Leading hair restoration physician and HypoThermosol user Dr. Alan J. Bauman and YouTube Celebrity Kevin “Nalts” Nalty draw largest audience in history, spark new consumer interest with recent hair transplant webcast.

Over 70,000 consumers tuned in to the first ever YouTube Live hair transplant on November 18, as renowned hair restoration physician Alan J. Bauman, M.D. performed a second NeoGraft Follicular-Unit Extraction (FUE) on weblebrity Kevin “Nalts” Nalty. The live hair transplant surgery was broadcasted live on YouTube’s new, interactive webcast platform, YouTube Live, and simulcasted on Spencer Kobren’s The Bald Truth radio show, Andrew Zarian’s GFQ web radio network, Ustream, JustinTV, Switcher radio, iTunes radio and other outlets.

“This first live hair transplant on YouTube was a remarkable success in terms of total viewership and audience engagement,” said Dr. Bauman. “Broadcasting this procedure proved to be an incredibly effective way to reach and educate the public, and we were amazed by the sheer number of viewer comments and questions about hair transplants, the NeoGraft FUE procedure and other hair loss treatments. This event proved there is a considerable demand out there for patient education and this kind of interactive format.”

Best-selling author and prominent hair loss patient advocate Spencer Kobren, who hosted the live call-in segment, noted, “As a prominent IAHRS-accepted member and a surgeon well-known for cutting-edge technology and exceptional results, it was no surprise that Dr. Bauman’s recent YouTube live hair transplant surgery webcast was our most-watched, most-interactive and most-responded to event ever.” Mr. Kobren went on to say, ”In a field where so many myths and misconceptions abound and surgeons’ abilities and results vary greatly, Dr. Bauman helps us educate hair loss patients that top-tier hair transplant surgeons can reliably provide comfortable, effective, minimally-invasive procedures that yield consistently natural results.”

The live hair transplant webcast allowed viewers unique access to a typically private ‘event,’ becoming active participants in the surgical process like never before, including a live Q&A with Bauman and Nalty during the actual procedure. Viewers were also able to follow, connect and comment through social media channels Twitter, Facebook and LinkedIn during the broadcast.

Bauman brought in a webcast production crew, headed by David Waters, to coordinate the live broadcast from the operation room. Waters has 17 years of experience in television news production, including such networks as Discovery Channel and PBS.

“During the live surgery, the question I got asked the most about was the pain, but really, the procedure was pretty much pain free,” Nalty said. “I think viewers were surprised by how engaging the process is and that hair transplants are more art than science.” Nalty, who had previously documented and shared his first NeoGraft FUE hair transplant with Bauman in 2009, invited his ~250,000 subscribers and the rest of the general public to join him again in the operating room in hopes of de-stigmatizing hair transplantation and clarifying common misconceptions about hair loss treatments.

NeoGraft FUE and Other New Treatment Options:

Nalty’s hair transplant was performed using the state-of-the-art NeoGraft FUE hair transplant. NeoGraft FUE is the most advanced, minimally-invasive hair transplant procedure to-date. Instead of surgically removing a large strip of donor skin from the back of the head, which can lead to a tell-tale linear scar, the NeoGraft FUE mechanically extracts follicular-units one by one, requiring no stitches or scalpel and resulting in greater comfort, less downtime and no linear scarring.

“FUE is an extremely effective surgical option for patients that allows for a quicker, more comfortable recovery, less post-op activity restrictions, as well as avoiding the tell-tale linear scar associated with traditional hair transplants,” said Bauman, who also cautions patients about the recent proliferation of hair transplant surgeons without adequate training and experience because “a poorly planned hair transplant is hard to undo.”

Bauman, a diplomate of the American Board of Hair Restoration Surgery and one of the most experienced FUE hair transplant surgeons in the world, was the first to demonstrate ‘live’ the FUE method of hair transplantation at the 2003 International Society of Hair Restoration Surgery’s Orlando Live Surgery Workshop and the first to demonstrate the NeoGraft FUE device at the ISHRS Orlando Live Surgery Workshop in 2010.

In addition to NeoGraft, there are several other new technologies available at Bauman Medical Group that are bringing new hope to the estimated 100 million American men and women with hair loss:

• PRP Autologel™ – The FDA recently approved Autologel™ Platelet Rich Plasma, or PRP, (Cytomedix) as an advanced wound healing treatment. Dr. Bauman routinely uses Autologel™ to accelerate and improve hair transplant recovery.
• Ouchless™ Needle – A new syringe attachment uses a vapocoolant spray aimed at making needle injections totally painless. Bauman recently used the Ouchless Needle (BellaNovus) to perform the world’s first ‘ouchless’ hair transplant.
• Latisse™ – This eyelash growth product from Allergan stimulates hair follicles to increase length and thickness by mimicking body hormones known as “prostaglandins.” It’s FDA approved for the eyelashes, and in clinical trials for use on the scalp. Bauman has been prescribing the treatment off-label for male and female pattern hair loss cases and is already seeing positive results.
• LaserCap™ and Hand-Held Lasers – In recent years, low-level laser therapy has become more accepted in the treatment of hair loss, evidenced by FDA clearances of one specific brand of comb-laser, an in-office clinical device and a dramatic increase in prescriptions by Hair Restoration Physicians. The first completely cordless and hands-free laser “hat” also recently became available and aims 224 laser diodes at the scalp.
• HypoThermosol (BiolifeSolutions) – Is an advanced storage solution used to hold the hair follicles before they are transplanted, it is designed to preserve the follicles and maintain their viability for healthy transplantation.

“The science behind hair loss is advancing at an amazing rate and promising new treatments are being developed each year,” Bauman explains. “Consumer interest is also higher than ever which is creating some exciting opportunities for the industry.”

Since the live hair transplant event received overwhelmingly positive feedback, Bauman is already looking into future opportunities to combine new technology and social media platforms for patient-education outreach campaigns. “We’ve had an unbelievable response to the event and we plan to go even bigger next time, which will include HD syndication on LiveStream.”

For those who missed the historic YouTube Live broadcast, the archived video is available. For more information on Bauman Medical Group, please visit http://www.baumanmedical.com or call 1-877-BAUMAN-9 or (561) 394-0024.

ABOUT DR. ALAN BAUMAN:
Alan J. Bauman, M.D., founder of Bauman Medical Group in Boca Raton, Florida, is a full-time board-certified and internationally renowned hair transplant surgeon whose pioneering work has been featured extensively in the national and international print and television media, such as Newsweek, The New York Times, Cosmo, Vogue, Allure, Men’s Health, Today Show, The Early Show, Good Morning America, Extra, Access Hollywood and Dateline NBC.

Dr. Bauman is recognized within the medical profession as a top U.S. medical expert on the treatment of hair loss in men and women. A board-certified hair restoration surgeon, Dr. Bauman was the first to demonstrate ‘live’ the FUE method of hair transplantation at the 2003 International Society of Hair Restoration Surgery Orlando Live Surgery Workshop and the first to demonstrate the NeoGraft FUE device at the ISHRS Orlando Live Surgery Workshop in 2010. His practice is divided equally between male and female patients, and Dr. Bauman provides state-of-the-art diagnostic procedures and a multi-therapy approach to the medically treatable condition of hair loss. Dr. Bauman is a member and often a featured speaker at the American Academy of Anti-Aging Medicine and the International Society of Hair Restoration Surgery Annual Scientific Meetings. He is a Diplomate of the American Board of Hair Restoration Surgery as well as a member and frequent lecturer at International Society of Hair Restoration Surgery Annual Scientific Meetings.

Athersys is developing MultiStem^TM, a proprietary adult stem cell product currently being using in multiple clinical trials including Phase I and II trials in indications of Acute Myocardial Infarction, transplant support (Graft Versus Host Disease prophylaxis), Ulcerative Colitis and Stroke. MultiStem is a cell therapy product derived from the bone marrow of a healthy donor.

Unlike other adherent cell types, after isolation from a qualified donor, MultiStem can be expanded on a large scale for future clinical use and stored frozen until needed using a banking system (Master and Working cell banks). These Master and Working cell banks allow for the MultiStem cells to be expanded to numbers such that a single donor will be sufficient to treat hundreds of thousands of patients. These banks are extensively characterized to ensure product consistency and safety including testing for viral contamination and genetic stability.

As MultiStem has progressed through clinical development, different final product configurations have been utilized to supply the MultiStem product to the clinical site for administration. The end user has been taken into consideration when looking at how the final product will be delivered.

Initially, clinical trials in this space were performed at institutional stem cell processing labs, but progression into larger later stage trials has incorporated many physician centers not associated with academic stem cell processing laboratories. Athersys has developed configurations where cells have been supplied to the clinical sites in syringes and transfer bags where the personnel at the clinical sites have little or no manipulation to perform and can receive and deliver the product to the patient.

In one trial, the demands of the final product were such that we needed to process the MultiStem sample and ship the product to the clinical site, overnight, to be delivered to the patient the next morning. This required that cells remain viable over a period of 24 hours with no processing occurring at the clinical site.

After evaluating the stability profile and bedside logistics of several alternative formulations, qualification runs were performed to incorporate HypoThermosol as a dual shipping media and excipient solution for MultiStem. HypoThermosol can be cross-referenced to a US FDA Master File.

The qualification steps for HypoThermosol included an on-site supplier quality audit, in-vitro cell characterization assays and a series of in vivo safety studies in rodents and primates to demonstrate the safety of the HypoThermosol as an excipient solution for the MultiStem cell therapy product. These studies were performed over several months with regular consultations with personnel from Biolife.

The HypoThermosol formulation eliminates any thawing and washing steps at the clinical site and can be delivered immediately to the patient with no processing once received. We found that HypoThermosol enables an improved stability profile that supports expanded distribution over longer distances and shipping intervals and minimizes the need for cell therapy processing labs to be located at clinical sites.

DCPrime B.V. (DCPrime) is a Dutch biotechnology company which develops a novel approach for making cancer vaccines. DCPrime holds a unique platform technology based upon a sustainable dendritic progenitor cell line (DCOne™).

Upon loading with cancer antigens, this generates off-the-shelf DC-based therapeutic products that stimulate a cancer patient’s immune system to recognize and destroy cancer antigens. DCOne combines the power of DC-based vaccines with the advantages of allogeneic immune stimulation, with simpler off-the-shelf clinical logistics. With this powerful platform, DCPrime is developing the next generation of cancer vaccines.

DCPrime is the first to test an allogeneic (non-patient-derived, standardized product) dendritic cell-based immunotherapy. This is based on the DCOne cell line, and the processes to produce DC from this line. Such a standardized product is much more attractive from a production, operational and clinical perspective. Moreover, it concerns a technology platform that allows for different products to be made, each tailored to a specific kind of cancer.

In April 2011, DCPrime initiated a phase I clinical trial, with a goal to investigate the safety and tolerability of DCPrime’s first therapeutic cancer vaccine in patients with acute myeloid leukemia (AML).

The candidate vaccine was administered to twelve AML patients whose immune responses will be closely monitored. The study was performed at the medical center of the Vrije Universiteit, Amsterdam (VUmc), under supervision of hematology specialists Prof. Dr. Gert Ossenkoppele and Dr. Arjan van de Loosdrecht.

Finding a clinical grade freeze media for DCPrime’s final vaccine dose was a high priority.

We considered the cost and quality aspects of formulating a freeze media in-house against selecting a pre-formulated GMP manufactured commercial product, and completed a series of comparative experiments.

CryoStor from BioLife clearly outperformed all other formulations in biopreservation efficacy, and its serum-free, protein-free formulation supported our quality requirements.

Our validation process for CryoStor was supported by several discussions with BioLife’s scientific team members. We know our DCOne cell line is stable, with a long shelf life.

Our stock cells have been frozen for three years now. When thawed and processed, they are identical to the starter cells.

Therefore, with our stock of vaccines, we won’t have the variability that occurs naturally in autologous vaccines.

Evaluation of VAVELTA^® Burns, Wound Scarring, and a Genetic Skin Disorder

Intercytex is funded in part by a series of grants from the North West Development Agency, the UK Government’s Technology Strategy Board, the European Union and by an agreement with the US Department of Defense as well as private investment. Intercytex Ltd is focused on developing and marketing VAVELTA to ensure its potential and benefits can be realized.

VAVELTA (ICX-RHY) is a proprietary suspension of human dermal fibroblasts (naturally derived skin cells) in HypoThermosol cell storage medium, for injection into the skin. VAVELTA is thought to repair the extracellular matrix to improve skin structure and function. VAVELTA is designated as one of the first Advanced Therapy Medicinal Products (ATMP) by the European Medical Agency and has already been used in clinical trials and compassionate use programs in over 100 patients in a variety of indications.

Burns account for approximately 10% of all combat casualties caused by Improvised Explosive Devices (IEDs), an increasingly common feature of today’s conflicts. IED injuries are associated with extensive traumatic skin loss. As a result, burn and trauma scar contractures (where skin around the wound contracts, thickens and becomes inelastic) are a significant and growing problem for injured war heroes.

VAVELTA has already been used in a small number of patients suffering from scar contractures and the outcome of these treatments has led to a Phase II trial in military personnel with burn scars. The work is funded by a significant agreement from the US Department of Defense and the clinical trial is underway at the University of Pittsburgh Medical Center in partnership with the McGowan Institute for Regenerative Medicine.

“VAVELTA HAS ALREADY BEEN USED IN CLINICAL TRIALS AND COMPASSIONATE USE PROGRAMS IN OVER 100 PATIENTS…”

Also, a phase II trial of VAVELTA is underway at King’s College London to treat skin erosions in patients suffering from the severe genetic skin disorder Recessive Dystrophic Epidermolysis Bullosa (RDEB). In such patients the skin blisters at the slightest knock or rub, causing painful, open wounds which result in scarring and fusion of fingers.

Early in the development of VAVELTA, we completed a thorough evaluation of several commercial and generic hypothermic storage and preservation media products. HypoThermosol clearly outperformed all competing alternatives and meets our quality and regulatory requirements.

City of Hope is recognized worldwide for its compassionate patient care, innovative science and translational research, which rapidly turns laboratory breakthroughs into promising new therapies.

We are one of only 40 National Cancer Institutedesignated Comprehensive Cancer Centers nationwide and a founding member of the National Comprehensive Cancer Network. An independent biomedical research, treatment and education institution, we are a leader in the fight to conquer cancer, diabetes, HIV/AIDS and other life-threatening diseases.

The Laboratory for Cellular Medicine supports numerous pre-clinical studies and FDA approved clinical trials with process development expertise, in vitro and in vivo analysis of cell characterization, mechanism of action, and engraftment, and GMP manufacturing of final packaged doses.

Effective preservation of source material, whether peripheral blood or other tissues, is a critical determinant of overall processing success and yield of the final manufactured clinical dose. Cryopreservation of selected cells from source material and the final dose enables efficient clinical trial logistics, since a patient’s condition may change dynamically from one day to the next.

To maximize the quality of our manufactured cells for clinical trials, we selected CryoStor for its post-thaw viability and recovery of several cell types. The product’s serum-free, protein-free formulation, supported by a US FDA Master File, helped support our validation and adoption of CryoStor within our clinical production processes.

Scott Burger, MD

This is part one of a four-part series from Scott Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC.

I. IMPACT OF STABILITY
Raw material and finished product stability, or shelf-life, is a crucial factor in development and commercialization of biologic-based products.

You want extended cell stability. It impacts nearly all aspects of operations, from manufacturing and logistics to patient scheduling and ease of use (Table 1). Stability considerations drive a variety of critical decisions, from location and number of manufacturing sites to transportation methods.

Without cryopreservation, cell therapy products prepared with conventional biopreservation media have quite limited stability, often as little as three days (see Regen Med and FDA-CBER Product Approval Information).

This necessitates releasing the product without final 14-day sterility testing results, overnight shipping, and administration shortly after arrival at the clinical site. Short shelf-life presents other problems as well, not the least that it is quite unforgiving of unexpected events, such as a patient whose treatment should be delayed due to illness on the planned treatment day, or severe weather delaying product transport.

Raw material stability also must be considered, particularly as living, metabolically active cells comprise the critical raw material used in cell therapy manufacturing. This often means stability of 1-3 days in conventional culture media, entailing overnight raw material transport, and with major consequences for manufacturing operations, capacity, and site location.

Cell-based products can be challenging to develop even under the best of circumstances. Lack of stability adds obstacles to commercialization, increasing operational complexity, cost, and risk of failure. (See biopreservation economics.) For most cell-based products, increasing product stability is perhaps the single most effective way to reduce overall operating cost and risk.

Optimizing storage conditions can improve stability significantly. Both cryopreservation and non-frozen (hypothermic shipping media) storage may be used.

See:
Biopreservation Stability (Part 2): Enhancing Stability – Cryopreservation
Biopreservation Stability (Part 3): Enhancing Stability – Hypothermic Storage
Biopreservation Stability (Part 4): New Reagents, New Methods – Effective Process Modification

Scott Burger, MD

This is part two of a four-part series from Scott Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC.

II. ENHANCING STABILITY – CRYOPRESERVATION
Cryopreservation can greatly extend cell stability, often for years, and simplify certain aspects of operations. Product release can be performed after all testing has been completed, with products stored until needed, and administration scheduled with maximum flexibility.

The benefits of cryopreservation do not come without difficulties of their own, however. Transportation of cryopreserved products can be costly and adds operational complexity.

Depending on the composition of the cryopreservation cocktail, post-thaw processing may be necessary to remove cryoprotectant prior to administration. This is problematic, in that it adds a manufacturing step at the clinical site (a location that can be difficult to control), and triggers a requirement for additional safety testing on the thawed, washed cells. See FDA: “Information for Human Somatic Cell Therapy Investigational New Drug Applications.”

Washing the thawed cells prior to administration also introduces questions about post-thaw / post-wash stability.

In general, it is preferable to thaw and administer the product without additional processing, to more closely adhere to the risk mitigation approach of minimal manipulation prior to administration.

It is essential to optimize cryopreservation and thaw, as these methods and materials affect post-thaw viable cell recovery and survival; and, if suboptimal, can eliminate the advantages of cryopreservation.

Variables may include the cryoprotectant, cell concentration, cryopreservation container, cooling as well as thaw rates and methods.

Administering the thawed product without washing eliminates the risks associated with processing at the clinical site. Since the cryoprotectant is intended to be administered to the patient, it must be suitable for use as an excipient – a higher level of quality than needed for an ancillary material.

Like any other process step, cryopreservation and thaw should be validated.

See:
Biopreservation Stability (Part 1): Impact of Stability
Biopreservation Stability (Part 3): Enhancing Stability – Hypothermic Storage
Biopreservation Stability (Part 4): New Reagents, New Methods – Effective Process Modification

Scott Burger, MD

This is part three of a four-part series from Scott Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC.

III. ENHANCING STABILITY – HYPOTHERMIC STORAGE
Hypothermic storage is a simpler and perhaps more broadly applicable method to achieve extended cell stability.

Cells maintained in the presence of an effective hypothermic preservation agent at 2-8°C can increase stability by days or weeks, with varying results obtained with different cell types (see Mathew, et. al.) – some more than others.

Ideally, the hypothermic preservation solution will serve as an excipient as well, enabling administration of the product with no additional manipulation at the clinical site.

The potential for hypothermic storage to increase stability merits investigation for many cell-based products and associated cellular raw material. Extended shelf-life can eliminate several operational problems and make clinical and commercial success far more attainable.

Hypothermic storage may be particularly valuable for cell/scaffold combination products, and other three-dimensional tissue-engineered products for which cryopreservation is not currently feasible.

See:
Biopreservation Stability (Part 1): Impact of Stability
Biopreservation Stability (Part 2): Enhancing Stability – Cryopreservation
Biopreservation Stability (Part 4): New Reagents, New Methods – Effective Process Modification

Scott Burger, MD

This is part four of a four-part series from Scott Burger, MD, Principal, Advanced Cell & Gene Therapy, LLC.

IV. NEW REAGENTS, NEW METHODS – EFFECTIVE PROCESS MODIFICATION
Changing to a new biopreservation solution, like any manufacturing process modification, raises questions about unintended effects on the product.

These can be addressed by a validation study incorporating rigorous characterization testing to compare products manufactured using the original and modified biopreservation processes. Testing should include product purity and identity characterization parameters, as well as the relevant biological function, i.e., potency.

Introducing and validating a new reagent or process step does not invalidate the original process. In fact, the opposite is true.

Successful validation indicates the modified process is as capable of producing the desired product as the original method. A cell banking operation with an established, validated cryopreservation process could, for example, change to a different cryoprotectant, cryopreservation method, or product container, provided the new process could be validated. Cells banked using the original process would be no less valid than they were prior to introduction of the modified process.

During clinical development, it is preferable to introduce manufacturing process modifications, including new reagents, during the intervals between clinical trials. Changes made early in development are the simplest to implement.

Regulatory requirements become increasingly stringent and rigorous as clinical development progresses, necessitating more extensive validation and documentation.

• As one would expect, barriers to change are greatest after product approval (BLA) has been attained.
• Even in Phase 4, manufacturing process and analytical modifications are possible, if difficult.
• Stability-enhancing modifications ideally would be introduced at the earliest opportunity in clinical development.

The benefits of extended cell stability (shelf-life) may be realized at any stage, and the cost-benefit potential of improved biopreservation can be viewed as an aspect of the cell therapy process worthy of consideration throughout development and commercialization.

See:
Biopreservation Stability (Part 1): Impact of Stability
Biopreservation Stability (Part 2): Enhancing Stability – Cryopreservation
Biopreservation Stability (Part 3): Enhancing Stability – Hypothermic Storage

BioLife CEO Mike Rice

The materials and methods used in the biopreservation of source material, intermediate derivatives, and finished cell therapy products greatly influence several critical success factors for final product development and commercialization.

The Cost Per Delivered Dose of a cell therapy product (arguably the most important metric once safety and efficacy are proven) is driven by a yield-cost relationship throughout the biopreservation system. Relationship components include the cost, yield, and stability of source material, as well as the concentration, volume, potency, toxicity, and stability of the finished product.

Stability (in particular) limits the geographic distribution and, hence, revenue potential for the product.

The biopreservation system used in the development and commercialization of a cell therapy product, from source material through manufactured dose, has a cumulative impact on product economics.

When you optimize the biopreservation system, you positively effect downstream-processing operations and yield-cost relationship.

Biopreservation system optimization may be viewed as a matrix (above). Three key cell/tissue materials comprise the X-axis. The critical success factors (shelf life/stability, true post-preservation recovery and functional yield, and acquisition/processing costs) comprise the Y-axis.

System tuning should focus on enabling the longest stability, maximum functional yield, and lowest cost for each biologic type.

Cell Therapy Cost Per Delivered Dose

The blue shaded area between the yield and cost lines (above) represents the optimization potential for the system, with the upper-left corner representing the maximum optimized state.

Another critical success factor for a cell therapy product is the geographic distribution potential.

Logistics around the transportation of (1) source and intermediate material from origin to processing facility, and (2)  finished product from processing facility to clinical markets, are greatly impacted by stability of the material.

The image above depicts source material/finished product from the US and Europe with potential distribution constrained by poor stability. The red dashed circles represent potential limitations on intercontinental movement of source material and/or distribution of a finished product.

Specific biopreservation system optimization initiatives may include the evaluation of various commercial hypothermic storage and cryopreservation media products in comparison to in-house formulated cocktails.

Particular attention should be paid to the true preservation efficacy of the products. This can be measured in split-sample comparisons.

• Use extended cell stability assays capable of accurately indicating post-preservation viability and functional recovery.
• In the assay, measure the duration of cell stability of the biologic enabled by the biopreservation media.
• Also, compare the quality and regulatory footprint of the biopreservation media products vs. in-house formulations for robustness.
• Evaluate the quality of components (USP grade or multi-compendial, serum-free, protein-free), cGMP manufacturing, FDA/regulatory agency familiarity (i.e., Master File, technical file).
• Select a robust set of release criteria (sterility, endotoxin, and cell-based assays) to evaluate when selecting or changing biopreservation media used in cell therapy product development and commercialization.

Figure 3 illustrates the 72-hour cell stability footprint of human fibroblasts enabled by three commercial hypothermic storage media. Fluorescent staining for cytoskeletal integrity, mitochondrial activation, and cell nuclei is clearly visible in the micrographs.

Clearly, your best biopreservation economics will be realized via utilization of best-in-class biopreservation media because the media has a flow-through effect and impact on the yield-cost relationship.

The ability of optimized biopreservation media products to highly leverage source material and finished product cost, yield, and stability, impacts final product distribution and profit potential.