Practices production • Use final lessons learned to revise and maintain the training program
• Include adequate hands-on training with SOPs and batch records

Perform a lessons • Set up a formal meeting to discuss lessons learned at project

learned meeting closure, inviting the entire TT team and involving key supporting
team members
 Best Practices Handover Stage
Topic Practice
Ensure all • Verify that the post transfer operations team has everything needed
commercial needs to begin commercial production
are planned and • Work with the key functions at the RU site prior to closure of the
ready for project to ensure that key systems of the post –transfer production
commercial start plan are in place and needs are met
• Ensure all key aspects are ready including, materials, spare parts,
lead times, scheduling and third-party planning
Role of Create a long-term • Prior to handover, assess whether the production team needs
Quality in training plan for
production
additional training on the process and equipment
• Use final lessons learned to revise and maintain the training
TT & Best program
• Include adequate hands-on training with SOPs and batch records
Practices Transfer knowledge • Ensure that formal training, robust batch record updates, SOP
from TT team to instructions revision and simulation runs as needed are completed
post transfer prior to commercial start
operations team • Ensure that knowledge has been effectively transferred through
experience gained during the TT process, through lessons learned,
and through handover meetings
 Best Practices Handover Stage
Topic Practice
Ensure capacity • Throughout the project, monitor the commercial forecast and
meets commercial actual cycle times on equipment, including commercial, laboratory,
needs and any support system at the RU site, to ensure the final process
can meet the intended project and commercial requirements
• Ensure that the TT team assesses the product’s long term needs
throughout the project, involves appropriate commercial personnel
and leadership and verify requirements are met in lead-up to launch
Role of and handover.
• Ensure all lessons learned from the project are considered in
planning for commercial needs.
Quality in Ensure process • Ensure an adequate process qualification that meets all acceptance
TT & Best turned over
performs as
criteria is well controlled within the operating ranges specified in
the control strategy and is supported by sufficient data
Practices expected and is well • Ensure that robust monitoring and a control plan are in place to
controlled within monitor for any out of control events that may occur and require
specifications attention.
Summary
Overview of
• Significance of TT
Technology • Scope of TT
Transfer
Types of • Analytical Method Transfer to a different laboratory
Technology • Transfer to scale up a developmental product
• Transfer from a laboratory to cGMP production environment
Transfer
• Phases in Lifecycle: Product design and development
• Continuous Improvement
Pharmaceutical • Technology Transfer
Technology • TTs can be described on lifecycle phases like:
• Within Clinical phases (clinical – clinical)
Transfer • Transfer from Developmental phase (Development – Commercial)
• Transfer between Commercial Phases (Commercial – Commercial)

• The Six gate process

• Initiation
• Planning
• Knowledge Transfer
TT Process and • Readiness
Oversight • Execution
• Handover
• Role of Quality at each stage
• Best practices at each stage
References
• PDA Technical Report No. 65 (Revised 2022)
• ICH Q10 Pharmaceutical Quality Management System (PQS)
 THANK YOU
Technology
QUESTIONS?
Transfer