Translating academic research to clinical products: The case for improved interaction between academia and industry
Most commercial cell therapies originate form research funded at academic institutions. Yet despite the large amount of funding invested in academic research, the number of therapies that reach commercial stage is low, and the pace at which such translation occurs has been lagging.
Over the last few years, the Tissue Engineering & Regenerative Medicine International Society-Europe (TERMIS-EU) Industry Committee as well as its TERMIS-Americas (AM) counterpart has been involved in supporting programs aimed at addressing challenges associated with translating academic research into commercial cell therapy products. The TERMIS-EU Industry Committee has also strongly encouraged a tighter interaction between academics and industry via collaborative projects.
A number of findings from these efforts were outlined in 2014, in an opinion paper titled “Translating cell-based regenerative medicines from research to successful products: challenges and solutions,” and published in Tissue Engineering Part B Reviews. Authored alongside three Termis-EU Committee members, the manuscript outlined the consortium’s position on the challenges faced in speeding up the time it takes for academic research to be translated into practice.
On the heels of such efforts, a collaboration between the Leiden University Medical Center, the Medicines Evaluation Board (MEB) in Utrecht, Royal Free Hospital, University College London and the Technical University Munich’s Cells Interdisciplinary Center for Cellular Therapies, resulted in a manuscript addressing the current state of the industry-academic translation of cell therapies.
The manuscript is titled “Development of cell therapy medicinal products by academic institutes” and was published this Spring in Drug Discovery Today.
Issues such as lack of industrial feedback to academic institutions when developing research projects are discussed – which may be contributing to low clinical progression of academic discoveries, indicating that programs to support tighter interaction between academia and industry are not only welcome, but necessary.
Moreover, the case is made for academic institutions, being critically involved in workforce training, to collaborate more tightly with industry on targeting, through research as well as training and educational programs, industrially relevant and in-demand skills that will allow for a more integrated and targeted approach to be developed among researchers at the academic level which can directly benefit clinical translation.
One of the biggest hurdles to commercialization of stem cell-based therapies is the manufacture, under closed and sterile conditions, of validated stem cell products. Much has been said, on this blog and elsewhere, of the various guidances issued by the FDA that touch on the manufacture of stem cell-based products. Standardization agencies have invested significant effort in consolidating manufacturing processes and efforts at harmonization are consistently under way.
Various automated, single-unit systems have appeared on the market – some more sophisticated than others. Most of these closed systems, however, still rely on significant user input.
One new initiative, backed by the European Union, is called AUTOSTEM, and brings together a consortium of academic institution alongside industrial and EU support to create a fully automated stem cell production platform.
In their own words:
AUTOSTEM is an EU H2020 project that is developing a closed, automated, sterile pipeline for large scale production of therapeutic stem cells. It will enable lower-cost, higher-quality and more consistent stem cells to be produced, ultimately helping patients to benefit from new stem cell therapies.
The project, which is led by Dr Mary Murphy of the National University of Ireland, Galway, brings together a consortium of companies and academic institutions, including the Fraunhofer Institute for Production Technology (IPT) in Aachen, the University of Cork in Ireland and UK’s Cell Therapy Catapult.
The entire stem cell production process involves no hands-on human operations. In a recent paper, published in Regenerative Medicine, by Dr. Mary Murphy at the Regenerative Medicine Institute School of Medicine at the National University of Ireland, and colleagues involved in the AUTOSTEM project, discusses the initiative, describing it as a breakthrough way to achieve large scale hMSC production at clinical grade.
This project is backed by funding from the European Union’s Horizon 2020 research and innovation program.
Similar initiatives exist closer to home. The New York Stem Cell Foundation is developing the Global Stem Cell Array, a new technology platform for the production of induced pluripotent stem cell lines in a parallel automated process. This enables the standardization to be achieved through automation of the manufacturing process. The researchers involved in the project published a paper last year in Nature Methods which gives more details on the initiative.
These efforts are the first steps – though not the only ones – to achieving automation of large scale manufacture of stem cells, which will be increasingly more critical are new therapies mature to commercial stage.
To support these new systems, more sophisticated solutions – from ancillary materials to full scale validation controls – will have to be in place in order to shift the paradigm from the current highly laborious and poorly controlled landscape to one of compliance, quality and therapeutic efficacy.
3D bioprinting is fast becoming one of the most rapidly-growing areas of tissue engineering: the influx of new research, funds, patents and companies operating in the field is contributing to it becoming a multi-billion dollar business.
While bioprinted organs are still not a reality, big steps towards making such pipe-dreams become clinical therapies are being made: an overview of the field was given in a recent opinion article published in Trends in Biotechnology by Dr. Ibrahim Ozbolat at the University of Iowa, which highlights the state of the art of the field and issues with the scale-up of functional tissue and organ constructs for transplantation.
The most commonly used bioprinting techniques include laser, inkjet or extrusion/deposition bioprinting. Out of these, inkjet-based bioprinting is the most common. While proof-of-concept studies have demonstrated simple biological systems successfully in multiple applications, the organs that have been produced from these endeavors are small and relatively simple. More complex architectures and fully vascularized systems are yet to be produced.
A recent market analysis was made by Washington, DC-basedFinnegan IP law firm on the main players in the field in terms of awarded patents for 3D bioprinting-related work. The breakdown is shown in the table below.
|3D Bioprinting Patent Assignees||June 2016|
|Wake Forest University||40|
|The University Of Texas System||22|
|Medprin Regenerative Medical Technologies Co Ltd||14|
These numbers are growing rapidly every year, as are the companies entering this field.
Where next? There is no doubt that increased funding will keep trickling into the 3D bioprinting field, particularly as more compelling technologies are emerging demonstating increasingly more complex, functionalized constructs.
In order to remain competitive, the field will have to field the same challenges that the stem cell therapy field has encountered on its road to maturity: to demonstrate fully implantable, 3D bioprinted organs, multiple contributing factors will have to fall in place on the road to market, from manufacturing through to logistics. The complexity, particularly in the case of organs such as the kidney, liver or heart – all of which require critical vascularization to maintain cell function – will be greater than anything encountered before, but the potential rewards that much more compelling.
This past week, a new commentary paper on unregulated stem cell clinics made headlines throughout the media: Dr. Leigh Turner, an Associate Professor in the Center for Bioethics, School of Public Health, and College of Pharmacy at the University of Minnesota and Dr. Paul Knoepfler from the University of California Davis, authored a thinkpaper, published online in Cell Stem Cell, which analyzes the current state of the stem cell clinic market in the USA.
Titled “Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry,” the paper identifies
351 U.S. businesses engaged in direct-to-consumer marketing of stem cell treatment across 570 clinics. The hotspots for these businesses were identified as Los Angeles (particularly Beverly Hills) and New York, while metro areas of Miami, Denver and Dallas-Fort Worth were also described as “high density” with respect to stem cell clinics.
4 out of 5 of the businesses, the paper further found, administered autologous therapies, with 61% of those marketing adipose tissue-based treatments. Only one of the businesses was found to advertise what it claimed are induced pluripotent stem cells, but the authors could not determine further information about things such as source and type of these pluripotent stem cells.
The authors took particular issue with the claims that these clinics are making with regard to the treatments they are administering – many of which being quite liberal in their claims – mentioning that ethical, legal and safety concerns may be at play.
The question of stem cell clinics has been an issue brought up previously, with organizations such as ISSCR dedicating a session during their 2015 Annual Meeting to the topic, and this paper won’t be the last analysis that we will see.
It is, nonetheless, clear that a highly active field of clinics is thriving on the back of questionably proven stem cell treatments, operating without clear regulatory oversight. Arguments exist from both side of the fence, however, with proponents of deregulation, claims the paper, blaming the strict regulatory landscape that has resulted in too few approved treatments.
As we continue to support peer-reviewed, validated and standardized processes, this market will be interesting to follow.
On the afternoon of Saturday, June 25th, 2016, biochemist Dr. Robert Tijan’s keynote speech at San Francisco’s Moscone center closed this year’s ISSCR Conference.
It was a successful event – during the opening plenary session, earlier in the week on Wednesday 6/22, president Sean Morrison remarked this was the biggest ever meeting, with over 3,600 registered delegates. Over seven plenary sessions – covering topics as diverse as Cellular Plasticity and Programming, Stem Cells and Cancer, to Gene Therapy and Epigenetics – were scheduled, alongside 28 concurrent sessions, where the latest research in stem cell metabolism, tissue engineering, neural diseases and stem cell niches – among others – was presented.
This year, the 2016 McEwen Award for Innovation was jointly awarded to Dr. Austin Smith from the Wellcome Trust Centre for Stem Cell Research and Institute for Stem Cell Biology, UK and Dr. Qi-Long Ying from the University of Southern California, USA. Dr. Smith followed the presentation of the $100,000 award with a talk focused on his groundbreaking work on the ground state network of embryonic stem cells.
During the same session (Stem Cells and Cancer), Dr. Elaine Fuchs from Rockefeller University gave a remarkable speech which included her latest work in identifying a group of cancer cells, using skin as the model, resistant to cancer therapy. You can access the paper in question here.
Elsewhere, Dr. Michael Sadelain from the Memorial Sloan Kettering Center in New York City discussed his lab’s important work on the control on transgene expression in vivo in hematopoietic stem cells, with a particular focus on the effect of locus control regions.
Multiple other illuminating talks from luminaries in the field were spread over the 4 day event, including dozens of innovation showcases, networking and early career events. 150+ companies exhibited the latest in their products and technologies.
Over 600 posters were also presented at the conference during 3 well-attended sessions.
A quick survey of ISSCR indicated a strong focus – on the research side – on gene therapy. CRISPR has emerged as a mature g0-to technology for gene editing, and this was reflected not only through talks, but particularly exhibitor booths that prominently offered this as a service technology.
IPS cell and pluripotency once again enjoyed prominence, though there was lots of talk about reprogramming and differentiation and stem cell plasticity, indicating the field’s broad focus on tissue regeneration strategy and potential therapies.
When it comes to tissue engineering, new technologies – 3D printing, microfabrication, electrospinning and DMSO-free cryopreservation – highlighted some remarkable new avenues that are opening up the possibilities of stem cell research.
If you would like more information about Akron’s talk and posters, where we presented the latest research in DMSO-free cryopreservation and 3D scaffold fabrication, please contact us.
The 2016 Annual Meeting of the International Society for Stem Cell Research takes place this coming week in San Francisco. From May 22nd – 25th over 4000 scientists will converge at San Francisco’s Moscone West to present the latest in stem cell research, development, commercialization and related advancements, spread across over 150 talks and 130 exhibit booths.
Like every year, Akron will be attending the meeting, and will be represented via both talks as well as poster sessions.
For one-to-one meeting opportunities, please emails us at firstname.lastname@example.org, and we’ll be happy to schedule a one-on-one session to discuss out technologies and solutions for your needs.
Akron will present the latest in our R&D, from encapsulation technologies, novel natural DMSO-free cryopreservation media, 3D scaffold engineering, custom finish/fill solutions, bioassay development and cell therapy media, solutions and proteins (fibronectin, vitronectin, HSA) and GMP-grade cytokines, including our industry-leading immunotherapy portfolio.
For public opportunities to learn about Akron’s technology, please visit us at the following:
1. Wednesday, June 22ND from 9:00-12:00 (Moscone West, Level 2, Room 2004)
ISSCR Industry Committee Focus Session: A Practical Guide to Starting a Company
STARTING YOUR OWN COMPANY: HOW TO, Dr. Claudia Zylberberg
2. Friday, June 24 from 6:00 -7:00 PM
Poster Session III Odd
Poster #: F3032: ‘SMART’ SCAFFOLDS FOR IMPROVED TISSUE REGENERATION
2. Friday, June 24 from 7:00 -8:00 PM
Poster Session III Even
Poster #: F3032: NATURALLY-OCCURRING DMSO-FREE CRYOPROTECTANTS TOWARD CLINICALLY EFFECTIVE SOLUTIONS: UNDERSTANDING THE EFFECTS OF CPA TYPE AND DELIVERY ON DIFFERENT CELL TYPES
Akron’s Claudia Zylberberg named as “Most Influential in Cell Therapy”
Dr. Claudia Zylberberg was named as one of 15 most influential women in cell therapy by Phacilitate. She joins other leaders as Susan Solomon from the New York Stem Cell Foundation and Fiona Watts, director of King’s College’s Centre for Stem Cells and Regenerative Medicine. We invite you to read the entire report here.
A few weeks ago, the International Society for Stem Cell Research (ISSCR) released a new set of guidelines, updated for 2016, for Stem Cell Research and Clinical Translation. The guidelines, developed by an international task force of 25 experts in stem cell science, clinical research, and bioethics, and reviewed by 85 external individuals and organizations, seek out to establish the ISSCR’s current sentiments on stem cell research, clinical translation, as well as the responsibilities that the ISSCR feels scientists involved in the work have to the general public.
Available here, the Guidelines are built around five main areas:
- Embryonic Stem Cell Research
- Clinical Translation of Stem Cells
- Standards in Stem Cell Research
These guidelines are meant to outline, according to the ISSCR, “common principles of research integrity, patient welfare, respect for research subjects, transparency, and social justice.”
What do they mean and how important are they? The ISSCR is very clear to state that these guidelines are in no way meant to supersede or replace any laws or official regulations and are merely meant to be viewed as “best practices” for those involved in the activities discussed.
A big focus is on ethics, with embryo and related research issues receiving significant focus in the guidelines, which highlights the ISSCR’s continuous focus on continuing to promote responsible use of human subjects in stem cell research. The guidelines also hint at the ISSCR’s concern with the communication of new discoveries to the general public and media, favoring restraint over hyperbole and suggesting that any forward-looking statements should be “accurate, circumspect and restrained.”
While commendable, the guidelines, at 37 pages, are not comprehensive and are even reductive in certain areas. For instance, raw material sourcing and related manufacturing recommendations and standards are relegated to a few paragraphs, summarized as follows:
All reagents and processes should be subject to quality control systems and standard operating procedures to ensure the quality of the reagents and consistency of protocols used in manufacturing. For extensively manipulated stem cells intended for clinical application, GMP procedures should be followed.
This is not to say that there is expectation that the ISSCR should in any way be comprehensive in their guidelines in a way that would eliminate recourse to applicable laws, though further clarification as to certain statements and processes could be provided. For instance, the FDA has climbed a steep hill in trying to define “extensive manipulation” of cell-based products, and such efforts should ideally be acknowledged.
We invite you to consult these guidelines and applaud ISSCR for updating their 2008 version of the same, and hope that, as we move forward, with everyone’s help, the industry will be able to further tighten these guidelines as the field advances toward better regulation, standardization and commercialization.