Level 3

Volume 15 Issue 2 Article 8

2020

The 5C Framework and Maturity Assessment: a New Approach to

Technology Transfer in Biopharmaceutical Contract
Manufacturing
Layth Ujam
Technological University Dublin, [email protected]

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Recommended Citation
Ujam, Layth (2020) "The 5C Framework and Maturity Assessment: a New Approach to Technology
Transfer in Biopharmaceutical Contract Manufacturing," Level 3: Vol. 15: Iss. 2, Article 8.
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Available at: https://arrow.tudublin.ie/level3/vol15/iss2/8

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 Ujam: SC framework
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The 5C Framework and Maturity Assessment: A New Approach to

Technology Transfer in Biopharmaceutical Contract Manufacturing

Author: Layth Ujam

School of Chemical Pharmaceutical Sciences, TU Dublin

Abstract
A new framework has been developed to provide guidance for cultivating a pragmatic and
pro-active culture of technology transfer within the biopharmaceutical contract
manufacturing (CM) sector. A review of industry practise was performed, and survey and
interview feedback from contract manufacturers and their customers was obtained. The
research summarised in this paper describes current experiences of technology transfer in
biopharmaceutical contract manufacturing of those working in the industry and investigates
the factors currently being experienced that lead to transfer challenges, project delays and
difficulties faced by the contract manufacturing organisation (CMO) and customer. The
framework and associated maturity assessment model provide an opportunity for both CMO
and customer to adopt a culture that encourages shared ownership, managed expectations
and more efficient.

Key words: biopharmaceutical; contract manufacturing; framework; technology transfer

1.0 Introduction
Technology transfer (tech transfer) is a frequently debated topic in biopharmaceutical
manufacturing and never more so than during the global Covid-19 pandemic of 2020
because of the importance it has in the product lifecycle. The industry has been facing the
challenge of intense tech transfers and a shift towards a wider outsourced product portfolio,
shorter timelines and increasingly more complex biological products. The role of CMOs is
changing and their customers’ demands are driving CMOs to adapt their services, facilities
and technical capabilities. Recent interviews with Business Development professionals at
contract development and manufacturing organisations (CDMOs) highlighted that biotech
companies are looking to establish strategic manufacturing partners in the true sense, and
not just fee-for-service providers. Multiple products with efficient chemistry, manufacturing
and controls (CMC) operations supporting pipeline fast-tracking into, and through clinical
development is what is being asked of CDMOs (Interviewee 1, 2020). Customers are
presenting with different requirements, whether it be full development, optimisation and

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scale-up or process transfer (Interviewee 2, 2020). The demand is so intense that a senior
scientist interviewed for this research reported customers wanting to get into the clinic with
a new product within 12 months and transfers having gap analysis, small scale work, pilot
and GMP production stages overlapping (Interviewee 3, 2020).

The biopharmaceutical (biopharma) sector needs effective support processes and systems
in place to fulfil the requirements of the changing tech transfer landscape. Greater demand
over the past year due to Covid products, more collaboration and partnerships with global
pharma to support accelerated tech transfers are the drivers for change (Interviewee 5,
2020). This paper summarises the changes that are currently occurring, the challenges that
are being faced and determines if the industry is matching the technological demands with
equally robust tech transfer processes. The research investigates the following questions:

1) Are CMOs and their customers running effective tech transfers and analysing quality of
the outputs?

2) Do industry guidance documents adequately support tech transfers to address the issues
that are currently being experienced?

3) Has technical advancement been at the expense of properly managed technology

transfers?

To answer these questions, the research utilised the following methodologies:

1) Tech transfer guidance documents and published literature were reviewed in context of
the research questions,

2) An online survey was issued to gather experiences of those working in the industry from
a CMO/CDMO and customer perspective,

3) One-to-one interviews were held with industry professionals with direct experience of
biopharma tech transfers.

The scope of the research includes elements of business strategy and processes that, due
to a company’s competitive advantage, could not be reported publicly. The range of
methodologies used supports the gap by gaining insights through feedback from an
anonymous survey and by seeking information from industry professionals.

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2.0 Literature Review

There are several references that describe tech transfer, the process and detail the general
requirements at each stage.

1. WHO guidelines on transfer of technology in pharmaceutical manufacturing (World

Health Organisation, 2011)

2. ISPE Good Practice: Technology Transfer, 3rd Edition (ISPE, 2018)

3. PDA Technical Report 65 Technology Transfer (PDA, 2014)
4. ICH Guideline Q10 on Pharmaceutical Quality System (European Medicines Agency
(EMA), 2015)
5. Eudralex Volume 4 Chapter 7 Outsourced Activities (EudraLex Volume 4 Chapter 7,
2009)

6. Contract Manufacturing Arrangement for Drugs: Quality Agreements Guidance for

Industry (Food and Drug Administration, 2016)

The WHO defines the transfer of technology 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
(World Health Organisation, 2011). The guidance serves as a framework with general
coverage of transfer of development and production (processing, packaging and cleaning,
transfer of analytical methods), 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, and qualification and validation.

ICH Q10 defines technology transfer as the second stage of the product lifecycle, where
“the goal of technology transfer activities is to transfer product and process knowledge
between development and manufacturing, and within or between manufacturing sites to
achieve product realisation. This knowledge forms the basis for the manufacturing process,
control strategy, process validation approach and ongoing continual improvement”
(European Medicines Agency (EMA), 2015). Aspects of ICH Q10 apply to technology transfer
during 1) the process performance and product quality monitoring system, 2) the corrective

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action and preventive action (CAPA) system, 3) the change management system and 4)
management review of process performance and product quality.

2.1 What makes a successful Tech Transfer

Technology transfer of bioprocesses is common in the biopharmaceutical industry yet can
be complex and presents numerous challenges. The process introduces additional risk to
the development and commercialization of biopharmaceuticals, so minimizing risk is
fundamental to success. Challener (Challener, 2020) summarises that experience,
communication, collaboration, transparency, planning and prioritisation contribute to
success and that CMOs/CDMOs and customers can facilitate this by using pragmatic
approaches that mitigate risks and ensure collaboration between all parties involved. It is
important though, that all parties define what a “successful” transfer is, and ultimately this
should be success of the first GMP manufacturing campaign.

Successful tech transfers have been summarised to have the following principles, omitting
any would have serious consequences on the outcome (Perry, 2010):
1. Robust information exchange, providing the receiving party with all information
that is relevant to the process and associated assays.

2. Careful front-end planning and project management, with the designation of point
people for specific portions of the project.

3. Ensuring that analytical assays are transferred ahead of the process

4. Performing small-scale verification at the receiving site.
5. Always perform pre-GMP engineering runs.
6. Put the tech transfer project in context by defining GMP success and failure and
don’t dismantle the project team until success here has been verified.

2.2 What are the challenges?

One of the first challenges to overcome in transferring a manufacturing process is to fit the
process into the receiving facility (Newcombe, 2020) and (Newcombe and Brown, 2020). In
the initial stages of the technology transfer, a comprehensive review of process
requirements and comparison with facility capabilities should be performed (Chang, 2011).

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Additional challenges are faced when tech transfer is to a facility in a different country than
the originating site. There may be additional communication challenges of a different
culture, different language, and/or different time zone. Even where English is spoken
proficiently by all team members as the common language, different cultural influences can
result in different interpretations for a given word or phrase (Chang, 2011); technology
transfer can mean different things to different people.

Technology transfer is embedded as part of a pharmaceutical quality system (European

Medicines Agency (EMA), 2015) and audit findings and regulatory inspections are not always
associated directly with deficiencies in tech transfer. However, there are examples where
customers have questioned the change control process for when a process transfers out of
one site to a sister site. Process documentation and comparability strategy may be reviewed
from a quality perspective, and process history documents and risk assessments can be
requested during a tech transfer audit (Interviewee 10, 2020).

A survey of problems experienced by executives at 10 global companies was carried out in

2011 by Uydess and Schmidt (Uydess and Schmidt, 2011) and despite the frequency of
transfer, the results showed the following problems:

1. Corporate decision makers make tech transfer plans primarily on basis of financial
and marketing considerations, failing to take into account the effect on the
organisation.

2. Senior management significantly underestimate the need for resources and

scheduling that supports tech transfer.

3. Little oversight is provided once high-level decisions are made, leaving the work to
those without much control.

4. Lack of early and effective coordination between receiving and sending sites is
further complicated by lack of clearly defined roles and responsibilities, lack of
communication and poor visibility of timelines, progress and results.

5. The transfer runs into problems because a thorough and detailed assessment has
not been conducted on comparability of equipment, manufacturing environment
and supply chains.

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6. Participating organisations fail to clearly identify, define and agree upon which
standards and procedures to follow.

7. The organisation fails to take into account impact that the tech transfer has on
functions such as quality, regulatory, laboratory and supply chain.

8. Poor process understanding coupled with incomplete documentation of all the

required parameters.

The consequences of these common factors in the planning and implementation of tech
transfers include budget and schedule overruns, disruption to both sending and receiving
organisations, compliance problems, excessive rejects and rework, slower time to market
and supply unreliability.

3.0 Effectiveness of current Technology Transfers – Industry Survey

A survey was developed to determine the challenges being faced by those working in the
industry and establish if sentiment was widespread amongst those working at CMOs and
their customers. The survey was created electronically through an online survey
management client and limited to ten questions. A total of 61 participants responded; 39
responded that they were currently working for a CMO that performs technology transfer
and 22 were employed by a company that transfers technology out to a CMO. Figure 1
shows the overall distribution of participants based on job roles with representation from a
wide range of experience.

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12

10

Figure 1: Distribution of survey participants based on job role.

Employees at CMO and their customers were asked what factors were most important to
them during technology transfer of a new biopharmaceutical product/process. Table 1 below
shows that both groups of respondents shared the same top three responses.

Table 1: Top five factors considered most important by employees at CMOs and their customers.

Factor CMO Rank Customer’s Rank

Effective communication 1st 2nd
Good project management 2nd 3rd
Expertise of CMO 3rd 1st
Well characterised process 4th 5th
Good knowledge Management 5th -
Capacity of the CMO facility - 4th

When asked what factors they had actually experienced during transfer of a new
biopharmaceutical product/process, the participants reported the following (Figure 2 and

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Table 2). Analysis of the data shows that those working for a CMO have the same top five
factors as their customers, see Table 2 below.

Poor Project Management

Poor communication
Poorly characterised process
Insufficient knowledge of Key Quality Attributes
Insufficient knowledge of Critical Process Parameters
Insufficient expertise of CMO staff
Poor knowledge Management
Flexibility of CMO not as expected
Frequent or excessive Deviations or Quality incidents during…
Poor Quality of Risk Assessments
Pharmaceutical Quality System ineffective in some areas
Poor Validation services
Insufficient capacity of the CMO facility
Data integrity issues
Regulatory pressure
Location of CMO and Customer created obstacles to…
Other (please specify)

0 5 10 15 20 25 30 35 40 45

Responses

Figure 2: Factors experienced during tech transfer by employees at CMOs and their customers.

Table 2: Top five factors experienced by employees at CMOs and their customers during tech transfer.

Factor CMO Rank Customer’s Rank

Poorly characterised process 1st -
Poor project management 2nd 1st
Poor communication 3rd 1st
Insufficient knowledge of CPP 5th 2nd
Insufficient knowledge of KQA 4th 2nd
Insufficient expertise of CMO - 3rd

The use of assessments prior to a tech transfer was investigated, and the survey responses
showed that a range of tools and formats were being used (Figure 3).

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Figure 3: Summary of tools used prior to a technology transfer

Figure 4 shows that a wide variety of post tech transfer review tools were being used.

Lessons Learned meetings

Review meetings

Post project review meetings

Audits

Site visits

Operational Excellence tools

Other

We do not monitor the outcome of transfers

0 5 10 15 20 25 30 35 40 45
Responses

Figure 4: Tools used to monitor outcome of the technology transfer.

To determine the success of assessments compared to the overall outcome, participants

were asked to select the outcome they experienced. The data shows a broad range of
responses and experiences were varied amongst CMO professionals and their customers.

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Figure 5: Outcome of the tech transfer assessment process.

The survey concluded by asking participants what aspects of technology transfer they
thought could be improved and what could contribute to shortening the transfer cycle.

Realistic timelines
Communication
Risk Assessment process
Process/product knowledge
Project Management
Managing expectations better
Documentation
Initial facility fit assessment
Staff expertise (CMO or Customer)
Accelerating the technology transfer cycle
Reduced CMO costs

0 10 20 30 40 50
Responses

Figure 6: Aspects that could be improved, overall feedback.

Table 3: Top 5 aspects of tech transfer that could be improved from a CMO and customer perspective

Factor CMO Rank Customer’s Rank

Communication 2 nd
1st
Realistic Timelines 1st 2nd

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Process/product knowledge 5th 3rd

Risk Assessment Process 3rd 4th
Project Management - 5th
Managing expectations better 4th -

Table 4: Aspects that were thought may possibly contribute to shortening the tech transfer cycle.

Aspect CMO Rank Customer’s

Rank
Cultivating the "one-team" approach between CMO and Customer,
1st 1st
sharing staff and knowledge earlier in the product lifecycle
Bigger emphasis on shared ownership between CMO and
2nd 2nd
Customer
CMOs providing a development service to Customers and
3rd 4th
engaging earlier in the product lifecycle
Educational initiatives in the biopharmaceutical industry focused
4th 5th
on technology transfer
Regulators working closer and sooner with CMOs and Customers
5th 3rd
to reduce regulatory pressure

The participants agreed that creating a “one-team” approach and bigger emphasis on
mutual collaboration with shared ownership were most important, with general agreement
that a wider service offering by CMOs, support from regulators and educational initiatives
would also benefit.

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4.0 Trends in Technology Transfers – Expert Interviews

Following from the literature review and industry survey, interviews were held with various
professionals with extensive experience of technology transfers to understand the detail
behind the trends they had observed, the changes within the industry and what the current
challenges were. Technology transfer policy and procedures are business sensitive and
therefore commercial advantage limited the availability of reference material and disclosure
of specific processes. The identity of the participants has been concealed and it must be
noted that the opinions expressed by the interviewees are solely their own and do not
represent that of any of their previous or current employer. What follows is a summary of
the discussions.

4.1 Challenges in Tech Transfer and Collaborating with a CMO/CDMO

Choosing the right CMO and engaging in technology transfer requires amongst other things
good knowledge management, technical expertise and facility fit. When all these are in
place, what makes a customer select one CMO over another?
Partnering with a CMO is the reason why companies outsource, because to do it in-house is
slower, more difficult and more expensive when the biotech companies do it themselves.
Biotechs know this and they outsource their risk and exposure, so they will push to justify
their outsourced decision and return as they are answerable to their financial backers
(Interviewee 1, 2020). CMOs also have different levels of previous tech transfer experience,
dedicated project management support, communication skills (bilingual, where necessary),
inspection history and previous regulatory approvals (Interviewee 5, 2020). A strong quality
function, and personnel and cultural fit (operational and management) are also important
(Interviewee 1, 2020) especially in this era of globalisation.

The challenge is that there are different pressures at each stage of a product lifecycle, which
may include change of ownership of the product or the company and the focus is often on
short term goals for a specific product with regards to clinical development, so this whilst it
sounds good, may not be possible to achieve (Interviewee 4, 2020).

Lean organisations and professionals are always challenging themselves to be more

productive with their time application and ability to prioritise & plan accordingly. Often, it’s

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not on a Biotech’s radar to engage a CDMO when in R&D/pre-CMC phases. Also, some
CDMOs only want to engage when the project is CMC/facility ready or near ready, and the
associated funding is secured. Hence prioritisation is a factor, as is available budget. But
there is frequently an element of naivety in early stage of looking to run before you can
walk, underappreciating some of the constraints, limitations, of scale-up and manufacturing
under GMP (and regulatory pathway). Education (training), knowledge sharing and
awareness are factors to avoid the common pitfalls (Interviewee 1, 2020).

4.2 The Earlier the Better

Witcher is the ultimate “the earlier the better” proponent when it comes to working with
external partners. “You might call it science transfer,” he said. The biotech with few internal
resources should partner with a CDMO as early as possible (Garguilo, 2020d).
Selecting potential CMOs in early stage (e.g., during phase 3 clinical manufacturing) ensures
the process can be adapted to fit better at the CMO, resulting in lower costs, higher quality
and operationally faster processes. Experts agreed that it’s always a good idea to get both
teams together when developing in the R&D phase and introduce controls and practices
that make the transfer easier, e.g., evidence of successful testing, analytical method
development and validation.

Of readiness to transfer, the interviewees agreed that all too often a product is developed
in R&D by people who have no experience beyond test tube scale manufacturing and don’t
appreciate that changes to processes may have to be accompanied by comparability
exercises. All too often a poorly developed product is presented to a CMO (or in house
manufacturing unit) and has to be sent back because the product is not capable of being
manufactured using the R&D method within a GMP environment (Interviewee 6, 2020).

Smaller companies with limited funding often wait as long as possible for clinical data before
partnering with a CDMO, larger companies often try to manage large scale manufacturing
based on internal capacity and other manufacturing options. Global pharma also consider
adding a CMO as a second site of manufacture. Most companies are aware that tech transfer
is likely to take at least 6 months and try to initiate discussions at least a year before the

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first engineering batch. Engaging earlier in the product lifecycle may not add much benefit
as there may be limited process information available (Interviewee 5, 2020).

Bringing in the vendors / suppliers to share in the objective from the early stages, offering
their knowledge & expertise supporting the process design come together, is a big plus
point. At the same time, you support to mitigate your supply chain. Effective (not excessive)
risk mitigation planning, using solid yet simple tools, helps to focus the effort, eliminate the
blind spots & ignore non-value adding waste. A successful tech transfer process is well
structured, managed, tracked and continually assessed for very good reasons, because
without doubt this is the highest risk and unfortunately often most overlooked phase of the
CMC project (Interviewee 1, 2020).

4.3 Managing Expectations

“How can we say we are ineffective at tech transfer, but at the same time have established
a thriving industry of virtual biopharma and start-ups reliant on outsourcing most all
development and manufacturing to external partners? We must be doing something right”
(Garguilo, 2020c).

The fact that biopharmaceutical products are making their way to market is testament to
the dedication of CDMO and Sponsors to manufacture safe, potent products on time when
faced with numerous tech transfer challenges. Nevertheless, if expectations are clear and
agreed earlier, then the process could run smoother (Interviewee 4, 2020).

Expectations can be unrealistic especially if the client has no experience of working with
CMOs. They are often not aware of the intense work which goes on behind the scenes
(Interviewee 2, 2020). Project management experience is a critical factor in CDMO selection
and key to achieving the outcomes expected by the client. One industry expert said that he
had seen a deterioration of the management skills necessary to complete such projects.
Problems seem to be occurring because projects get badly over managed with full time
project managers building overly detailed schedules (Gantt charts, etc.) that are out of date
almost immediately and too many regularly scheduled meetings that do not address
problems in a timely fashion. Successful projects are usually run by project managers that

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focus much more on doing by making things happen as fast as possible rather than planning
(Interviewee 8, 2020).

Customers generally understand the timelines required for a typical tech transfer as project
deliverables and costs are provided as part of a project proposal and typically expectations
are aligned. Often additional batches are requested at short notice and whilst everything is
done to accommodate, this is often not possible due to scheduling and capacity constraints
and some clients may expect too much. Technical issues associated with timely closure of
manufacturing deviations may be an issue if a CMO has limited technical or QA experience
(Interviewee 5, 2020).

CMOs understand their own processes and facility limitations, but the more complex the
product, more work may be required to de-risk the manufacturing. For other transfers, the
customer is the expert, and sometimes they either forget this, are not willing to share data
or haven’t got the data to support the process (Interviewee 3, 2020). When transferring a
legacy process, there is sometimes too much reliance on a carbon copy. One should explore
new possibilities and technology upgrade, even if it may increase validation activities.

Most CDMOs do not have significant flexibility in accessing manufacturing resources. Even
very large CDMOs have trouble accessing the necessary resources as the manufacturing
requirements increase as the product progresses through the clinical pathway to launch.
Those that can afford it, are building assets, but these assets use the same inflexible facility
design concepts (Interviewee 8, 2020). There is a current shortage of Qualified Persons
(QPs) with biologicals experience in the UK (Interviewee 11, 2020), and it is unclear if
Quality staff, on both sides of the transfer process really have the necessary skills and
knowledge to directly support tech transfers (Interviewee 4, 2020).

Having an experienced gate keeper is key to business success says one industry expert
(Interviewee 7, 2020). At the start of the process few team members have the same
understanding and skill, but towards the end of the process they do. That journey needs
someone to guide the team who has knowledge of the technology (Interviewee 7, 2020).

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Post-tech transfer reviews are indeed common, but all too often they are only “end of project
tick box exercises”, and they aren’t well contributed to by either CMO or the sending unit.
There is almost total disregard for lessons learned in the following project as there is usually
no mechanism for sharing information and as such, the lessons-learnt file gathers dust in
the previous project files. There is a great lack of implementing /following-on lessons-learnt
reviews. Poor communication and poor project management are usually the result of a
failure at the start of the project to understand, align and agree technical and business goals
alongside realistic expectations (CMOs promise the world to get the work – even though
they know they can’t achieve and thus make unrealistic promises to clients, and clients aften
“mis-inform CMOs of the true state of product development at the start of the project)
(Interviewee 6, 2020).

The process for technology transfer can be improved by putting some clear objectives and
targets working off a benchmark. If there's a sister site within the company which is
performing better than perhaps that could become a very good start. The key to establishing
if a tech transfer performed better or at least as expected is by gaining good quality data.
Knowledge management becomes very useful in collecting data.

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5.0 The 5C Framework

“Technology transfer is an intelligent way of thinking. It is not a formula or a standardised
process, otherwise we only get black Ford Model Ts but the use of standardised processes
form the backbone” (Interviewee 7, 2020).

The research undertaken shows that the industry is challenged with less than ideal
communication, project management (expectations and collaboration), process
characterisation, knowledge management and risk assessment during technology transfer,
some of which have already been discussed with Louis Garguilo, Chief Editor of Outsourced
Pharma (Garguilo, 2020b) and (Garguilo, 2020c). Although guidelines are detailed
documents, feedback from industry professionals suggests that the ISPE and PDA guidelines
over complicate the process (Interviewee 4, 2020) and (Interviewee 6, 2020).

Early engagement, open communication, good knowledge management, a willingness to

share knowledge and early planning or understanding of a product’s manufacturing
requirements and regulatory constraints are clearly good goals, and well known throughout
the industry, yet these factors have not been perfected.

Taking all the findings of the research in to consideration has resulted in the development
of a new framework for biopharmaceutical technology transfer that highlights the biggest
issues as five categories. The 5C Framework aims to instil a pro-active, pragmatic culture of
tech transfer driven by specific triggers in organisations.

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The 5C Framework

Early engagement

Collaboration with CMO

Project
Management
One Team
(CMO & Customer)
Communication

Characterisation
Documentation

Risk and
Facility Fit
TECHNOLOGY Assessments

Coordination TRANSFER

Training

Continuous Improvement Regular

incremental
Regular Review
of KPI
improvements

Figure 7: The 5C Framework for Technology Transfer (image source Layth Ujam, Nov 2020)

The 5C Framework supports a tech transfer process that has it’s foundations based on early
engagement with a CMO and initiating the project as a team. The technology transfer
process, as a whole, supported by project management, documentation, risk and facility fit
assessments and training. Regular review of key performance indicators (KPIs) allow regular
incremental improvements to the process to be made. The 5Cs feed into the technology
transfer process and are enables for success.

5.1 Communication as an intrinsic tool

An enabler for the entire Framework and tool for effective tech transfer, Communication
runs through each of the other four categories. Modern methods of communication allow
people to instantly meet and talk through live video conferencing, email and instant
messaging, remote working is a reality and tech transfer teams can be far apart yet continue
to converse and work together. However, occasional face-to-face meetings are still
invaluable in establishing relationships and developing an innate understanding of each
team member’s communication style. With these tools and technology at our disposal, there
is no excuse for “poor communication”.

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5.2 Collaboration

Too often, people blame poor communication for problems during tech transfer (Interviewee
9, 2020) and (Garguilo, 2020b). Yet communication itself may not be the root cause. If
Collaboration is ineffective, expectations aren’t managed and as a result, the appearance is
that project management is not good and communication is poor (or it gets the blame). The
integration and combined effort of both teams ultimately determines the success, or failure,
of a project. A successful relationship is genuinely mutual and Customers would not want a
subservient CMO partner. The aim is knowledge sharing to get to the clinic faster, safer and
within budget. This is why expectations management (both ways) in the bidding and
outsourced selection phases is essential to managing the true success of the relationship
longer term.

Expectations of effective collaboration include:

1) Early engagement between CMO and Customer.
2) Share the company's mission.
3) Communicate your expectation for collaboration.
4) Define and communicate your team's goals.
5) Highlight individuals' strengths.
6) Promote a community working environment.
7) Foster honest and open communication.
8) Encourage creativity.
9) Share knowledge, insight, and resources.
10) Lead by example.
11) Visit the sending/receiving site and see for yourself.
12) Invest in collaboration tools.
13) Celebrate and reward successful teamwork.

5.3 Characterisation
The Characterisation factor relates to product and process knowledge leading up to a well-
developed process based on scientific principles, with an organisation demonstrating
maturity from the following examples:
1) Consistent and controlled procedures.
2) Knowledge of CCP, CQA and other important parameters.
3) Use of prior knowledge from similar products.

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4) An assessment of transfer readiness.

5) Assurance of equipment understanding and capability.
6) Assurance of analytical method robustness.
7) Request information from the Customer related to raw materials, equipment and facility.

5.4 Coordination
This factor relates to effective transfer management, planning and assessing the product
and business risks:
1. Clearly defined CMO tech transfer process.
2. Risk assessment and risk mitigation procedures.
3. Assign a single project manager for the entire lifecycle of the project, this best serves
the client’s needs and leads to project success. Project management teams should
comprise of professionals with a strong background in technology transfer. A tech
transfer process will face problems if a project manager leaves during the transfer.
This happens quite often during mergers and acquisitions or if a tech transfer project
continues for many years (Interviewee 4, 2020).
4. CMOs should continuously improve their project management operations through
ongoing training and development, both with formal education and training, and with
company internal development programs.

5.5 Continuous Improvement

Tools for continuous improvement are numerous (George et al., 2005) and are often applied
to manufacturing processes, where their benefit could also be realised during tech transfers.
Continuous improvement in tech transfers would be to:

1) Improve the tech transfer as you would a manufacturing process.

2) Working with metrics in a way that measures and monitors effectiveness.
3) Scientific support for identifying the root cause of failures or problems.
4) Work to create behavioral changes to address lessons learned.
5) Use satisfaction surveys.
6) Roll out effectiveness checks for aspects of tech transfer and change management.
7) Visualize successes and share with the organization.

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For an organisation to implement effective tech transfer processes with the 5C Framework,
each factor is required to be an active part of the process. When one of the 5C Framework
factors is missing the outcome of a tech transfer is not achieved as the end result is a
multiplier of each factor (based upon the engagement equation by Rice, Marlow and
Masarech, 2012). Figure 8 shows an ideal process and one where the consequences of any
of the 5C factors being missing or is under developed adversely influences the outcome of
the tech transfer process.

Ideal 5C Framework Engagement

Continuous
Communication × Collaboration × Characterisation × Coordination × = Tech Transfer Success
Improvement

Consequences of poor 5C Framework Engagement

Communication Continuous Duplication of effort,

× Collaboration × Characterisation × Coordination × =
Improvement Mistakes, Delays

Continuous Work in silos, No

Communication Collaboration × Characterisation × Coordination × =
× Improvement coordination, Delays

Mistakes, Problems or
Defects, Reduced
Continuous production rates,
Communication × Collaboration × Characterisation × Coordination × =
Improvement Decreased process
reliability

Re-work, Wasted
× Continuous
Communication Collaboration × Characterisation × Coordination × = effort, Missed
Improvement
deadlines

Frustration, Errors
Continuous
Communication × Collaboration × Characterisation × Coordination × = persist, Inefficient
Improvement
process, Cost

Figure 8: An engagement equation as it applies to the 5C Framework showing an ideal process and the
consequences if any of the factors is missing or is under developed.

5.6 5C Framework Maturity Assessment Model

The Maturity Assessment Model uses five levels of maturity to determine effectiveness of
each of the five Framework factors. Each maturity level has a definition clarifying what it
means to be at that level, see Table 8 below. The output of the assessment is documented
on a table as shown in Table 9.
Table 8: 5C Framework Maturity Levels

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Maturity Level Definition

Initial No standards are in place and inconsistency exists across the organization.
Processes are unpredictable, poorly controlled and reactive.
Managed A process is in place and activities are managed, but the responses are
reactive.
Defined A process is defined as a standard across the organization and is tailored
for individual projects. Responses are pro-active and data is used to
understand why situations occur.
Quantitatively Managed The process is measured and any deviation from the standard is controlled.
Data is used for trending and improvement.
Optimizing The process is continuously improved. Organisation adopts data-driven
strategy. Data is used to create performance culture.

Table 9: Table for the 5C Framework Maturity Assessment Model (based on IBM IT Maturity Model, 2020).

Maturity Level
Quantitively
Initial Managed Defined Optimizing
Factor Managed

Communication

Collaboration

Characterization

Coordination

Continuous
Improvement

Overlaid onto the table are indications of both the As-Is and To-Be states for the particular
organization (see the example in Table 10). Where As-Is defines where the organisation
assesses the maturity for that Framework factor is, and where To-Be is the level the
organisation is aiming for. The transition from As-Is to the To-Be state can cross any number
of levels since progress does not have to be in single steps.

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Table 10: Example 5C Framework Maturity Assessment Model

Maturity Level Quantitively
Initial Managed Defined Optimizing
Factor Managed

Communication

Collaboration As-Is To-Be

Characterisation As-Is To-Be

Coordination

Continuous
Improvement

The criterion for each level of the maturity model must be specific and it must be clear how
each of the criteria for that level is met. Each criterion can be a statement of fact or can
contain a measurement that must be achieved. Table 11 below gives example KPI criterion
for three maturity levels using collaboration and characterisation as examples of the 5C
Framework factors. It is the responsibility of the organisation to determine the KPIs that
define the criteria for each maturity level.

Table 11: Example criterion for Maturity Assessment Levels for Collaboration and Characterisation

Factor Managed Defined Quantitively Managed

Criterion Criterion Criterion
A process is in place and activities A process is defined as a The process is measured and
are managed, but the responses are standard across the organization any deviation from the standard
reactive. and is tailored for individual is controlled. Data is used for
projects. Responses are pro- trending and improvement.
active and data is used to
understand why situations
occur.
Collaboration Documents are issued for review but The time taken to review A regular review of adherence to
the required turnaround time is not manufacturing documents is no schedule is in place.
specified. more than three working days.
Characterisation Customers are asked if they have A standard checklist exists for A scheduled review of stability
process buffer stability data at the obtaining process buffer stability data is in place and regularly
start of the tech transfer process. data. Out of specification data is reported.
used to investigate the reasons
behind the finding.

The As-Is state should be defined by cross functional collaboration across a number of
involved parties. A face-to-face workshop is an ideal forum, where attendees discuss and

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respond to comments and questions, and where they can decide on a level that they all
agree with.

When defining the To-Be state, the objective isn't to achieve the highest level in all areas.
That objective entails a huge amount of expense because it might require changing
significant parts of the current process and utilise resources that may not be available. It
may also be inappropriate, especially when the needs of the organization can be met with
a lower level of maturity. Each level indicates the gap that must be closed for each factor,
based on the maturity aspirations.

Application of the maturity model should be regularly reviewed to avoid complacency within
the organisation. Reapplying the maturity model provides a coarse indication that things are
heading in the right direction towards the To-be state.

6.0 Conclusion
1) Technology transfer processes are well defined and supported by guidance documents,
yet biopharmaceutical transfers continue to be hampered by factors that are not
necessarily associated with the science. The success of transfers heavily relies upon
sharing of explicit knowledge and it is this element that professionals working in the
industry report to cause most challenges. The need for improved transfer of information
is evident given the findings presented in this research and is shared by CMOs and
Customers that partner them.

Industry associations, CMOs and biopharma companies recognise technology transfer as

a critical activity in the product lifecycle. Guidance documents and articles related to the
subject all provide a representation of what an ideal tech transfer should be, yet the
same problems highlighted nearly a decade ago are still being reported. Tech transfer
clearly relies on explicit knowledge, and guidance documents provide extensive lists of
activities and knowledge that should be transferred but little means of how to do this or
how to measure effectiveness of a transfer. Industry professionals and those partnering
with CMOs share the same common issues of project management, management of
expectations, collaboration and communication. The PDA has recognised this and are

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initiating change to their guidance document, Technical Report 65 Technology Transfer

(Haas, 2019).

2) Technological advances have surpassed those of collaboration and coordination yet

these are factors that are relied upon for a successful tech transfer outcome. As more
biotech companies outsource and partner CMOs, the need to collaborate effectively
becomes more important, and effective means of doing this will be required to sustain
the intensification of biological, and soon to be gene and cell therapy products.

Of the 5C Framework categories, collaboration is the one that is least supported by tools.
Collaboration requires the right mindset and perhaps the industry has progressed
communication, characterisation, coordination and continuous improvement at the
expense of collaboration. People fit and cultural alignment will determine the success or
failure of the project.

The search for a Covid vaccine is a prime example of how the industry is collaborating
effectively. Many tech transfer projects have been fast tracked due to Covid through
accelerated regulatory procedures, such as emergency use authorisation (O’Sullivan,
Rutten and Schatz, 2020) and (Garguilo, 2020a). There is a general view that accelerated
tech transfers of 3-4 months may now become an industry expectation moving forward
and accelerated programs will become the ‘new normal’. However, such accelerated
programs are largely dependent on lead times for equipment and raw materials and may
require materials to be shipped from customer sites. In addition, the timelines may not
permit full analytical testing at the CMO site, requiring some release testing at the client
site or third party facilities also (Interviewee 5, 2020). Accelerated tech transfers may
be considered to provide pandemic treatments with a global unmet medical need, but
also present higher risks of delays and possible batch failure (Interviewee 5, 2020).

3) A change of mindset is required within the industry to truly adopt the one-team
approach; sharing ownership, openly sharing information and regarding the CMO as an
extension of the customer’s team rather than a pay-as-you-go service provider. This
change in culture can be brought about by focussing on collaboration, good project

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management and continually assessing effectiveness of tech transfer processes. The

industry has shown to be capable of collaborating, but it has taken a global pandemic to
realise this.

The 5C Framework and associated maturity assessment model provide a pragmatic

approach focussed on the factors that heavily influence the outcome of tech transfers.
It is hoped that this tool can bring about measurable changes within an organisation’s
approach to an effective tech transfer programme.

7.0 References

1. Challener, C. (2020) ‘Ensuring Smooth Tech Transfer of Bioprocess Operations’, BioPharm

International, 33(4).
2. Chang, J. H. (2011) ‘Process Validation Challenges for Technology Transfer’, Pharmaceutical
Outsourcing, (July 01).
3. EudraLex Volume 4 Chapter 7 (2009) ‘EudraLex Volume 4 Chapter 7: Outsourced Activities Legal’,
EudraLex, (January 2013), pp. 1–15.
4. European Medicines Agency (EMA) (2015) ‘ICH guideline Q10 on Pharmaceutical Quality System’,
European Medicines Agency, 44(June 2008), pp. 1–20. Available at:
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC5000028
71.pdf.
5. Food and Drug Administration (2016) ‘Guidance for Industry - Contract Manufacturing Arrangements
for Drugs : Quality Agreements’, Pharmaceutical CGMP Regulations, (November).
6. Garguilo, L. (2020a) ‘2 Years For Vaccine Tech Transfers? COVID-19 Won’t Wait’, Outsourced
Pharma, (September 3).
7. Garguilo, L. (2020b) ‘A Real Dissertation on Tech Transfer’, Outsourced Pharma, (October 11).
Available at: https://www.outsourcedpharma.com/doc/a-real-dissertation-on-tech-transfer-0001.
8. Garguilo, L. (2020c) ‘Tech Transfer, Self-Esteem, And A Fitting Facility’, Outsourced Pharma, October
15. Available at: https://www.outsourcedpharma.com/doc/tech-transfer-self-esteem-and-a-fitting-
facility-0001.
9. Garguilo, L. (2020d) ‘The Witcher Way: Can We “Eliminate” Tech Transfer?’, Outsourced Pharma,
(October 18). Available at: https://www.outsourcedpharma.com/doc/the-witcher-way-can-we-
eliminate-tech-transfer-0001.
10. George, M. L. et al. (2005) The Lean Six Sigma Pocket Toolbook. McGraw-Hill.
11. Haas, B. (2019) ‘Technology Transfer (TT) IG. Presentation at the 2019 PDA Annual Meeting’.
12. IBM IT Maturity Model (2020). Available at: https://www.ibm.com/garage/method/practices/think/it-
maturity-model/.

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13. Interviewee 1 (2020) ‘Interview with Business Development Manager CDMO, Europe, October 2020’.
14. Interviewee 10 (2020) ‘Interview with Regulatory Affairs Manager CDMO, UK, October 2020’.
15. Interviewee 11 (2020) ‘Interview with Biotech Recruiter, UK, October 2020’.
16. Interviewee 2 (2020) ‘Interview with Business Development Director CDMO, UK, October 2020’.
17. Interviewee 3 (2020) ‘Interview with Principlal Scientist MSAT CDMO, UK, October 2020’.
18. Interviewee 4 (2020) ‘Interview with Technical Director CDMO, UK, September 2020’.
19. Interviewee 5 (2020) ‘Interview with Technical Director CDMO, Far East, September 2020’.
20. Interviewee 6 (2020) ‘Interview with Tech Transfer Consultant, >30 years experience, October
2020’.
21. Interviewee 7 (2020) ‘Interview with Bioprocess Consultant, >30 years experience, October 2020’.
22. Interviewee 8 (2020) ‘Interview with Bioprocess Consultant, >35 years experience, October 2020’.
23. Interviewee 9 (2020) ‘Interview with industry journal Editor, October 2020’.
24. ISPE (2018) ‘ISPE Good Practice Guide: Technology Transfer’, (Third Edition).
25. Newcombe, A. (2020) ‘Key Considerations to Ensure a Successful Drug Substance Transfer’,
Outsourced Pharma, (March 5).
26. Newcombe, A. and Brown, D. (2020) ‘Accelerating biopharmaceutical tech transfer to address unmet
medical needs’.
27. O’Sullivan, C., Rutten, P. and Schatz, C. (2020) ‘Why tech transfer may be critical to beating COVID-
19’, McKiinsey & Company Pharmaceuticals & Medical Products, (July).
28. PDA (2014) ‘Technical Report 65 Technology Transfer’, p. 67.
29. Perry, S. (2010) ‘Tech Transfer: Do It Right the First Time’, Pharmaceutical Manufacturing, (Jan 06).
30. Rice, C., Marlow, F. and Masarech, M. A. (2012) The Engagement equation: Leadership Strategies
for an Inspired Workforce.
31. Uydess, I. and Schmidt, W. (2011) ‘Keys to Executing a Successful Technology Transfer’,
Pharmaceutical Technology, 2011 Suppl(2).
32. World Health Organisation (2011) ‘Annex 7 WHO guidelines on transfer of technology’, WHO
Technical Report Series, No. 961, 2011, (961), pp. 285–309.

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