That the cost of development of any new drug is extremely high has been a known fact that the biotech and pharmaceutical industry has grappled with for a long time. This issues have recently become more publicized as high profile clinical trials have shed light on the dichotomy between keeping the development, testing and manufacturing processes in line with regulatory constraints and the business-dependent issues of development costs, profits and selling price.
This week, a United Nations panel issued a report that addresses the rising costs of commercial drugs, patent issues as well as associated development-related matters.
One of the most urgent points involved the allegedly disproportionate cost of drugs relative to what the UN believes, or recommends, they should cost. The report, specifically, calls on governments to negotiate a binding treaty “de-linking” R&D costs from the final price of drugs in areas where market incentives have been insufficient, such as for new antibiotics or for tropical diseases.
The report on the United Nation’s Secretary General High Level Panel on Access to Medicines is publicly available and can be read here.
That the cost of developing a new drug is high is not news. A recent manuscript, published earlier this year, titled Innovation in the pharmaceutical industry: New estimates of R&D costs, estimated that the cost to bring a new drug to market is approximately $2.56 billion.
The pharmaceutical industry has largely criticized the report, with the Biotechnology Innovation Organization saying:
“Sadly the United Nations High Level Panel ignored the real issues that impact or delay delivery of innovative treatments and cures throughout the developing world, while focusing on policy recommendations in the one area – intellectual property – that would actually undermine ongoing research and development by hundreds of companies, universities and researchers.”
While much of the UN’s report is focused on developing countries, there are parallels and potential impacts of such actions that would affect the pharma and biotech industries globally.
There is no doubt that the cost of drugs has lately become a significant topic with high international interest, and it will be interesting to see how things play out now that the report has seen light.
New study mobilizes T cells to become therapeutic + State of the Science in Regenerative Medicine Workshop Coming Up
New study describes mobilization of adult T cells to become therapeutic
We wanted to highlight an interesting new paper that came out this week with potentially significant applications for adoptive T cell therapy. In this type of therapy, tumor-specific T cells are isolated and expanded ex vivo prior to being administered. T cells in adult bodies are typically maintained by the differentiation of a small population of adult stem cells.
A new study study, published in the Journal of Clinical Investigation, described the identification of genes involved in the mobilization of a quiescent subset of tissue-resident memory (Trm) cells. The genes are ABC transporters and the NR4A family of transcription factors, and they influence the function and differentiation of Trm cells.
in doing so, the authors effectively were able to “boost” and create Trm cells from otherwise quiescent T cells, which would have a significant impact in adoptive T cell therapy, which relies on sufficient numbers of T cells for efficacy.
The study came out of the lab of Dr. Madhav V. Dhodapkar at the Department of Medicine at Yale University and can be read here in full.
Akron to attend Cell & Gene Meeting on the Mesa Partnering Forum
As previous years, Akron will this year attend the upcoming Cell & Gene Meeting on the Mesa, and will participate in the preceding Partnering Forum. The Partnering Forum takes place October 5 – 6, 2016 and brings together over 500 participants from every facet of the academic, research, cell and gene therapy and pharmaceutical as well as business fields. If you want to meet us please check partnering session opportunities at the Cell & Gene Meeting on the Mesa website or contact us directly.
State of the Science in the Field of Regenerative Medicine: Challenges of and Opportunities for Cellular Therapies – A Workshop
We are also excited to share some information about a workshop by the Forum on Regenerative Medicine at the National Academies of Science, Engineering and Medicine, set to take place on October 13.
The purpose of the workshop is to highlight, and discuss, challenges associated with developing cell-based therapies for regenerative medicine. The planning committee has developed a great agenda for the day (link below) and the public registration is now open. We encourage you all to share the information with colleagues who may be interested in attending. The workshop takes place on October 13th at the National Academy of Sciences Building (125) • 2101 Constitution Avenue, NW, Washington, DC with an 8:30 AM start time.
The coming week is heavy on CAR-T and cell therapy developments. Not only is the FDA holding a public hearing on cell therapies (which you can read about here), but the CAR-T Summit is taking place in Boston (more on that below) alongside satellite meetings such as Cell & Gene Therapy (which takes place September 12 and 13, 2016).
Additionally, the Blue Ribbon Panel of the Cancer Moonshot initiative presented its report to the National Cancer Advisory Board earlier this week on September 7, 2016.
The report, which can be downloaded here, describes “10 transformative research recommendations for achieving the Cancer Moonshot’s goal.”
President Barack Obama has requested about $1 billion over two years for the project — however, the funding has yet to be approved.
On the subject of immunotherapies, the report recommends the generation of a “cancer immunotherapy clinical trial network.” More specifically, the purpose of the network would be to:
“[…] provide a national infrastructure to take advantage of a standardized baseline protocol (including drug treatments and prevention strategies for high-risk individuals, tissue acquisition, and biomarker interrogation) embedded in the broader community (both academic and industry) to test novel immunotherapies efficiently and with a deep understanding of fundamental obstacles to success.”
The Blue Ribbon Panel’s report is part of a larger initiative, and another important milestone in the current government’s plan to advance much-needed funded for the development and commercialization of therapies for serious diseases that currently have no cure.
Akron to present at CAR-TCR Summit 2016
Akron Biotech will be attending the CAR-TCR Summit which this year takes place in Boston from September 13 – 16, 2016. Alongside having a booth set up at the meeting which will feature our latest innovations in product and process development, Akron will also be featured as a speaker at the conference.
Dr. Claudia Zylberberg, Akron’s CEO, will speak during the Manufacturing, Supply Chain & Commercialization session which is scheduled for Wednesday, September 14th, 2016. The talk, titled “Innovating CAR-T Manufacturing: Challenges and Considerations for CMOs” will take place at 12:40 pm and will address issues relevant to the manufacturing of CAR-T therapies and focus on current challenges and bottlenecks in the manufacturing as well as new concepts and strategies that can bring opportunities to in-process improvements of CAR-T therapies.
For more information or to schedule private meetings, contact us directly.
Earlier this year, the FDA announced it would hold a hearing on cell therapy, originally scheduled for April 13, 2016. However, due to overwhelming public interest, the FDA decided to postpone the meeting. Now, finally, that time for the meeting has come.
Taking place over two days later this month (September 12 and September 13, 2016) at the NIH campus in Bethesda, MD, the meeting is officially dubbed a “Public Hearing.” The impetus behind this hearing is to provide comments to the FDA about the draft guidances issued recently. In the FDA’s own words, the purpose of the hearing is:
“[…] to obtain comments on the four draft guidance documents relating to the regulation of human cells, tissues, and cellular and tissue-based products (HCT/Ps). […] FDA would like comments on the scope of the four draft guidances, including the particular topics covered, the particular questions posed, whether there are additional issues for which guidance would be helpful.”
Open to the public as well as researchers involved in stem cell-based work, it is unofficially said the FDA is also curious about receiving feedback so that it can better assess the state of the industry in order to provide greater oversight of stem cell clinics operating in the country.
The meeting comes on the heels of the latest guidances, issued in late 2015, on the
Regulation of Human Cells, Tissues, or Cellular or Tissue-Based Products.
Registration was closed on July 1st, 2016 – and while the previous hearing, that took place in October 2015, featured over 50 speakers which were given either 3 or 6 minutes of “talk time,” this meeting is expected to far surpass the previous one in attendance due to it taking place over two days.
The FDA will make the meeting available via Webcast from their website, so for those of you who haven’t managed to register, here is your chance.
For more information on the hearing, go here.
We will be following the meeting, and – as we continuously closely follow regulatory developments in the cell therapy field – will report on any industry-wide relevant updates.
Good Manufacturing Practice (also referred to as cGMP or current Good Manufacturing Practice) is one of the key quality control systems within the life sciences industry, the aim of which is to ensure product quality and safety as well as manufacturing consistence. These guidelines are in place so that products consistently meet the requirements for their intended use, and to ensure therapies are safe and efficaceous when administered.
In order for a cell therapy product to meet the regulatory requirements which include cGMP compliance, controls at multiple levels of the manufacturing cascade must be in place. Understanding GMP and ensuring a process is “GMP-compliant” can be complex and involved, and must be tackled from the earliest stages of product development.
While GMP guidelines are established, they are very often product and process-specific, which has led to confusion among cell therapy product manufacturers – which is unfortunate, because ensuring a compliant process through proper, early planning eliminates bumps that otherwise appear during the more advanced stages of the drug development process.
As a company that often provides guidance and support to other cell therapy manufacturers with implementation of cGMP practices, here we highlight 5 of the key elements to keep in mind when planning – or executing – your cell therapy process.
- Sourcing of raw materials
Raw and ancillary materials are at the core of every successfully commercialized cell therapy product. Traceability, source, quality, cost and grade are all considerations that must be made at the earliest stages in order to properly scale and plan the manufacturing stages.
Patient safety is of paramount importance when developing cell therapy products. Ensuring safety through proper traceability of raw materials and consumables, as well as their qualification and validation is a good first step to ensuring success. Other considerations, including in-process testing, final release testing, product sterility and how its intended use might impact sterility are key to eliminating contamination.
- Clearly defined and validated manufacturing process
Doing it once is fine, but making sure the process is robust and transferable is what the industry is really after. Cell therapy products are often difficult to quantify, therefore efforts within the industry are aimed at consolidating specifications and standardizing as many elements of the manufacturing process as possible. As a company, having a clearly defined, tested, and validated process goes a long way towards ensuring reproducibility. This is easier said than done, and there is a wide misunderstanding within the industry as to what proper validation includes. For those reasons, having a manufacturing partner who is well-versed in cGMP processes and robust manufacturing practices is beneficial.
- Up-to-date batch records
Tied in with robust, validated processes, having batch records that reflect those manufacturing processes to every minute detail is key. Straightforward, user-tested, and actively followed batch records can be thought of as a work of art, and – again – a manufacturing partner with a robust quality assurance department will go a long way to helping you achieve that.
- Suitable, validated release specifications
Certificates of Analysis, which outlines product quality attributes, accompany the release of most products in the industry. Yet setting those attributes in harder than it sounds – often, guidelines are set by the regulatory agencies as to the acceptable criteria, but often such guidelines do not exist.
There are multiple industry-wide initiatives that are attempting to standardize various parts of the cell therapy process. Akron has participated, just last year, in a workshop at the National Institute of Standards and Technology, the aim of which was to consolidate and standardize potency assays for cell therapy products. This is just one example – though there are many other organizations attempting to tackle the various disjointed elements of the cell therapy process in order to facilitate in setting clearer guidelines to companies developing cell therapy products.
Even without a comprehensive set of rules in place, developing a product that meets tight criteria is a challenge. A strong manufacturing partner, again, is key.
Here at Akron, we assist and support companies in their manufacturing campaigns – both on the regulatory level as well as on the process level. Please contact us to learn more and tell us about your process.
Fibroblast Growth Factor’s remarkable biological function, now newly formulated for cell therapy use
The fibroblast growth factor (FGF) family counts 22 characterized members – since their discovery over 6 decades ago, the FGF proteins have been linked to essential roles which include cell proliferation, differentiation and apoptosis, embryonic development and differentiation, neuron differentiation, survival and regeneration, normal skeleton development, and the proliferation of various types of cells.
Other roles include the regulation of vitamin D metabolism and osteogenesis and post-natal bone mineralization by osteoblasts, with new evidence supporting their regulation of appetite control.
Just recently, more significant implications about FGF in tissue regeneration were reported. The lab of Dr. Atsushi Kawakami at the Tokyo Institute of Technology published, in the journal Development, their observations on the mechanism by which FGF signaling is involved in tissue regeneration. They studied this by investigating the regeneration of damaged fins in zebrafish, and identified FGF-20a and FGF-3/10a as major FGF ligands in wound epidermis and blastemas, respectively, important for the regeneration process. Because FGF-20 and FGF-3 are present in all vertebrate species, this study may uncover potential cues to how tissue regeneration is regulated in mammals, as well as humans.
Clinically, studies such as the above one, as well as discoveries made over the past few decades have resulted in an increasing focus from the part of pharmaceutical and cell therapy companies developing biologics to target FGF receptors that are implicated in important therapeutic functions via their signaling and regenerative roles. Companies such as Boehringer Ingelheim are involved in clinical studies for new biologics targeting, among others, signal transduction pathways regulated by FGF.
And the market has responded – FGF is ubiquitous and readily available. It can be found stable, functional, and lyophilized, often with excipients to improve its stability.
However, as the clinical development of biologics advances – and such advances are progressing rather rapidly – so should the industry’s response to the shifting needs of clinical developers. Such needs include a more thorough consideration on safety, sterility and cell therapy use.
While Akron has been a strong, leading supplier of multiple FGF proteins for many years, we have now gone one step further and developed a formulation of FGF which directly addresses the use of the protein in cell therapy settings.
Our new FGF is a ready-to-use, fully-formulated and reconstituted, liquid-phase FGF basic. Having formulated FGF in liquid form makes the protein amenable to single use scenarios and eliminates the need for cumbersome reconstitution. In doing so, we have addressed common contamination issues that arise during handling of the powder. Moreover, sterility, critical in cell therapy processes, is maintained in a single-use configuration.
Filled to multiple sizes, the new liquid FGF is a revolutionary solution that removes ambiguity during use, being formulated to exact activity specifications.
As a first step to showing you how this new FGF can simplify and improve your workflow, contact us to discuss – we would be happy to learn about your application.
Fibronectin’s new implications in wound healing + Akron to present course at Amgen’s Bioprocessing Center
Following on from last week’s post on our capabilities to exclusively derive virus-inactivated fibronectin as the first such type of fibronectin on the market, this week we want to expand and highlight two new studies that have implicated fibronectin as having key roles in wound repair.
As widely known, fibronectin is one of the key proteins of the extracellular matrix, and has significant implications in wound healing and repair as well as cell growth. In brief, during the wound healing process, fibroblasts grow and produce fibronectin as well as other protein such as collagen that form a new extracellular matrix to fill the wound bed. This process has been studies extensively, as has fibronectin’s key role in cellular adhesion and growth. Two new studies highlight how fibronectin can be implicated, positively or negatively, in both wound healing as well as cell growth processes.
The first study, by Dr. Jonathan Garlick’s lab at Tuft’s University, is titled
Altered ECM deposition by diabetic foot ulcer-derived fibroblasts implicates fibronectin in chronic wound repair and is published in Cellular Reprogramming.
The authors investigated the wound healing process of diabetic foot ulcers (DFUs). DFU-derived fibroblasts were compared to healthy ones in their ability to generate the ECM during the wound repair process. the authors discovered that fibronectin generated by DFUs was deficient in its ability to promote growth factor beta regeneration, indicating it as they key protein regulating the process.
The second study looks at the role of fibronectin from a biomaterials perspective. Titled ”
Fibronectin-modified surfaces for evaluating the influence of cell adhesion on sensitivity of leukemic cells to siRNA nanoparticles,” it was published by the lab of Dr. Hasan Uludağ at the University of Alberta in Canada in the journal Nanomedicine. The authors have demonstrated that fibronectin (FN)-grafted (by crosslinking), plasma-treated PTFE surfaces can be used as suitable platforms to investigate the influence of leukemic cell adhesion on siRNA treatment. Improved adhesion and growth of chronic myeloid leukemia K562 cells was possible on FN-grafted surfaces.
Akron at Amgen Bioprocessing Center
We are pleased to announce that Akron Biotech will participate in an industrial/academic training course at the Amgen Bioprocessing Center at the Keck Graduate Institute in Clermont, CA. Akron will lecture participating delegates, who will attend an intensive hands-on course on Bioprocessing, on proteins and their use in bioprocessing – from structure and function to purification techniques and analytical measurements. The course starts on September 19th.