International Journal of Management (IJM), ISSN 0976 6502(Print), ISSN 0976 - 6510(Online),

Volume 5, Issue 8, August (2014), pp. 01-09 IAEME

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TECH TRANSFER: MAKING IT AS A RISK FREE APPROACH IN
PHARMACEUTICAL AND BIOTECH INDUSTRY


Samaraj S.Thiyagarajan, PMP

Biogenn Corporation, Austin, Tx, USA, 78749




ABSTRACT

Tech transfer is a common methodology for transferring new products or an existing
commercial product to R&D or to another manufacturing site. Transferring product knowledge to the
manufacturing floor is crucial and it is an ongoing approach in the pharmaceutical and biotech
industry. Without adopting this process, no company can manufacture its niche products, let alone
market them. Technology transfer is a complicated, process because it is highly cross functional. Due
to its cross functional dependence, these projects face numerous risks and failure. If anidea cannot be
successfully brought out in the form of a product, there is no customer benefit, or satisfaction.
Moreover, high emphasis is in sustaining manufacturing with highest quality each and every time. It
is vital that tech transfer projects need to be executed flawlessly. To accomplish this goal, risk
management is crucial and project team needs to use the risk management approach seamlessly.

Keywords: Risk Management, Tech Transfer, Pharmaceutical, Biotech, Risk Assessment,
Risk Mitigation.

INTRODUCTION

Pharmaceutical companies increasingly adopting acquisitions and mergers is becoming a
trend. One of the main goals after merger is to leverage the synergies of both companies and to do
that tech transfer projects are crucial (Teller J et al. 2014). With regulatory agencies increasing their
vigil on tech transfers, planning and executing these projects become more interdependent on
effective risk management. In pharmaceutical and biotech product life cycle, the process of
transferring product and process is becoming increasingly complex and cumbersome. To make the
transfer more thoughtful and metrics oriented, FDA had added numerous guidance and regulations
through CFR and QSR. High importance is given to Process Validation (PV) and clear guidance
wasissued by FDA in January 2011. FDA focuses to ensure variability of process and parameters are
controlled and sufficient in the face of the rigors of a commercial production environment. Also, a
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critical aspect to measure the successes of transfer projects is to verify parameters that are
established during development are holding as developed and confirmed parameters, even at the
scale up manufacturing.
For executing successful transfer of the product and process from one site to another site
requires an extensive and adequate risk management process. With squeezing margins and reduced
profits, it is imperative to execute and sustain transfers with pristine quality (Thamhain H. 2013). For
achieving the goal of successful transfers, pharma companies are increasingly adopting several
project management strategies. A core strategy that needs to be developed and executed efficiently is
risk management. A robustly developed product if not transferred with meticulous care will lead to
several production and regulatory issues along the life cycle of the products.
To understand the risks, it is critical to know how risks are categorized. Risks are categorized
as known risks and unknown risks (Samaraj S T. 2014). Known risks are the ones that can be
identified, analyzed and risk mitigation strategy can be established beforehand. The alternative to
this is the unknown risks, which may present itself at any point in the project. To handle this type of
risk, the transfer team needs to be prepared (Krane H P et al. 2012)
This article discusses about optimal risk management strategies for each phase of the tech
transfer project. In order to develop a successful strategy, potential risks need to be enumerated,
analyzed and registered by the project team (Kutsch E and Hall M. 2009). A comprehensive risk
management plan will be drafted. The team uses various risk management tools to identify, analyze,
and register the risks. Risk mitigation is brainstormed and executed. Each phase of the tech transfer
project has several potential risks. Successful identification of all potential risks is the first step in a
more complex endeavor.

PROJECT SCOPE AND PLANNING

For an organization to turn its mission into a meaningful purpose, the only vehicle exists is
project. Hence, project planning and initiation is the foremost pivotal task for an organization. In
particular, high risk projects like tech transfer in pharmaceutical industry need to be planned to
utmost usefulness without any room for error (Teller J. 2013). It is critical to understand the risks of
inadequate planning. Most management in pharma or biotech industry is mainly concerned about the
bottom line. It is common there is much oversight on what pharmaceutical products transfer project
entails. Many innovative products suffered in the upstream manufacturing after they were
transferred. One of the main reasons is the execution of the projects without complete planning and
understanding of the risks associated (Teller J. et al. 2014). A common risk, which lead to project
failure is; putting together a plan without understanding the sending and the receiving (pitching and
catching site) sites culture, facility requirements, regulations, time constraints, budget and scope of
the project. These risks were not fully identified, or even if identified, they were not characterized
and assessed for its occurrence and its impact. To make a project successful, risks associated project
planning need to be clearly identified and addressed.

PROJECT SCHEDULE

An important factor for any project, irrespective of industry, is the project schedule, without
which there is no metrics to measure. In tech transfer projects, a high level project schedule will be
developed initially with very little information about the scheduled activities. Risks of this approach
need to be captured or assessed during the planning stage (Kuchta D. 2014). A transfer project can be
as efficient as only when the project schedule developed with an understanding of known risks and
having a contingent plan based timeline for tackling the unknown risks. Once the project is initiated
and project team formed and the transfer activities are understood, the team develops detail task
International Journal of Management (IJM), ISSN 0976 6502(Print), ISSN 0976 - 6510(Online),
Volume 5, Issue 8, August (2014), pp. 01-09 IAEME


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based schedule. The detail work breakdown structure is compiled; the team then establishes a more
task level timeline. Few of issues and risk during this process includes the sponsors of the project are
totally unaware of the operating mechanisms in both sending and receiving sites. Failure of the team
to comprehensively understand the scope and the actual work required to execute the project on time.
Few failures based on the historical data includes: Failure in terms of not having a contingency plan
for mitigating any unforeseen issues (Yang Q Lu et al. 2014). Inadequate time scheduled for dealing
with regulatory, environmental, and other problems. Teams unfamiliarity with the products and
process is a risk.Failure to have clear-cut milestones and gate reviews in the project schedule will
lead to project not following the track for completion (Khamooshi H and Golafshani H. 2014). A
common pitfall during the scheduling is to understand the market demand for the products that are in
the transfer pipeline, leaving the business with either short supply in the market. It is crucial for the
project team to understand risks of this nature and it will make the project team to navigate the
project more successfully.

ESTABLISHING THE PROJECT TEAM

There is no formal risk assessment for the team formation, but this as crucial as any other
factor to the success of the transfer project. Upper managementsfailure to take the cultural
difference between the sending and receiving sites in its perspective may result in numerous issues
after the products were transferred (Zhang J and Wei W X 2012).Risks of not having a complete
representation from impacted departments should be assessed. Some of the prevalent risk associated
with the transfer project team involves;failure of the team to understand the culture difference
between the sending and the receiving sites.Project manager not understanding the operational
differences between the two sites will be a risk.Lack of motivation and engagement could also be a
potential risk factor for successfully completing the project (Fernandes G and Ward S.2014). This
risk will rate high in risk analysis, because as there may be some potential for job loss in the sending
site. This will de-motivate the team members and prevent them from imparting their full knowledge
to the receiving site. Especially if the subject matter specialists arenot cooperating,the transfer
process may suffer significantly. Risk assessment and risk mitigation steps should be focused to
resolve this problem.

GAP ASSESSMENT

Pharmaceutical tech transfer projects cannot be executed with high success, unless a
complete gap assessment is performed (Pedram Alaedini et al. 2007). Gap assessment is to identify
the gaps between the sending sites and the receiving sitein the areas indicated in the figure 1.
Without knowing the existing difference for all the aspects shown in the figure 1, a transfer project
cannot be completed successfully. It is a potential form of risk assessment. Certain projects may not
have any form of gap assessment. These projects may have a hard time in keeping the project on
track as new challenges occur at every stage. In some instance, the project team realizes the
importance of understanding the gap,and will then initiate the process midpoint in the transfer
(Wiliam Schmidt and Ian Uydess. 2011). For any tech transfer projects, mainly transfer between
sites, this is a critical step in the project. Risks or weakness in this process needs to be identified. The
incomplete nature of the gap assessment process and how it could potentially impact the project and
process during and after the transfer is crucial for avoiding any unforeseen challenges.

International Journal of Management (IJM), ISSN 0976 6502(Print), ISSN 0976 - 6510(Online),
Volume 5, Issue 8, August (2014), pp. 01-09 IAEME


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PROCESS MAP

One of the foremost tasks in project planning and execution is to create a detailed process
map for all the parts that will be transferred. Process maps are an excellent source for identifying the
risks at each and every step of the process. Failure to develop a process map or a map that did not
capture all relevant and necessary steps in the process will create problems for the receiving team
(Bikash Chatterjee and Mark Mitchell. 2012). As high emphasis is given to LEAN manufacturing
and more and more pharmaceutical companies adopting that approach shed light on the importance
of Value Stream Map, whichin addition to the process map significantly reduces risks. A transfer
team should comprehend the risks of not utilizing both these vital tools for their benefit. Like any
other aspects in the transfer project, risks that were not identified, analyzed and mitigated will result
in considerable constraint for the success of the tech transfer. Value stream maps serve as a great
deal in identifying the non-value add activities, also, assess and minimize risks from eliminating
those non value add activities.

FACILITY

More importantly, and often overlooked aspect in the tech transfer project is the foot print of
the sending site and the comparative assessment of the receiving site. Often times, the management
when assessing the synergies, they form the opinion about the ease of adaptation or modification of
the footprint at the receiving site, but they fail to understand the extent to which the
receivingorganization can be flexible (Lam Wei Chak Joseph. 2007). Even if the receiving site can
be adapted to the requirements, a thorough assessment of financial requirements to eliminate any
risks should be properly budgeted in the project. Project teams should be able to identify and
mitigate these risks, failure to capture and act upon these risks will lead to project overrunning the
budgeted costs. Few critical risks identified from the past projects are:

Risks from facility floor plan not conducive for certain manufacturing process flow.
Risk from suboptimal environmental factors like temperature, humidity, airflow.
Risks due to potential natural uncertainties like tornado, snow, wild fire, floodingetc., which
may threaten the normal operations of the plant.
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Access and transport facilities to the plant.
Risks including available recycling and waste disposal facilities.
Risks involving facility sanitation and cleanliness, especially if the transferred product is
GMP manufacturable quality.

PRODUCT CHARACTERIZATION

Product characterization is an important aspect of a transfer project, both from R&D and
from other commercial sites. If the product transferred lacks an adequate characterization, it assumes
significant risks in terms of product manufacturability, safety to users, and regulatory compliance
(Butler M S 2004). Few critical risks that project team needs to identify during the transfer activities
include, but not limited to are: risks due to inadequate product characterization with respect to
product requirements and Target product profile.The team need to be aware of the risk from
incomplete transfer of product stability studies and related data. In some instance, receiving site may
not perform an adequate product physical characterization, especially for API and filler
materials.Often times, characterization of molecular and particulate aspects of the products will not
be fully vetted in the receiving site;thesejeopardize the continuous manufacturing of the products
without any failure in in-house and in the field (Clarke, G S 1994).Raw materials availability and
characterizations of their impurities and their impact on the final performance of the products need to
be elucidated and both teams should understand the risks.Due to frequent mergers and transfers,
critical information like PRD, Trace matrix, voice of the customers could be lost or unavailable from
the database.

PROCESS CHARACTERIZATION/ PROCESS VALIDATION

The core of the transfer is transferring the process efficiently so that any manufacturing unit
can adapt it. Due to the nature and significance of this step, the risks assessment becomes an inherent
and important process in this phase of tech transfer project (Riley C M and Rosanske T W.
1996).Critical risks that we normally assess include the following:

Risks of failure to develop a robust process in the first place.
Risks including process, not able to withstand the variance in the inputs.
Risks including the adapting of the process to achieve the specification required.
Failure due to developing a process that might be inundated with numerous non value add
activities.
The risksof having the flow of the process, not suitable for the receiving site layout.
Risks from the broken process with low capability index, resulting in producing more failed
products.
Risks from fixing the process that results in utilizing resources more than planned.
Inadequate development of the master validation plan, resulting in failed validation.
Risks of not addressing the regulatory requirements in the validations.
Due to timeline constraints, performing a less number of process validations than the standard
three batch requirement.
Risks of validation providing ambiguous or unreliable data.
Risk resulting from inadequate cleaning validations.



International Journal of Management (IJM), ISSN 0976 6502(Print), ISSN 0976 - 6510(Online),
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ANALYTICAL/QUALITY TEST METHOD TRANSFER

Transferring analytical method and quality control methods need to be given more attention.
Developing test methods are an important process during the product development. Not having a
suitable method will either result in accepting bad lots as good lot and shipping them to the customer,
or rejecting a good lot as bad. Both these events will affect the business. In the first instance, bad lot
mistakenly passed as good lot and released in the field will eventually fail at the customer s hand,
making the customer unhappy and creating product recall and regulatory warnings (Green J M.
1996). On the other hand, rejecting a good lot as a bad lot after an in house testing will result in a
business losing revenue, impacting the bottom line. It is utmost important to understand the risks
involved in analytical transfer. Critical risks include the following.

Risks resulting from a process not well characterized for the receiving site to incorporate into
their process flow.
Failure to identify bottleneck in the sampling and testing process like the methods past
performance, the familiarity of the receiving site with the testing process.
Risk of testing method developed may not efficiently discriminate between good and bad
products resulting in consumer risk, or business risk.
Risks associated with the variability of the assay.

DOCUMENTS

Manufacturing, testing protocols, SOPs: For any successful tech transfer projects, it is crucial
to transfer the knowledge in pristine condition. It is also the common source of variation between the
sending and the receiving sites. Every organization will have different template and documents
style, and even different language. It makes transferring documents a more challenging process. In
addition to the different format and language, sites may have different document management
systems like SAP, E1, Agile, and many other. The project team needs to understand the risks for the
manufacturing. Risk analysis and mitigation need to be planned. There are also some other risks like
risks including instructions not explicitly stated for the operator to carry out without any room for
interpretations.Risks including calculation errors, resulting in potential formulation errors, which
could lead to potential recalls, if not captured in testing.

EQUIPMENT

Equipments are a critical part of the transfer process. In depth IQOQ protocols need to be
developed. Risks are assessed; includinga greater risk is the instrument capability and variability.
Risks are assessed for the instrument gage and their precision to tolerance. Risks are understood by
running MSA on the instrument to understand the variability provided by the instrument to the total
process variability. Risks including cost of upgrading the instrument to meet the standards.

REGULATORY

Major risks in any transfer projects that require regulatory approval is failing to provide data
and follow the guidelines required for FDA submission. Any risks in the above category may have a
cascading effect on the regulatory submissions and the sustainability of the transfer.



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Volume 5, Issue 8, August (2014), pp. 01-09 IAEME


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RISK ANALYSIS

As the risks are identified, the transfer team assesses them to understand their impact on the
success of the tech transfer and sustained manufacturing of the products. Several approaches have
been identified. The team can use both qualitative methods and quantitative methods. Qualitative risk
analysis: Team can use risk probability and impact assessment. Brain storming, Monte Carlo
analysis. Delphi techniques (PMBOK Guide. 2013). The team need to do a SWOT analysis. The
team can use Failure mode effect analysis. Risks can be ranked based on the severity and
occurrences.

FMEA


Figure 2: FMEA Failure mode and effect analysis helps team to identify failure modes, severity for
the failure mode, effects of the failure and residual risk monitoring.


Evaluation Method


Figure 3: Impact analysis for each failure mode is assessed based on severity

RISK MITIGATION STRATEGIES

The project team based on the risk analysis need to plan for risk responses and risk mitigation
strategies. Commonly adopted risk mitigation strategies are risk avoidance. If a certain risk ranks
high, team can make the decision to entirely avoid that particular task or strategy for avoiding the
risks in that approach. Alternatively a tech transfer team can either mitigate risks by identifying a
solution or identifying a root cause approach.


Figure 4: Levels of risk acceptability

International Journal of Management (IJM), ISSN 0976 6502(Print), ISSN 0976 - 6510(Online),
Volume 5, Issue 8, August (2014), pp. 01-09 IAEME


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CONCLUSION

Risk identification, analysis, and mitigation is an iterative process. Irrespective of project
types and industry, risk management is inherent to the success of the projects. Highly regulated
industry like pharmaceutical and biotech risk management guidance is formulated by the regulatory
agencies like FDA and other EU agencies. Risk management is more crucial for the tech transfer
projects to prevent any failure in the future at the manufacturing.

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