Dude Where is My CAR-T?

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Ravi Nalliah, CEO at TrakCel talks about the new era of "personalized logistics" in this article in BioPharma Reporter.

Note: see our April Blog entry about our collaboration with TrakCel here

Dude where’s my CAR-T? Personalised meds need personalised logistics, says TrakCel

By Dan Stanton+, 01-Sep-2017

After receiving approval Kymriah, Novartis must prove it can handle the supply chain complexities of manufacturing high-value and time-sensitive CAR-T cell therapies, says logistics firm TrakCel.

http://www.biopharma-reporter.com/Downstream-Processing/Novartis-must-prove-it-can-handle-complex-CAR-T-supply-chain-TrakCel

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BBC: Zika virus used to treat aggressive brain cancer

Getty image from BBC post

Getty image from BBC post

Fascinating article on using Zika virus to fight brain cancer.

"It looks like there's a silver lining to Zika."

"latest research shows the virus can selectively infect and kill hard-to-treat cancerous cells in adult brains....Zika injections shrank aggressive tumours in fully grown mice, yet left other brain cells unscathed."

Article posted on  BBC website (read post here), from a report in the Journal of Experimental Medicine

Nanoparticles and Gene Therapy @ The Hutch

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Scientists seeking a simple and gentle way to provide short-term gene therapy have a new tool: nanoparticles. In a paper published August 30 in Nature Communications, Dr. Matthias Stephan at Fred Hutchinson Cancer Research Center describes nanoparticles he has developed that can streamline the delivery of bundled genetic material to specific cells.

“What we’re doing is ‘hit-and-run’ gene therapy,” a strategy in which a brief change to certain cells can have a permanent therapeutic effect, said Stephan, an immunobioengineer who led the study.

Currently, scientists pursuing gene therapy must choose either targeted approaches that permanently alter cells’ DNA, or short-term approaches that are damaging to cells and can’t be restricted to a particular cell type. Now there is a third option.

The nanoparticles’ ability to gently and temporarily provide gene-editing proteins to specific cells is “really the key” that makes the new approach stand out...

 The nanoparticles are formed by bundling synthetic messenger RNA (modified to be safer and more stable than natural RNA) into miniscule packages surrounded by a biodegradable coat. The coat itself is studded with molecules that help the nanoparticles home in on exactly the right cell type.

The researchers showed that hours after the nanoparticles are taken up by target cells, the cells begin churning out proteins based on the new messenger RNA they’ve received. Then, within days, production ceases as the messenger RNA degrades.

Read the full Fred Hutchinson Cancer Research Center article here.

Historic Day!

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 FDA announcement on approval of Kymriah CAR T therapy from Novartis.    Historic announcement:  First gene therapy to be approved in the US.  FDA announcement:  read here

"The safety and efficacy of Kymriah were demonstrated in one multicenter clinical trial of 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL. The overall remission rate within three months of treatment was 83 percent."

And from Novartis' announcement:

"This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients' lives," said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine, who is a pioneer of this new treatment. 

 

Note:  my August 30 original post had a mistake in it.   I referenced a section in the FDA announcement that referred to Actemra instead of Kymriah.   I have corrected the post.

Intriguing data with Juno's new CAR-T therapy

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These new therapies continue to amaze...

Article here

"CAR-T developer Juno Therapeutics has reported data suggesting the benefits of this type of cancer immunotherapy could extend long after the treatment is delivered."

"...the case study 'shows the ability of anti-CD19 CAR-T cells to re-expand in vivo months after the initial CAR T-cell infusion and to re-exert antitumor activity' "

"The big question now is why the CAR-T cells re-activated. The researchers suggest that it may have been a result of the biopsy procedure itself, triggering the response when the presence of the tumour on its own was not sufficient."

Increase Control, Reduce Costs?

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When on message boards we have all read the familiar phrase “don’t hijack this thread” which means don’t stray off topic.   With this post, I am dangerously close to doing that.  So, first let me point you to a new post and white paper offered by Simon Ellison at Fisher Bioservices called “Controlling Complexity [Not Cost] of Advanced Therapy Supply Chain”.   You can visit that page here.  Read it and digest it.   There, I have done my part…now on to the hijacking.

In reading that post, I came across three phrases which combine to support a very similar point that we have been making to decision makers about switching to our evo Cold Chain 2.0 system.  Adopting our evo system increases your CONTROL of your supply chain.  Simon makes the very important point that costs are reduced by increasing control:

…if therapy developers can reduce complexity, they can reduce cost

…complexity is driven by the fact that the therapeutic product is moving between organizations and every movement, although mitigated by SOPs, is a change of location, and personnel.

…complexity is reduced when there is control over chain of custody transactions. 

This may be a bit non-intuitive as control is usually a function of effort (labor hours and activity) which suggests that increasing control inevitably results in higher cost.   However, in the era of “always on”, connected devices this traditional assumption is wrong.   Higher control reduces costs because of the incredibly low, incremental cost of monitoring and communication when it is automated.  [note: there is no “free lunch” and the up-front cost of developing the evo technology and building the software that keeps it running was substantial but, the result is a very low incremental cost per shipment for the user].  

High control/high communication in the evo system results in the production of actionable data and lower losses.  Once configured, the evo system automatically handles communication to all important parties so, labor cost is reduced while decision making quality is increased.  evo.is delivers location data plus, alarms when packages are opened.   Using fully integrated shippers (integrated through our evo.is API) allows monitoring of courier actions throughout the trip.   All of these capabilties increase shipper control and reduce labor costs.

The evo system further increases control by eliminating dependence on remote sites because there are no buttons to push to start cooling or data recording.   evo is always on and always recording.  Outstanding autonomy allows for “3 Pier” shipments with no interim actions or recharge by remote sites.   These features increase your control and decrease costs by eliminating losses and mistakes.

evo Cold Chain 2.0 is a highly integrated SYSTEM made up of advanced technologies that combine to increase CONTROL for therapy developers and DECREASE COSTS arising from compliance, loss, and coordination.  

Fighting Tumors With Gold!

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Very interesting article about combining gold nano stars with immunotherapy.

"The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips,"

"When a tumor dies, it releases particles that trigger the immune system to attack the remnants," said Vo-Dinh. "By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding."

Read more at: https://phys.org/news/2017-08-gold-nanostars-immunotherapy-vaccinate-mice.html#jCp

Another interesting 2016 article ("Exploding nanobubbles can kill cancer cells") in Science Magazine about using gold nanoparticles:  here

As hoped, this prevented the heat from spreading to surrounding normal tissues. But the approach had an even more important effect: It caused temperatures to rise higher where there were large clusters of gold nanoparticles. This vaporized adjacent water molecules, creating tiny bubbles that quickly expand and burst, ripping apart the cancer cells. They key, Lapotko says, is that “nanoparticle clusters produce nanobubbles in cancer cells and not normal tissue.”

SAVSU in the news: "Pharma’s cold chain is going below zero"

Cellular and genetic therapies drive a ‘new paradigm’ for logistics

Very good article highlighting the challenges of moving the new cell therapies and industry's response.   Savsu, Bruce McCormick, and our DV-10 featured in the article along with folks from BioLife, TrakCel, Fisher BioServices, and Cryoport.    Thanks to Pharmaceutical Commerce for presenting such a good article and including us.

"While all of this is generating high enthusiasm in R&D circles, logistics service providers are scrambling to revise their processes to meet the new demands of these therapies. A “new paradigm” is evolving, in the words of Bruce McCormick, President of Savsu..."

http://pharmaceuticalcommerce.com/clinical-operations/pharmas-cold-chain-going-zero/

 

Way To Go! First Approved Cell and Gene Therapy for Osteoarthritis

The use of pre formulated hypothermic storage and cryogenic freeze media is becoming the cell therapy standard practice. BioLife Solutions is the scientific leader in this field. The ability to store and freeze cells to achieve maximum post thaw viability is a critical process leading to successful cell therapy commercialization. This news represents one more important step forward in bringing the advances of cell therapies into practical commercial application. Congratulations to our friends at Biolife Solutions!

FDA Briefing Document: Novartis/Tisagenlecleucel

We are NOT Doctors but, we read this very important briefing document from the FDA because our evo Cold Chain 2.0 system will be part of the manufacturing process for Car-T cells.   Very interesting that the FDA highlighted the challenges in manufacturing this new therapy.   Specifically, they mentioned the challenge of controlling process variability: "It is also critical to understand and address sources of variability seen in the individual products. This can be a challenging issue given the complex and labor-intensive manufacturing processes involved with making a CAR T cell product"

Control of process variability is one of the most important outcomes of adopting the evo Cold Chain 2.0 system.  The superior thermal performance and data reporting of our 2-8C evo's (designed specifically for the inbound leg), and our new DV -196C cryo shippers dramatically reduces process variability.

4.1.1 Control of tisagenlecleucel quality through manufacturing process controls

A major consideration for manufacturing tisagenlecleucel is the establishment of a well- controlled manufacturing process that can consistently produce high-quality CAR T cells that are safe, pure, and potent. Consistency in product quality is necessary to provide reasonable confidence that each lot (batch) of tisagenlecleucel will perform as expected at a given dose in patients.

In order to control the manufacturing process for consistency, it is necessary to thoroughly understand the manufacturing process and critical product quality attributes unique to the autologous CAR T cell products. It is also critical to understand and address sources of variability seen in the individual products. This can be a challenging issue given the complex and labor-intensive manufacturing processes involved with making a CAR T cell product (Figure 1). These challenges can include variability in the starting materials (e.g., patient’s own leukapheresis cells) and human or animal derived reagents (e.g., serum, antibodies); and control of critical components that may be manufactured under contract (e.g., transfer vectors that encode CAR, final container).

Novartis Briefing Document: Click Here

FDA Briefing Document: Click Here

Brooks Automation: Study Comparing Two Methods of Preparing, Transporting, and Storing Live T-Cells

A recent poster authored by Brooks Life Science Systems and BioLife Solutions compared two methods of preparing, transporting and storing live T-cells at both -80°C and -190°C to demonstrate best practices to achieve the highest post-thaw viability.

The quality of procedures and products used for preparing, transporting and storage of cells at both -80°C and -190°C temperatures have a direct impact on post-thaw viability and functionality. Sub-standard preparation, handling, storage, and products may subject cells to improper cryoprotectant exposure, poorly controlled shipping and storage conditions and temperatures.

Savsu participated in this study with Brooks and BioLife.  Great work.

You can download this poster instantly here: http://go.brooks.com/Preserve-T-Cells

 

Unanimous Advice To FDA: Approve Landmark CAR-T Cancer Therapy

“It’s the most exciting thing I’ve seen in my lifetime,” said Timothy Cripe, a blood cancer and bone marrow transplant specialist at Nationwide Children’s Hospital in Columbus, OH.

...The therapy would involve genetically modifying a patient’s T cells to kill cancer and then infusing them back into the body. The dramatic effect of the treatment, known for years as CTL-019, was never questioned at the meeting. Of 68 young people receiving it, 52 of them had an excellent response almost immediately, with their cancer disappearing within the first three months. Three-quarters of those patients remained cancer-free six months after treatment.

This is a really big deal for the industry.

  Read the full article here

Savsu and the DV Series Comes to Bio International - San Diego!

Along with a ton of new, fabulous microbreweries, Meow Wolf, great skiing and mountain biking, New Mexico also has an emerging biotech scene and we are part of it!  Will will be exhibiting with NMBIO and a host of other NM ventures at BIO International in San Diego June 19-22.   Come visit us at Booth 4529 in the New Mexico pavilion.

Savsu will be introducing our new DV series of dry vapor shippers for the first time in the United States.   The DV series, powered by our new Fusion System is absolutely rewriting cryo shipper performance, which means biotech companies can rethink what is possible in logistics.   The DV Series is part of a system that we developed specifically for for moving live cell therapies called evo® Cold Chain 2.0

By the way, here is an interesting article on NMBIO from February of this year.

See you there!

Hello From ISCT - London!

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Having a terrific time at ISCT 2017 - London.   We are here through Saturday, May 6 and are sharing booth space with our partner, BioLife Solutions.   Come visit us at Booth 410!

Response to the announcement of our new dry vapor shippers, and the evo® 2-8 XL has been overwhelming.  Thanks to all who have stopped by the booth so far to discuss working with us.  This conference has such intelligent, imaginative people doing such interesting things...fun to talk to!

DV-4 is a smart dry vapor shipper designed for domestic shipments of 4-5 days duration (example: within US and Europe).   DV-4 is about half the size of full sized dry vapor shippers, still has a wide neck to accommodate full size cassettes, charges in 20 mins, uses the same evo Vision cloud based platform as all other evo products, and cleans easily.  

DV-10 is our long range dry vapor shipper, offering 10-15 days autonomy, and, like the DV-4,  features our new Fusion technology which speeds charging, dramatically improves dynamic performance, and improves protection of precious  payloads.

evo 2-8C XL is designed primarily for larger volume, fresh cell, inbound shipments.   Simple pack out , very long autonomy, and the evo Vision platform combine to give leading biotech companies and specialty couriers unprecedented information and control over their process.  The evo Cold Chain 2.0 system significantly lowers risk in one of the riskiest sections of the suppy chain. 

See you at the booth,

Dana

SAVSU Technologies Announces New evo® DV™ line of Dry Vapor Smart Shippers with New Fusion™ Technology

SAVSU Technologies Announces New evo® DV™ line of Dry Vapor Smart Shippers with New Fusion™ Technology for Rapid Charging and Superior Dynamic Performance

 

-196°C Liquid Nitrogen Shippers Expand Existing Cold Chain 2.0™ System

 

ALBUQUERQUE, NM — May 4, 2017 -- SAVSU Technologies, the leading developer of smart, precision shipping containers and cloud-based cold chain management SaaS solutions, today announced that it is extending its product line with the addition of two new evo dry vapor liquid nitrogen shippers for frozen transport of biologic materials at -196°C. The products are making their debut at The International Society for Cellular Therapy Annual Meeting, May 3-6 in London. Both new models share the brand-new evo Fusion System™ which combines the Fusion Smart Cap™ and Fusion Quick Core™ for extended dynamic performance and dramatically faster charge times. The two new models are the evo DV-4 with four-day autonomy for domestic shipments and the DV-10 with 10-day autonomy for international shipments. The DV-4 is approximately half the weight of standard, full size, large neck, dry vapor shippers.

 

In addition to rapid charging, the new evo Fusion system is safer and easier to load and unload, provides a safer method of storing the biologic materials such as a manufactured cellular therapy, and, in the case of the DV-4, offers improved ergonomics for cell therapy manufacturers and clinicians.

 

Both evo DV models are smart and communicate with evo Vision™, SAVSU’s IoT award-winning,  cloud-based data and communications SaaS. With the addition of the -196°C product line, SAVSU is now the only company offering products to support the entire temperature range (CRT, 2° - 8°C, -80°C and -196°C) for source materials and manufactured cell therapies; all sharing a common data system, specifically designed for live cell therapy companies.

 

evo Cold Chain 2.0 is a disruptive live cell visibility platform consisting of the evo Smart Shipper family and evo Vision cloud-based, live cell visibility platform for temperature sensitive biologic materials and drug products.

 

“Despite numerous requests from our customers to develop an evo shipper in the -196°C range, we said we wouldn’t do it unless we could dramatically advance the existing dry vapor shipper technology. We don’t do ‘me too’ products,” said Bruce McCormick, President of SAVSU. “Well, now we have done it!  With the development of the new evo Fusion technology powering our new evo DV line, we have significantly advanced dry vapor shipper technology, which hasn’t changed much in 40 years. We believe these are important new products to support the commercialization of new personalized cell therapies.”

 

Both new evo DV models will be available for order on May 3, 2017.   Visit SAVSU at the BioLife/SAVSUbooth at ISCT in London.   For more information, please visit www.savsu.com.

 

 

About SAVSU Technologies

 

SAVSU is a leading designer and manufacturer of innovative high performance cloud-connected passive storage and transport containers for temperature sensitive biologics and pharmaceuticals. Our mission is to improve global health by greatly reducing the waste and risks associated with the improper freezing and overheating of thermal-sensitive medicines and biologics. SAVSU has developed proprietary state-of-the-art technology to ultimately lower costs and improve delivery of these most essential materials. For more information please visit www.savsu.com.

 

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SAVSU and TrakCel announce collaboration to integrate Cell Therapy Manufacturing and Cold- Chain data management platforms

Integrating Cell Orchestration and Live Cell Visibility Platforms Will Provide Enhanced, Auditable Vein-to-Vein Documentation Supporting Clinical Trials, Commercial Distribution and Reimbursement of Cell-Based Therapies  

  

ALBUQUERQUE, NM and CARDIFF, UK — April 25, 2017 -- SAVSU Technologies, the leading developer of smart precision shipping containers and cloud-based cold chain management SaaS solutions, today announced that that it will collaborate with Cardiff-based TrakCel Ltd to integrate  its evo® Cold Chain 2.0™system with TrakCel’s Cellular Orchestration Platform™.

evo Cold Chain 2.0 is a disruptive live cell visibility platform for management of time and temperature sensitive biologic materials powered by the evo cloud-connected Smart Shipper and evo Cold Chain Management SaaS. This cloud-based, cold chain management platform integrates shipping container pack-out, freight carrier selection and purchase, and real-time GPS location and payload temperature monitoring, with critical alerts provided to stakeholders in the clinical delivery chain, including shipment, approaching destination, delivered, opened and remaining shelf life.

TrakCel’s Cellular Orchestration platform facilitates efficiency and compliance to quality standards in cell therapy manufacturing by enabling program-critical information to be collated, tracked and and documented. Detailed processes and managed workflows for every participant in the value chain enable safe and efficient scaling outward and upward as production increases. Conditional logic workflows for all participants including clinicians, logistics and manufacturing partners ensure standardization and compliance with validated procedures.

Bruce McCormick, President of SAVSU Technologies, remarked, “Our optimized technologies represent the next generation of integrated, cloud-connected cold chain technologies. We are very pleased to collaborate with TrakCel and look forward to integrating our respective data platforms to provide even more value to our mutual customers. We are committed to driving a paradigm shift away from traditional, risk-laden cold chain practices based on the use of poor performing shipping containers and disconnected data systems.” 

Ravi Nalliah, CEO at TrakCel, commented, “We scoped the packaging and cold chain technologies space to identify best of breed ecosystem partners. SAVSU is so far ahead of traditional container and data logger suppliers, and we are very keen to integrate their innovations into our Cell Orchestration Platform. The timing of this collaboration is perfect as the cell therapy market continues to mature and awareness is peaked on the need to use better tools to enable clinical trial success, commercial scale-out, and reimbursement supported by evidence of compliance throughout manufacturing, distribution and patient administration.”

 Chain Link Research and Pharmaceutical Commerce market research estimate that there are 80 million to 130 million annual temperature sensitive pharmaceutical shipments requiring cold chain management, resulting in $12 billion spent annually on cold chain logistics, with $9 billion for transportation and $3 billion for specialized tertiary packaging and instrumentation such as insulated boxes, blankets, phase change materials, temperature sensors and dataloggers. The use of currently available cold technologies results in $15 billion to $35 billion spent annually replacing products lost due to temperature excursions.

 

About SAVSU Technologies

SAVSU is a leading designer and manufacturer of innovative, high performance, cloud-connected passive storage and transport containers for temperature-sensitive biologics and pharmaceuticals. Our mission is to improve global health by greatly reducing the waste and risks associated with the improper freezing and overheating of thermal-sensitive medicines and biologics. SAVSU has developed proprietary state-of-the-art technology to ultimately lower costs and improve delivery of these most essential materials. 

For more information please visit www.savsu.com.

 

About TrakCel

TrakCel's cell, gene and immunotherapy management solution improves clinical study efficacy and accelerates global scale-up and scale-out by implementing communications technology to integrate the delivery path from needle-to-needle. The technology provides interactive instructions to

professionals across the supply chain and gives stakeholders on-demand visibility of procedural results and chain-of-custody data for immediate traceability, validation and compliance audits. 

TrakCel technology is increasingly being adopted by leaders in the cell, gene and immunotherapy industry. TrakCel is headquartered in Cardiff, Wales with a U.S. offices in Newport Beach, Californiaand Bridgewater, NJ. 

 

For more information please visit www.trakcel.com

 

SAVSU Media & Investor Relations                                      

Dana Barnard                                                                                       

Chief Executive Officer                                                        

SAVSU Technologies, Inc.                                                                   

505.466.1962

info@SAVSU.com

 

 

TrakCel Media & Investor Relations

Hannah James

Marketing manager

TrakCel Ltd.

pr@trackcel.com