Irish Pharmachem Summer 2021 Edition - Focus on Advanced Therapeutics by Retail News

Summer 2021 Edition – Focus on Advanced Therapeutics

In Association with BioPharmaChem Ireland

We have operated in Ireland for more than 80 years bringing innovative medicines to patients and consumers to improve health and wellbeing. Our Dublin headquarters is home to our Pharmaceuticals and Consumer Healthcare business. Our Pharma business is one of the largest providers of vaccines to the Health Service Executive and all vaccinated babies in Ireland receive at least one GSK vaccine, while our Consumer Healthcare business is a leader in oral care and pain relief in Ireland. Our Dungarvan manufacturing site started operations in 1981 and produces 8.2 billion Panadol products a year for export to over 70 markets worldwide. And at our Cork hub, we have staff working in a variety of global roles within GSK.

CONTENTS

2 Minister’s Foreword 2 Minister’s Foreword

The ingenuity, hard work and dedication of the life sciences sector has been key to the development of the vaccines against Covid-19, writes Leo Varadkar TD, Tánaiste and Minister for Enterprise, Trade & Employment.

4 Industry Overview

As we begin to emerge from the unprecedented effects of Covid-19, the time is right for Ireland to capitalise on its strengths to become a world leader in the growing area of Advanced Therapeutics, writes Matt Moran, Director, BioPharmaChem Ireland.

8 IDA Ireland

10 NIBRT

Darrin Morrissey, CEO, NIBRT, believes that with a joined-up approach from Government, state agencies and pharma companies, Ireland can become a world leader in the development and manufacture of Advanced Therapy Medicinal Products.

14 The Future of Advanced Therapeutics

Paul McCabe, Chair of BioPharmaChem Ireland and COO of VLE Therapeutics Ltd, assesses the challenges and opportunities facing Ireland’s biopharma sector if it is to take its place as one of the leading locations for Advanced Therapeutics going forward.

16 Health Research Board

The Health Research Board is helping to create the right environment for the development of Advanced Therapeutics in Ireland, including special attention to critical issues in designing and performing clinical trials, notes Teresa Maguire, Director of Research Strategy & Funding, HRB.

20 Regenerative Medicine & Medtech Ibec Medtech and Engineering Director Sinead Keogh examines some of the groundbreaking innovations in the world of regenerative medicine and medtech with the potential to completely disrupt how we deliver healthcare in the future.

22 Cell & Gene Therapies

EY teamed up with Microsoft to create a a digital ecosystem and supporting information exchange to help Ireland take its place at the forefront of Cell & Gene Therapy, explains Cillian Leonowicz, Head of Markets & Alliances, EY Microsoft Services Group.

Irish PharmaChem – Summer 2021

36 Cell Engineering

8 IDA IRELAND 26 Regulation

44 BioPharmaChem Skillnet

Innovations in Advanced Therapeutics must be combined with a reliable and adaptable regulatory system, writes Dr Lorraine Nolan, CEO of the Health Products Regulatory Authority.

28 Enterprise Ireland

Cell and Gene Therapies are the newest frontier in drug development and a growing number of Irish companies are at the vanguard, notes Deirdre Glenn, Head of Life Sciences at Enterprise Ireland.

30 Training & Development

The Biopharma Data Champions Kickstarter’ programme, developed by Siemens, NIBRT and the IDA, was created to guide participants on a journey to data project success and accelerate digital transformation in the Irish biopharmaceutical sector, explains Siobhán Fleming, Collaboration Manager, Siemens.

32 Services

Kuehne+Nagel’s European Pharma Fleet provides a crucial link in the chain to ensure compliance and the highest level of quality and service in the delivery of Covid-19 vaccines across Europe.

36 Cell Engineering Technology

Avectas is a cutting edge cell engineering technology company, developing a proprietary, simple, highly effective, automated non-viral cell engineering system, Solupore®, to enable efficient and safe genetic modification, accelerating the manufacture of cells for the next generation of immuno-oncology therapies.

39 API’S & ADVANCED INTERMEDIATES

SK pharmeco specialise in small molecules, and large ones now too, thanks to the addition of the newest part of the team in the form of YposKesi, a Paris-based large molecule CDMO.

40 Eli Lilly

Eli Lilly and Company is celebrating its 40th anniversary in Kinsale, Co. Cork, this year.

Susan Costello, Network Manager, BioPharmaChem Skillnet, reports on some of the BPC Skillnet’s successes in furthering the skills set within the Irish pharma and biopharma sector.

46 Waste Management

Indaver’s new track & trace software system offers state-of-the-art traceability for both hazardous and non-hazardous waste.

48 PROCESS DATA

A smarter approach to process data with Bonner.

49 Stability Studies

A growing number of pharmaceutical companies are choosing to outsource their stability storage trials, rather than undertaking them in-house, according to Source BioScience.

52 Chemical Sourcing

Paul Power, Strategic Sourcing & Supply Chain Executive, NCC, advises on how a new approach can ensure your supply chain is more adaptable, flexible and durable.

54 Pharmaceutical Ingredients

James Peterson, Vice President of Pharmaceutical Ingredients for Univar Solutions, explains why the company has the technical support, ingredient guidance and is a dependable partner to support its partners in addressing the opportunities ahead.

56 Cleaning Services

Clean Habit have almost 40 years’ experience as professional contract cleaners for the commercial, industrial and pharmaceutical industry, with extensive cleanroom experience.

59 Public Policy

The ‘Pathfinder Study on the Adoption of Cell and Gene Therapies in Ireland’, carried out by PwC on behalf of the Irish Pharmaceutical Healthcare Association, has called for a new policy on the adoption of Cell and Gene Therapies by Ireland’s health services.

Irish PharmaChem is published by: Tara Publishing Ltd 14 Upper Fitzwilliam Street, Dublin 2. Tel: 00 353 (0)1 678 5165 Email: kathleenbelton@tarapublications.ie Web: www.irishpharmachem.com

Advertising Sales: Brian Clark Aaron Stewart Production: Ciara Conway Printed by: W&G Baird

Managing Director: Patrick Aylward Editorial and Marketing Director: Kathleen Belton Editor: John Walshe

Minister’s Foreword

Life sciences key in the fight against Covid-19 The ingenuity, hard work and dedication of the life sciences sector has been key to the development of the vaccines against Covid-19, writes Leo Varadkar, Tánaiste and Minister for Enterprise, Trade & Employment. It’s been an unprecedented year for everyone working in the life sciences sector. Thank you all for your efforts, your initiative and your dedication. Now, thanks to the ingenuity and hard work of many working in the pharmaceutical industry, we have a lifesaving vaccine against Covid-19, a vaccine that did not exist a year ago for a virus that did not exist only two years ago. It is a triumph of science and enterprise. Ireland is home to several major life sciences companies. By keeping manufacturing operations open and critical supply lines in place despite exceptional circumstances, these companies have played a really important role in Ireland’s overall fight against the pandemic. That work is much appreciated by Government. Furthermore, despite unprecedented challenges to Ireland’s economy in 2020, the pharmaceutical sector remained strong, boosting state resources and helping us to support struggling businesses and workers. We aren’t out of the woods yet and there will be bumps in the road but now, thanks to the success of the vaccine and the efforts of the Irish people, there is every reason to be hopeful again.

development in this area, and it is imperative that we now prepare the country for a new wave of innovation focused on personalised medicines.

NIBRT An important element of our rich biopharmaceutical landscape is the National Institute for Bioprocessing Research and Training (NIBRT). NIBRT was set up by the Government to support the growth and development of the biopharmaceutical industry in Ireland and conducts cutting-edge research focusing on the advancement of biopharmaceutical manufacturing, including in the area of Advanced Therapeutics. NIBRT significantly enhances our skills and production capacities, and plays a pivotal role in increasing Ireland’s research talent pool. This point is worth emphasising, because our highly skilled and flexible workforce is crucial to our ongoing success in attracting operations from

Leo Varadkar, Tánaiste and Minister for Enterprise, Trade & Employment.

Advanced Therapeutics This edition of the PharmaChem Yearbook is focused on Advanced Therapeutics. The Government, through the IDA, has worked hard to attract investments and embed the pharma sector in every region of the country. Our high-quality manufacturing and depth of knowledge provide us with a significant competitive advantage to meet the future needs and demands of the sector. Advanced Therapeutics represent a significant new area of product

Irish PharmaChem – Summer 2021

Minister’s Foreword major life sciences companies to Ireland. In 2020, in anticipation of technological and scientific developments, NIBRT submitted a proposal to Government for new investment in Advanced Therapy Medicinal Products (ATMPs). I am pleased that funding for the expansion proposal has been approved and that the planning and design phase is well underway. The right collaboration between industry and Government will enable us to build on Ireland’s reputation as a global leader in biologics manufacturing and to drive investment in life sciences across Ireland.

Covid-19 Products Scheme We will continue to engage with pharmaceutical and life science companies to reinforce our strong and ongoing commitment to this critical sector and to assist innovative companies taking the lead in developing the new products and processes to further develop the industry here in Ireland. The Covid-19 Products Scheme introduced in 2020 remains open for companies developing or producing medicinal products used in the fight against Covid-19. The Scheme provides targeted State funding to accelerate the production of medicines and equipment used to fight against Covid-19. Thank you again for your efforts over the past year. Government remains fully committed to further growing and developing the biopharmaceutical industry in Ireland. I look forward to working together in the times ahead.

Leo Varadkar, Tánaiste & Minister for Enterprise, Trade & Employment

Irish PharmaChem – Summer 2021

Industry Overview

Advanced Therapeutics: the next opportunity for Ireland

Now that we start to slowly and carefully emerge from the unprecedented effects of the Covid-19 pandemic, we can take time to look back and reflect a little and maybe look forward with increased optimism. BioPharmaChem Ireland (BPCI) and its members have remained fully operational throughout. Even before then-Taoiseach, Leo Varadkar TD made that fateful announcement from the steps of The White House in Washington DC, biopharma companies were mobilising all their available resources to ensure that they could keep the supply of essential medicines and other critical chemicals available to the globe. This was critical as Ireland plays a very important role as a global supply hub for these products. Many of these companies located here are household names to those who work and benefit from the contribution that they make to the local and indeed national economy. Names such as Pfizer, Janssen, Eli Lilly, Thermofisher, Hovione, GSK, MSD, Abbvie, Gilead, Merck, BASF, Biomarin, GE Healthcare, Novartis and Recordati, to name but a few. BPCI and its member companies met every single week to share knowledge and expertise as to how to keep up and running in the teeth Irish PharmaChem – Summer 2021

Industry Overview of the Covid-19 storm. Valuable know-how was shared, support given and technology exchanged. This meant that no company was forced to fully close its doors throughout the period. Companies did not limit their discussions to Covid-19; they also discussed other critical issues, such as sustainability and delivering on the European Commission Green Deal to ensure that we protect our planet as well as the lives of the patients and consumers that we serve.

Growing role of Advanced Therapeutics So as light appears at the end of a very long tunnel, what could the future bring? There is no doubt the early discovery and regulatory approval of a range of vaccines against the virus was staggering in its rapidity and success. Multi-year timelines were telescoped into months and mass vaccination offers a sustainable way out of lockdown. However, it does seem likely that Covid-19 will be with us in some form for many years to come so the biopharma sector cannot rest and it will continue to devote time, energy and resources to coming up with the next vaccine for the next variant of this dangerous virus. It was great news to hear that Pfizer, the first biopharma to establish in Cork, will invest €40 million at its Grangecastle biotech facility to manufacture the drug substance used in the manufacture of the Pfizer-BioNTech Covid-19 vaccine. A major take-home from the pandemic and the impressive response of the biopharma sector to it is the increasingly important role that Advanced Therapeutics will play in the future of disease management. The mRNA vaccines developed by Pfizer-BioNTech and by Moderna are excellent examples of this. In fact, the Alliance for Regenerative Medicines (ARM) estimates that there are over 980 companies worldwide working in the Advanced Therapeutics space. This ranges from Cell and Gene Therapies (CGT), Car-T, regenerative medicines through to cell based immuno-oncology. 1,600 clinical trials are underway and €10 billion was invested in the sector in 2019. This is an important and rapidly emerging part of the biopharma sector. Ireland needs to be part of this new wave. BioPharmaChem Ireland (BPCI) sees two opportunities. 1. Allogeneic manufacture Allogeneic products are manufactured for multiple patients where cells donated from healthy patients are processed to produce a cellular product that can be used to treat multiple patients. Here, products are made in a more traditional manufacturing setting and would represent a shift from traditional biologics manufacture to cell-based platforms. This is an emerging area, and the time is right to invest in the necessary infrastructure and skills. To this Irish PharmaChem – Summer 2021

Advanced Therapeutics will play a huge role in the future of disease management. end, BPCI is working closely with a group led by NIBRT that is exploring this in detail. Already Takeda have established cellbased manufacture at their site in Grangecastle, Dublin, and recently announced a further investment of €36 million with the creation of 100 jobs to expand this facility further. UK based biopharma company, MeiraGTx, announced a multi-million euro investment in Shannon, where they will manufacture viral vectors and plasmids, creating 100 jobs in the process. Recently, Pfizer announced a €40 million investment at its Grangecastle facility into

the manufacture of key drug substance for its mRNA Covid-19 vaccine. Maynooth based company Avectas has developed an exciting platform technology in the area. Cherrywood based CDMO and medicines accelerator APC recently announced its intention to move into the cGMP manufacturing space for CGT via a new vehicle VLE Therapeutics Ltd. 2. Digitisation of supply of autologous products Autologous treatments entail a unique personalised batch produced from the

Matt Moran, Director, BioPharmaChem Ireland.

BioPh toget in the

Industry Overview

Given Ireland’s importance as a manufacturer and supplier of biopharma products, it seems logical that it enhances this capability by developing a strong CGT and vaccines sector in the country.

BPCI), the research community, funders and State Agencies. This seminal report has kickstarted a range of activities supported by six working groups. These will identify the talent and infrastructure that will be needed to take Ireland into this next phase of manufacture and research. The Forum has engaged Government, as well as striving to learn from experiences in other countries. There will be an opportunity for indigenous companies to invest in this space, as well as attracting new foreign direct investment in the space. Ireland has many strengths that can be leveraged to support such investments. Given Ireland’s importance as a manufacturer and supplier of biopharma products, it seems logical that it enhances this capability by developing a strong CGT and vaccines sector in the country. There is real momentum and impetus now developing in the space as industry and research comes together to secure this next phase of the biopharma sector for Ireland. The country certainly has the know-how and the drive to work to achieve this goal, a goal which will benefit patients and the economy here alike.

patient’s own cells and destined only for that patient. More suited to a hospital setting, autologous CGT products have complex and sensitive value and supply chains. BPCI is working with EY and IDA Ireland to explore opportunities to manage these supply chains out of Ireland, harnessing the capabilities of the technology based sector in the country. Given the prevailing trend among a number of major biopharma players to centralise services into Ireland, this could present an opportunity here, especially when coupled with the significant expertise in the digital space in Ireland, with a number of major technology companies already situated here.

White Paper on CGT A group chaired by Niall Barron of NIBRT published a White Paper supporting the case for Cell and Gene Therapy on behalf of the Cell and Gene Therapy Forum in 2019. The Forum comprises industry (including

“A major take-home from the pandemic and the impressive response of the biopharma sector to it is the increasingly important role that Advanced Therapeutics will play in the future of disease management. The mRNA vaccines developed by Pfizer-BioNTech and by Moderna are excellent examples of this.” 6

The Covid-19 pandemic has had an unprecedented effect on our world, with no aspect of society left untouched. Irish PharmaChem – Summer 2021

As the world finds its way forward

We never stop working toward a future where disease is a thing of the past.

Learn more at www.janssen.com/ireland/

IDA Ireland MSD Biotech’s new biologics drug substance building in Swords, North Dublin.

Positioning Ireland for the next wave of pharma investment Ireland is an undisputed global location of choice for the manufacture of high value medicinal products. The Irish pharmaceutical sector has a reputation for high reliability, quality and an exemplary regulatory track record. Built from strong foundations in small molecule API and OSD manufacturing, recent years have seen the emergence of

Rory Mullen, Global Head of Biopharmaceuticals, IDA Ireland, and Dr Lorcan Brennan, Senior Scientific Advisor, IDA Lifesciences Division, examine Ireland’s success in biopharmaceuticals, and how Ireland can stay at the forefront of the industry in the coming years. significant capability in the development and manufacture of high value biologics products. The rise in biologics activity in Ireland has resulted in significant capital investment with the development of 20 state-of-the-art manufacturing plants. The impact this has on the Irish economy cannot be understated through the value of exports, purchases of both equipment and services, in addition to the salaries of those highly skilled employees at manufacturing plants all over the country.

Expanding on our capabilities and competencies

Rory Mullen, Global Head of Biopharmaceuticals, IDA Ireland.

The evolution of the biopharmaceutical sector continues at pace with the emergence of Advanced Therapy Medicinal Products (ATMPs), particularly Cell & Gene Therapies (CGT). For Ireland to maintain its strong global reputation and actively compete for the next wave of pharmaceutical investment, it will be critical for the sector in Ireland to expand on current capabilities and build further core

competencies aligned to the needs of this emerging sector. There is no doubt that the emerging products we are seeing coming from our clients are becoming increasingly complex. This added complexity requires advanced manufacturing solutions and specific skillsets to enable reliable and robust manufacturing.

Leading from the front Throughout the small molecule sector, higher potency materials with increased molecular specificity have seen the arrival of smaller batch sizes, continuous manufacturing platforms with an ever-increasing appetite for digital adoption and Industry 4.0 technologies for enhancing performance across development, manufacturing and supply chain. We are also seeing the effects of digitally enabled manufacturing across our biologics sector, coupled with single-use technologies, real-time and predictive analytics and a move towards reconfigurable modular facilities Irish PharmaChem – Summer 2021

IDA Ireland capable of supporting multiple therapeutic platforms. Recently announced investments of scale from MSD in Swords and Dunboyne, along with those from Pfizer and Wuxi, highlight Ireland’s ability to lead from the front in biologics development and launch.

Agility and flexibility Agility and flexibility will be the key for enabling transformation across the entire pharmaceutical sector, particularly as new and emerging therapeutic platforms reach maturity. The ongoing Covid-19 pandemic has highlighted the speed at which this change can materialise, particularly when we see the effect of the mRNA platform on vaccines and as a potential future therapeutic entity. Transformation of manufacturing sites will, of course, require the constant upskilling of staff and investments in new equipment, technology platforms and manufacturing processes. We in IDA Ireland will continue to work with our clients on an ongoing basis to support training needs and process R&D across the country. In the long term, Cell & Gene Therapies or ATMPs are likely to transform the industry. With the commercialisation of two autologous CAR-T therapies and the recent approval of a spinal muscular atrophy (SMA) gene therapy product, these therapeutic products offer treatments for patients with unmet needs and are increasingly coming into focus.

Mergers and acquisitions We have already seen significant mergers and acquisitions in the ATMP space. Gilead acquired Kite for US$11.9 billion and Celgene acquired Juno for US$9 billion. Roche acquired Philadelphia based Spark for US$4.3 billion in 2019. There have also been some major investments by Pfizer in gene therapy capabilities. These give some indication that the major global biopharma companies will be developing in this space. In addition, with the personalised nature of these medicines and the exciting opportunities in new, more targeted disease areas, there is a group of new companies that are developing independently in this space. This area today has over 1,000 potential products in clinical trials, with many therapies residing with innovator companies, lacking specialisation in process development and optimisation for manufacturing. As these companies will be deciding where to do further development work, where to manufacture and when to internationalise from their home base, a real opportunity presents itself to product innovators, suppliers and academics to collaborate and design process technologies to streamline and optimise the necessary manufacturing steps. This will again play into the skills and experience of Ireland, where development for manufacturing is our sweet spot and where we have gained our Irish PharmaChem – Summer 2021

international reputation for delivery. Our strong international reputation for delivery has resulted in Ireland gaining momentum in ATMPs, with recent significant investments of scale. 2019 saw the arrival of gene therapy company MeiraGTx to Limerick, where they will develop and manufacture plasmids and vectors for gene therapies, while recently, a further €36 million investment by Takeda in their Grange Castle facility will serve to support the expansion of the company’s cell therapy manufacturing facility with the addition of 100 highly skilled jobs.

Meeting future skills needs As the biopharmaceutical sector in Ireland matures and welcomes the arrival of CGT, the future skills needs of the industry will likely change to meet the manufacturing demands of more personalised and targeted medicines. The role of data analytics and data science will play a pivotal role in creating an environment suited to the development and manufacturing of complex medicines; however, this emphasis on data must be underpinned by foundations in the core sciences, particularly biology and chemistry. Future workers in the sector will understand the subtleties and complexities of their manufacturing processes and will simultaneously leverage data to drive process efficiencies, increase manufacturing reliability and reduce downtime. IDA continues to engage closely with the third level sector to ensure that the future skills need of the industry is being reflected in educational programmes. Crucial to transitioning the skills base of the industry towards personalised medicines, particularly Cell & Gene Therapies, is the IDA-supported strategic investment into the expansion of NIBRT (National Institute

Lorcan Brennan, Senior Scientific Advisor, IDA Lifesciences Division.

for Bioprocessing Research and Training). This strategic investment will serve as a major catalyst for developing the future skills needs of the industry, while simultaneously developing the significant research capabilities underpinning CGT manufacturing. Ireland’s skill base, track record and regulatory reputation will allow us to be a strong player in this new sector over time, but we must put our hand up now in our companies, our educational institutions and with Government to make sure everyone is aware of the opportunity and the imperative that our country continues to lead in future medicines manufacture. Let us not lose sight of our success and the continued growth in the sector but let us also grasp this new opportunity to be a player in next generation medicines for all.

Takeda’s €36 million investment in their Grange Castle facility will serve to support the expansion of the company’s cell therapy manufacturing facility with the addition of 100 highly skilled jobs.

NIBRT

Building Ireland as a global leader in biopharma’s next wave Darrin Morrissey, CEO, NIBRT, believes that with a joinedup approach from Government, state agencies and pharma companies, Ireland can become a world leader in the development and manufacture of Advanced Therapy Medicinal Products. Over the last 10-15 years, Ireland has established itself as a global leader in biopharmaceutical manufacturing and has had tremendous success in attracting multinational companies to establish manufacturing operations across the country. Since 2009 biopharmaceutical foreign direct investment (FDI) has topped €10 billion, with the number of manufacturing facilities having grown steadily to over 85 by the end of 2020, 25 of them in a biopharma setting. Over 30,000 people are now directly employed in the sector, which contributes over €40 billion in national exports annually (Source: www.idaireland.com/doing-businesshere/industry-sectors/bio-pharmaceuticals). In recent years, there has been significant research and development growth in Advanced Therapy Medicinal Products (ATMPs); a category that comprises cell-based, genebased, and oligonucleotide-based therapies, as well as novel-modality vaccines. It is widely predicted that ATMPs collectively represent the next big wave of biopharma innovation and growth. At the start of 2020, there were over 900 startup companies operating globally in the ATMP space, with increasing numbers of the large biopharma players also entering the arena, mainly via the acquisition of smaller biotech companies. In January 2019, the US Food and Drug Administration (FDA) stated that it expected to receive more than 200 annual applications for permission to commence Cell and Gene Therapy trials by the end of that year, from a position where the agency already had more than 800 such applications on file (Source: w w w.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm629493.htm). During the Covid-19 pandemic, the industry’s focus on ATMPs has become even

more intense, with several Covid-19 vaccines launched and in development, incorporating mRNA and viral vector technologies, being advanced much more quickly than previously thought possible.

Advancing Ireland’s leadership position It is clear that Ireland, given its previous success in biopharma, has much of the required collateral, in terms of facilities, experienced workforce, supply chain, cost benefits, etc, that can be utilised to advance its leadership position in ATMP manufacturing. Nonetheless there is more that can be done. In 2018, under the leadership of NIBRT, the CGT Forum was established, pulling together a range of stakeholders with interests in the Advanced Therapeutics area; including representatives from MNCs, SMEs, representative bodies, engineering firms, consultancy firms, academic researchers, and government agencies (including IDA Ireland, Science Foundation Ireland and Enterprise Ireland).

manufacturing and development, (including scale-up facilities, test-beds, incubators, training facilities, etc). 4 Public-private sector alignment: Ensure a joined up approach across government, state agencies and companies to advance the ATMP sector. Progress has been made over the last 18 months against each of these recommendation areas.

Training staff for ATMP manufacturing Since mid-2020, the CGT Forum has attracted

Work done in the first phase of the CGT Forum led to the publication in 2019 of a White Paper that made a number of recommendations and described potential actions that could be taken to develop Ireland’s ATMP manufacturing ecosystem. These recommendations included: 1 Talent development: The provision of national higher and further educational supports to ensure biopharma companies can source highly trained staff for ATMP manufacturing operations. 2 Research excellence: Ensuring strong supports for scientific and engineering research in ATMP manufacturing within the broader Irish research system. 3 Infrastructure: Provide the necessary infrastructural investments in ATMP Irish PharmaChem – Summer 2021

NIBRT

NIBRT will see an additional capital investment over the next 5-6 years, which will include a 1,600m2 facility extension, including extra laboratory and practical training space, which is expected to be operational in late 2022. increased membership and has established seven working groups to deliver against a number of action areas in the 2021-22 timeframe. Of particular note has been the establishment of a ‘Training and Education’ working group, which is focused on setting direction and driving action in ATMP manufacturing skills development. This group, with representatives from the higher and further education institutes, MNCs and SMEs, has developed a comprehensive set of priorities and planned actions.

‘Practical operational skills for first right time CGT manufacturing’, ‘Analytical lab skills, such as cell-based assays and viral vector analytics’, etc – and Transferrable Skills – including ‘CGT process & analytical performance monitoring’, ‘CGT logistics & cold-chain management’, etc.

Priorities are categorised under two headings; ATMP Technical skills – including

(2) the integration of digital skills into higher education programmes in ATMPs.

The working group also recommend: (1) the establishment of a national CGT/ ATMP Skills Academy to develop a centralised coordinated approach for ATMP training content, with stackable modules for CPD purposes;

Allied with the important work of the Forum, NIBRT, as Ireland’s primary training institute for biopharma manufacturing, has launched various ATMP training programmes during 2020/21 (Source: www.nibrt.ie/wpcontent/uploads/2020/11/NIBRT-TrainingCatalogue-2021-.pdf ), which include: • Introduction to ATMPs/CGT (a two-day blended course); • Advanced Cell Therapy Manufacture (three-day blended), in collaboration with Cytiva; • Introduction to Stem Cell Therapy (three- day blended); • Fundamentals of Stem Cell Manufacture (four-day blended), in association with the Centre for Cell Manufacturing (CCMI), Galway; • Introduction to Gene Therapy Manufacturing (two-day blended); • Manufacture of Viral Vectors (three-day blended); • Fundamentals of Vaccine Manufacture (four-day blended); • NIBRT Online Academy modules: vaccine manufacturing; cell therapy; gene therapy. Additionally, NIBRT is delivering increasing numbers of immersive Biopharma 4.0 courses, with the aim of supporting improved uptake of technology and automation, and better utilisation of the volumes of data emerging from advanced biopharma facilities.

Research and Development in ATMPs The production of a diverse range of ATMPs is complex and presents unique challenges for manufacturers. Like the productivity Irish PharmaChem – Summer 2021

NIBRT challenges experienced with monoclonal antibody manufacturing in the 1980s, process development, analytics and manufacturability are widely recognised to be critical success factors for ensuring that ATMPs can be produced consistently, safely and affordably. Two of the CGT Forum working groups are focused on: (1) identifying the top manufacturing challenges associated with ATMP manufacturing; (2) identifying where Ireland has complementary research strengths and skills across the academic research community and company-base to play a strong role in addressing these challenges. Each of the major state funders of biopharmarelated research (i.e. SFI, EI, IDA, etc) are participating in these working groups and it is hoped that their involvement will ensure alignment between ATMP manufacturing challenges and the required research funding in the coming years. Already, there has been an increase in state and above-state funding flowing into ATMP research. Most recently, the third round of Disruptive Technology Innovation Fund (DTIF) awards, announced in April 2021, saw funding with a combined value of over €20 million (from a total funding pot of €95 million) awarded to five ATMP-related projects. Some of the ATMP manufacturing projects funded were: • Development of a prototype centre of excellence at the St James’ Hospital/ TCD campus for the discovery and delivery of next generation precision cell therapeutics through modular ‘GMP in a box’. Awarded to Remedy Biologics Ltd, ACGT Vector Designated Activity Company, Trinity College Dublin (TCD) and National University of Ireland, Galway (NUIG). •

Using Artificial Intelligence to create fast cell analytics for biomanufacturing, for use in media screening and bioprocess controllers. Awarded to Valitacell Ltd, Intel Research and Development Ireland Ltd, Waters Corporation and National University of Ireland, Galway (NUIG).

•

Development of a digitalised cellular engineering system to produce cell therapy cancer treatments with a focus on allogenic off-the-shelf therapies and those for solid tumours. Awarded to Avectas Ltd, BlueBridge Technologies Ltd and National Institute for Bioprocessing Research and Training (NIBRT).

Future thematic calls in advanced biotherapeutics manufacturing are anticipated at a national level and internationally in the coming months. Of note, the European

12 10

Innovation Council (EIC) have recently announced a CGT manufacturing-themed Pathfinder Challenge call to run in the latter half of 2021.

Investment in ATMP manufacturing and development infrastructure During 2020, following the publication of the CGT Forum White Paper, NIBRT developed a business case for the expansion of its existing facility to enable additional ATMP training and research activities. This business case has been approved by IDA Ireland, as the primary state funder of NIBRT, and will see an additional capital investment into NIBRT over the next 5-6 years, which will include a 1,600m2 facility extension. The extension, including extra laboratory and practical training space, is currently undergoing design and planning approval, and is expected to be operational in late 2022. Several large scale private sector investments in ATMPs have also recently been announced. These include: •

Takeda’s announcement in early 2021 of a €36 million expansion at its Grange Castle facility to support expansion of its cell therapy capacity, with the creation of approximately 100 new jobs over three years.

•

Meira GTx’s announcement of Shannon as the site of its new cGMP viral vector manufacturing facility and cGMP plasmid production facility. The facilities will produce commercial- grade gene therapies in a fully integrated manner and will created 100 new jobs from the end of 2021.

• APC Pharma’s announcement of a €25 million investment in a new global centre of excellence to accelerate the development and manufacture of Covid vaccines and other medicines, as well as a €17 million investment in the creation of new CGT contract manufacturing company, VLE Therapeutics, resulting in the creation of 120 jobs.

Joined-up ATMP approach across Government, state agencies and companies The work of the CGT Forum has already demonstrated the tremendous alignment that can happen between the state and private sector when there is a concerted effort to tackle an area of national strategic importance. In addition, BioPharmaChem Ireland (BPCI) and EY have established an initiative involving a wide range of stakeholders that is exploring the digital and business services opportunities associated with advanced therapies. Also, the Irish Pharmaceutical Healthcare Association (IPHA), working with PwC, has done some work focusing on the patient access challenges

associated with the growth in innovative medicines and vaccines. With this excellent collaborative work happening, IDA Ireland and the Department of Enterprise, Trade and Employment in 2020 commissioned a comprehensive study on the broad ATMP opportunity for Ireland. This study, funded by the European Commission and conducted by Innovation 21, engaged with an exhaustive range of national and international stakeholders in the ATMP arena. At the time of writing, publication of the ATMP Report is still awaited, but it is anticipated that it will recommend the advancement of ATMPs as a national priority and the establishment of a National ATMP Coordination Body at government department and agency level.

In conclusion The manufacture of Advanced Therapy Medicinal Products (ATMPs), including cell and gene-based medicines, oligonucleotide-based therapeutics, and novel-modality vaccines, for the supply of global markets represents a major opportunity for Ireland in the coming years. NIBRT looks forward to playing a key role in helping capitalise on this opportunity and will endeavour to work with the MNC and SME industry players in the area, with IDA Ireland and with all stakeholders to ensure Ireland continues its impressive track record of success in biopharma manufacturing. The National Institute for Bioprocessing Research and Training (NIBRT) is a worldclass institute that provides training and research solutions for the bioprocessing industry. NIBRT provides sector specific training to over 4,000 people annually and operates from its state-of-the-art, multifunctional building specifically built to serve the needs of Ireland’s biopharma sector. Irish PharmaChem – Summer 2021

Breakthroughs that change patients’ lives INVESTING INVESTING INVESTING INVESTING ININ IN IRELAND IN IRELAND IRELAND IRELAND SINCE SINCE SINCE 1969 1969 1969 19691969 INVESTING INSINCE IRELAND SINCE

Pfizer Pfizer Pfizer Pfizer

Pfizer Pfizer employees employees employees B e f o r e i t b e c a m ePfizer a m e d i c i n e , I t Pfizer w aPfizer semployees 5inPfizer ,roles 0in0employees 0workracross s eacross arched ineroles work work work in work roles in work inroles across roles across across roles across

4,000 4,000 4,000 4,000 4,000 employees 8 B7 e fdemployees feemployees e ri temployees e nbte cparm o tee ian mset dr ui cc itnuer ,e s . oi fremployees

Before it became Pfizer employees

was one of the first pharmaceutical firms

was one was was was ofone one the onewas of first of ofthe the the one first first first of the first pharmaceutical pharmaceutical pharmaceutical pharmaceutical firms pharmaceutical firms firms firms firms

a medicine

c o m p o u n d s . 8 B7 e fdoi fr fee ri te nbte cparm o l a b t e s t s . 1 ,I 6t 0w0 assc i5e, n0 t0i0s t rse. s8e0a- r Manufacturing 87 different pro Manufacturing Manufacturing Manufacturing Manufacturing ManufacturingResearch & Development o f b r e a k t h r o u g h s a n 5d 0s0e, t0 0 b 0a clk Research Research Research Research & Development Research &&&Development Development Development & Development Shared Services p a t i e n t v o l u n t e e r s . A1 n, 6d0 0m so cr ei 80-hour w Shared Shared Services Shared SharedServices Services Services Shared ServicesCommercial operations w e c o u l d1 c4 oyuenat r. sB oe ff obr ree iatk bt he rc o Treasury Commercial Commercial Commercial Commercial operations Commercial operations operations operations operations n fi ca i d e a i n t h e 3m6i ncdl i o e CasTreasury Treasury TreasuryTreasury 8,500 patient tTreasury ng N do wm iot r’ se ap rmoebdl ei cmi ns e t To hsaot An

to locate in Ireland

in locate Ireland Ireland Ireland Ireland c o mto locate p toototolocate ulocate ntoininindlocate s .in Ireland 500,000 l a b t e s t s . 1 ,I 6t 0w0 assc i5e, n0 t0i0s t rse. s8e0a- rhcohuerdwcoor m k pwoeue nk sd.s 1. 4 y e a r s 8 7 d i f f IRISH einvested r einn t p r o t e i n s t r u c t u r e s . invested inr o invested in in o f b r e ainvested k tinvested hinvested uin g hin s a n 5d 0s0e, t0 0b 0a clkasb. 3t e6 sct lsi .n i c a l t r i a l s . 8 , 5 0 0 IRISH IRISH IRISH IRISH IRISHsince 1969 p asince t i since esince n t1969 v1969 o l u1969 n t e e r s . A1 n, 6d0 0m so cr ei e np tr iosbt lse. m s t o s o l v e t h a n since 1969 SITES SITES SITES SITES 0 - SITES hour workweeks. in Ireland8 100 countries w e c o u l d1 c4 oyuenat r. sB oe ff obr ree iatk bt he rc oa umgeh as m a nedd iscei nt be a, cI tk sw. a s a n in Ireland in in inIreland Ireland Ireland in Ireland countries countries countries countries n fi caa lP ft irzi ea rl s s. c i e n t i s t . i d ecountries a i n t h e 3m6i ncdl i o 8,500 patient volunteers. N do wm iot r’ se ap rmoebdl ei cmi ns e t To hsaot l vs ae v tehs alni v w e se ecvoeur lydd ac yo u n t . An Before it became a medicine, It was an idea in the mind of a Pfizer scientist. and has operated here since

Gra

G Grraa G ra

Gra

gsend iningin gsgseesnnednd d ingsend Rin RRR R D D D D D U B L I N UUB UBLBLILINN OPERATIONS IN U BLIN DU

BLIN

ywe

Ireland is a manufacturing base for Pfizer globally. Many of Pfizer’s leading medicines are manufactured from Irish sites.

N o w i t ’s a That saves liv

st itmanufacturing DDD U NNN D U Ireland isIreland aIreland Ireland manufacturing isisis aaCmanufacturing a Ireland manufacturing is a manufacturing B L I N UUB BLBLILI I B L I Nbase for Pfizer base base base for globally. for for Pfizer Pfizer Pfizer base globally. globally. globally. for Pfizer globally.

SITES

Many of Pfizer’s Many Many Many of of leading of Pfizer’s Pfizer’s Pfizer’s Many medicines leading leading leading of Pfizer’s medicines medicines medicines leading medicines

BLI

Part of Pfizer’s Worldwide Research and Development (WRD) is based in Ireland.

RR R

e ee

K rbridiU rdgidgg NeDwDU bD b DrU idg NNN D U ewbridg eeww ebw B L IN UB BLBLILI I B L I N IL DA R E askidd nnggnag asaskksidikddidN CORK dd ngaskNiNdNd ing ii i i

askidd ing

to approximately

y yy

to approximately to toto approximately approximately approximately to approximately

are distributed

100 100 100 100

are distributed are are are distributed distributed distributed are distributed

BLIN

are manufactured manufactured manufactured from are Irish manufactured from from sites. from Irish Irish Irish sites. sites. sites. from Irish sites. wew ee are manufactured ywest itityiytwy ywesare tare Cit CCC ssttst Cit DU wbridg N

The medicines manufactured

The medicines The The Themedicines medicines medicines The medicines manufactured manufactured manufactured manufactured manufactured

Before it becam It was an idea in the mi

gsend Rin

5 555 le llee

OPERATIONS OPERATIONS OPERATIONS OPERATIONS OPERATIONS

888 8

aa e Cast ggeg eC eCaC e Cast ng nnn ssttst ng

Gra

and has operated and and and has has has operated here operated operated and since has here here here operated since since since here since

KI KKK K L D A R E IILLIDLDA DARARERE E I L D A R E C O R K CCO COR ORKRKK C O R K

Part of Pfizer’s Part Part Part of of Worldwide of Pfizer’s Pfizer’s Pfizer’s Part Worldwide Worldwide Worldwide of Pfizer’s Worldwide Research and Research Research Research Development and and and Research Development Development Development (WRD) and Development (WRD) (WRD) (WRD) (WRD) is based inisisIreland. is based based based ininin Ireland. Ireland. is Ireland. based in Ireland.

Please visit

Pfizer FP Advert.indd 2

N o w i t ’s a m e d i c i n e That saves lives every day

Pfizer.ie

Pfize

For more If you are interested in a career with Pfizer, pl opportunities – www.pfi

The Future of Advanced Therapeutics

Facing the future h Paul McCabe, Chair of BioPharmaChem Ireland and COO of VLE Therapeutics Ltd, assesses the challenges and opportunities facing Ireland’s BioPharma sector if it is to take its place as one of the leading locations for Advanced Therapeutics going forward. 50 years ago, it was Small Molecule Synthetics; 20 years ago, it was large molecule Biologics; over the next 10 years, Advanced Therapeutics is expected to explode and become the next frontier of the global Pharma industry. Advanced Therapeutics include technologies such as Cell & Gene Therapies (CGT) and new generation vaccines – the Global CGT market will alone be worth more than US$57 billion in sales by 2030. They will be more targeted to disease states, tackling rare diseases and more effectively addressing existing illnesses, ultimately leading to personalised medicines. The nature of the manufacturing and supply of Advanced Therapeutics will drive the need for more agility in our manufacturing and supply chains, embracing disruptive technologies and broadening our ecosystem to evolve our indigenous SME Pharma companies to ensure future success for the sector in Ireland. From my role as Chair of BPCI and my years in the sector, I have gotten to see first-hand the strength of the sector in Ireland, the challenges ahead and the opportunities for the future. Ireland has played a significant global role over the last 50-60 years in both small molecule and large molecule. The pharma sector continues to be a very strong contributor to the sector and to the Irish economy, with the sector in Ireland now worth over €100 billion to the economy in terms of exports. There are over 60,000 highly skilled people directly and indirectly employed in the sector, with the anticipation that this will increase by another 10,000 jobs over the next five years.

Challenges for the sector in Ireland The challenges facing Ireland in the coming months and years include:

Covid-19 • The biopharma sector in Ireland, being an essential

business, not only remained open since March 2020 but in most cases actually had to change strategies and run faster than ever before, despite

the challenges, ensuring we delivered our critical therapies to patients around the world.

•

Covid is not gone, though, and its after-effects will likely remain with us. Changes to supply chains and demand will likely impact lead times for materials, consumables, equipment, will continue for some time.

OECD Corporate Tax changes • There are heightened pressures on corporate tax and

potential challenge to Ireland’s value proposition. FDI is likely to come under more scrutiny, especially on new investments.

•

BPCI has engaged with Ibec and Department of Finance on this on behalf of the sector.

Competitiveness • The biopharma sector is under increasing pressure to continue to provide affordable healthcare solutions to society. At the same time, we are moving to personalised medicine and hence even more agile supply chains will be needed. The full impact of Brexit has not manifested itself yet and we will likely see impact to competitiveness for many companies.

•

As a country, we need to maintain a competitive manufacturing base into the future to underpin the sustainability of high-quality jobs and export-led economic growth.

Availability of skilled resources • Nationally, we continue to struggle to encourage students into STEM courses and careers. Our Irish PharmaChem – Summer 2021

The Future of Advanced Therapeutics

e head-on the speed-to-market offering.

•

BPCI is working with EY and IDA Ireland to explore opportunities to manage these supply chains out of Ireland, harnessing the capabilities of the technology-based sector in the country.

Create a deep & broad pharma ecosystem • Given the anticipated changes to Corporate Tax, the impact to supply chains due to Covid-19, and digitisation becoming critical, there will be more pressure on being able to remain as competitive with such a heavily focused FDI model.

•

challenge is to increase the pipeline of talent into the sector. Take-up of Apprenticeships is still poor in the sector and Diversity & Inclusion, particularly gender balance, has come under pressure during the pandemic; we need to put it back on the table in our businesses if we want to encourage more skilled talent into STEM.

Opportunities for the sector in Ireland At the same time, there are ample opportunities for Ireland Inc. to excel, including:

Seize the Advanced Therapeutics manufacturing space • Many of the new technologies suit the existing manufacturing base in Ireland.

•

MNC Companies such as Takeda, MeiraGtx and Pfizer have recently announced investments and Irish SME’s such as VLE Therapeutics and Avectas are making significant advancements. BPCI is working closely with a cross functional group led by NIBRT that is exploring this in detail.

Digitise our industry to enhance Speed-to-Market offering • Advanced Therapeutics will mean manufacturing of multiple smaller, personalised batches and a bidirectional supply chain.

•

We have a window of opportunity to collaborate with the tech and medtech sectors to digitise our manufacturing and supply chains, to optimise the cycle time from product development, through clinical to commercial manufacture. This can give Ireland the opportunity to be leaders in enhancing

Irish PharmaChem – Summer 2021

We have a real opportunity to develop more breadth and depth to Ireland’s pharma ecosystem, by evolving our indigenous SME pharma companies, which can then deliver a more balanced and sustainable sector into the future.

• BPCI is currently collaborating with multiple industry working groups to focus on how to support and grow indigenous pharma companies.

Skilled resources • We have a great opportunity to create a talent pool

of graduates with high-tech skills and this will be key to maintaining our innovation and competitiveness as a country.

• BPCI is inputting into the Expert Group for Future

Skills Needs, which is a Government-led initiative. As part of the EY/IDA/industry group, we have developed proposed chapters which will focus on updating STEM education and encouraging cross sector skills e.g. life science with IT & supply chain.

Pharma in a positive spotlight The pharma sector in Ireland has been in a positive spotlight for the last 12 months and governments now understand the pharma supply chain more than even before. I believe there is a great chance to implement changes and grab the opportunities. BPCI’s vision and ambition is to be the globally recognised centre of excellence for innovation and development of biopharmaceutical, pharmaceutical and chemical manufacture and supply and to be the location of choice for the launch of new products. Given Ireland’s importance in this space, it seems logical that it enhances this capability by developing a strong Advanced Therapeutics sector in the country, thereby ensuring the pharma sector in Ireland thrives into the future.

Health Research Board

HRB: creating the right environment for advanced therapies

The Health Research Board is helping to create the right environment for the development of Advanced Therapeutics in Ireland, including special attention to critical issues in designing and performing clinical trials, writes Teresa Maguire, Director of Research Strategy & Funding, Health Research Board.

Irish PharmaChem – Summer 2021

Health Research Board The Health Research Board (HRB) Strategy 2021-2025, Health research - making an impact, details ambitious plans to advance health and social care research, data and evidence to benefit Ireland’s people, society and economy. We are committed to ensuring that research and evidence translate into important breakthroughs that improve people’s health, deliver new treatments and inform health policy and practice. To honour this commitment, we must always be aware of new and emerging technologies in health research. We, therefore, recognise that the fast-evolving field of advanced therapies has huge potential to address major unmet healthcare needs, offering new opportunities for the treatment and cure of many diseases. Combined with digital technologies, even greater opportunities arise. To avail of these opportunities, we must overcome significant challenges. Collaboration and coordination will be required between all stakeholders, nationally and globally, to achieve this, and the HRB will play a significant role with partners in addressing many of the challenges below: • Moving to scalable manufacturing solutions; • Minimising high costs;

• Establishing appropriate ethical and regulatory frameworks; • Ensuring appropriate patient involvement;

• Securing funding to advance a vibrant research agenda comprising biomedical, clinical, population health and health services research.

Clinical trials International evidence shows that patients benefit from access to high quality clinical trials (https://jamanetwork.com/journals/ jamainternalmedicine/fullarticle/414107), and outcomes are better in health systems that support them (https://journals.plos. org/plosone/article?id=10.1371/journal. pone.0118253). The economy also benefits through enterprise in areas such as pharma and diagnostics, which in turn creates jobs and benefits the exchequer. Since 2010, the HRB has been driving the growth of clinical trials in Ireland and has invested over €100 million in clinical trials infrastructures. Facilities are located at hospital sites to enable trials and intervention studies, deliver specialist supports, link with Clinical Trial Networks (CTNs), and provide trial design and methodology supports. They are a single point of access to resources, knowledge and skills, and a key part of the national research landscape. The clinical development of Advanced Therapeutics Medicinal Products (ATMPs) requires special attention to critical issues in designing and performing clinical trials. Irish PharmaChem – Summer 2021

Complex interventional procedures for their administration often restrict them to centres of excellence, and there are additional challenges in design and assessment, including safety and efficacy endpoints. Often, clinical studies evaluating ATMPs are more dependent on surrogate outcomes instead of clinical outcomes, and additional assessment issues will arise when these new therapies are combined with conventional treatments. IDA Ireland is promoting cell and gene manufacturing 2021– capabilities in Ireland 2025 . and current and future Healt h makin research HRB investments in g an im – pact. trial facilities, design, and conduct will be critical to help realise the benefits of this development for patients in Ireland, most notably deriving from the specialist facilities and skills to deliver clinical trials of such therapies in the HRB-funded Clinical Research Facilities (CRFs) in Galway and St James’ Hospital in Dublin.

Strat egy

Under our new strategy, we will continue investing in CRFs to improve the quality and quantity of trials in Ireland; support a single point of access for multi-site clinical trials in Ireland (the National Clinical Trials Office); and fund CTNs (www.hrb.ie/news/press-releases/ single-press-release/article/hrb-announcese6-million-investment-for-clinical-trialnetworks- on-the - eve - of-internationalclinical/), which assemble groups of clinicians and patients to enable trials. The HRB also provides the only dedicated funding stream (i.e., Definitive Interventions and Feasibility Awards) for clinical trials and interventions in Ireland, and through our previous strategy (2016-2020), we invested €22 million across 33 studies.

Rese arch. Evide nce. Actio n.

The Health Research Board (HRB) Strategy 2021-2025, Health research - making an impact, details ambitious plans to advance health and social care research, data and evidence to benefit Ireland’s people, society and economy. has increased the demand for high quality specimens and associated laboratory data. National, collaborative approaches and investments to ensure optimum treatment of biospecimens are key to the outcome of a multitude of studies. The HRB, with the support of the Department of Health, will soon award funding to establish and maintain a National Covid-19 Biobank, and it is anticipated this model will inform future investments in biobanking in Ireland.

Supporting research infrastructures

Optimising the use of health and social care data for research and innovation

The HRB strategy commits to working with other stakeholders to advance national shared, high-cost research infrastructures, such as biobanking and genomic research, which should be key enablers of next generation medicines and technologies. The HRB highlights particular areas we will develop with other stakeholders which are relevant to advanced therapeutics, such as exploring opportunities for investments in genomic research and personalised medicine.

The development of an enabling infrastructure and regulatory environment is particularly important to progressing research and innovation in advanced therapies in Ireland. Electronic Health Records (EHRs) and patient registries provide highly valuable but also sensitive data. Access to this demands the necessary infrastructure, skills and safeguards to ensure that advancing this important research does not diminish patients’ right to privacy.

To optimise the translation of advanced therapies into clinical practice, the collection of biological samples and related clinical data in high quality biobanks is critical. Advances in genetics, genomics and advanced therapies

Over the next five years, the HRB will work with others to ensure better collection, sharing, linkage and re-use of health and social care data. This will align with the development of a new national health information systems

Health Research Board h Rese Healt

price to achieve commercial viability. The HSE and other payers must develop innovative financing models to ensure access. As the main funder of health services and systems research in Ireland, we are well placed to support a research agenda that addresses this.

ard arch Bo als Propos g Data Enablin for an

Collaboration for impact

for He ment Environ d alth an Related ch Resear d in Irelan

e Sláint

d Taighd n An Bor htarac Gratta Mhóta Íoc Teach an Sráid ath 2 67-72 Cli Átha Baile 38 D02 H6 Éire rd ch Boa Resear Health House t Street n Moun Gratta Lower 67-72 2 n Dubli 38 D02 H6 d Irelan 5000 3 1 234 2335 +35 t 3 1 661 ie f +35 @hrb. ie e hrb w.hrb. w ww

reland

@hrbi

The HRB published a report detailing their vision for progressing the necessary data infrastructure and support services in Ireland: Proposals for an Enabling Data Environment for Health and Related Research in Ireland.

strategy by the Department of Health and the rollout of electronic health records, summary care records and the unique identifier in the HSE. We previously published a report detailing our vision for progressing the necessary data infrastructure and support services in Ireland (www.hrb.ie/fileadmin/publications_ files/Proposals_for_an_Enabling_Data_ Environment_for_Health_and_Related_ Research_in_Ireland.pdf ), and we are currently engaged in activities to advance this, including through involvement in an EU Joint Action - Towards a European Health Data Space (TEHDAS) (https://tehdas.eu/). The HRB also recently collaborated with the Department of Health and the Central Statistics Office to establish a mechanism to provide access to individual-level data in the Covid-19 Data Research Hub for research purposes. Learning from countries with legislation and infrastructure to optimise use of health and social care data (e.g., Finland, France and Estonia), we are ambitious to be part of a collaborative approach to enable the responsible and secure use and re-use of health data to support policy and planning, public health surveillance and research and innovation. Ensuring adequate and transparent dialogue with the public, and the adoption of best practice in all aspects of data management and governance, will be key to maintaining high levels of public trust and confidence in health research in Ireland.

18 16

nt onme Envir land Data in Ire bling h a n rc a E e r an d Res sals fo elate Propo lth and R ea for H oran lyn M Rosa

Involvement of public, patients and carers The growing role of patients in influencing policy decisions, as well as early patient engagement in research, is key to attaining market access goals. Ireland has a vibrant patient organisation community and growing expertise in Public and Patient Involvement in research (PPI), which will further drive patientrelevant therapeutics and healthcare solutions. The HRB has been leading the development of PPI in Ireland to improve the quality and relevance of research we fund. In January we made a new investment in PPI, in partnership with the Irish Research Council, which is designed to improve the capacity of researchers to partner with patients and carers and increase the patient voice and impact in research.

Capacity building and leadership Developing the right skill base, building capacity and leadership across research, industry and healthcare is essential to expand advanced therapies in Ireland. Building on a strong track record in capacity building, the HRB career framework provides opportunities for people from a wide-ranging disciplines, across different career stages, and based in academic or health and social care settings. Under the current Strategy, we will continue exploring opportunities for strategic investments that meet health research and healthcare needs.

Health services and systems research Realising the potential of advanced therapies requires an appropriate scientific, regulatory, and reimbursement environment, so patients can access these products in a timely and equitable manner. Despite their significant potential, advanced therapies face pricing and reimbursement challenges because they have high manufacturing costs and smaller patient populations, which demand a high target

EU and international collaboration is key to advancing research and innovation, and the HRB is already participating in a number of initiatives with particular relevance to the advanced therapeutics agenda. This includes the International Consortium on Personalised Medicine (ICPerMed) (www.icpermed. eu/index.php), and the European Joint Programme on Rare Diseases (EJP RD) (www. ejprarediseases.org/). ICPerMed coordinates research across members to support research into the benefits of personalised medicine to citizens and healthcare systems, with a view to promoting its’ uptake across member countries. EJP RD aims to create an effective rare diseases research ecosystem for progress, innovation and the benefit of everyone with a rare disease, and supports rare diseases stakeholders by funding research, gathering data resources and tools, providing training, and translating high quality research into effective treatments.

Ethical issues Given the nature and disruptive consequences of ATMPs, their assessment and adoption raises important ethical questions, both at policy and society level. Hosted by the HRB, the National Office for Research Ethics Committees (https://www. nrecoffice.ie) is an essential new addition to the infrastructure for health research in Ireland, and fulfils an important role in health research regulation by facilitating ethics review by National Research Ethics Committees (NRECs) in areas of strategic importance. Appointed by the Minister for Health, the NRECs’ decisions are independent and respected nationally. The value of this ‘single national ethics opinion’ was proven by Ireland’s first NREC for Covid-19 health research, which was integral to the national response to the pandemic. The mission of the National Office is to embed a robust, transparent and cohesive research ethics review system that strengthens the national research infrastructure. The National Office recently launched three NRECs, two for clinical trials for investigational medicinal products and one for clinical investigations of medical devices. Their primary role is to protect the safety, dignity and wellbeing of research participants, while maintaining momentum in health research. The NREC system will bolster the research environment, ensuring Ireland is a first-choice location to develop innovative medicines and technologies and improving access for Irish patients and the public to outcomes in these areas. Irish PharmaChem – Summer 2021

Only .01% of all drug candidates entering clinical trials will reach the market. Budget. Capacity. Technical knowledge. These are just some of the obstacles that can stand in the way of your biologic’s market approval. Are you prepared for them? With Charles River supporting 80% of drugs approved by the FDA over the last three years, leverage our experience and expedite your time to market. We can provide the services, capacity and know-how that can help you bring your therapies to those who need them most.

Improve your odds at criver.com/biologics.

Regenerative Medicine & Medtech

The healthcare of tomorrow Ibec Medtech and Engineering Director Sinead Keogh examines some of the groundbreaking innovations in the world of regenerative medicine and medtech with the potential to completely disrupt how we deliver healthcare in the future.

Medical technologies are used for diagnosis, prevention, treatment, monitoring or alleviation of disease. In Ireland, the industry is represented by the Irish Medtech Association, which is the Ibec group. As we look to the future, our vision is for Ireland to be a global leader in innovative patientcentred medical technology developments, products and solutions. Ireland is already recognised as one of the top five global medtech hubs, with 17 of the world’s top 20 companies having a base here. The industry has major regional clusters in Galway, Limerick, Cork, Waterford, Sligo and Dublin that are making a global impact, with 80% of the world’s cardiovascular stents, 75% of the world’s orthopaedic knees are 40% of the world’s contact lenses manufactured here.

Sinead Keogh, Ibec Medtech and Engineering Director Before the Covid-19 pandemic, R&D spending in 2019 grew 11.5%, marking a return to doubledigit growth for the first time since the 2008 financial crisis. One area gaining huge investment and prominence is regenerative medicine: where ground-breaking innovations have the potential to completely disrupt how we deliver healthcare in the future.

Innovation in medtech There are more than 500,000 different types of medical technologies on the market, ranging from glasses and wheelchairs to pacemakers and MRI scanners. The sector’s success is underscored by constant innovation. Medtech is arguably the most innovative sector in Europe, with more than 14,200 medtech patent applications filed with the European Patent Office in 2020.

Tackling ageing and degenerative disorders The global regenerative medicine market was valued at US$29.1 billion in 2019 and is anticipated to reach US$178.6 billion by 2026, with growth of 31.5% (CAGR) forecasted for the period 2020-2026. These medicines are used to regenerate, repair, replace or restore tissues and organs damaged

by diseases or due to natural ageing. In particular, they can help in the restoration of normal cell functions and are widely used to treat various degenerative disorders such as cardiovascular disorders, orthopaedic disorders and others. There are approximately 1,000 regenerative medicine companies globally, with number of new companies established and investing in this discipline rising annually. This is considered a multidisciplinary field, spanning tissue engineering, developmental and stem cell biology, gene therapy, cellular therapeutics, biomaterials (scaffolds and matrices), nanoscience, bioengineering, and chemical biology.

Making a clinical impact It is clear that demand for this field is growing, with a report published by the Alliance for Regenerative Medicine revealing that financing for this area has reached US$19.9 billion in 2020, doubling from the previous year. Moreover, the report also highlights that there were 1,220 clinical trials ongoing, with 152 in Phase 3 in 2020. Currently, orthopaedic medical devices are designed to replace a damaged bone with a permanent metal or polymer implant, such as an orthopaedic hip or a knee replacement. Irish PharmaChem – Summer 2021

Regenerative Medicine & Medtech Regenerative medicines have the potential to disrupt these practices by deploying therapies which aid regeneration, ultimately avoiding more invasive transplant surgeries. Beyond knees, this market segment can drive improvements in spine, bone substitutes, bone grafts and more. Approximately 40% of the global population over 55 years old experience chronic knee pain and of those, 50 million suffer from disabling pain. To treat this, about 2.6 million turn to knee replacement surgery each year. The positive impact of this innovation will be felt by both patients and health systems as this field evolves. The cardiology and vascular market for tissue engineering is also growing rapidly, because of the prevalence of cardiovascular disorders globally. Here key players are involved in the development of stem cell therapies to repair, restore, and re-vascularise the damaged heart tissues. Additionally, gene therapy, advanced biologics, and small molecules are being studied to stimulate the regeneration of damaged heart cells. Ground-breaking therapy development takes time but are already making a real impact on patients today. Scientists at University College London have successfully restored sight in people with wet age-related macular degeneration (AMD) by implanting specially engineered patches of cells derived from stem cells thanks to 15 years of research. We are also seeing tissue engineering for skin repair to treat burn patients. This technology is an example that is now well established, with clinical trials active in multiple other areas such as nerve regeneration and much more.

The Regenerative Medicine Institute (REMEDI) is also recognised as a world leader in the field. REMEDI is home to Ireland’s only stem cell manufacturing facility. This state-of-the art facility will translate, as well as manufacture, research from REMEDI’s programmes into cell-based medicinal products for clinical trials. The adoption of best-in-class manufacturing protocols is still one of the most serious obstacles facing the cell therapy industry. The only way the field can progress is through the widespread adoption of highly automated production and testing protocols, which is research currently being undertaken by REMIDI. NUI Galway has launched an MSc in Cellular Manufacturing and Therapy to provide scientific and practical training in the production of these cells as therapeutics for clinical application. Recently, the Royal College of Surgeons in Ireland licensed multiple late stage orthobiologics technologies, including a technology that governs next-generation bone graft substitutes to Locate Bio, a diversified orthobiologics company. This technology was developed by the Tissue Engineering Research Group (TERG) at RCSI, and validates the excellent work being carried out by the group to attract businesses like Locate Bio to take these products to market. TERG is also part of the €58 million Advanced Materials and

BioEngineering Research (AMBER) Centre, which is focused on developing advanced next generation materials and medical devices in partnership with industry.

Ensuring adoption of regenerative medicine Globally payers are looking at new reimbursement models to help bring these technologies to market. Both the European Union and the US have developed a clear and specific regulatory pathway for tissue engineered products. Moreover, in the US, the Centers for Medicare & Medicaid Services (CMS) has created a diagnosis related group (DRG) for CAR-T therapies that will help with reimbursement for providers. However, in other jurisdictions, the oversight of these products remains a challenge. Regenerative medicine presents an incredible opportunity for both patients and the healthcare community to drive meaningful change, shifting the healthcare management of chronic diseases from treatment to prevention. But to achieve the field’s ambition to revolutionise health, we need to build on existing collaboration between industry, researchers and clinicians, to support the adoption of these technologies by engaging regulators, and payers as well as investors.

Lead innovators in Ireland With the promise of regenerative medicine, it’s no surprise that some of the largest medtech companies have invested: including Stryker Corporation, Zimmer Biomet, Medtronic, Allergan, Integra LifeSciences, and Baxter International, to name but a few. However, research in the sector is dominated by highly innovative start-ups and third level institutions. Over the past decade, Ireland’s research community has also been building its reputation internationally. Irish researchers are being recognised as best in class, evidenced by the number of highly competitive and prestigious European Research Council grants awarded to researchers in the field. One notable example is Professor Danny Kelly, Trinity Centre for BioEngineering, who has been awarded no less than four grants for his research work through this funding instrument. The group is focusing on developing new ways of building up complex tissue structures by using 3D printing with biomaterials and cells. Professor Kelly is using 3D bioprinting strategies to address some of the major challenges in tissue engineering, from prevascularising engineered tissues to developing constructs that mimic the composition and mechanical properties of biological tissues. Irish PharmaChem – Summer 2021

Images captured by Trinity Centre for BioEngineering research group, led by Professor Danny Kelly. The images depict a regenerative approach to a chondral defect, a chondral defect refers to a focal area of damage to the articular cartilage (the cartilage that lines the end of the bones).

Cell & Gene Therapies

Ireland and EY: partnering for the future of Cell and Gene Therapies EY teamed up with Microsoft to create a a digital ecosystem and supporting information exchange to help Ireland take its place at the forefront of Cell & Gene Therapy, writes Cillian Leonowicz, Head of Markets & Alliances, EY Microsoft Services Group. It is “the stuff that dreams are made of.” After more than four decades of scientific advancements, Cell and Gene Therapies (CGTs) and Advanced Therapy Medicinal Products (ATMPs) are becoming a reality. As a result, so are life-extending and curative possibilities for difficult-to-treat diseases such as inherited genetic disorders and cancers. With the volume of CGT patients expected to rise from thousands today to hundreds of thousands by decade’s end, the biggest question facing providers is: How can this nascent industry scale efficiently to meet demand, seamlessly connecting the patients’ community of care, whilst maintaining the highest levels of quality and managing and measuring the associated? Members of Ireland’s CGT community – including IDA Ireland, BioPharmaChem Ireland and industry leaders – have collaborated with EY to develop a cross-sectoral industry forum and Digital Accelerator to identify and assess the opportunity this presents for Ireland, as well as to appreciate and address CGT challenges,

which stem from an unprecedented and intricate supply chain. EY has been working as a facilitator for industry and have determined the area of CGT and ATMP critical for Ireland’s industry development, given Ireland’s track record as a biopharmaceutical hub. Together, the participants are working to determine how best to improve the global supply, management and manufacture of these transformative treatments, with Ireland leveraging its position as a base for the delivery of associated services.

Successfully scaling CGTs EY predicts the Cell and Gene Therapy global market will significantly outperform the pharmaceutical global market, from an estimated US$3 billion annually in 2021 to an estimated US$50 billion annually in 2027. There are more than 2,600 CGT clinical trials in different modalities at different stages of maturity worldwide, indicating a potential wave of 300 to 400 product approvals

between 2022 and 2027. While all transformational medicines come with their own set of challenges, these revolutionary treatments are unlike any other therapies in significant ways: 1 They cannot be mass manufactured; they must be tailor-made for small numbers of people or a specific individual as part of a complex process that varies greatly in each instance. 2 CGTs are difficult and expensive to administer, limiting their current availability to a small population. 3 Their manufacture and delivery offer zero room for error. Moreover, these challenges will multiply as CGT options and their usage increase. Central to the problem is a complex supply chain that relies on multiple handoffs of timesensitive information and materials across a diverse set of organisations and systems. Patient outcomes depend on getting these transactions right the first time, but they Irish PharmaChem – Summer 2021

Cell & Gene Therapies supply chain. Pointellis™ forms a secure and trusted collaborative arena that expedites the timely and transparent flow of data and materials and minimises dangerous and costly errors. In addition to the digital infrastructure, the platform offers a suite of applications to streamline and optimise the links in the supply chain: Slot Schedule for manufacturing/ treatment managers; Case Assist for patient operations case workers; and Logistics Integrate for logistics managers. By leveraging blockchain-based technology, the platform has inherent capabilities which provide key enablers for ensuring industry and process scale for CGTs and ATMPs – namely, a chain of custody and identity for patients and value chain enablers, including blood samples and gene specimens. In addition, a single source of immutable truth is created where participants can exchange data, minimising reconciliations and manual exception handling. The platform provides each of the participants in the CGT ecosystem – health care providers, health services companies, insurers/ payers and the biopharmaceutical industry – with the capabilities and information they need to do their job to the best of their ability. Next, EY sought to help close the gaps on the ground by enabling industry to promote Ireland as a location for CGT and ATMP within firms and at C-level. are subject to human error, travel delays, lab closures and even pandemics. CAR-T therapy, for example, where the patient’s own T cells are extracted, modified, activated, expanded, purified and returned to the patient, requires nearly triple the number of supply chain steps as chemotherapy – from doctor to leukapheresis centre to shipping company to drug manufacturer to shipping company to hospital to treatment centre. To successfully scale Cell and Gene Therapies, real-time signalling across this extraordinarily complex supply chain will be essential, so that problems can be detected early and speedy course corrections made. All the members of the supply chain must securely communicate and share information they trust.

An industry in need of leadership: an opportunity for Ireland Much like a city that springs up around an industry, the Cell and Gene Therapy ecosystem of the future will look very different from today. It is already ushering in a new era in research and development, regulatory oversight, manufacturing and delivery, and cost and reimbursement. In a series of roundtables, EY and Ireland’s CGT leaders outlined the critical requirements for success and Ireland’s unique qualifications to become a Centre of Excellence (COE) in the EMEIA region (EU, Middle East, India, Africa).

Location: Ireland is well placed geographically, with proximity to the North America, Europe, Middle East and Africa markets, and is the only native English-speaking, common law EU member state. The country also currently has an enviable corporate tax rate.

Manufacturing capacity and talent:

Ireland is a recognised leader in nextgeneration manufacturing technology, with a long track record as an international CGT nucleus. The country houses more than 85 biopharmaceutical sites, including substantial operations for the top 10 There are more than 2,600 CGT clinical trials in different modalities at different stages of maturity worldwide, indicating a potential wave of 300 to 400 product approvals between 2022 and 2027.

•

The case for a digital ecosystem EY conducted extensive research and collaborated with global biopharmaceutical companies and other members of the CGT supply chain and concluded that a digital ecosystem and supporting information exchange was needed to overcome the foregoing challenges. The company teamed up with Microsoft to create this cloud-based digital platform and called it Pointellis™. Pointellis™ is an open but private secure data exchange that forms the digital backbone connecting each participant along the CGT Irish PharmaChem – Summer 2021

Cell & Gene Therapies global biopharmaceutical companies. In the last decade alone, Ireland has invested more than €10 billion in biopharma manufacturing facilities. More than 30,000 people are now employed in the sector, which contributes more than €40 billion in exports annually and accounts for about 32% of GDP.

• •

R&D and training: The country supports research through substantial public and private sector funding, including: over €12 million in CGT research in the last 10 years by Science Foundation Ireland (SFI); €25.5 million for CGT projects by the Disruptive Technologies Innovation Fund (DTIF); and a variety of R&D and training grants, as well as a 25% R&D tax credit, both supported by IDA Ireland. The National Institute for Bioprocessing Research and Training (NIBRT) trains over 4,500 people annually, including in CGT development and manufacturing, while the Regenerative Medicine Institute (REMEDI) is a centre for multidisciplinary research in fundamental and applied cellular biotechnology. Ireland also has an evolving clinical trial ecosystem, with 291 trial sites now open across the Irish network, including multiple ongoing CGT clinical trials.

Management of complex data: One of the key drivers of the CGT revolution is

the convergence of the IT, medical technology and pharmaceutical sectors. Ireland is a global centre for data management and advanced analytics, housing operations for the world’s top five software companies, seven out of the top 10 technology companies, and the top five cyber security companies. In addition, the medtech industry is a stalwart of the economy, with significant MNC and indigenous capability.

Navigation of regulatory requirements: Ireland knows how to work with different regulatory agencies, having successfully navigated Irish, EU and US regulations. The country has an exemplary compliance record and a multidisciplinary stakeholder network.

Transport and cold chain logistics: Ireland has multiple global and speciality providers in CGT logistics, including six airports serving 43 countries and 10 freight forwarders and courier servicers.

All roads lead to Ireland According to the Alliance for Regenerative Medicine (ARM), more than 1,000 businesses have been established worldwide to expand the range and efficiency of Advanced Therapies. There may never be a better time for Ireland to play a central role in the ongoing evolution of the CGT industry. Already an international hub for biopharma operations and manufacturing, IT and medical

technology, and transportation and cold chain logistics, the country offers convenient geography, a universal language and a great tax rate. With Pointellis™ available as a key piece of digital infrastructure, and Ireland industry collaboration driving a CGT COE, there is no stopping the next wave of CGT innovation, the safe and effective delivery of these transformative therapies to the patients who need them, and the protection of GDP while Ireland continues to climb the value chain. References Adlai Goldberg. (2020, December 8). How collaboration will strengthen the future of Cell and Gene Therapies. EY. Retrieved May 23, 2021, from EY.com: https://assets.ey.com/ content/dam/ey-sites/ey-com/en_gl/topics/lifesciences/ey-pointellis-cell-and-gene-therapywhitepaper-final.pdf (Q3, 2020). Why Ireland for Cell and Gene Therapy Development and Manufacturing. IDA Ireland. Retrieved May 23, 2021, from IDA Ireland: http://www.idaireland.com/ getmedia/1d7808a8-0974-40cf-afc2001640c564b5/IDA_Cell_Gene_Therapy_ Infographic_V2.pdf.aspx?ext=.pdf (2020). Innovation in the Time of COVID-19. ARM Global Regnerative Medicine & Therapy Sector Report. Alliance for Regnerative Medicine. Retrieved May 23, 2021, from ARM: http:// alliancerm.org/wp-content/uploads/2020/08/ ARM_1H-Report_-FINAL.pdf.

Arial EY predicts the Cell and Gene Therapy global market will significantly outperform the pharmaceutical global market, from an estimated US$3 billion annually in 2021 to an estimated US$50 billion annually in 2027.

24 22

Irish PharmaChem – Summer 2021

WE LISTEN TO AND LEARN FROM PATIENTS EVERY DAY...

We are dedicated to improving patients’ lives through innovative medicines in Oncology, Neuroscience and Rare Diseases. Because patients can’t wait. www.ipsen.com

CR-IE-000003 May 2021 © Ipsen 03.2019 / PIERRE-OLIVIER / CAPA Pictures

Ipsen has been in Ireland for over 30 years, pioneering innovation across R&D, manufacturing and commercial activities at its site in Blanchardstown, Dublin

REGULATION

Regulation:

a key part of innovation

Innovations in Advanced Therapeutics must be combined with a reliable and adaptable regulatory system, writes Dr Lorraine Nolan, CEO of the Health Products Regulatory Authority. A robust and reliable regulatory system, combined with an agile and adaptive approach, will be necessary to capitalise on the promise presented by Advanced Therapeutics to treat disease and injury. The good news is we are already far down this road. Not only do we have very detailed, risk-based and flexible GMP guidance in place within the EU for the manufacture of Advanced Therapy Medicinal Products (ATMPs), the Covid-19 pandemic has helped us progress mechanisms that facilitate rapid regulatory policy development and rapid risk-based regulatory advancements. This was evidenced by the fact that by April 10, 2020, just a few months after the start of the pandemic in Europe, detailed regulatory guidance had been developed, agreed and published by the European network, which provided important regulatory flexibilities across a range of areas, including in the

supply chain. That guidance was expanded on two further occasions shortly thereafter to provide additional flexibilities, especially in the manufacturing area. This demonstrates the agility of the EU regulatory environment responding to a dynamic and evolving situation to ensure access to safe and effective medicinal products.

for critical medicines was enabled, it will be important to assess and analyse the adapted regulatory processes through consultation and engagement with key stakeholders, including the biopharmaceutical industry.

Following the introduction of the extraordinary suite of adapted regulatory procedures to facilitate manufacturing throughout the last 18 months, the HPRA and broader global regulatory community are committed to a period of reflection to consider the learnings from this response.

Notably, this period of reflection is not just happening at a national or even regional level. It is taking place via the work of the International Coalition of Medicines Regulatory Authorities (ICMRA) to identify common regulatory approaches employed across regions, to better understand their success, possible retention and future applicability. Greater knowledge sharing, alignment of procedures, wherever possible, and leveraging of expertise within the broader global regulatory network will be essential to ensure appropriate and proportional regulation.

While increased manufacturing capacity in response to the pandemic-related demand

This level of international cooperation will be fundamentally important as the level of

Considering the learnings

Irish PharmaChem – Summer 2021

REGULATION sophistication in manufacturing increases. This may include, for example, multidisciplinary capabilities, new processes and analytical methods, shorter product runs and potentially multiproduct ‘flexible’ factories as companies improve their abilities to adjust to everchanging market demands. We have already seen examples of dynamic manufacturing processes shifting focus to meet external needs in the context of new vaccine platform technologies used to manufacture safe and effective vaccines of high quality. In some cases, manufacturers are quickly updating their processes to generate new multi-valiant vaccines, which include a combination of mRNA transcripts that ultimately target variant strains of SARSCoV-2. Thanks to the almost real-time sharing of genetic information on the sequence of variants, facilities can rapidly alter the active substances.

Combined ATMPs Highly specialised and patient-specific therapies have fundamentally changed traditional approaches to drug development and manufacturing. Even in the context of already advanced biological therapies, cross cutting, innovative collaborations are leading to further potential treatment opportunities, such as drug-device combination (DDC) products with the ability to introduce ATMPs, such as Cell and/or Gene Therapies, in a sitespecific manner. This of course presents an interesting vista, and one that will need appropriate regulation to ensure the potential represented by future “combined ATMPs” are realised.

all be supported by so called ‘big data’. Moreover, we should not forget the importance of material sciences as Advanced Therapeutics, again, are very likely be developed using novel materials. Ireland is already very strong in this area and this positions us well to remain at the forefront of such advancements. Exciting as all this sounds, sustainable regulation that continues to add value will be important to ensure the safe application of these exciting and powerful scientific advances to ultimately improve the health and wellbeing of patients. Protection and enhancement of public health is, and will always be, the cornerstone upon which sustainable and effective medicines regulation is developed. The ground-breaking opportunities afforded by Advanced Therapeutic products to address many aspects of human, and indeed animal, health are incredibly exciting, particularly in areas of unmet need. Medicines regulation will continue to play an active role in supporting the development of important new therapies, but never at the expense of safety, efficacy and quality standards. We have seen an incredible period of biomedical research, development and innovation over the past 18 months, which is clear evidence of what science can achieve when enabled by an appropriate and adaptive regulatory system.

“Medicines regulation will continue to play an active role in supporting the development of important new therapies, but never at the expense of safety, efficacy and quality standards.”

As readers will be aware, all ATMPs are evaluated via the centralised procedure, thus ensuring that they benefit from a single evaluation and authorisation procedure applicable across the EU. Central to the success of DDC products that integrate ATMPs, will be the timely and effective interaction between notified bodies (NBs) and assessment teams. Consequently, an important consideration will be the capacity of NBs to contribute, when required, to the assessment of any market authorisation application for a combined ATMP. Competition and availability of resources within the medicines and medical device networks will be an important consideration in this field moving forward.

Advanced Therapeutics & Regulation The convergence between different scientific and technological disciplines will surely continue into the future given it is likely that Advanced Therapeutics will be directly linked with advanced manufacturing technologies, such as robotics, AI, assisted and augmented reality, and smart factories (sometimes referred to as ‘factories of the future’). These in turn will Irish PharmaChem – Summer 2021

Sustainable regulation that continues to add value will be important to ensure the safe application of these exciting and powerful scientific advances to ultimately improve the health and wellbeing of patients.

Enterprise Ireland

ATMPs: supporting a skyrocketing sector Cell and gene therapies are the newest frontier in drug development and a growing number of Irish companies are at the vanguard, writes Deirdre Glenn, Head of Life Sciences at Enterprise Ireland. From exciting research projects at third level, through to high-potential start-ups and established companies, Irish businesses are excelling in the development and production of next-generation human drug therapeutics, known as advanced therapeutic medicinal products (ATMPs). ATMPs treat people at the genetic, tissue or cellular level, offering ground-breaking new opportunities for the treatment of serious disease and injury. The market for cell therapies was estimated at US$2.7 billion in 2017, with that figure expected to treble within five years. At Enterprise Ireland, we are supporting increasing numbers of indigenous Irish firms in this field, building on our track record and reputation for research, development and manufacturing excellence in biotechnology and pharmaceuticals in general.

Developing a globally competitive Irish ATMP ecosystem This work is vital as research has found that developing a globally competitive Irish ATMP ecosystem represents a significant opportunity,

but the window to do so is relatively narrow. We’re seeking to ensure that Ireland becomes a leader at the forefront of this field, not only to help patients globally, but also to continue to secure high-value employment and economic impact in Ireland. Our ATMP clients primarily fall into two categories. They are either developing new drug therapeutics in this space or are supporting research and development into ATMPs and enabling their manufacture. Up to now, high-tech pharmaceutical manufacturing in Ireland has tended to happen at scale, but the ATMP manufacturing process is completely different. Effectively, companies produce customised drug therapeutics based on the cells or genetic makeup of individuals. Given that the product is so specific, the volumes are smaller, but specialist firms in the field seek to use process automation and digitised manufacturing to drive efficiency.

Turbo-boosting pre-start-up businesses Through our game-changing Commercialisation

Fund, Enterprise Ireland assists the creation of technology-based start-up companies by funding cutting-edge research within the third level in Ireland, working with Ireland’s brightest scientists and clinicians. This funding is key to ensuring Ireland remains competitive on the world stage in many sectors, including ATMPs. One such scientist is Professor Jane Farrar at Trinity College Dublin (TCD), who specialises in ocular genetics. She and her team recently received more than €400,000 in funding from the Commercialisation Fund to further develop, research and commercialise a novel gene therapy for the most common form of agerelated macular degeneration. StarMAT Technologies, led by Professor Sally Ann Cryan of the Royal College of Surgeons in Ireland, received a similar level of financial support from the Commercialisation Fund for its polypeptide-based materials platform, which aims to overcome the delivery challenges associated with getting many emerging advanced biotherapeutics into clinical use. This funding will enable StarMAT Technologies Irish PharmaChem – Summer 2021

Enterprise Ireland them accelerate the development and launch of quality, life-changing medicines, including Cell and Gene Therapy drugs. Powered by transformation research in APC and with support from Enterprise Ireland, VLE Therapeutics has been spun out to focus on the manufacture of such ATMPs. This will be the first Irish-owned facility expressly designed to provide Ireland and Europe with a local supply chain for these critical medicines. In April 2021, through our Disruptive Technologies Innovation Fund (DTIF), Enterprise Ireland funded a number of start-up and established Irish businesses to either develop or help support the manufacturing of ATMPs. Ireland’s biggest, Nasdaq-listed, indigenous drug discovery company, Amryt Pharma, specialises in novel drugs designed to treat patients suffering from serious and lifethreatening rare diseases. Amryt received €8.4 million under DTIF to develop a disruptive gene therapy platform, replacing viruses in the treatment of genetic conditions Avectas received €4.4 million to develop a digitalised cellular engineering system aimed at producing cell therapy cancer treatments with a focus on allogenic (off-the-shelf ) therapies and those for solid tumours. Mirai Medical, meanwhile, was funded with €4.78 million to help it produce its outpatient solution without side effects to deliver next

generation therapeutic and gene therapies for gastrointestinal cancer. On the manufacturing side, DTIF also recently supported two more Irish businesses in the ATMP space. Remedy Biologics received €6.8 million to establish a prototype centre of excellence on the St James’ Hospital/TCD campus to discover and deliver next generation precision cell therapeutics for solid tumours through ‘modular GMP (good manufacturing practice]) in a box’. The second firm in this space to receive DTIF funding was Valitacell, which will use this financial support to harness artificial intelligence in the creation of fast cell analytics for biomanufacturing, for use in media screening and bioprocess controllers.

On the cusp of an explosion One thing is clear, regardless of the business stage of your company, the industry around advanced therapeutic medicinal products is on the cusp of an explosion. Enterprise Ireland has the supports to help our ATMP companies take their innovative solutions from the concept stage, right through to the marketplace. We are here to help such Irish businesses on their journey and to help them succeed. To find out more about how Enterprise Ireland can help you and your business, visit www.Enterprise-Ireland.com.

to develop scalable processes for drug payload incorporation, product refinement and further toxicology studies. Its technology is expected to be particularly well suited to applications in respiratory and regenerative medicine.

Helping high-potential start-ups Early-stage funding is crucial for any start-up but in biotech in particular, it’s a necessary lifeline. Companies at this critical growth juncture need support with developing and funding their business plan. At Enterprise Ireland, we work with HPSUs to manage rapid growth and to connect them with funders and other key stakeholders. Once such firm is ONK Therapeutics, which is developing natural killer cell therapies to target solid and haematological cancers. It aims to develop off-the-shelf treatments using this medical technology. While it is still at prerevenue stage, it has significant potential and raised US$14.6 million in two funding rounds in 2020.

Supporting established businesses One of the most exciting projects we are working on has sprung from Applied Process Company (APC). APC is one of Ireland’s most impressive research and development companies that works hand in hand with large pharmaceutical and biotech companies to help Irish PharmaChem – Summer 2021

Enterprise Ireland has the supports to help our ATMP companies take their innovative solutions from the concept stage, right through to the marketplace.

Training & Development

Kickstarting your digital transformation

The Irish life sciences sector is a true success story. From small foreign direct investment in the late 1960s, today Ireland is now home to 24 of the top 25 pharmaceutical and medical device companies. Perhaps even more successful is the growth in biopharmaceutical manufacturing. In the early 2000s, there were just two biologics manufacturing sites in Ireland; today there are over 20, exceeding the overall growth in demand for biological treatments but also reflecting the success of the skilled Irish workforce. In 2020, Ireland exported €62 billion of pharmaceutical products, an increase of 25% on 2019, and nearly 50% of these were biopharmaceutical products. Thus, Ireland is today a global centre of excellence for biologics manufacturing. With a strong and growing indigenous ecosystem, the Irish manufacturing base remains largely comprised of global biopharmaceutical giants. Bioprocessing is more complex than manufacturing traditional pharmaceutical products, and engineers and scientists working in the Irish biopharmaceutical industry have developed deep knowledge and expert capabilities in bioprocessing and supporting technologies. However, several global trends are likely to impact the future of the industry in Ireland. These include; an ever-increasing demand for Cell and Gene Therapies which make up a large portion of the drug development pipeline; pressure to reduce time to market for new therapies; and a combined demand for

The Biopharma Data Champions Kickstarter programme, developed by Siemens, NIBRT and the IDA, was created to guide participants on a journey to data project success and accelerate digital transformation in the Irish biopharmaceutical sector, explains Siobhán Fleming, Collaboration Manager, Siemens. increased titres and yields, while reducing costs. These trends have been accentuated by the arrival of Covid-19, and we now see a greater emphasis on establishing ‘local’ R&D bioprocessing and vaccines facilities by most countries, including Ireland. Supply chain robustness is also receiving more attention, particularly around availability of supplies and raw materials.

Building on Ireland’s reputation The challenge arising from these trends is to build upon Ireland’s place as a world leader in biopharma manufacturing. Aligned with the transformation objectives of IDA Ireland, in their new strategy 2021-2024, Driving Recovery and Sustainable Growth, we believe that the answer lies in digital transformation. By achieving manufacturing excellence through process improvements and operational effectiveness, Ireland will be positioned to attract higher value investment in new and advanced therapies. The global data strategies of biopharma organisations tend to focus on areas outside of manufacturing, primarily drug discovery and real-world evidence / patient data, rather than on manufacturing and supply chain. This

creates a real opportunity for creating value across the manufacturing and supply chain landscape. In fact, we know that taking control of the local strategy is a focus topic. Killian O’Driscoll, Director of Projects at NIBRT, recently said: “Our clients have a keen interest in the application of 4.0 technologies in biopharma manufacturing.” Digital transformation is a process of using digital technologies to change business processes and models, creating new opportunities for value. The challenge for many leaders is where to start, developing an overall strategy and identifying and growing the required skills.

Accelerating digital transformation For several years now, Siemens and NIBRT have collaborated to improve bioprocessing using advanced data analytics and big data. Working with partner companies, we have worked on complex datasets to improve lab connectivity, process development, design of experiments, complex investigations, yield and crossdepartment reporting. We have now designed the ‘Biopharma Data Champions Kickstarter’ programme to guide participants on a journey to data project Irish PharmaChem – Summer 2021

Training & Development Siemens and NIBRT have collaborated for several years to improve bioprocessing through advanced data analytics and big data.

Grant support for this programme may be available from IDA Ireland. To express interest in the Biopharma Data Champions Kickstarter programme, please contact Siobhan.Fleming@siemens.com. allow participants to learn from experienced subject matter experts. Unique to this programme is the emphasis on delivering value. In parallel to the group sessions, participants will avail of a series of individual coaching days, guiding them through aspects of their own projects that could benefit from additional support. Through these one-to-one sessions with subject matter experts, they will be guided to make confident decisions around project delivery.

Empowering engineers and scientists

success and accelerate digital transformation in the Irish biopharmaceutical sector.

A practical programme This is a practical programme, aimed at helping companies to deliver on the potential of data analytics to improve operations in your organisation. In a rapid six-month Kickstarter cycle, participants will be guided in selecting a real use case project from within their business and making progress in addressing it through data analytics. They will gain the knowledge and practical skills required to identify value-creating opportunities, manage stakeholder groups, and deliver real value to their organisation.

theory sessions and individual coaching sessions delivered online and in person. Designed around the lifecycle of a data analytics project, group sessions will cover strategy, project selection, business case development, stakeholder management, data and technology selection and deployment. Delivered by experts from Siemens and NIBRT and external specialists, these sessions will

We believe that empowering our engineers and scientists to exploit the potential of data analytics will help them to take ownership and champion the use of data, advancing their organisation on the path to digital transformation. Ireland’s biopharma leaders are in an enviable position. Engineers and scientists working on Irish manufacturing sites have developed an incredible depth of knowledge in biopharmaceutical processes and systems. This knowledge, when combined with a digital transformation mindset, can serve to further embed Ireland’s reputation as a world leading biopharmaceutical cluster.

Who is it for? The modern pharmaceutical industry needs cross-functional teams, rich in expertise across science, engineering, and comfortable with using data. The Kickstarter programme is therefore designed for professionals from any biopharmaceutical function who wish to develop capabilities in delivering successful data projects. This includes R&D, process science and engineering, automation and IT, manufacturing science and technology, quality, and continuous improvement.

Programme structure and content The Kickstarter programme will be delivered over six months. It will consist of both group Irish PharmaChem – Summer 2021

Siobhán Fleming, Collaboration Manager, Siemens.

Services

Kuehne+Nagel’s European Pharma Fleet - ready to roll Quickly delivering the Covid-19 vaccine to people across Europe is a complex undertaking. Having GxP-compliant vehicles available for road transportation is a crucial link in the chain to ensure compliance and the highest level of quality and service. This situation calls for Kuehne+Nagel’s European Pharma Fleet, writes Adam O’Sullivan, Director of Pharma & Healthcare, Kuehne+Nagel Ireland. Covid-19 vaccines are now being shipped from manufacturing sites around the world, to be administered locally. A successful roll-out depends on a variety of logistics solutions. Thanks to the geography of Europe, with its high population density, and the need to carefully control storage conditions in transit, the distribution of vaccine consignments from filling centres to clinical

settings will mostly be conducted by road. The very specific storage requirements for the Covid-19 vaccine make this a challenge: some vaccines need to be kept at a constant temperature of minus 70 degrees Celsius until shortly before the administration. Additionally, clinics and vaccination centres have limited capacity to administer the vaccinations.

Adam O’Sullivan, Director of Pharma & Healthcare, Kuehne+Nagel Ireland.

Therefore, smaller consignments must be delivered in batches. Doses for the follow-up injection must also be delivered at precisely the right times and locations.

Adapting to needs Having our own European Pharma Fleet, integrated with our own global logistics

Irish PharmaChem – Summer 2021

For when it matters the most.

T: +353 18239777 | E: Ireland.sales@kuehne-nagel.com | W: www.kuehne-nagel.ie

Services

to specialist facilities. Later, being able to predictably assign higher capacity deliveries will be valuable as larger groups of people are assigned more stable vaccines.

Speed and precision For five years, we have been investing in our specialist European Pharma Fleet. We saw that Kuehne+Nagel’s rapidly growing pharma client base needed a combination of factors: reliable transportation, compliance with global standards, capacity and agility. Today, we have 210 specially designed and fitted trailer units, 90% of which are configured for dual temperature storage. These trailers have been thermally mapped and qualified for multiple pharma-relevant temperature ranges, both positive and negative. This means that they can carry consignments at both minus 20 degrees – cool enough to sustain the dry ice packing for the ultra-cold Covid-19 vaccines – as well as vaccines that just need to be chilled. To minimise downtime, all our Pharma Fleet trucks have two drivers. All the trailers have special security features; many are equipped with doors operated remotely using GPS coordinates. And the fleet is compliant with Transported Asset Protection Association (TAPA) standards. That means manufacturers and governments have reassurance on physical security, and also better control of information flows and traceability. There’s one more factor that we know is crucial to the pharma industry in the decadeplus we’ve been serving it: holistic service provision. Our European Pharma Fleet is tightly integrated with our air, sea and warehousing infrastructure. That will be especially valuable in the coming months, as new vaccines are introduced from different manufacturing facilities all over the world.

Time to get moving

network as well as those of our industry partners, makes our distribution effective and adaptable as the Covid-19 vaccination programme evolves. This is essential since there is no one-sizefits-all approach to vaccine distribution. Different manufacturers and governments have come to a variety of arrangements. In one country, for example, initial batches of

32 34

the ultra-cold vaccine that require dry icecompatible transportation will go to a large variety of locations. That demands highly coordinated local distribution. Other vaccines, that are stable at higher temperatures, will follow a different path. Furthermore, the race to get risk-group patients and frontline health workers immunised requires rapid distribution

The Covid-19 vaccination programme is still defined by uncertainties and the only way the logistics can work around these unknowns is to have properly certified, high-quality capacity that can be assigned to the task at a moment’s notice. Our specialised European Pharma Fleet is already rolling, fully integrated with our global network. And that’s great news for a supply chain that cannot afford any weak links. Your contact for Pharma & Healthcare Logistics: Adam O’Sullivan, Director of Pharma & Healthcare, Kuehne + Nagel Ireland Irish PharmaChem – Summer 2021

Your Partner to Design, Develop and Manufacture your next Medical Device

PBC Biomed are certiﬁed to ISO 13485:2016 for the Design, Development and Manufacture of Medical devices. Please contact us if you: ✔

Require a Design / Development proces compliant to the ISO Standard

✔

Require access to a highly experienced Advisory Board for Voice of Customer input

✔

Support to navigate the Regulatory / Approval Process

✔

Contract Manufacturing

Please contact us at 4D, Western Business Park, Shannon, Co. Clare, Ireland T +353 (0) 61 704740 E info@pbcbiomed.ie

Cell Engineering Technology

Avectas: at the forefront of cell engineering Avectas is a cutting edge cell engineering technology company, developing a proprietary, simple, highly effective, automated non-viral cell engineering system, Solupore®, to enable efficient and safe genetic modification, accelerating the manufacture of cells for the next generation of immuno-oncology therapies.

Irish PharmaChem – Summer 2021

Avectas is a pioneering cell engineering technology company, enabling the development of engineered cell-based immuno-therapeutics to treat cancer. Avectas is developing Solupore®, a proprietary, simple, highly effective, automated, non-viral cell engineering system to enable efficient and safe genetic modification, accelerating the manufacture of cells for the next generation of immuno-oncology therapies. Avectas is a private, international company with research facilities in Dublin, Ireland, Toronto, Canada, and a business development group in Cambridge, MA, USA. Avectas has raised over US$40 million to date and employs almost 40 professionals and is led by a team of highly experienced pharmaceutical executives, supported by a world-class Scientific Advisory Board of cancer cell therapy experts guiding its technology innovations and applications. The company’s proprietary technology, Solupore®, has strong intellectual property protection through granted and pending patents, including in the US and Europe.

Enabling the next wave of cell therapies – Solupore® technology Currently approved cell therapies such as CAR-T therapies Kymriah, Yescarta, Tecartus and Breyanzi have a single transgene insertion modifying the cell. Next-generation platforms require: • Complex cell engineering capabilities that are non- viral; • Compatibility with viral engineering; • Maintenance of cell viability and functionality. Avectas is developing the Solupore® Technology to address these needs. Solupore® is an end-to-end cell engineering platform with a proprietary delivery solution and automated fluid-handling device, enabling controlled, rapid, transient permeabilization of the cell membrane. The technology allows for the non-viral delivery of biomolecular cargos, including nucleic acids and proteins, to cells to make genetic modifications. Solupore® overcomes the limitations of other technologies, such as electroporation and viral vectors, by efficient reversible Irish PharmaChem – Summer 2021

permeabilization of the membrane, which causes minimum perturbation, resulting in cells that remain viable and fully functional. The cell engineering system has been developed in two formats. The first, aimed at discovery and feasibility studies, is called Solupore® RT (Research Tool), and the second is a clinical-grade cell engineering system, the Solupore® SUS (Single Use System). The RT device is currently in operation in several partner sites internationally, thanks to welldeveloped protocols and a comprehensive data set to support the adoption of the Solupore® Technology. The clinically aligned device, the SUS, enables non-viral, ex vivo transfection of cells to manufacture cell therapy products in an automated system using a closed, sterile, single-use assembly. From a regulatory standpoint, Avectas has designed the SUS with clinical trials in mind and has had a strong focus on biocompatibility and sterility throughout. Avectas intends to file supporting documentation with FDA DMFs. Avectas recently published data in the leading international cell and gene therapy publication, Cytotherapy, supporting DMF documentation with FDA. This publication follows a previous one in PLOS ONE, with citations in both Nature Biomedical Engineering and Chemical Reviews. Dr Shirley O’Dea et al. examined the suitability of Avectas’ Solupore® system for engineering primary human T cells for cell therapy applications. The paper describes how the next generation of immune cell therapy products will require more complex cell engineering (Source: www.sciencedirect.com/science/article/pii/ S1465324921001845). Further, it describes the engineering technologies that can maintain high levels of cell function and how non-viral engineering methods such as Solupore® have the potential to address limitations associated with viral vectors.

Partnerships: national & international The company is developing its cGMP aligned Solupore® clinical-grade system, SUS, with cell therapy companies to address emerging cell delivery challenges associated with multiple cell modifications and engineering of limited supply or fragile cells. Additionally, it will provide regulatory support to partners in their regulatory filings. Avectas has disclosed development partnerships with ONK Therapeutics (Galway, Ireland) and Vycellix (Florida, USA). In addition, Avectas has several key R&D

Cell Engineering Technology

collaborations to support its technology development in cell types, transfection cargo and scale-up. These collaborations include; CCRM (Canada), Cell and Gene Therapy Catapult (UK), University of California, Davis (USA), Karolinska Institute (Sweden) and University College London (UK). On a national level, Avectas leads a consortium that will invest €7.23 million, including €4.4 million awarded under the Irish Government’s Disruptive Technology Innovation Fund (DTIF), to develop a high-throughput scale of its proprietary cell engineering platform, Solupore®, with consortium partners Bluebridge Technologies and the National Institute for Bioprocessing Research and Training (NIBRT). The project expands Avectas’ development towards commercialising an advanced largescale, digitalised cell engineering platform optimised to manufacture ‘off-the-shelf’ cell-based therapies for cancer treatment, intending to support Ireland’s goal of being at the forefront of cell therapy manufacturing. All parties will work synergistically to disrupt the manufacture and delivery of cell-based therapeutics to patients.

The DTIF Consortium Team from Avectas, Bluebridge Technologies and NIBRT.

The Disruptive Technologies Innovation Fund (DTIF) is a €500 million fund established under Project Ireland 2040 and run by the Department of Enterprise Trade and Employment with support from Enterprise Ireland.

Looking forward Avectas continues to make strides at a national level through the award recognition of the DTIF funding and on an international scale where Avectas continues to partner and seamlessly integrate the Solupore® technology at leading research institutes.

Solupore® Research Tool (RT) in a lab setting: this device is currently in operation in several partner sites internationally.

“It’s an exciting time for the industry as developers look to address solid mass tumour and allogeneic therapies by performing more complex cell modifications,” said Michael Maguire, PhD, Avectas’ CEO. “This has created high demand for clinical-grade, non-viral, enabling technologies for cell therapy manufacturing, and the Avectas team is excited to be developing and commercialising such a technology.”

Solupore® Single Use System (SUS) enables non-viral, ex vivo transfection of cells to manufacture cell therapy products in an automated system using a closed, sterile, single-use assembly.

Irish PharmaChem – Summer 2021

APIS & ADVANCED INTERMEDIATES

SK pharmteco unveils new large molecule CDMO SK pharmteco, a global CDMO, specialises in small molecules, and now large molecules, with the addition of the newest part of the team in the form of YposKesi, a Paris-based large molecule CDMO. SK pharmteco has added a new family member. The most recent addition is YposKesi, a large molecule CDMO based in Paris, France, providing access to a modern 5,000m2 facility, capable of developing and producing Adeno Associated Viral and Lentiviral Vectors for gene and cell therapy. With the addition of YposKesi, SK pharmteco have seven facilities with almost 1,000m³ of small molecule reactor capacity, four independent manufacturing suites for large molecule bulk drug substance production and two fill and finish suites for drug products. Their state-ofthe-art facilities offer a highly differentiated technology toolbox that is second-to-none, delivered by their talented workforce of over 1,500 employees.

Providing the highest quality services SK pharmteco is the customer-facing team comprised of SK biotek, AMPAC Fine Chemicals, and YposKesi, combining highly complementary assets and expertise, providing the highest quality services to their customers. Their multi-purpose facility in Swords, Co. Dublin, has more than 60 years’ experience, including 30+ years in HPAPI manufacturing OEB Class 5 (1-0.1 µg/m3.shift) providing bespoke development from early clinical phases to commercial manufacture (batch sizes 1kg to 50kg+). Their expertise lies in process R&D, analytical, plant-scale chromatography, hydrogenation, operational excellence, secondto-none audit record, RTP, and STP. And their strengths don’t stop there; working Irish PharmaChem – Summer 2021

reveals. “From your first encounter with our Business Development Team to your dedicated Project Manager, flowing down to every team member that comes into contact with every stage of your project; it makes us unique.”

with SK pharmteco on your small or large molecule project, you are supported from Having SK pharmteco on your team development through to commercial launch. This SK pharmteco is: is where their size and history matter: they have A team that has a strong track record in resources, capacity, and financial strength that developing and commercialising NCEs, provides long-term viability for the business and meeting all standards required by the world allows them to support the most complex and regulatory authorities; high-value supply chains. This longevity enables A team that supports Global Supply Chain SK pharmteco to form deep, lasting relationships solutions; and bring multiple projects to market. A team that appreciates the value of innovative science; A true partnership approach A team that provides both consultancy and “With scientific and technical understanding, guidance through the clinical development practical experience and full commitment, we put pathway through to commercial success; ourselves in your shoes, understanding the long A team that strives towards true partnership complex journey you are on, and provide support rather than an arms-length supplier through the application of a science-driven, riskrelationship, who is committed to work with based approach at every step,” explains Steve you and stand over your product as if it were Barr PhD, VP Business Development. “We value their own; the relationships we have with our customers, A team that now has expanded its offering vendors and suppliers. It is more than just into the biologics space with the inclusion of drafting an agreement; it is a relationship that YposKesi. relies on clear expectations, communication and “We’re not finished yet,” insists Barr. “Our trust. We see it as a partnership. For a partnership entrepreneurial spirit means we are constantly to work, we must share similar values, clear lines looking for new services, and capabilities to of communication and regular updates to foster enhance our offering to our customers.” trust between the innovator and us the CDMO.” If you are looking for a CDMO specialising in SK pharmteco believes in a ‘One Viral Vectors, HPAPI, Continuous Flow Processing, Team’ approach: internally, across three Particle Engineering, Energetic Chemistry, continents, ensuring teamwork, open lines Controlled Substances, SMB Chromatography or of communication and multi-disciplinary simply a partner that offers a secure development collaboration and externally, with their pathway for your NCE, SK pharmteco would be customers. “The ‘sense of ownership/in it delighted to work with you. together with the customers mentality’ is a For more information, email: proud facet of SK pharmteco’s culture,” Barr skpharmteco@sk.com.

•

• • •

•

Eli Lilly

Lilly celebrates 40 years in Cork Eli Lilly and Company is celebrating its 40th anniversary in Kinsale, Co. Cork, this year.

Eli Lilly first arrived in Cork in 1978, when the company purchased a farm located between Kinsale and Innishannon and began construction of a new pharmaceutical manufacturing plant. In March 1981, the site produced its first batch of active ingredient for a Lilly medicine, and this is the date the company celebrates as operations start-up. As Lilly Kinsale celebrates its 40th anniversary

this year, the site today is unrecognisable compared to 1981, with a much-expanded chemical synthesis site and an extensive biologics site now operating within one campus boundary. 30 years after Lilly Kinsale was established, the company strengthened its presence in Ireland when Cork was selected as the location

for its new global services operation, and the Global Business Solutions (GBS) Centre began operations in Little Island in April 2011. From its beginnings as a financial services centre, Lilly Cork GBS now works across many areas of the enterprise, including Global HR and Clinical Trials, and provides support to patients and healthcare professionals globally. Irish PharmaChem – Summer 2021

Lilly unites caring with discovery to create medicines that make life better for people around the world For over 145 years Lilly has been committed to bringing life-changing medicines to those who need them, advancing the understanding and management of disease and supporting communities where we live and work. In 2021 as we celebrate the 40th anniversary of our site, we couldn’t be more proud of the talented Lilly team in Kinsale, who make medicines for people who rely on them to make life better every day. We value integrity, excellence and respect for people. Eli Lilly Kinsale Limited Dunderrow, Kinsale, Co. Cork.

www.lilly.ie

Eli Lilly

Lilly’s Kinsale under construction in 1980 and as it looks today, March 2021.

Today, Lilly’s activities in Cork are a significant part of the company’s global operations and there is a combined employee and contractor workforce of over 2,500 people between the sites in Kinsale and Little Island.

A strategically important site Over the last 40 years, Lilly Kinsale has grown to become a strategically important site for Lilly. Todd Winge was delighted to have the opportunity to relocate from Indianapolis in June 2019 to take up the position of Vice President and General Manager at Lilly Kinsale. “The campus in Kinsale is one of the most exciting places to work at Lilly right now,” Winge explains. “Over US$1.5 billion has been invested in Kinsale over the last decade and it is a truly unique site in the biopharma world.

42 40

Our most recent biotech expansion is just starting up, we’ve never been busier on the chemical synthesis side of the business and we are also building a high-tech new synthetic peptide manufacturing facility that we plan to bring online in the next 18 months.”

Working together through the pandemic Winge has been impressed by the passion Kinsale employees have for their work, which has never been more evident than over the last 15 months. “Keeping employees safe is always our top priority,” he insists. “We’ve had employees coming to site every day throughout the pandemic to make and test medicines for patients, and they were supported by a team of dedicated colleagues working remotely from their homes. Everyone was united in their

determination to ensure continued supply of Lilly medicines to the people who rely on them every day.” Lilly also has a significant focus on diversity and inclusion, as well as sustainability, and recently published new global environmental, social and governance goals. The Cork sites are very active in these programmes, with Kinsale planning to power up a new solar farm later in 2021 to provide additional sustainable electricity capacity to the site. The Lilly teams in Kinsale and the Cork GBS are keen to build on their success, with plans for growth and expansion in both locations, as they continue to play a key role in delivering a robust pipeline of potential new medicines for the company, which makes the future look very bright for Lilly’s Irish operations in the years ahead. Irish PharmaChem – Summer 2021

Our family just got bigger….. SK pharmteco provides a range of services to our customers throughout the clinical development pathway to commercial success, focusing on every step along the way but never forgetting the end goal. We offer a partnership rather than a supplier relationship... we are committed to work with you and stand over your product as if it were our own! SK pharmteco is the single customer-facing team supporting SK biotek, AMPAC Fine Chemicals, AMPAC Analytical and the newest member of our family,Yposkesi. In addition to a proven track record as a leading provider of small molecule API products and services, we now compliment this through added capability in the adeno-associated viruses (AAV) and lentiviral vector development and production sector. With world-class state-of-the-art facilities and technology, we now have 6 API cGMP small molecule manufacturing and development sites, across 3 continents, with ~1000 m³ of capacity and a dedicated Analytical Services Facilities addressing small molecule compounds, large molecules and drug products. In addition, we now can provide ~5,000 m³ of biologics development and manufacturing capacity, across 4 independent manufacturing suites, for bulk drug substance and two Fill and Finish suites. We look forward to working with you.

USA | Ireland | France | Korea www.skpharmteco.com skpharmteco@sk.com

Volume m3

132.840 litres

BioPharmaChem Skillnet

Using technology to deliver on training Susan Costello, Network Manager, BioPharmaChem Skillnet, reports on some of the BPC Skillnet’s successes in furthering the skills set within the Irish pharma and biopharma sector, including the recent development of groundbreaking bioprocess operations training using Virtual Reality.

BioPharmaChem Skillnet was established in 2006 with the aim of fostering a climate of wholecompany development in the provision of industry specific technical training and non-technical training within the pharmaceutical, biopharma, chemical, and medical device sectors. The Skillnet is a national Government-funded network that supports the growth and development of global and indigenous organisations across Ireland. Promoted by BioPharmaChem Ireland and co-funded through Skillnet Ireland and member companies, the BPC Skillnet, through continuous interaction across the sector, has developed into a network with unique capabilities to support learning and development activities for organisations. The pharma sector has transformed itself numerous times over the past 50 years and has in the process enhanced the skills of the workforce. From its early focus on chemical Active Pharmaceutical Ingredient (API) manufacturing and filling operations, Irish facilities now include biopharmaceutical manufacturing, filling and finishing operations, global business services, clinical trial management, contract manufacturing and supply chain management. These changes require new skills at an increasing scale.

professionals to work with the network and its members to source, develop and deliver learning solutions of the highest standard to meet the business needs. The network has a range of training programmes aimed at new entrants, as well as those requiring reskilling and upskilling as the sector evolves, and introduces new manufacturing technologies such as digital technologies and compliancerelated training. Unfortunately, this sector is not exempt from site reductions and closures and there have been a number of announcements to this effect over the last few years. When these situations arise, the BPC Skillnet works in collaboration with these companies and the wider industry to identify, source and deliver relevant programmes

to aid in the upskilling of the workforce ahead of redundancies, enhancing the employees existing skills base with the aim of increasing their employment opportunities. Networking (even in a virtual world) is another key area of focus for the BPC Skillnet and we are delighted to be able to both sponsor industry learning events and organise seminars on relevant ‘hot topics’, providing the sector with a space to knowledge share and benchmark amongst their peers.

Network steering committee The network steering committee, which consists of member companies, plays a significant role in identifying and articulating the learning needs

Driving initiatives to enhance skills potential The BPC Skillnet is proud to be at the forefront of these changes and works with industry to develop solutions and drive initiatives to further enhance the skills potential within the sector. Over the years, the network has developed strong partnerships with academia and L&D

Virtual Reality allows participants in the bioprocess operations training to immersive themselves

in a purpose-built virtual environment in which they can interact and perform actions.

Irish PharmaChem – Summer 2021

49.20

40 litres

49.200 litres

101.680 litres

BioPharmaChem Skillnet of the sector and the challenges they are facing. The network has been active in taking the lead in sharing and promoting new technologies in learning and is currently working on adaptive learning, whereby course content is developed and structured in such a way as to allow the participant to demonstrate their understanding of the content, allowing them to bypass content that they already know, thus saving time and creating a more productive interaction for the participant.

Bioprocess operations training using Virtual Reality In the past year, the BPC Skillnet has worked with bioprocess member companies to identify a need for aseptic training of process technicians. Training on bioprocess operations can be challenging due to the controls relating to the cleanroom environment. This restricts the number of personnel allowed in rooms and the operations themselves may not run often enough to allow novices to develop the operating skills within a suitable timeframe. Using the Future Skills Programme funding received from Skillnet Ireland, the network, working with industry, successfully partnered with an expert vendor to scope and develop a training programme for bioprocess technicians using Virtual Reality technology. Virtual Reality allows participants to immersive themselves in a purpose-built virtual environment in which they can interact and perform actions. The aseptic technique programme is a highly interactive programme utilising 21st century immersive technology. The programme is delivered using Virtual Reality headsets, allowing the novice to be immersed in a virtual cleanroom in which they have to perform a number of tasks. The programme consists of three modules: The first, Basics of Microbiology reinforces the core knowledge of microbiology using 3D imagery of common contaminants. The second, Sources of Contamination and Contamination Prevention, reinforces key knowledge of contamination. This module also demonstrates the correct pace of leg and arm movement in cleanroom environments. The third module consists of a Q&A room in which the participant checks their understanding of the key knowledge included in the programme.

The BPC Skillnet aims to be at the forefront of learning technologies that enable member companies to upskill and reskill efficiently and effectively, maximising the capabilities of their workforces. As new technologies such as Advanced Therapeutics and Cell and Gene Therapy evolve, the BPC Skillnet will work with the sector to develop and deliver programmes that will enable the workforce to adapt to these new and innovative technologies. For further information please contact Susan Costello, Network Manager at susan.costello@bpcskillnet.ie or 087 2876731. www.bpcskillnet.ie.

The BPC Skillnet has worked with bioprocess member companies to identify a need for aseptic training of process technicians.

The practical activities include the interactive cleanroom tasks of:

• • •

Gowning sequence, in which participants follow the correct sequence of gowning, hand washing and sanitising; Cleanroom issue identification, whereby the participant will identify a number of problems within the virtual cleanroom; Glove inspection and sanitising, where the participant dons and inspects gloves before performing a virtual task of opening a settleplate and take finger dabs and moving vials within an isolator.

Irish PharmaChem – Summer 2021

Waste Management

Indaver introduce revolutionary track & trace system Indaver is the perfect partner in safe, innovative and sustainable waste management. State-of-the-art traceability via Indaver’s new tracking system helps deliver the most efficient and effective service.

Indaver’s new track & trace software system offers state-of-the-art traceability for both hazardous and non-hazardous waste.

Smart & efficient tracking of your waste

Indaver use a thermal process to separate the precious metals from solvents and collect them in the residue, ensuring a constant and sustainable supply of precious metals.

In partnership with an Irish pharmaceutical customer, Indaver reintroduced track & trace software, IndaScan 2.0. The purpose of the tracking system is to ensure traceability and to optimise the performance of both hazardous and nonhazardous waste flows. The waste is assigned a unique data carrier, a QR code. The QR code records the necessary compliance data required to safely collect, package, store, transport and treat the waste throughout its entire lifecycle. An insightful, auditable solution, the system guarantees full traceability from customer creation to final safe treatment. IndaScan data reports can provide valuable insights for customers. The data recorded at the initial point of generation is vital to understand how waste types and volumes relate to Indaver’s customer products and manufacturing practices; visibility in this regard provides impetus to drive sustainable waste reductions. The IndaScan data contributes many other benefits, including storage area inventory management, waste activity levels and visibility throughout the lifecycle. IndaScan takes care of every traceable step in the waste management chain, while you observe with track & trace.

Waste Properties Passport for hazardous bulk liquids As a waste producer, you are responsible for your waste at all times. To guarantee the safest treatment of your waste streams, the quality of

information on that waste is crucial. As your waste partner, it is vital for Indaver to be able to guarantee the safe handling and treatment of your waste, whether that is done on Indaver’s own sites or those of their subcontractors. Therefore, Indaver introduced the Waste Properties Passport (WPP) for new hazardous bulk liquid waste streams provided for thermal treatment. This WPP will be automatically generated from Indaver’s systems, based on the available information on sample analyses, (M)SDS sheets and knowledge exchanges and needs to be approved. This way, the accuracy of the information is guaranteed and any unnecessary risks further on in the treatment process avoided.

Carbon management awareness campaigns Smart waste management can help you in further reducing your CO2 impact. Opting for safe and sustainable transport and waste processing solutions is important to minimise environmental impact. Through its material recycling facilities

and installations with the highest energy recovery performance, Indaver realises the best available techniques. Providing insight in the recovery rates based on its data management systems creates awareness, not only at management level but especially with the workforce who are responsible for the waste segregation at the source. The results of such efforts were made visible through different awareness campaigns.

Precious metal recovery from industrial waste Precious metals like palladium and platinum are rare and valuable. They are used as industrial catalysts in pharmaceutical processes but are lost in the liquid waste. Recovering these metals is ecologically and economically beneficial. Indaver manages this with Inda-MP (Indaver Metal Processing) for several Irish customers. At Indaver’s site in Antwerp, a thermal process separates the precious metals from solvents and collects them in the residue. This way, their pharmaceutical customers have a constant and sustainable supply of precious metals and as a result, they are less dependent on raw materials from outside Europe. Irish PharmaChem – Summer 2021

Your partner in sustainable management of chemical & sensitive waste

On-site manpower

Innovative web portal with reporting

Knowledge & expertise

Integrated total solution in line with your budget and process

Safe ADR transport

Best-in-Class treatment technology

Repackaging, storage & transfer

Material & energy recycling

info@indaver.ie Tel. +353 1 6972900

The circular economy. Together we make it happen. www.indaver.ie

adv A4_IERL_20191212.indd 1

12/12/19 14:49

Process Data

A smarter approach to processing with Bonner These days, everything is getting smarter. The data we generate every day can now be harnessed to help us live and work in better, more productive ways. This smart technology has entered all aspects of our lives, and the processing industry is no different. However, in Ireland, many factories are still relying on outdated equipment and processes that do not produce usable data; or, if they do, it is often unreliable. Moving to a modern system that collects process data, analyses it and presents it back in an actionable format can save a business considerable time and money. Process information can be transformed into an asset through data acquisition and control applications, allowing factories to streamline production and identify any non-performing processes. This improves a plant’s Overall

Bonner helps customers to unlock the value within their process data. Equipment Effectiveness (OEE) by increasing the efficiency of the equipment or area.

Getting more from your data Bonner specialises in the delivery of bespoke, plant-wide systems that help customers get more out of their data in the most effective way. Whether tackling Energy Monitoring, Condition Monitoring, Predictive Maintenance

or Remote Asset Monitoring, the team designs solutions that best meet the needs of each individual plant. And, as the systems can be integrated with new or legacy equipment, Bonner can create a solution to work for any process, traditional or cutting-edge. Bonner helps customers to unlock the value within their process data, enabling them to make smarter decisions for their business.

bonner.ie

We can add the Smart to your factory to help make decisions in real time based on reliable and available data. Factory automation systems including Process Data Acquisition, Condition Monitoring and Energy Monitoring can improve your factory’s OEE by making data intelligence and predictive maintenance part of your process. Produce more efficiently with Bonner.

STANDARDS YOU CAN TRUST

48 48

IrishPharmaChem PharmaChem– –Summer Summer2021 2021 Irish

Stability Studies Stability storage is a key process in bringing a pharmaceutical product to the market. Fundamentally, the objective of stability storage trials is to determine and substantiate the shelf life of the product and packaging, and to verify that the APIs (active pharmaceutical ingredients) do not deteriorate over time, given those environmental conditions.

Why outsource A growing number of pharmaceutical companies are choosing to outsource their stability storage trials, rather than undertaking them in-house, for a variety of reasons. CAPEX vs. OPEX By its very nature, stability storage equipment (including cabinets, reach-in rooms or walk-in rooms) can be a sizeable investment, not only in the units themselves, but in all the other associated costs, such as monitoring systems, annual service and validation plans. Stability equipment can be large and so laboratory refurbishment / new build / extensions are sometimes required, so this can all factor into the decision of whether to outsource stability storage trials, which can be more financially beneficial. More and more companies are choosing to outsource storage and pay a monthly storage fee, and ‘pay for what you use’ so to speak. Depending on the internal systems within the company finance teams, it can often be easier and quicker to raise OPEX rather than CAPEX, which can all cause delays of setting products down on store and getting product to market. Physical Space Stability storage equipment can be sizeable, especially allowing for large walk-in rooms and their associated chillers. Many companies do not have the physical space to accommodate such equipment without the requirement for laboratory refurbishments / extensions, so choose to outsource their stability trials. On-going management Stability equipment must be managed and maintained to safeguard against equipment failure and therefore the associated headaches and documentation which can occur should a piece of equipment go out of specification. The Laboratory / Stability Manager will usually be responsible for organising annual service and validation activities, ensuring daily, weekly, and monthly checks and procedures are undertaken, data monitoring is backed up and working correctly, ensuring stock inventory is up to date, co-ordinating stability set downs and pulls for analytical and microbiology testing and perhaps being called out at one o’clock in the morning when things have gone wrong! By outsourcing stability studies to a trusted partner, all off those headaches, worries and hassles are taken away. Irish PharmaChem – Summer 2021

Outsourcing stability studies: choosing the right partner A growing number of pharmaceutical companies are choosing to outsource their stability storage trials, rather than undertaking them in-house, according to Source BioScience.

Stability Studies Focus on core activities More and more companies choose to outsource non-core business activities. This allows the company to concentrate on revenue generating activities such as Research and Development and contract manufacturing. Speed When speed is of the essence; when things ‘just happen’ and product needs to be placed on store, it can be a lot a quicker to simply send out samples to an established storage partner.

What to look for in an outsourcing partner Once a company has decided that they want to find an outsourcing stability storage partner, although this is not an exhaustive list, they should consider the following points: Quality systems / accreditations Quality is at the heart of the pharmaceutical world and this is reflected in all activities of drug development, manufacture, storage, and testing. An outsourcing partner should demonstrate that they have the appropriate QMS (Quality Management System) in place, to manage documentation, CAPA’s, deviations, nonconformances and to track relevant Standard Operating Procedures. This should be evidenced and shown at a formal audit at the provider’s site, where they can demonstrate how they operate a stability storage facility. They should be asked what quality standards they work to, such as ISO 9001: 2015 and whether they adhere and operate to cGMP. Data logging monitoring facilities Having data to support stability storage is a key necessity in bringing product to market. An outsourcing partner must be asked what monitoring systems it has in place? Whether those systems are 21-part CFR part 11 compliant? How is data kept and stored? How is that data backed up?

to demonstrate a suitable LIMS (Laboratory Information Management System) which can fully track storage samples from receipt of product, to return. The software needs to be fit for purpose and be able to detail such as: are the rooms validated? Can the outsourcing partner demonstrate how the equipment is validated and show you this? On-call duty engineers What provisions does the storage provider have in place should the equipment fail / go out of specification, out of hours? Does the provider have staff on call to respond to such occurrences from a technical point of view but also from a stability GMP point of view? Critical / spare parts As an extension from the point above, does the storage provider keep spare parts on site, so any equipment failures can be easily rectified to reduce out of specification times and occurrences? Back-up generator Does the service provider have a back-up power supply in case of mains failure? What would happen if a freak accident occurred and the site lost its power? How would the equipment be maintained? This is a consideration for the equipment and the monitoring system. Controlled access & CCTV How does the service provider ensure that only authorised personnel have access to the stability suite or the rooms themselves? How is this safeguarded? What security measures are in place? LIMS system A storage outsourcing partner should be able

• Product • Conditions • Quantities • Duration • Return dates • Other relevant study information

Staffing and training Questions should be asked of the outsourcing partner as to how staff training is undertaken, reviewed, and monitored, to ensure that all SOP’s (Standard Operating Procedures) are being followed. Proven track record A company’s trading history can give a great deal of confidence to a company if they are looking to secure an outsourcing partner. Can the accounts be checked to see if they are of good standing? Can the outsourcing partner provide clients who would recommend them? Have they a credible name in the market? What is their reputation like? Although the above points are not an exhaustive list, they are very worthwhile factors to explore when considering who you would like your outsourcing partner to be. For more information on Outsourced Stability Storage, contact the team on +353 (0) 51 338435 or email stability.experts@sourcebioscience.com.

Equipment management & maintenance Another determining factor which is paramount when choosing an outsourcing partner is considering their infrastructure. As a company, you need to have complete trust and confidence in your outsourcing partner and that they have the necessary structures in place.

Having trust in your partner Such considerations should include: Service and validation Does the provider have well maintained, serviced, and validated equipment? Is this documented? How often are they serviced? How is the equipment log kept up to date? How

More and more companies choose to outsource non-core business activities. This allows the company to concentrate on revenue generating activities such as Research and Development and contract manufacturing.

Irish PharmaChem – Summer 2021

Chemical Sourcing

Building resilience into your supply chain Paul Power, Strategic Sourcing & Supply Chain Executive, NCC, advises on how a new approach can ensure your supply chain is more adaptable, flexible and durable. Most people reading this will be aware of the enormous challenges that 2020 brought in relation to supply chain logistics. Unfortunately, these challenges have continued into 2021. It has become more apparent as the world slowly goes back to normal that many businesses in the supply chain need to be future-proofed by becoming not only more durable but also more adaptable and flexible.

Fully integrated supply chain Here at NCC, we have evolved from a chemical manufacturers’ representative to a customer focused chemical sourcing expert and a fully integrated supply chain partner for our clients’ raw material needs. In real terms, this means more than delivering the right product at the right time. It is about understanding our customers’ goals and having the agility to deliver the right product at any time. We achieve this by analysing the vulnerabilities of specific supply chains and working towards solutions that ensure a reduced impact to production when something inevitably does go wrong. It’s about moving from the risks of “just in time” to the assurance of “just in case”.

Identifying vulnerabilities and prepare for disruption An in-depth vulnerability analysis should be the first action in building a supply chain

An example of this would be approving two suppliers of the same component/raw material. It could come to light that both suppliers are sourcing from the same manufacturer or using identical manufacturing processes, which are vulnerable to the same market challenges, meaning that in the case of disruption, both suppliers would be unable to provide the required product.

reduce the risk of the lower value raw materials that are essential to your operations. This is often because a key stakeholder in the supply chain, for example a manufacturer, does not view your requirement as integral to their sales plan. In addition, they also may not regard your company as being a key client. As your supply chain partner, we can consolidate your requirements with other customers for the same material, as well as leveraging our own relationships with key manufacturers, thus ensuring that the same priority is provided across the board.

Managed additional stock

Failure to plan…

With products that are deemed high risk in your vulnerability analysis, it is recommended that managed extra stock is stored. Though it does tie up finance and there is the risk of obsolescence, the costs pale when compared with the expense associated with production downtime. If additional stock is managed correctly and efficiently, with planned rotation, then there is little risk of significant obsolescence.

Leveraging the position of your low value, production-critical raw materials

No one could have foreseen the combination of supply chain challenges that we are presently experiencing. However, that said, we believe that it is now time to take a different approach, with low-risk materials utilising more lean inventories and just-intime approaches, whilst medium to high-risk materials are improving resilience by having secondary sources and additional managed stock. Taking this perspective should reduce the risk and most importantly, the associated costs.

A common mistake is focusing on high volume materials and mitigating any risks associated with them but being unable to effectively

To learn more about how NCC can build resilience into your supply chain call (01) 6131400, or email hello@ncc.ie.

resilience plan, and it must include more than just first or second tier suppliers. It should encompass how the suppliers within these tiers interact with each other, to help expose any significant hidden risk.

Irish PharmaChem – Summer 2021

Pharmaceutical Ingredients

Advancing solutions for changing demands James Peterson, Vice President of Pharmaceutical Ingredients for Univar Solutions, explains why the company has the technical support, ingredient guidance and is a dependable partner to support its partners in addressing the opportunities ahead. The pharmaceutical ingredients industry has come under the microscope in recent months due to the global Covid-19 pandemic. However, even before Covid-19 and the increased demand for pharmaceutical, health and wellness solutions, Univar Solutions took an agile, dedicated team approach to serve the pharmaceutical ingredients market. This approach allows the company to effectively and efficiently react to global industry and economic changes, responding to industry trends and customer demands. Univar Solutions has a dedicated team of pharmaceutical ingredients experts in all major geographic regions, backed by a premier portfolio of ingredients from global suppliers and a network of state-of-the-art Solutions Centres. As the Global Vice President of Pharmaceutical Ingredients for Univar Solutions, James Peterson leads the team responsible for meeting the needs of customers and suppliers, advancing innovation and growth while preserving the organisation’s focus on safety and reliable customer service. With more than 30 years of experience in the regulated chemical industries, he lends strategic insight to customers and suppliers who need support for their pharmaceutical, ophthalmic, nutraceutical, biopharma, animal health and medical device applications. What is Univar Solutions’ approach to meeting the needs of the pharmaceutical ingredients market globally? “First, we recognise that we can create

greater value through specialisation. So, our businesses are organised around major global industrial and consumer industries, such as pharmaceutical ingredients, beauty and personal care, homecare and industrial cleaning and many more. “Our goal remains to safely and reliably deliver ingredients our customers need to innovate and grow. We take a unique approach to the market to deliver on this goal, combining our dedicated resources and unmatched distribution footprint with our renowned supplier base and deep supply chain expertise. “Our global Pharmaceutical Ingredients organisation comprises a devoted team of experienced pharmaceutical account managers, sales professionals, regulatory and technical experts with a global and regional focus, insight and service. In this way, we create value by delivering global expertise locally for customers and suppliers, enabling us to build closer, more productive relationships and provide a greater depth of focus.” How has the changing business landscape impacted the market? “In today’s environment, pharmaceutical manufacturers require an agile and responsive partner who can be there when the unexpected occurs. With a worldwide pandemic, global supply shortages and natural disasters, it’s more important than ever to partner with suppliers that can navigate

the intricacies and complications of a global supply chain and serve as a contingent partner when a crisis happens. Fortunately, we have some of the longest-standing relationships with the world’s leading producers, a global logistical footprint and an operations team vital to maintaining security of supply. We are committed to delivering solutions to help our customers and suppliers provide the products that help society thrive. But when unforeseen events force us to pivot and adapt to changing conditions in realtime, our focus is on greater assurance that the global network of distribution logistics you rely on is working relentlessly to meet your needs.” What will be vital to the pharmaceutical ingredients industry in the near future? “Pharmaceutical manufacturers are seeing shifts in demand based on changes in medicinal therapies. From patent cliffs enforcing moves toward generic drugs to an increased focus on biopharma and growing interest in nutraceutical alternatives, pharmaceutical manufacturers require technical support, ingredient guidance and a dependable partner to support them in addressing these opportunities. “I’m confident we have the foundational knowledge and team of experts to support our customers every step along the development and production stages as they innovate and grow in these areas.” Irish PharmaChem – Summer 2021

Ireland’s leading source of high-quality pharmaceutical ingredients Our team is here to help. With Univar Solutions, you have an ally equipped with a premier product portfolio, technical capabilities and specialized market expertise to help your business innovate and grow. As the partner of choice for many of the world’s leading pharmaceutical ingredient manufacturers, we can provide the support and solutions you’re looking for. From APIs, excipients and process chemicals to solvents and intermediates, our dedicated pharmaceutical ingredients team brings together technical and regulatory support and industry-leading sourcing options from around the world to help give you a competitive advantage. To discuss your specific needs, please contact us at +353 1 4019800 or Irelandsalesoffice@univarsolutions.com

Cleaning Services

Clean Habit have on call fully trained and designated operatives to provide emergency, on call services, at short notice, 24/7, to ensure their clients’ needs are met at all times.

A clean sweep Clean Habit have almost 40 years’ experience as professional contract cleaners for the commercial, industrial and pharmaceutical industry, with extensive cleanroom experience. Having identified a considerable demand for expert, dedicated cleaning services in Ireland, Amanda Tubridy founded Clean Habit in 1983. Securing the Guinness Peat Aviation cleaning contract in 1989 was a significant landmark for the business, along with the award of a contract with Vistakon Limerick shortly afterwards, marking the start of Clean Habit’s impressive track record as a commercial, pharmaceutical, industrial and office cleaning company. 38 years later, Clean Habit continue to provide cleaner, healthier environments for their extensive client list under the ownership and management of Amanda Tubridy. The mission of Clean Habit is to provide professional, customised contract cleaning services of the highest standard. “We are committed to delivering quality, expert and safe cleaning services with a personal touch,” Amanda explains.

Cleanrooms and contamination control Clean Habit have a proven track record, as well as a vast amount of experience and knowledge working with Cleanrooms and Contamination Control. “We are fully ISO9001:2015 and ISO14001:2015 certified and all of our employees are trained in the correct cleanroom

cleaning procedures and maintenance protocols to ensure the highest industry standards are exceeded,” notes Amanda. “All of our cleaning operatives are fully trained in line with each of our clients’ GMP and other specific requirements. We consult and work in partnership with all of our clients to achieve the standards required for FDA and HPRA Audits.” Clean Habit have on call fully trained and designated operatives to provide emergency, on call services, at short notice, 24/7, to ensure their clients’ needs are met at all times. They provide cleanroom cleaning services not only to their current clients in the pharma sector but also as once-off cleans. The Clean Habit culture encourages continuous improvement through innovation, participation and communication. “Always future-focused, the expansion of our Cleanroom Environment services is one of our main priorities,” Amanda stresses. Over almost four decades, Clean Habit have earned an infallible reputation as dependable and innovative contract cleaners in Ireland.

“Providing flexible, quality cleaning services that offer excellent value for money, we pride ourselves on our exemplary customer service,” Amanda says. “The cleaning world knows no bounds, and neither do we! With contract cleaners available in Limerick, Clare, Cork and Galway, wherever you are, our expert team are on-hand to provide an outstanding and timely cleaning service.” Clean Habit’s reliability is reassuringly built around your business services, Amanda notes, delivering superior quality cleaning with superbly competitive value: “Our versatile range of services, qualifications, and our dedication to standards maintenance make us the ideal partner for your business or office.” For more information, visit their website, cleanhabit.com, where you will find a comprehensive guide to their services and their commitment to quality. You can also read some of the testimonials from many of Clean Habit’s satisfied clients. If you’d like to arrange a consultation, please contact Clean Habit for more information about how they can help you.

Contact details: Clean Habit, E2 Smithstown Industrial Estate, Shannon, Co. Clare. Tel: 061 361461. Email: info@cleanhabit.com. Web: www.cleanhabit.com. Irish PharmaChem – Summer 2021

Serving Business and Industry for over 30 years

An Irish owned company providing specialised cleaning services for Businesses and industries for over 30 years. Specialising in Pharmaceutical, Cleanroom, Logistics, and Financial sectors. Clean Habit have played a big part in the success for BSI Audits, Corporate and FDA Audits.

E2 Smithstown Ind Est, Shannon, Co. Clare. 061-361461 info@cleanhabit.com

We ca s

SPECIALIST REFRIGERATION ENGINEER We can provide th We can p solution to su We can p solu solu Utilising the most energy

Utilising assisting legislativ complete Insulatio clients.    With a va the Phar choice fo maintain equipme cabinets

assisting our clients to be Utilising the m legislative and environm Utilising the  assisting our  complete solution of Mec SPECIALIST REFRIGERATION ENGINEERING  legislative an SPECIALIST REFRIGERATION ENGINEERING  assisting our Insulation and a wealth o complete solu clients.  SPECIALIST REFRIGERATION ENGINEERING  legislative an Insulation an   clients.  complete sol With a vast knowledge of   the Pharmaceutical secto With a vast kn Insulation an Utilising the most energy choice for our large clien the Pharmace maintaining, and replacin clients.  choice for our efficient technologies and equipment  from large ca maintaining,    assisting our clients to be fully cabinets and temperatur equipment  fr   With a vast k cabinets and  compliant with the current     PRODUCTS & SERVICES  the Pharmac legislative and environmental   • Site survey & system  recommendation   choice for ou guidelines. We provide a • Supply, installation & commissioning  complete solution of Mechanical • Project management  maintaining, • Energy Saving Packages  equipment  f Equipment, Fire Rated Insulation • Monitoring Systems  and a wealth of application knowledge to ourPRODUCTS & SERVICES  clients. • Plant service and maintenance  cabinets and PRODUCTS & SERVICES  • Site survey & system  recommendation     Cross Technical Solu • Site survey & system  recommendation   Unit 26, Cookstown Industr PRODUCTS & SERVICES  • Supply, installation & commissioning  Cross T • Supply, installation & commissioning  With a vast knowledge of the refrigeration industry and the   Cookstown, Tallaght,  • Site survey & system  recommendation   Unit 26, Cook • Project management  Co. Dublin • Project management  • we Supply, installation & commissioning  Cooksto • Energy Saving Packages  Pharmaceutical sector in particular, are the first choice for Tel (+353) 01  • Energy Saving Packages  • Project management  • Monitoring Systems  Fax (+353) 01 our large client base when• itMonitoring Systems  comes• to servicing, maintaining, Energy Saving Packages  • Plant service and maintenance  sales@crosstechnicalso • Plant service and maintenance  • equipment Monitoring Systems  and replacing all types refrigeration from large www.crosstechnicalso sales@cro • Plant service and maintenance

SPECIALIST REFRIGERATION ENGINEERING  SPECIALIST REFRIGERATION ENGINEERING

capacity chillers to medical storage cabinets and temperature control systems. Cross Technical Solutions Ltd. PRODUCTS & SERVICES  9/10 Broomhill Road, PRODUCTS & SERVICES  Tallaght, 24 • Dublin Site survey & system  recommendation   Co.•Dublin - Ireland • Site survey & system  recommendation   Supply, installation & commissioning  Tel •(+353) 01 405 6777 • Supply, installation & commissioning  Project management  Fax (+353) 01 4136932 • Energy Saving Packages  • Project management  jmcgrath@crosstechnicalsolutions.ie • Monitoring Systems  • Energy Saving Packages  www.crosstechnicalsolutions.ie • Plant service and maintenance

• Monitoring Systems  • Plant service and maintenance

Suppliers of a wide range of raw materials/blending services to the pharmaceutical, biopharma and medical device industries

Carbon Group, Ringaskiddy, Co. Cork, Ireland, P43 R772 T: +353 21 4378 988 Contact: Carol Deegan T: +353 86 261 2485 E: carol.deegan@carbon.ie

www.cro

Cross T Unit 26, Cook Cr Cooksto Unit 26,

sales@cro www.cro

sales ww

Public Policy

IPHA calls for official policy on CGTs The ‘Pathfinder Study on the Adoption of Cell and Gene Therapies in Ireland’, carried out by PwC on behalf of the Irish Pharmaceutical Healthcare Association, has called for a new policy on the adoption of Cell and Gene Therapies by Ireland’s health services, given the potential new developments bring to patient care. THE Irish Pharmaceutical Healthcare Association has called for a policy on the adoption of Cell and Gene Therapies (CGTs) by the health services as a new study shows the breakthrough treatments have the potential to tackle unmet medical needs. The Irish Pharmaceutical Healthcare Association recently published its ‘Pathfinder Study on the Adoption of Cell and Gene Therapies in Ireland’ which was carried out by the global professional services firm, PwC. The study was supported by Pfizer, Janssen, Novartis, Gilead, Bayer, Takeda and Astellas. It urges a cross-stakeholder approach to realising the clinical potential of CGTs, bringing together government, industry, clinical and patient leaders to create a policy on adoption. Such a policy would emerge from a Paper, led by the Department of Health. The industry is keen to engage in structured cross-stakeholder dialogue on a pathway for the urgent adoption of Cell and Gene Therapies by the health services. Oliver O’Connor, Chief Executive of IPHA, said the study was aimed at moving Ireland closer to having a policy on the adoption of CGTs by the health services. “That will take dialogue and careful planning – but, on the basis of clinical evidence so far, it is the right thing to do for better patient care, aligned with the goals of Sláintecare,” he said. “We must be open to adopting new innovations affordably Irish PharmaChem – Summer 2021

We need to explore how we can deliver both clinical benefit and value for money from CGT adoption.”

Key recommendations

Oliver O’Connor, Chief Executive of IPHA. and at pace in our health services.” O’Connor described the PwC stude as “an industry contribution to an urgent public policy need”. “We were keen to gather experts’ perspectives, including from doctors, patients and our own industry,” he continued. “We hope the study can prompt structured dialogue in the form of a cross-stakeholder forum, led by the Department of Health, which would ultimately yield a national policy on the adoption of CGTs in Ireland. This is important for patients and for their clinicians. It recognises, too, that current reimbursement models will not work for CGTs.

Across the world, Cell and Gene Therapies are either in use or in research for the treatment of a range of disease areas, including cancer, blood disorders, ophthalmology, neurology, and musculoskeletal, metabolic and endocrinological conditions. In the US, the medicines regulator, the Food and Drug Administration, says it expects to approve between 10 and 20 new Cell and Gene Therapies between now and 2025. Europe’s medicines regulator, the European Medicines Agency, has approved Cell and Gene Therapies for diseases affecting the eyes, for gastroenterology, for spinal muscular atrophy, for metachromatic leukodystrophy and for cancer. PwC examined globally available efficacy data on CGTs and interviewed a range of stakeholders in Ireland, including patient, clinical and industry leaders, in compiling the study. It makes several recommendations that would help patients to access the potentially life-changing therapies, including the development of novel payment models. The key recommendations are: The development of a CGT adoption policy, guided by a structured dialogue led by the

•

Public Policy

• •

•

Department of Health, which draws together proposals for tackling the related strands of assessment, access and reimbursement; The introduction of novel reimbursement models for CGTs that ensure broad access and value for money for patients; Improving the information infrastructure and implementing new policy initiatives to enable real-world evidence collection for key disease areas likely to benefit from CGTs in the short term and the start of planning for a broader rollout of CGTs in other areas in the medium term; Continuing to invest in facilities and staff to ensure a smooth national rollout of CGTs, exploring the creation of centres of excellence at certain hospital sites and allied investment in training and engagement for clinicians and patients.

Healthcare policy change PwC’s Shane Gannon, the report’s lead author, said he hoped it would lead to healthcare policy change in the near term. “The new therapies bring clear clinical benefits but they can be expensive,” said Dr Gannon. “How the health system pays for them, and how their value is measured in the community, are areas for further exploration. We hope this study can prompt a debate among all stakeholders for how Ireland can realise the potential of new therapeutic interventions in a way that makes

sense for the healthcare system. Ultimately, we will need a pathway everyone can support.” The study shows that CGTs have achieved ground-breaking results in several therapeutic areas, including in cancer, degenerative diseases (eye disease), neurological diseases (spinal muscular atrophy) and haemophilia. CAR-T, a form of cell therapy, is used to treat leukaemia, lymphoma and multiple myeloma. Two CAR-Ts for three indications in cancer are available to patients in more than 15 EU countries, but not in Ireland. Irish patients are travelling to the UK to receive CAR-T treatment on the Treatment Abroad Scheme, which covers treatments not available in Ireland or where there is delay in getting a treatment. In 2019, the scheme cost the State €54 million, according to the Health Service Executive. CGTs are usually one-time treatments that can add months, sometimes years, to a patient’s life, replacing a lifetime of treatment. The study argues that, although the upfront cost of CGTs is significant, they could reduce the direct and indirect costs of chronic treatment for certain illnesses, as well as improving patient outcomes. The study cites cancer, haemophilia and SMA Type 1 as diseases where CGTs could yield economic and clinical upsides.

The clinical potential of CGTs Professor David Keegan, a consultant at the Mater Misericordiae University Hospital Dublin, and a specialist in ophthalmology,

said Ireland should move with urgency in seizing the clinical potential of CGTs: “CGTs are revolutionising medicine. They often offer better treatment options for life-threatening illnesses. In some cases, they have the potential to cure diseases altogether. Gene therapy for ocular diseases is a significant area of research, especially since many rare, blinding retinal diseases do not have treatments now. We can work on the eye more easily because it is an enclosed organ with elements of immune privilege and several identified genetic mutations that could be targeted. The way forward is to have a policy on CGTs that makes it possible for doctors to prescribe approved CGTs for their patients locally.” Brian O’Mahony, Chief Executive of the Irish Haemophilia Society, said CGTs offer hope for patients with blood disorders. “Standard treatment since the 1970s has been intravenous infusions of the missing clotting factor. Now, science is offering potentially breakthrough treatments for haemophilia,” he said. “Last March, the first Irish person with haemophilia B was treated with gene therapy as part of a clinical trial. It was a landmark moment for the haemophilia community in Ireland. We are moving closer to making gene therapy a possible functional cure for haemophilia. This study is an important signpost on a journey towards the adoption of approved CGTs in the health services. The impact on patients’ lives could be transformational.”

Irish PharmaChem – Summer 2021

We understand how leading-edge products and process improvements are critical in your business.

INNOVATE + ACCELERATE

You are enabled to achieve a faster time to market, improve plant productivity and reduce risk.

Kaiser Raman Rxn2: Optical analysis of chemistry & composition • Inline measurement to enable QbD and PAT • Lab-to-cGMP scale up and scale out with Raman probes, including single-use bioprocessing • Realize 24/7 process control and automation • Maximize yields and boost product quality

Do you want to learn more? www.ie.endress.com/process-analytical-technology

Inventing for Life At MSD we have and always will be...Inventing for Life. These three powerful words reflect our commitment to inventing new medicines and vaccines that help save lives by preventing and fighting disease. MSD Ireland is one of the country’s leading healthcare companies, having first established here over 50 years ago. We currently employ approximately 2,700 employees across six sites in Ballydine, Co Tipperary, Brinny, Co Cork, Carlow, Dublin and Meath. We believe the most important thing we make is a difference - to patients, to our employees, to our communities and to the Irish healthcare landscape generally. We are proud that our Irish sites manufacture approximately half of MSD’s top twenty products, helping save and enhance lives in over sixty countries around the world. Visit msd-ireland.com to find out more about our work.