NATIONAL STEM CELL
MANUFACTURING FACILITY VALIDATED
National Centre
for Biomedical
Engineering Science,
National University of
Ireland, Galway
T: 00 353 91 495166
E: info@remedi.ie
W:www.remedi.ie
SENIOR NSCMF
TEAM MEMBERS
Prof. Timothy
O' Brien,
NSCMF
Director
Prof. Frank
Barry,
NSCMF
Director
Dr. Karen
Duffy,
NSCMF
Manager
n May 2009 the National Stem Cell
Manufacturing Facility (NSCMF), based at the
National University of Ireland, Galway,
successfully underwent a cleanroom environment
inspection by Diamond Scientific. Cleanroom
certification is one of the key milestones towards
achieving a facility which is fully licensed by the
Irish Medicines Board (IMB) for production of
human cellular therapeutic product, enabling
licensed processing/manufacturing activity for
clinical trials to begin in 2010. This major
milestone could not have been achieved without the
hard work of the dedicated staff of the facility as
well as the NUI Galway Buildings Office.
I
The facility will be operated under licensed
validated conditions (both premises and equipment)
according to EU legislation. Part of this process
will be to obtain an IMB tissue establishment
REMEDI REVIEW
ISSUE 6
OCTOBER 2009
IN THIS ISSUE
NATIONAL STEM CELL
MANUFACTURING
FACILITY VALIDATED
ABOUT THE NATIONAL
STEM CELL
MANUFACTURING
FACILITY
INTERVIEW WITH
KAREN DUFFY, MANAGER
OF THE NSCMF
WWW.REMEDI.IE
The NSCMF is operated by the Regenerative
Medicine Institute (REMEDI) who has a key
strategic goal to advance to phase one human trials
using IMP generated in the facility. Discussions are
ongoing with internal faculty and external clients
and it is expected that the first GMP product to
support a clinical trial will be allogeneic or
autologous adult MSCs for either cardiac function
repair, treatment of Host versus Graft Disease
(HvGD), or Irritable Bowel Disease (IBD).
ABOUT THE NATIONAL STEM CELL
MANUFACTURING FACILITY
T
Dr. Keith
Madden,
NSCMF
Quality
Assurance
Manager
licence for the procurement, processing,
preservation, storage and distribution of human
tissue samples (i.e. blood or bone marrow aspirates)
as well as an Investigational Medicinal Product
(IMP) manufacturing licence for the in vitro culture
expansion of adult Mesenchymal Stem Cells (MSC)
also in line with current EU directives.
he NSCMF is a purpose-built Good
Manufacturing Practice (GMP) cleanroom
facility for the production of cellular and gene
therapy agents for clinical use is operated by
REMEDI and based at NUI Galway. The facility
encompasses
a
working
floorspace
of
approximately 250 M2 and possesses two equipped
production suites comprising of three processing
rooms (Preparation Room, Downstream Process
Room, Filling Room) for various stages of cell
isolation and culturing.
Given the standards of regulatory compliance, cost
and criticality of the cleanroom operations to be
undertaken, the materials being processed and the
particular material storage conditions, considerable
emphasis is placed on validation (IQ/OQ/PQ/PV)
of facility equipment and systems, preventative
maintenance, re-calibration, and emergency backup systems/services in the event of equipment or
system failure.
The facility is serviced by dedicated utility systems
such as a CO2 gasline and liquid nitrogen, and
highly filtered air is provided to both production
suites by independent air handling systems. As
dictated by current EU legislation, the processing
rooms are classified as Grade B according to Annex
I of the EU sterile medicinal product manufacturing
guidelines, with any open manipulations of the
product being performed in a Grade A
environment.
The facility is presently staffed by a select group of
dedicated GMP personnel. The services of a
Qualified Person are obtained on a contractual
basis to assist in the establishment of the GMP
processes and for authorization of final stem cell
product release as dictated by the relevant EU
legislation for medicinal products.
2 REMEDI REVIEW
INTERVIEW WITH KAREN DUFFY, MANAGER OF THE NSCMF
CAN YOU TELL US A LITTLE BIT ABOUT YOUR BACKGROUND?
I
completed my B.Sc. and Ph.D. training in the Microbiology Department at NUI, Galway. My Ph.D. work under the tutelage of
Dr. Cyril Carroll focused on the regulation of heat-shock proteins in the food-borne pathogen Campylobacter jejuni in response
to various applied stresses. During my research I became increasingly conscious of and interested in quality systems and standards,
such as Hazard Analysis and Critical Control Points (HACCP), used by the food industry to ensure food safety and to protect public
health. After completing my Ph.D. research, I undertook a number of post-doctoral research projects in the field of food safety
including a project in collaboration with Boehringer Ingelheim to develop a diagnostic immunoassay for detection of prions in
fractionated bovine blood, which gave me my first exposure to the requirements of industry from basic research outputs and an
opportunity to be involved in the set-up of a biohazard level 2+ containment facility. In 2002, I completed a Diploma in Quality
Management awarded by Excellence Ireland Quality Association and decided to gain more practical experience of private industry.
I next worked as a Product Development Biochemist working on the development of a novel detection medical device and diagnostic
immunoassay for detection of the human pathogen Streptococcus pyogens in saliva. I also worked in The Centre for Liver Disease
at the Mater Misericordiae Hospital, Dublin before returning to NUI, Galway to take up my current position in REMEDI as GMP
Facility Manager. Having realised the importance of the business operations element of the NSCMF and always keen on improving
my skills base, I am presently undertaking a part-time Executive Masters of Business Administration (EMBA) run in NUI, Galway by
the J.E. Cairnes School of Business & Economics.
WHEN DO YOU ANTICIPATE THE NSCMF WILL BE FULLY LICENSED?
Due to the complexity of the task to hand it’s difficult to name an exact date for the facility being fully licensed but the team at
NSCMF are actively working to achieve this goal. A Quality Management System (QMS) has been established and developed, as this
is a current ‘live’ system it requires constant development and management as it evolves complementary to the activities of the GMP
facility. To date the QMS contains over 300 approved documents including policies, standard operating procedures, material
specifications, forms and records. The facility has undergone some engineering retrofits and validation exercises to ensure compliance
to current requirements, earlier this year the facility cleanrooms were successfully certified to the strict standards of air cleanliness
required for aseptic manufacturing operations in Europe. This certification is very important for the facility and since then the focus
has been concentrated on the tasks involved in process verification of the manufacturing operation as a prelude to regulatory
compliance audit by the IMB for manufacture of cellular therapy product.
WHAT ARE THE POTENTIAL BENEFITS OF HAVING A LICENSED FACILITY?
Based in close proximity to an academic environment, the NSCMF is a unique opportunity for Ireland as very few similar facilities
exist in Europe. The potential benefit of a licensed stem cell manufacturing facility is enormous - human cell therapy is an emerging
field of medicine which holds great promise for treating a number of conditions such as diabetes, cardiovascular disease, osteoarthritis,
irritable bowel disease, and age-related macular degeneration amongst many others. These regenerative medicine treatments could
pose significant economic benefits for state healthcare systems with respect to the long term treatment costs for these patients, as well
as improving the quality of life for patients and their families.
For Ireland, a licensed facility will facilitate human cellular therapy clinical trials within the country, allowing evaluation of the clinical
applications of new therapies. In Galway, there has been significant effort made to create the infrastructure required to support
human clinical trial activities through the ongoing translational research programmes at NUI, Galway and the establishment of the
Clinical Research Facility (CRF) with whom the NSCMF is presently collaborating. The potential for the NSCMF is tremendous;
globally the current market for human cellular therapy products is estimated at $1.5 billion and growing. A market report published
earlier this year forecasts that the largely untapped global market potential for these products will exceed $118 billion by 2013, with
markets in Europe growing at significantly higher rates than the United States.
ONCE LICENSED WHAT WILL THE NSCMF HAVE CAPACITY TO PRODUCE?
Once licensed by the European Medicines Agency (EMEA) via the Irish competent authority, the Irish Medicine Board (IMB), the
NSCMF will be licensed to produce clinical-grade autologous or allogenic adult bone marrow-derived MSC for use as therapeutic
medicines.
WHO WILL BE ABLE TO AVAIL OF THE NSCMF?
The facility will be available to anyone interested in producing GMP-grade cells including Irish and international academic institutions,
hospitals and industry.
The National Stem Cell Manufacturing Facility has received funding from:
●
The Higher Education Authority (HEA) Programme for Research in
Third Level Institutes (PRTLI)
●
Science Foundation Ireland (SFI) Centre for Science Engineering and
Technology (CSET) programme
●
NUI Galway
●
European Union