Personalised medicines involve an increased degree of complexity when it comes to manufacturing and supply in comparison to traditional pharmaceuticals. The Horizon 2020 Advisory Group defines personalised medicine as ‘a medical model using the characterisation of individuals’ phenotypes and genotypes (e.g. molecular profiling, medical imaging, lifestyle data) for tailoring the right therapeutic strategy for the right person at the right time, and/or to determine the predisposition to disease and/or to deliver timely and targeted prevention.’ Personalised medicine focuses on treating patients based on their individual clinical characteristics, the diversity and severity of symptoms, and genetic traits. Cell and gene therapies (CGTs) are an increasingly important segment of personalised treatments. CGTs are typically expensive treatments manufactured in low volume. Due to the time-sensitive nature and challenging temperature conditions associated with manufacturing, handling and treating patients with cell and gene therapies, this article outlines some considerations for the handling and supply of CGT products.
Consideration 1: Transportation
Many CGTs are transported and stored at ultra-low temperatures including cryogenic temperatures below -80 °C. Primary materials and therapies may be required to be shipped from the site of manufacturing to the clinical setting within 40 to 50 hours typically. Maintaining the integrity of cell and gene therapy products during shipping, as well as ensuring that they arrive on time and within the appropriate temperature constraints, is a major challenge. CGT companies should consider:
Has the optimal courier been selected who has experience with transporting high-value, temperature-sensitive cell and gene therapies?
Is the selected shipping system suitable and validated for transporting the materials?
Has a risk assessment been performed to mitigate any delays or incidents that may arise during transportation?
Is the necessary documentation available to successfully export and import the CGTs across territories?
What processes are in place at the receiving site to ensure the CGTs arrive undamaged, viable and fit for administration?
Issues experienced during transportation can be possibly devastating for patients and highly costly for clinical trial sponsors as CGTs can cost $200,000–2,000,000 per dose. A commercially viable supply chain is recommended to be in place at the start of clinical trials (even in Phase 1) as many of these therapies are given orphan (US) and prime (EU) status which could allow them to gain approval in a shortened timeframe should the clinical trials be successful.
Consideration 2: Sourcing of Materials
Materials and equipment used in the manufacturing and supply of cell and gene therapies may be more challenging to acquire in contrast to traditional pharmaceutical products. For example, high quality specialised reagents are critical to maintaining healthy cell cultures that perform optimally and consistently. In many cases, companies may only have single-source suppliers and this may increase the risk of supply chain disruption. With CGTs requiring specialised raw materials and unique manufacturing equipment, CGT companies commonly chose to outsource manufacturing to CDMOs with experience in small volume, high value manufacturing and the ability to manage specialised packaging and labelling.
CGT companies may take into consideration:
Has an inventory management system been developed to ensure there are optimal levels of materials available?
Are there alternative suppliers of materials and equipment that may be qualified as a back-up source?
Have your key suppliers been qualified for use and audited?
Have Critical Quality Attributes (CQA) and Critical Process Parameters(CPP) been defined and agreed with suppliers?
Has a Business Continuity Plan (BCP) been developed and implemented?
Selecting and qualifying the optimal vendors to support your clinical and commercial needs is a crucial activity. Identifying risks to the provision of materials and implementing mitigation strategies could prevent detrimental impacts to product supply and ultimately to patients. Furthermore, effective communication with suppliers to coordinate and schedule activities is essential to avoid disruption.
Consideration 3: End-to-end Visibility
End‑to‑end traceability from manufacturing to final delivery of CGTs to patient treatment centers is an important consideration for successfully providing personalising treatments. A CGT supply chain may involve many different entities including contract development and manufacturing organisations (CDMOs), thermal shipping system suppliers, diagnostic companies, specialised couriers and distributors. Ensuring there is alignment between all entities should be a key area reviewed during the pre-clinical and clinical development phases.
A Chain of Identity (COI) linked to the unique identifier should be generated at patient enrolment. This identifier should be visible and traceable throughout a patient’s personalised treatment. For example, as part of the COI, an autologous donor’s patient number should be associated with their unique donation number (e.g. Donor identification number/DIN) and the manufacturing batch number. Chain of custody (COC) refers to the ownership/stakeholder ‘in‑custody’ of the cells or drug product, at any stage of the value chain. COC typically incorporates numerous critical parameters to ensure high quality standards and integrity of the cells at every step. COI and COC are key components to ensure traceability over the course of the personalised treatment and to safeguard patient safety. This can present more challenges that the traditional biopharmaceutical product supply model as adequate infrastructure and systems must ensure the correct CGT is available in time for the scheduled administration at the correct treatment site for the correct patient. Autologous cell therapies, for instance, must have robust controls in place to ensure patients receive the CGT from their own donor cells and not another patient’s cells. Important areas to closely examine in relation to end-to-end visibility include:
Have the COI and COC requirements been reviewed and defined?
Is there full traceability from the start to the finish of the CGT product lifecycle?
If using a CDMO, how will manufacturing activities be monitored and how will key updates be provided?
What processes are in place to ensure the correct CGT reaches the correct patient?
Advanced technologies including software systems can support the coordination of last mile deliveries with treatment centers. As the CGT industry continues to grow rapidly, so too will the development of technologies to provide end-to-end traceability.
To learn more about HiTech Health CGT services – contact us.
Cell and Gene Therapy products and other Advanced Therapy Medicinal Products (ATMPs) have to comply with European Medicines Agency (EMA) legislation at different stages of the development process, including Good clinical practice (GCP), Good manufacturing practice (GMP) and Good Laboratory Practice (GLP) requirements. Potential new Cell and Gene Therapies or Advanced Therapy Medicinal Products firstly require laboratory tests and clinical trials to evaluate their benefits and side effects. Understanding the EU legal and regulatory framework, providing details of the benefits and risks of the products and obtaining approval from regulatory authorities for their use is therefore essential to providing the best possible treatments for end users. So this article will cover the basic EMA regulation of Cell and Gene Therapies (CGTs).
Research and development of Cell and Gene Therapies:
From 10th to 12th November, HiTech Health hosted ‘Cell and Gene at the Abbey’, a world-leading conference focusing on Production, Scale-up and Globalisation of cell and gene therapies. We would like to sincerely thank all the speakers, sponsors and attendees of this year’s conference and are already looking forward to hosting the event in 2022.
Over the course of 3 days at the beautiful setting of the Glenlo Abbey in Galway, there were amazing insights from global leaders in the cell and gene therapy space. Overcoming production and supply chain challenges was a key focus with speakers from around the world attending the event. The exciting list of speakers included Power List 2020 in Advanced Medicines featured experts Bruce Levine, Massimo Dominici and Qasim Rafiq who spoke about development and regulatory approvals, challenges in scaling up, supply chain and manufacturing and the opportunities to solve them. An update on the European regulatory environment for Advanced Medicines from Niamh Curran of the HPRA was of benefit to all.
Attendees were able to see first-hand some of the latest technologies in cell processing technologies from many of the event’s sponsors Cellexus, ChemoMetec, Miltenyi Biotec, Sexton Biotechnologies, Terumo, VivaBioCel, AccuScience and MeiraGTx. Cell and Gene therapies are at the forefront of regenerative medicine and HiTech Health are continuing to grow rapidly in this sector. Find out how we can support you on your development and commercialisation journey by contacting us today.
HiTech Health awarded with €7m government funding for ‘disruptive’ project
HiTech Health and our partners, Relevium Medical and Professor Garry Duffy’s Laboratory at NUI Galway are honoured to receive €7 million from the Disruptive Technologies Innovation Fund (DTIF), administered by Enterprise Ireland. This award will support the development of a novel treatment for Knee Osteoarthritis with the potential to regenerate the damaged knee joint whilst providing long-lasting pain relief.
Dr Brian Harrison, MD Hi-Tech Health, “We are excited to work with Relevium and Prof Garry Duffy’s team on the process development, scale up and GMP manufacturing of this novel therapeutic candidate at our Galway facilities. With all parties in the local area, we believe this will strengthen our partnership and help with developing this novel Knee Osteoarthritis therapy.”
Dr Alison Liddy, Founder and CEO Relevium, “This funding will enable Relevium and our partners to develop this ground-breaking treatment that has the potential to transform the lives of people living with Knee Osteoarthritis.”
Professor Garry Duffy, NUI Galway, “My team at NUI Galway are delighted to be part of this project and to work with industrial leaders to develop an impactful solution for Osteoarthritis.”
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Hitech Health's Cell and Gene Therapy Operations Manager Aoife Duffy and Global Head of Commercial Clare O’Sullivan will be attending Phacilitate's Advanced Therapies Week 2023 in Miami from January 17th – 20th. Advanced Therapies Week is the destination for...
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HiTech Health and blood cancer charity Anthony Nolan have entered into an agreement to facilitate the development of novel cell and gene therapies.
Anthony Nolan Cell & Gene Therapy Services will support HiTech Health’s supply chain through the provision of a reliable, scalable source of high-quality starting material. Initially provision of cellular material will be for research and development (R&D) programmes with a view to scale up in the future to clinical application and manufacturing. The parties are open to collaboration with cell and gene therapy developers and will work with them to provide bespoke offerings specific to the client’s requirements.
Anthony Nolan Cell & Gene Therapy Services brings expertise in cell sourcing, selection and provision of high-quality starting material to complement HiTech Health’s end-to-end service from product development to manufacturing and launch of life-changing treatments.
In partnering we aim to support cell and gene therapy researchers and developers to bring life-saving treatments to patients who need them.
Diana Hernandez, Head of Immunotherapy Research at Anthony Nolan says: “This is a significant step towards establishing a sustainable chain in cell and gene therapy development as we move towards allogeneic therapies. This collaboration ensures supply of ethically sourced starting material to developers of new therapies, which we hope will improve the treatment and care of thousands of patients in the future. It also allows the parties to share information regarding quality attributes of the material, which can help inform future improvements.”
Aoife Duffy, Cell and Gene Therapy Operations Manager, HiTech Health says: “HiTech Health’s collaboration with Anthony Nolan will be a great benefit to our clients. Anthony Nolan’s reputation for supply of high quality starting materials provides assurance to our clients and collaborators that a robust supply chain is in place for the manufacturing and supply of Cell and Gene Therapy Products. With this collaboration with Anthony Nolan, we now have a supply of starting material that is crucial to enable manufacturing of these novel therapies. This collaboration adds to our current R&D experience and future expansion into GMP manufacturing. Our expertise in quality, QP approval, and management of product supply and logistics will also be an important role in this collaboration. We are very excited about this collaboration and are looking forward to the possibilities that we can achieve together with the ultimate goal of treating patients who have an unmet medical need.”
About Anthony Nolan Cell and Gene Therapy Services
Anthony Nolan is the pioneering charity that saves the lives of people with blood cancer and blood disorders who need a stem cell transplant. Anthony Nolan’s Cell and Gene Therapy Services aim to facilitate ethical research and development through the sourcing and supply of donor starting materials to researchers and developers. With a register of over 850,000 donors, a cord blood bank, and four decades of experience providing stem cells, Anthony Nolan has the infrastructure, the expertise, and the skills to support the needs of the cell and gene therapy industry
HiTech Health bring an in-depth knowledge and experience of Cell and Gene Therapy products, We offer a range of services to help develop and supply life-changing treatments. Our experts can provide comprehensive solutions and strategies for process development, supply pre-clinical products and quality control assay development. We also have the GMP experience and expertise including QP support to ensure GMP compliance and product release. We also have the demonstrated supply chain and logistics expertise to enable cell and gene therapy products to be imported into Europe and the UK.
HiTech Health, SextonBio and MedInstitute announce collaboration to develop and publish workflows for integrating unit operations in cell therapy manufacturing using flexible automation systems.
Sexton Biotechnologies, in partnership with HiTech Health and Med Institute, is working towards continued innovations in flexible automation. As cell and gene therapy manufacturers move to close and automate processes, the challenge of integrating existing systems is a pain point for the industry. Flexible automation of traditionally manual process offers a new solution with lower capital expenditures and greater potential for downstream success.
HiTech Health is focused on product development, manufacture, launch, and supply of cell and gene therapies. Aoife Duffy, Cell and Gene Therapy Operations Manager, leads a team that has successfully developed multiple cell and gene therapy products.
“We think it is important to collaborate with other companies so that we can add to our expertise in operational activities,” said Aoife. “Cell and gene therapy products are expensive to develop and manufacture. Working with Sexton and the Med institute to bring the new fluid management system to the market will help with making processing more efficient. HiTech Health is bringing our extensive operational and GMP Manufacturing expertise to this collaboration. We are expanding our capabilities to cell and gene therapy process development and manufacturing. Additional expertise we bring to the collaboration includes quality, QP approval, and management of supply chain. In the end, we believe that this collaboration will lead to time and cost savings, along with greater downstream success in the manufacture of cell therapy products.”
