THREE PHASES TO SUCCESS IN STERILE INJECTABLES TECHNOLOGY TRANSFER
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Pfizer CentreOne
THREE PHASES TO SUCCESS
IN STERILE INJECTABLES
TECHNOLOGY TRANSFER
In this article, Jennifer Quint, Senior Manager at Pfizer CentreOne Technical
Services, offers insights into how to plan and execute technology transfer effectively,
explaining Pfizer CentreOne’s three-phased approach that can successfully support
this pivotal event in a drug product programme’s journey to commercialisation.
Central to every commercial relationship
with a contract development and
“With sterile injectables,
manufacturing organisation (CDMO) is the
technology transfer. A number of subject both the SU and the RU
matter experts from both the sponsor and need to gather additional
the CDMO may be involved in developing
and manufacturing a product, making the
information – and do
technology transfer process both complex so as early in the
and critical to success. process as possible.”
Many organisations have their own
definition of what constitutes a technology
transfer, but the US FDA points to
ICH Q10, “Guidance for Industry Q10 A priority for many sponsors, therefore,
Pharmaceutical Quality System” published is finding partners with the specific scientific
in 2009, to define its guidance. “The goal and technical capabilities to transfer their
of technology transfer activities”, the formulation chemistries from a source
guidance states, “is to transfer product and unit (SU) to the commercial-scale receiving
process knowledge between development unit (RU) in compliance with regulatory
and manufacturing, and within or between guidance. All successful technology transfers
manufacturing sites to achieve product require discipline and collaboration.
realisation. This knowledge forms the basis However, when it comes to the aseptic
for the manufacturing process, control finishing and filling of sterile injectable
strategy, process validation approach and therapeutics, obtaining this base knowledge
ongoing continual improvement.” can present specific challenges (Figure 1).
As explained in ICH Q10, this Jennifer Quint
internationally harmonised guidance is START A WELL-DEFINED Senior Manager, Pfizer CentreOne
intended to help pharmaceutical manufacturers SCOPING PROCESS Technical Services
by describing a model for an effective quality
management system. It is a systematic, logical With sterile injectables, both the SU and the Pfizer CentreOne
procedure that transfers the documented RU need to gather additional information – 235 East 42nd Street
knowledge and experience gained during and do so as early in the process as possible. New York
NY 10017
chemistry and formulation development to The earlier a well-defined discovery begins,
United States
an appropriate, responsible and authorised the better it will be at communicating and
commercial manufacturing entity. transferring the main agenda of the drug www.pfizercentreone.com
Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 35
Pfizer CentreOne
additional protective measures are
called for. Before actual due diligence is
conducted, there should be a confidentiality
agreement signed and in place. Programme
managers and sponsors should both know
that, throughout the drug development
programme, all project information and
data must remain confidential and secure.
Role alignment is another tactic that
supports a successful technology transfer.
All outcomes should be documented
on an ongoing basis, such as having a
comprehensive product transfer plan (PTP),
so that a mutual understanding is shared
across all team members and stakeholders
from the beginning of the project to the
very end.
THE THREE PHASES OF A
Figure 1: Technology transfer is never a simple process, but there are additional SUCCESSFUL STERILE INJECTABLE
challenges when dealing with sterile products such as injectable therapies.
TECHNOLOGY TRANSFER
programme. Four key considerations should Project and Site Talent
feature prominently when scoping sterile It is also critical to engage with the CDMO’s In most “lessons learned” shared among
injectable technology transfer: core team and subject matter experts early sponsors and commercial partners, the
and to continue to ask questions throughout common reasons for technology transfer
Geography the process. As with any aspect of drug failure include:
The location of the RU may impact the development, a technology transfer can
completion of a compliant, efficient only be successful if all teams actively work • Not anticipating the impact of changing
technology transfer, as changes that are together from the start. facility or equipment (batch failures)
permissible in one jurisdiction may not be • Not anticipating the new regulatory
allowed in another due to the regulatory PICK THE PROFESSIONALS environment or requirements (scope creep)
environments in which they operate. AND ALIGN ROLES • Tacit knowledge of the product not
captured or transferred to the partner or
Compliance When a sterile injectable technology RU.
Although compliance is a broad term, a transfer project involves multiple partners,
“compliant” technology transfer begins Taking a systematic approach during
with a careful evaluation of the applicable the scoping phase of technology transfer
regulatory guidance that pertains to a is important. Conducting a deep dive and
product’s finished commercial state.
“Conducting a deep dive thorough assessment of gaps between
For example, more mature commercial and thorough assessment the SU and the RU can help the project
product transfers may see more compliance of gaps between the SU team understand, document and manage
challenges in the dossier and equipment/ the risks associated. Pfizer CentreOne,
facility contemporisation.
and the RU can help the defines three key phases of a technology
project team understand, transfer (Table 1):
Technical document and manage
Sterile injectables are typically considered • “Define and Scope”
to be a high-risk product, in large part the risks associated.” • “Plan”
due to the duration of a drug development • “Execute”.
project. Sterile injectables can take
2–10 years to move from Phase I clinical
trials to full commercialisation. Such a Phase One – Phase Two – Phase Three –
Define and Scope Plan Execute
project is prone to outside factors, such
as regulatory changes (e.g. nitrosamines, Key success • Knowledge • Establish project • Collect project data
elemental impurities) or supplier changes, factors gathering schedule • Analyse variance
impacting the overall project scope and • Gap analysis • Check and optimise • Mitigation plans
timeline. Defining the technical bases and • Risk assessment • Have a risk • Communicate
outlining process elements should be a part management plan project progress
of early discovery and a critical dialogue that
sets the stage for a more formal technology Table 1: Pfizer CentreOne defines three phases that are a key part of any successful
transfer process. technology transfer.
36 www.ondrugdelivery.com Copyright © 2021 Frederick Furness Publishing LtdPfizer CentreOne
PHASE TWO – PLAN overall project timeline. Such plans also
function to define the project’s overall
“The benefit of having a
In Phase Two, the planning stage, the agreed risks and provide a good
documented charter and CDMO’s technology transfer team will communication tool when checking in
a PTP is that it ensures develop a work breakdown structure with sponsors and key stakeholders. A risk
and outline critical milestones. This management plan can help to reduce the
that there is a shared phase includes the development of the risk of failing to file in accordance with the
understanding of the preliminary schedule and the generation agreed timeline.
project and its objectives.” of resource estimates. During this phase, The risks associated with a technology
the involved parties each develop their transfer project include technical risk,
own risk management plans, refine transfer regulatory risk and supply chain risk.
protocols, establish a clear schedule and lay Technical risk assessment, also known as
PHASE ONE – DEFINE AND SCOPE the groundwork for the transition to the a robustness assessment, employs various
execution phase. tools to identify the highest risks associated
Phase One defines the scope of the project with the technical aspects of the technology
and helps to establish organisation and a Why is Planning Important? transfer. The technical risk assessment relies
project charter. This is accompanied by Not having a project schedule can lead to on the development and manufacturing
a knowledge-gathering process that confusion pertaining to which stakeholder history of the product and is a documented,
encompasses the programme’s current status is responsible for each activity at each data-driven process.
and future outcomes. Phase One also sets the stage and whether the end goal of A regulatory gap assessment handles
stage for a gap analysis and failure modes the project is still on track. Too little strategies associated with various change
and effects analysis risk assessment. Lastly, detail can paint an unclear picture, scenarios, as well as contemporisation
long lead-time items are covered, and the whereas too much detail can obscure requirements. The outcome of the
transfer protocol is defined. At a high level, important information. With the right regulatory gap assessment is typically a
at the beginning of the project, it is important amount of information, the project may be regulatory strategy document, also known
to define what is in and out of scope: tracked and managed effectively. Ideally, as a risk registry, which is used throughout
every project plan should have some lag the transfer project to communicate and
• What type of transfer is it – is it from built into the schedule to accommodate any manage the regulatory risks.
development to commercialisation or is it unforeseen circumstances. A supply chain risk assessment will yield
transferring from an existing commercial a supply chain transition plan. This includes
site to a new one? Optimise Project Review Frequency supply chain changes that might impact
• What is the status of each receiving Determining the right frequency to review the robustness and regulatory assessments.
site – is it a green field site or is it GMP and, if need be, optimise project timelines The outcome of the technical and regulatory
certified? How many receiving sites are and charters can be just as important as assessment will be used as the basis for the
involved in the project? the amount of detail that is put into each supply chain transition plan.
• Is this an intra-company transfer or is it document upon its creation. If managers
an inter-company transfer? check too infrequently, they might miss PHASE THREE – EXECUTE
• If an external partner is involved, what is something. On the other hand, if managers
in the contract regarding the technology review too frequently, then it may appear Phase Three is an exciting milestone
transfer scope, roles and responsibilities? that the project is not moving along as it where the programme team tracks and
• How many stock-keeping units are should be. Additionally, reviewing the project manages the project and collects status data.
involved? charter against the timeline ensures that the As operational data arrives, the programme
• What are the targeted markets in which project goals that have been communicated team analyses variances and looks for
the sponsor intends to file? to key stakeholders are in alignment with the adaptive actions to ensure that quality
• What is the current supply chain (APIs, project’s current progress. and process optimisation goals are met.
raw materials, excipients, etc) versus the Project status reporting is vital during this
future supply chain? Define a Risk Management Plan phase to ensure transparency and clear
A risk management plan can track items communication.
Even though the teams may not have that were not scoped and assign a level Depending on the complexities of
concrete answers to these questions up of risk to activities that could impact the the programme, weekly team meetings
front, they must be asked, documented and
tracked so that information stays visible and
can be actioned by the team. “It is crucial to pay close attention to the transfer
It is never too early to define the project
charter or to work on the PTP. The benefit process, carrying out proper definition and planning
of having a documented charter and prior to any execution. Failure to do so could lead
a PTP is that it ensures that there is a
to unnecessary delays and downtime,
shared understanding of the project and its
objectives. The project charter and PTP are with implications for project timelines.”
also tools to facilitate project planning.
Copyright © 2021 Frederick Furness Publishing Ltd www.ondrugdelivery.com 37Pfizer CentreOne
and sometimes sub-meetings may be planning prior to any execution. Failure Pfizer CentreOne was founded in 2015
necessary to track actual progress against to do so could lead to unnecessary delays when Pfizer CentreSource, a global leader
the established PTP and timeline. Check- and downtime, with implications for in specialty APIs, and Hospira One 2 One
ins can become even more critical when project timelines. merged. Backed by Pfizer resources, the
unforeseen issues arise. Working together Working closely with the CDMO and company delivers technical expertise, global
to troubleshoot and correct issues can have other stakeholders from the very beginning regulatory support and long-term supply.
a significant impact on a timeline in the of the definition and planning phases is an
long run, but might also make a process essential part of any effective transfer. Such
more robust. collaboration can ensure that any potential ABOUT THE
Communication within the CDMO’s
team is often just as critical as communication
pitfalls and risks are accounted for and
mitigated against before they become a
AUTHOR
with programme stakeholders. All problem. It can also help all parties ensure Jennifer Quint is the Senior Manager for
stakeholders want to know is: that they have the capacity, capability and the Pfizer CentreOne Technical Services
infrastructure in place ready for the project team. Ms Quint leads a team of chemists
• Are there any issues or emerging risks handover, helping to ensure development and microbiologists who execute
that could significantly impact the continues smoothly and efficiently. compendial and method development
project? in support of internal and external
• How is the programme tracking against ABOUT THE COMPANY Phase II/III technology transfer projects.
the agreed budget and timeline? Her focus is on GMP compliance while
Pfizer CentreOne is a large global CDMO driving alignment of cross-functional
FOLLOWING THE PROCESS IS within Pfizer and a leading supplier of development teams. Ms Quint joined
CRITICAL TO PROGRAMME SUCCESS specialty APIs. Its service offering is broad, Abbott in 2003 and has been a part
spanning development and manufacturing of the Pfizer CentreOne organisation
Technology transfer is complex, particularly services for sterile injectable and oral for over 17 years with experience in
for sterile products. With this in mind, it is solid dosage forms. Pfizer CentreOne’s leadership, science and customer
crucial to pay close attention to the transfer manufacturing network includes more than manufacturing business activities.
process, carrying out proper definition and 35 sites across six continents.
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