Cell Therapy: Three Predictions for the Future of the Industry

There is a palpable air of excitement and enthusiasm around the cell therapy industry and a sense that, as Christopher Bravery of Consulting on Advanced Biologicals, puts it: “cell therapy has taken off”.

There have been tremendous breakthroughs as the field has matured over the last 10 years, but we want to know what’s next: what exciting developments can we expect going forward, over the next 5 to 10 years? We put this to our panel of experts and these were their top 3 breakthrough areas:

1) Cures, not just treatments.

To date, most biopharmaceuticals offer treatment, not a cure. All that could be about to change: Jason Carstens, of the Fred Hutchinson Cancer Research Center, is excited about the advancements made in the CAR T-cells field. He says it’s mind-boggling that we are actually talking about a cure for cancer. He continues, “if I had a crystal ball and was looking forward to some potential breakthroughs, I would say it’s in the area of regenerative medicine where we have the ability to repair spinal cord injury for example, cartilage injury, bone damage, cardiac damage and really have a great impact on the quality of life for people.”

2) Cell kits: the microchip of the healthcare industry

John Rowley, of RoosterBio, says the future of our biotechnology healthcare products are going to incorporate stem cell technologies. For this to happen, stem cells need to be provided, very similarly to microchips, in formats that enable product development. He explains, “technology revolutions happen when kits come on the market. They allow anybody to gain access to a technology – making it easy to use, simple, affordable, and robust. Something that works every time.” Looking to the future he sees, “a day of a true stem cell reagent where you’re able to take out 50 million, 100 million cells from the freezer, thaw it out and use it directly in an experiment. And where that’s really going to be huge is the tissue engineering world.”

3) Improvements in Manufacturing Technology

Aby Mathew of BioLife Solutions, believes that over the next 5 to 10 years we will see developments on both the clinical and manufacturing sides. On the clinical side he expects that more therapies will get approval and we’ll know they’re working at the patient level.

On the commercial side, he sees that “manufacturers of these therapies will be able to optimize their processes a little bit better and also be able to drive the cost down, in combination with relationships with suppliers, who can now generate these tools and supplies on a larger scale.”

He hopes that the lower costs will mean that these therapies can reach a much wider patient population, whether you are in a first world or third world country.

Over 50 speakers and 200+ industry pioneers will be discussing the future of cell therapy at the Cell Therapy Manufacturing & Gene Therapy Congress in Brussels on 2nd – 5th February 2016. Join the conversation at https://celltherapy.knnlab.com.

Bringing Orphan Drugs and Gene Therapies to Market: Maximising ROI through an Effective Communications Plan

Businessman with business plan concept analysis strategy questions

Howard Sinclair, Strategic Director – Rare Diseases and Gene Therapy, The Prime Medical Group, UK, and Andrew Jobson, PhD, Senior Editorial Manager – Rare Diseases and Gene Therapy, The Prime Medical Group, UK, are talking at Cell Therapy Manufacturing & Gene Therapy Congress on Wednesday 3rd February in Brussels. Here they explain what they’ll be talking on:

“There are a multitude of urgent and critical areas to address in further developing your orphan drug or gene therapy to achieve the next milestone. They consume all your team’s energy, resources and time, and there never seem to be enough hours in the day. Against this reality, is creating a communications plan really that important? – Yes! Won’t the external communications just happen naturally anyway, as the relevant data become available? From decades of experience supporting everything from mega-blockbuster first-in-class agents, to very specialised medicines for the most obscure ultra-rare diseases, we would respectfully and emphatically answer: No.

Unique challenges exist for rare diseases, orphan drugs and gene therapies that require tailored solutions, distinct from standard approaches. Creating a robust, evidence-based, authentic and compelling scientific narrative is the starting point – and you will need a sound plan to effectively share this with potential product users, key influencers and the broader healthcare community. This could include clinical trial investigators, practicing specialty clinicians, primary care providers, nurses and payers.

An effective strategic communications plan is critically important, enabling you to optimally engage with your target audiences at the right time (which will likely vary over the course of the development of your asset) to achieve your immediate and long-term goals, whether it’s accelerating clinical trial accrual or ensuring optimal awareness and adoption into clinical practice upon market authorisation. Early development and initiation of a tailored, proactive and cohesive communications plan is arguably even more critical for orphan drugs and gene therapies to ensure your limited resources are most effectively channelled.

Topics to be covered will include:

  • Adding value to your product/clinical studies programme with a tailored medical communications plan.
  • Addressing the specific challenges for a medical communications plan in orphan drugs, rare diseases and gene therapy.
  • Driving the communications strategy through a focus on the unmet needs of both the patient and the healthcare professionals.
  • Defining the key elements of an optimal communications plan.
  • Making the plan happen – driving the initiation, management and delivery.

Creating a robust and tailored strategic communications plan is critical to success – we will explore the why, what and how.”

See the full agenda for Cell Therapy Manufacturing & Gene Therapy Congress and buy tickets at https://celltherapy.knnlab.com.  

Christopher Bravery: Justification for the Specification

Late last year we were fortunate enough to catch up with Christopher Bravery, Director, Consulting on Advanced Biologicals Ltd and a member of the ISCT EU Legal and Regulatory Affairs Committee. We asked him about the reasoning behind the topic of his talk ‘Setting Specifications’ at the Cell Therapy Manufacturing & Gene Therapy Congress on 3rd February 2016 in Brussels:

“I try and think of a topic that I don’t feel has been covered enough each year and choose that as my topic that I try and speak on. Particularly at the Cell Therapy Bioprocessing & Commercialization conference run by IBC in the U.S and Informa Cell Therapy Manufacturing and Gene Therapy congress in Brussels, because I think there are topics that somehow fall under the radar. The thing with justification of specifications is that you rarely have to write much during clinical development, and I often see ‘not applicable’ written for the justification in the specifications, which in many cases, the regulators will pay no attention to.

The ones that people are probably familiar in having to justify, are the things like endotoxin levels, where there is some reasonable guidance to what is a reasonable daily exposure to endotoxins, so you divide that by your dose and come up with a figure to justify the limit you’ve set for your endotoxin. Although, if you’re needing to do some sort of viral testing then it’s usually a no brainer that it is usually not detectable, and you don’t need to justify that specification much either.

Once you get to market authorisation, it is a substantial amount of work and text in the dossier, and I think what interested me when I thought about it was how it draws upon all of development. So I produced a figure actually where I laid out the CTD sections in a mind map, and showed all the links about the dative for justifying your product specification and where it will come from, and your data for your processes will come from.

Potency is a brilliant example of how do you justify your potency specification? It’s probably a bit easier for gene therapy than it is for cell therapy, but it is very difficult. That almost certainly might need to draw on non-clinical data as evidence that something sub-potent, that you’re not getting the effect you want, and that at another value on your potency assay is actually potent. Often the appropriate non-clinical models that might allow you to support that might be missing so you might be relying on in-vitro assays.

But really, I think the main reason I chose it is that in my consulting work I have seen a move towards later stage development.  There are certainly more companies thinking now about what they need for market authorisation, either planning or embarking on their pivotal studies. And really if you haven’t done the work on the process you’re taking into pivotal that is suitable for early commercial, then you would have an enormous amount of work to do in phase II. In phase III when you’re supposed to be validating the process, validating the methods and writing a dossier, all those things take a lot of time, so in phase II you really should have your characterisation of the process out of the way; identified your critical process parameters, your critical quality attributes and so on. But, there is always a lot to do!

What worries me is that this work might not be getting done, and then it would be very difficult to justify specifications when you have no data to base them on. Obviously if this is the case, then there is the pressure not to wait, but to get on with phase III, and so suddenly it’s done in parallel and you have six months to do what you really need two or three years for.

And this is why I chose that topic. It has really struck me as being something that we needed to start talking about – how you do that. What I have seen particularly with the cell therapy community, somewhat less with the gene therapy because it’s more like biotech, is really significant deficiencies in characterising the process and understanding what those critical parameters are. Without that characterisation data, you wouldn’t be able to justify those parameters.

I also have fears, as I’ve been through this myself, that decisions get made in corridors or at lunchtime about how you’re going to go about doing things early in development and sometimes if they don’t get recorded, then at the end you’re not sure why you even did it that way, let alone having a justification for the specification!”

Christopher’s talk is on day two of the Cell Therapy Manufacturing & Gene Therapy Congress at 16:00 on the Cell Therapy manufacturing stream, and no doubt will be extremely insightful. See the full agenda and buy tickets at https://celltherapy.knnlab.com/. We look forward to seeing you there!

Revolutionary Algorithm Mogrify Set to Transform the Field of Regenerative Medicine

mappingout
Credit: Nature Genetics & Rackman et al.

This week a paper published by a team of international researchers at the University of Bristol has sent excitement rippling through the cell therapy community. The team comprised of collaborators from Bristol, Australia, Singapore and Japan published the breakthrough last Monday (18/01) in Nature Genetics. They presented the creation of a predictive system (Mogrify) that can forecast how to create any human cell type from another cell type directly, bypassing the need for exhaustive trial and error.

The team led by Julian Gough have so far applied Mogrify to 173 human cell types and 134 tissues, outlining an index of cellular reprogramming.  Speaking about the breakthrough Gough, professor of bioinformatics, revealed to the University of Bristol that “the barrier to progress in the field is the very limited types of cells scientists are able to produce. Our system, Mogrify, is a bioinformatics resource that will allow experimental biologists to bypass the need to create stem cells”.

Secondly, when listing further achievements from the research, conducted in collaboration with Professor Jose Polo at Monash University in Australia, Gough confirmed that Mogrify had validated two new transdifferentiations. The algorithm succeeded first time in validating both of the new transdifferentiations, and it is this speed in achieving results that lends clear indication to the claim of Mogrify being revolutionary. Professor Gough added that he hoped “Mogrify will enable the creation of a great number of human cell types in the lab”.

This is a huge result for the regenerative medicine field and will no doubt speed up advances in life-changing medicines. Particularly, the ability to produce a number of types of human cells will directly lead to new tissue therapies, and a much improved understanding of cell production at a molecular level. One hope going forward is the potential to grow whole organs from someone’s own cells.

For five years Gough collaborated with Dr Owen Rackham to create a computational algorithm to predict the cellular factors for cell conversions. This was achieved largely in thanks to data collected as a part of the FANTOM international consortium, of which Gough is a member.

To highlight the size of the achievement, it must be remembered that scientists have only been able to discover conversions of human cells a handful of times since Japanese researcher Shinya Yamanaka created the first human artificial pluripotent stem cells in 2007.

The algorithm has been released and made available online for others to use, so that the field may advance at a much faster pace.

The paper ‘Mogrify: An Atlas for Direct Reprogramming Between Human Cell Types’ by Rackham et al in Nature Genetics.

Challenges Facing the Cell Therapy Community – And how to Overcome those Hurdles

It’s no surprise that cell therapy companies face a myriad of hurdles when developing a product from bench to bedside.

The range of challenges can sometimes feel overwhelming – even for the most seasoned pros in regenerative medicine. So we set out to ask some of the leading names in the industry what some of the biggest hurdles are, and what can be done to overcome them.

Aby Mathew Ph.D., Senior Vice President and CTO, BioLife Solutions.

Aby believes one of the biggest challenges is that companies set up their processes for clinical feasibility, not necessarily commercial viability. ‘So they’re focused on, does the therapy work, not necessarily can we scale it up, can we make it economically viable, can we deliver it globally?’ Aby says.

So what’s the solution? Aby believes it’s down to human capital and mass manufacturing: ‘Down the road, what they might look to do is automate their processes, so instead of having a manufacturing process that might take 50 or 100 people, they might be able to implement a machine that can reduce the head count, but can also reduce the possibility of human error.’

Another solution, Aby says, is to buy in bulk. ‘In the manufacturing process, things such as media components, instruments that you have to use, or components where its packaged up, all of those end up adding to the individual cost. But when you go and buy that from your suppliers, you’re going to get a much better price if you order 1,000 units rather than 10 units and that’s really where that scale-up starts showing the cost of goods benefit.’

Jon Rowley, Ph.D., Chief Executive and Technology Officer, RoosterBio, Inc.

Jon Rowley agrees. He believes a big challenge that many companies have is being able to manufacture products at commercially relevant lot sizes while maintaining all the quality parameters of the cells. ‘They need to make sure that those stem cells don’t lose the biological functionality that they have that makes them therapeutic in the first place. And during scale-up, this can definitely be lost if you’re not looking at the right things,’ Jon says.

His solution? Jon says companies need to understand what the quality parameters are, get the technologies in place to manufacture at a much larger scale, and then manufacture these cell therapy products at costs that enable companies to go to market with them and actually have a profit left over at the end of the day.

Julie G. Allickson, Ph.D., Director, Regenerative Medicine Clinical Center, Wake Forest Institute for Regenerative Medicine

Julie Allickson notes that regulation and due process can pose a challenge to many companies. She advises, “moving to regulatory approval in an efficient manner means really early discussions with the FDA, being able to share with them your knowledge in regards to the technology, and to be able to get their input.” She adds there are several opportunities to talk to the FDA along the way that companies should take advantage of in order to make the process run as smoothly as possible.

Discover more technical and commercial strategies to deliver cell and gene therapy products to patients at the Cell Therapy Manufacturing & Gene Therapy Congress. View the agenda and buy tickets here: https://celltherapy.knnlab.com/

How to Master Data Management during Bioproduction?

With the advancements in technology we are able to make better and wiser decisions that can impact the way we develop products nowadays however with better analytics comes more data and the question now is how to manage this. We asked Jarrod Medeiros, Product Specialists at the leading data management company IDBS about their thoughts on the subject and what advice they could share.

Jarrod

Informa: you recently published a white paper on the subject. Why was that?

IDBS: Because we wanted to educate the community on some of the problems we’ve solved for similar customers.

Informa: How can ineffective data management impact the development of biologics?

IDBS: There are a few effects. A major one is efficiency, we’ve found through working with various customers that a large portion of scientists’ time is spent looking for data, transcribing data, and other low value activities associated with paper notebooks, binders, and MS Excel. Another big effect we’ve seen is on quality. This includes the quality of the data itself which can be compromised due to hand writing and transcribing between systems. But also the quality of the output, when data is ineffectively managed the reports and analyses that can be done are limited.

Informa: What advice would you give to industry to handle the vast volumes of data produced in biological development?

IDBS: Use E-WorkBook?! Come talk to us!? I suppose the first step is to admit it is a problem, and then work with vendors that have expertise in solving these challenges.

Informa: How should data management systems be applied to improve decision making in the development and manufacturing of biological products?

IDBS: One of the largest impacts on decision making comes from the ad-hoc analyses that can be done. It’s easy to prepare data and visualizations that need to be used regularly, but when something unexpected happens it is time consuming and sometimes impossible to pull data together in an ad-hoc manner. Data management systems should capture the relationships and context required to be able to quickly view traceability and make decisions.

Informa: What do you see as the best strategies for gaining insight from the increasing amount of data generated and translating this data into knowledge outcomes for products and processes?

IDBS: The best strategy is to move away from a paper and MS Excel-based process as soon as possible. The longer you wait to implement an electronic system for data management, the more of your historical data continues to be in an unusable state.

Join us at BioProduction 2015 to hear more from Jarrod Medeiros, where he will be presenting on leveraging laboratory informatics for the bioprocessing industry on 15th October at 12:05.

The Economic and Operational Benefits of Single-Use Technologies

Single-use or disposable bioprocessing technologies continue to gain greater acceptance within the biopharmaceutical industry and are now commonly used. The nature of the decisions that bioprocess engineers needed to make around single-use technology has changed since its introduction which was actually relatively early in the history of the biopharmaceutical industry. Early studies investigated whether manufacturing in disposable equipment was even feasible but once technical feasibility had been established the focus switched to whether there were economic or operational advantages in investing in the technology to a greater or lesser extent. Many bioproduction practitioners came to the conclusion that the benefits of single-use were real.

Single-use technologies: The economic case

From an economic perspective single-use technologies reduce capital expenditure on equipment and on utilities. Although the costs of consumables may have an upward pressure on the ‘cost of goods’ this is balanced to some extent by the reduction in costs of running steam, cleaning and water generating facilities used in stainless steel facilities to clean and sterilize re-useable equipment. The time taken to build and validate facilities is reduced as their complexity decreases which further reduces costs, however, critically it also allows the decision to invest in a facility to be delayed until the likely success of the biopharmaceutical product in the clinic is better understood. Given the high attrition rate of pharmaceutical products as they pass through the clinical trials process the benefit to the sponsoring company is significant.

Single-use technologies: The operations case

From an operations point of view, single-use technologies increase speed by reducing downtime required for cleaning and sterilization protocols and increase flexibility both by allowing multiple process configurations for different products to be implemented readily in the same facility and enable process modifications to be facilitated particularly prior to the process being approved by regulatory authorities. The quality performance of operations can be improved by using disposables as the risk of product and batch cross contaminations can be avoided, however, debates continue to rage regarding the nature and extent of testing that must be performed on the single-use parts to show that they have no impact on the safety or efficacy of the biopharmaceutical. Further, the nature of biomanufacturing operations must change to accommodate disposable with sponsors becoming increasingly reliant on the quality organizations of their suppliers. Sponsors must also consider the robustness of their supply chain ensuring the dependability of their own operations so that their biological medicines are always available to the patients that need them.

The future of single-use technologies

New single-use technologies are being developed and evaluated, companies are applying single-use concepts to increasingly diverse bioproduction processes and the technology is being utilized in new manufacturing paradigms such as continuous biomanufacturing. To an ever growing extent, however, the debate is switching from ‘if disposables should be implemented?’ or ‘to what extent?’ towards the questions about how to implement most effectively. Key questions remain on extractables testing, supply chain security, standardization and facilities designs that best accommodate single-use processes. All of these and more will be discussed at BioProduction 2015 in Dublin on the 14-15 October.

Dr Nick Hutchinson

Dr Nick Hutchinson

Join me at #Bioproduction15

Contact me at nick.hutchinson@parker.com

Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker’s strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.