BioCer Release Test Data on "PURE"-ity of Latest Hemostat Innovation HaemoCer Vs. Perclot

A year ago Cryolife CEO Steve Anderson was embroiled in the meltdown of the CRY/Medafor relationship as the distribution agreement for first generation polysaccharide hemostat Arista came to a very bitter and public disintergration.......more HERE. Following this debacle CRY have entered into an agreement with merchant Starch Medical a San Diego based company with manufacturing facilities for Perclot (generation 2 of the polysaccharide powders) based in Beijing, China.http://www.docstoc.com/docs/60831472/PerClot-Arista Our 2009 Poll indicates concern, results HERE.

Now it's Q2 one year later and newly released test reports commissioned by German based BioCer, manufacturers of HaemoCer (conducted by a third party laboratory) offer compelling information supporting the contention their PURE (Polysaccharide Ultra-Hydrophilic Resorbable Engineering) process is much more than marketing hype. The report comparing CRY's Chinese Perclot with German made HaemoCer is available HERE or by clicking the thumbnail below.

Meanwhile video of HaemoCer shows the latest polysaccharide plant based hemostats formation of a powerful adhesive gelled matrix in comparison to generation 1 product Arista by Medafor Inc.

CRY Q2 2011

Comment: Solid growth from CRY this Q2...Hemostasis portfolio buoyed by off-label use of Bioglue (Purified bovine serum albumin (BSA) and glutaraldehyde) in Japan and a suggested move of Perclot manufacturing to the USA from China. For Perclot this should be useful considering how many markets require a Free Trade Certificate (i.e. These certificates are required by governments in a growing number of countries that need assurance that products exported from the United States to their countries are the same as products sold in the United States , presumably meeting all state and federal laws and regulations, thus posing no threat to their subjects. Exports to these countries must be accompanied by a valid certificate, or the product will not be admitted.)


Steve Anderson 

...Japanese BioGlue sales in early July continue to be strong and demonstrate that the product is being well received. BioGlue is also doing very well in Brazil where our distributor is on track by a $1 million during calendar 2011. Sales of BioGlue in Brazil have increased from $150,000 for 2005 to about $1 million in 2011. BioGlue is projected to comprise 40% of company’s sales in 2011.As you will recollect, BioGlue’s gross margins are in excess of 80%.

We are also very pleased with the early European market acceptance of PerClot. During the second quarter of 2011, sales of PerClot in Europe increased by 76% over the sales of HemoStase, a product we formally distributed for the same timeframe a year earlier. Sales of PerClot for the first six months of 2011 in Europe were $1,271,000 versus $721,000 of HemoStase for the same period in 2010.

In our opinion, PerClot is a more effective product than HemoStase [Arista, Medafor Inc.]. We believe that PerClot is a second generation powdered hemostatic agent and the doctors are genuinely pleased with what it does on the surgical setting. Sales in Australia have also been excellent.

During the first quarter conference call we stated that we had filed our US IDE for PerClot with FDA. The FDA had a number of questions and comments regarding our initial IDE submission. We have been addressing the FDA’s issue and are working on our responses. It’s important to note that HemoStase’s gross margin were 55%, and that when approved in the United States we will replace that product with PerClot whose gross margin will be an excess of 80%. I believe that PerClot sales will be a revenue and earnings growth engine for CryoLife going forward....

Ashley Lee

..Once we get PerClot, the manufacturing process transferred here [from current Starch Medicals Chinese manufacturing site] and approved in the US, that’s going to be an 80 plus percent gross margin product...

Steve Anderson

In addition to that, we’re working hard on getting third quarter approved in Brazil and in Canada, and we’re making good progress on that, its just a matter of working our way through the bureaucracy that is involved in approval in those countries. And so they should come on here in the next six to nine month and that products then would be looking at significant sales increases as a result of that. And the success we’re having in Brazil was of course with BioGlue it is sort of piggyback on that. And so, I would expect with the larger volumes late this year and next year with PerClot that those margins probably will continue to increase...

Raymond Myers - Benchmark

On the last call I asked you about this and you were a little more cautious at that time about Japan BioGlue sales, because that market is small you said that you thought you would have to do an additional clinical study to enter the $150 million general surgical sealant market in Japan. And I wonder are we being more optimistic now that we can broaden the use before having to do that study?

Steve Anderson

I think it’s evident that the Japanese physicians are using it off label for other uses. I think it’s too early. I don’t happen to know where they are using it at this time, but it’s obvious from the volume that they are using it an addition to and other places in addition to aortic dissections. We are going to do an additional clinical study, but we have the same exact approval from the FDA initially when we marketed that product in the States and of course and it ended up being used a lot for certain neurological indication and maybe that’s where it’s being used in Japan. I would have to ask our distributor we happen to know that I don’t at this early stage.

Joe Mondillo - Sidoti & Company

With the growth that you guys are seeing in BioGlue and PerClot, we assume to see an increase in CapEx going forward to support the growth that you are seeing?

Ashley Lee

Not necessarily. That’s one of the parts of our business that we think is very leverageable. We have got the infrastructure here currently at our facility to ramp production for BioGlue. We do not perceive any significant spend on CapEx for PerClot and getting that manufacturing process migrated [from Beijing, China] to our US facility....

Blood Stored Too Long May Threaten Patient Safety

THURSDAY, July 21 (HealthDay News) -- New research links medical problems caused by blood transfusion to the breakdown of red blood cells during blood storage. The findings suggest that a better way to store blood is needed.
When transfused, older blood or high amounts of blood can lead to complications, including infection, kidney and lung failure and death, said study co-author Dr. Mark T. Gladwin in a news release from Wake Forest University, which led the study.
The study examines the interaction between nitric oxide (NO) and the byproducts created as red blood cells break down over time. The researchers found that the interaction in older blood can reduce blood flow and perhaps damage tissues in the body.
"When blood sits for a while, some of the cells break down and release their contents, which include molecules of hemoglobin and red blood cell microparticles," said Gladwin, chief of the division of pulmonary, allergy and critical care medicine at the University of Pittsburgh School of Medicine. "These accumulate in the stored bag of blood and are transfused into the patient with the blood. In the bloodstream, the hemoglobin and microparticles bind to and destroy [nitric oxide], a very important molecule that is used by the body to keep blood vessels dilated for normal blood flow."
"Transfusion of stored blood is one of the most common medical therapies," said study senior author Daniel B. Kim-Shapiro, professor of physics and director of the Translational Science Center at Wake Forest University, in the news release. "For example, perhaps we can restore nitric oxide activity that is lost upon transfusion, use preservation solutions that better limit the degradation of blood cells, or develop agents that scavenge free hemoglobin."
Future studies will examine the safety of blood stored more than 14 days. Under current federal guidelines, blood can be stored for up to 42 days.
Each year in the United States more than 5 million people receive blood transfusions, according to the study.
The study is published in the journal Circulation.

Baxter Q2

Sales in regenerative medicine, which includes our BioSurgery products, totaled $147 million and increased 11%. Excluding foreign currency, sales increased 6%, driven by double-digit growth of surgical sealants and hemostats.....

Robert Parkinson

Yes, I would -- this is Bob Parkinson, David. A number of pieces to that. The reality is the European markets continue to be challenging, particularly the more developed Western markets. But having said that, we continue to benefit significantly by emerging developing markets, China, Brazil and so on. Also, generally speaking, the plasma proteins across the board, including developed Europe, were very strong in the second quarter. So it's tough to generalize regarding all markets outside the U.S. We are pleased by the overall strength and growth of our sales outside the U.S., but it is really -- the dynamics are very different between developed Europe, which continues, and we anticipate it's going to continue to be challenging versus our expanding investment and presence in emerging and developing markets, which consistently has been a growth priority for us...

Stryker Q2 2011

In addition, the company's biosurgery business manufactures hemostasis product such as the Vitagel, which are designed to control interoperative and postoperative bleeding. We believe the collective talent of our sizable sales forces across multiple franchises positions us to build on Orthovita's success and accelerate sales growth....Matthew O'Brien - William Blair & Company L.L.C.

Okay. And then the second question on the biologic side with the Orthovita acquisition. Can you just talk a little bit about where your utilization was with your biologic portfolio before the Orthovita deal in terms of all the spine cases, spinal fusion cases you were involved with? And then where you think that may go over the next 6 months or a couple of years even with that broad portfolio available to you now?

Katherine Owen

I would view that the acquisition is very similar in that if we're going to leverage the product offering that we got with the Orthovita deal through our much broader distribution channels in both inpatient and outpatient and across multiple divisions, Instruments, Spine, as was mentioned earlier. I wouldn't view this as leveraging the revenue that we were generating within our biotech specifically. This is where we're rounding out our product portfolio where there was a gap and, again, focusing on our core and leveraging the distribution capability that we have.

J and J, Q2 2011

We've been driving well above market growth in our biosurgicals platform through new products like the SURGIFLO Hemostatic Matrix Kit, one of the first product launches resulting from our 2008 acquisition of Omrix Biopharmaceuticals. We've also driven growth to the rapid globalization of the EVICEL Fibrin Sealant also acquired from Omrix. When we acquired Omrix, EVICEL is available in 1 country, Omrix's home country, Israel. But by the end of 2009, the product was available in 10 countries. And at present, we're at the 21 countries....

So let's start by taking a look at the overall MD&D market and what we're seeing. We continue to believe this market has solid long-term growth potential due to a number of tailwinds that you see on the left-hand side of this slide. I'll highlight each briefly. First, populations in the developed world are aging rapidly. In large countries like Japan, Germany and Italy, more than 20% of the total population is already over 65 years of age. That percentage is rising rapidly in other developed nations, including the U.S., with a first of approximately 77 million baby boomers began turning 65 this year at the astonishing rate of 1 person every 8 seconds. As most of us know from personal experience, we consume more healthcare as we grow older. In fact, those over the age of 65 consume an average of 7 times more healthcare per year than those under the age of 65.

A second tailwind is the growing demand for healthcare that we're seeing in emerging markets. China, for example, has lifted more than 400 million people out of poverty in the last 20 years. As standards of living rise, people increasingly expect and are able to afford better healthcare.

A third tailwind is the fact that significant unmet medical needs remain in both the developed and the developing world. The diseases that our products help treat, osteoarthritis, cardiovascular disease, diabetes, presbyopia, obesity, affect hundreds of millions of people today with prevalence rates that are on the rise globally.

Finally, we live in a time of tremendous scientific and technological progress. I was in Asia just a few weeks ago and had the pleasure of visiting with the number of high-tech companies outside of the healthcare industry. When you think about the advances that are being made in terms of our understanding of disease, and you couple that with some of the incredible new technologies that are being developed, it's a very exciting time to be in our space.

Scientists Develop Communicating Nanoparticles that Boost Targeted Drug Delivery to Tumors

Scientists have developed a two-stage communicating nanoparticle approach to tissue targeting and drug delivery that they claim can target 40 times higher doses of chemotherapeutics to tumors than traditional nanoparticles. Basing the new approach on communications systems found in nature such as insect swarming, immune-cell trafficking, and platelet self-assembly, the collaborative team led by Massachusetts Institute of Technology professor Sangeeta Bhatia, M.D., has devised a system that combines signaling nanoparticles or engineered proteins with receiving nanoparticles that carry the diagnostic or therapeutic agents.
Essentially, the signaling molecules home in on the tumor and activate the coagulation cascade, which results in recruitment of the clot-targeting receiving nanoparticles to the tumor site to deliver their cargo. Reporting in Nature Materials, the researchers claim their work provides the groundwork for a systems nanotechnology approach to targeting that could lead to more sensitive location, diagnosis, and treatment of tissue- or cell-specific diseases. Their paper is titled “Nanoparticles that communicate in vivo to amplify tumour targeting.”
Current approaches for targeting nanomaterials in vivo have focused on tuning the properties of individual nanoparticles (NPs) including their geometry, surface chemistry, ligand type, and ligand density, Dr. Bhatia and team notes. In contrast, the two-stage approach led by the MITresearchers and their collaborators uses two types of nanoparticles that work in concert.
They hypothesized that two signaling modules could selectively activate the coagulation cascade in tumors: NPs (gold nanorods, NRs) that target tumors and convert external electromagnetic energy into heat to locally disrupt tumor vessels, and engineered human proteins—more specifically tumor-targeted tissue factor, tTF—which autonomously survey host vessels for angiogenic tumor receptors and, in their presence, activate the extrinsic coagulation pathway. The receiving modules were constructed using a prototype imaging agent (magnetofluorescent iron oxide nanoworms, NWs) and a prototypical therapeutic agent comprising doxorubicin-loaded liposomes (LPs).
The first step was to test the capacity of the signaling modules to induce coagulation in tumors. Previous work had confirmed that PEG-coated gold NRs have a circulation half-life of over 17 hours in mice and can passively target tumors. The researchers intravenously administered PEG-NRs into tumor-bearing mice, and subsequently irradiated the treated tumors with near-infrared (NIR) light to increase focal tumor surface temperatures. After 24 hours the irradiated tumors in NR-treated mice demonstrated evidence that tumor blood vessel disruption had activated extravascular coagulation.
The researchers then moved on to investigate the potential for a biological signaling module to autonomously survey the host vasculature for angiogenic tumor receptors and, in their presence, engage the extrinsic coagulation cascade. This type of system would operate without the need for any external electromagnetic inputs (such as NIR energy) and could potentially amplify NP targeting to deep-seated and disseminated cancers, they note. For this the team used a truncated, tumor-targeted version of the human protein tissue factor (tTF-RGD), which harnesses an RGD peptide motif to induce coagulation on binding to angiogenic αvβ3 receptors. As occurred following PEG-NR administration, the tumors of mice injected with t-TF-RGD proteins also demonstrated vascular coagulation.
The next step was to construct receiving NPs that could efficiently target regions of coagulation and deliver therapeutics or imaging agents. To this end, a peptide substrate for the coagulation transglutaminase FXIII was tagged to magnetofluorescent iron oxide nanoworm imaging agents to act as an FXIII-NW imaging receiver.
Having verified the coagulation-targeting properties of the receiving FXIII-NW NPs in isolation, the researchers evaluated the two-stage signaling-receiving approach in combination. PEG-NRs were intravenously injected into mice bearing bilateral tumors. After NR clearance from circulation mixtures of active and inactive receiving NPs (FXIII-NWs and FXIIIControl-NWs) labelled with distinct NIR fluorochromes were co-injected intravenously, followed by NIR irradiation of just the right flank of the mouse.
Ninety-six hours later, imaging studies revealed pronounced homing of FXIII-NWs to the NR-heated tumors on the right flank, when compared both with the unirradiated tumor-bearing left flank, and with control, saline-injected mice. Histological examination showed that integrated NP generated intense regions of FXIII-NW fluorescence relative to controls, particularly in tumor boundaries where blood vessels were well perfused. Equivalent results were confirmed in different xengraft tumor models, which also demonstrated a several-fold amplification in the homing of targeted receiving NPs compared with untargeted controls.
In a separate set of experiments, the researchers evaluated the ability of autonomous communication between tTF-RGD signaling modules and FXIII-NW receiving modules to amplify tumor targeting. When co-injected alongside FXIII-NW receivers, the tTF-RGD signaling modules where shown to amplify the receiver targeting response several-fold compared with both noncommunicating controls and with NWs that are directly targeted by RGD-targeting ligands. Closer examination demonstrated that FXIII-NW receivers injected alongside tTF-RGD proteins produced a dendritic pattern of accumulation in tumors, corresponding to abundant intravascular localization immunohistochemically, the authors note. This amplified vascular targeting was found to be specific for tumors and was absent when the coagulation inhibitor heparin was administered alongside signaling and receiving modules.
To demonstrate proof of principal that the approach could improve tumor drug delivery and therapy, the researchers evaluated the efficacy of a therapeutic communicating nanosystem in which the receiver comprised doxorubicin-loaded LPs with tethered active FXIII. When these therapeutic receivers were used in place of the imaging receivers, the team was able to show that communication between NR signaling modules and FXIII-LP receivers amplified the accumulation of doxorubicin in NR-heated tumors by over 40-fold compared with LPs alone, and more than sixfold when compared with an optimized LP formulation that targeted endogenous vascular receptors (αvβ3 for high-affinity cyclic-RGD peptide-targeted LPs).
This amplification of drug delivery probably has at least two components, the authors suggest. Heat-dependent increases in passive accumulation due to improved extravasation in tumors, and specific biochemical recognition of the coagulation process by the peptide coating.
In a final set of studies the team evaluated the therapeutic efficacy of the communicating strategy using PEG-NRs as the signaling molecules and an intravenous dose of FXII-LPs in mice bearing a single human tumor. The PEG-NRs were injected into mice, and once cleared from the circulation, a single intravenous dose of FXIII-LP was given followed immediately by irradiation with NIR energy. The treatment resulted in prolonged inhibition of tumor growth that was significantly more effective than system components in isolation, without any detectable weight loss due to system toxicity.
“Given the diverse NP and synthetic biological 'building blocks' under development, coupled with the plethora of robust biological cascades that could be repurposed to enable communication between synthetic components, we believe that a wide array of nanosystems could be engineered to more sensitively locate, diagnose, and treat a diversity of focal human diseases,” the authors conclude. “We believe that this work motivates a paradigm of systems nanotechnology directed toward the construction of communicative diagnostic and therapeutic agents with sophisticated in vivo behaviors.”

Feds, states split $25M in settlement

WASHINGTON (Legal Newsline) - The U.S. Justice Department announced on Friday that a Danish pharmaceutical manufacturer will pay $25 million to resolve its civil liability arising from the allegedly illegal promotion of its hemostasis management drug.
The Food and Drug Administration approved Novo Nordisk's hemostasis management drug NovoSeven to treat certain bleeding disorders in hemophiliacs. After FDA approval, a manufacturer may not market or promote a drug for uses not specified in its new drug application or for uses not approved by the FDA. Unapproved uses are known as "off-label" uses.
Novo Nordisk's U.S. subsidiary, which is located in Princeton, N.J., allegedly promoted NovoSeven to healthcare professionals for off-label uses, including as a coagulatory agent for trauma patients, general surgery, cardiac surgery, liver surgery, liver transplants and intra-cerebral hemorrhage.
False claims were submitted to government healthcare programs that were not reimbursable because of Novo Nordisk's unlawful promotion, it was alleged. The federal share of the civil settlement is $21,425,790.59. The state Medicaid share of the civil settlement is $3,574,209.41.
"Health care patients should be able to trust that their prescription drugs are safe, effective and prescribed only for FDA approved uses," Maine Attorney General William Schneider said. "These off-label promotions waste Maine taxpayer dollars and we will seek recovery from pharmaceutical companies for this kind of healthcare fraud."
The settlement resolves a a whistleblower lawsuit filed under the qui tam or whistleblower provisions of the False Claims Act that is pending in the District of Maryland. Under terms of the resolution, the whistleblowers are set to receive more than $3.5 million from the federal share of the civil recovery.
Novo Nordisk also agreed to enter into an expansive corporate integrity agreement with the Office of the Inspector General of the Department of Health and Human Services as part of the settlement. That agreement creates procedures and reviews meant to avoid and promptly detect similar conduct in the future.

Jury Rules Against Baxter In Contaminated Chinese Heparin Case - "The Cheap Stuff"

An Illinois jury on Thursday awarded $625,000 to the estate of a Chicago-area man who was administered a blood-thinning drug that contained a contaminated ingredient medical-products company Baxter International Inc. (BAX) manufactured in China.
It was the first of hundreds of pending lawsuits against Baxter to go to trial.
The cases are related to a 2008 finding by the Food and Drug Administration, which discovered a link between contaminated heparin marketed by Baxter to Chinese suppliers of the active ingredient used in heparin. In the U.S., the contaminated heparin was linked to dozens of deaths and hundreds of allergic reactions.
Plaintiffs contended 63-year-old Steve Johansen received low doses of contaminated heparin during dialysis and a bolus dose during a subsequent hospitalization at Palos Community Hospital in late 2007.
The active pharmaceutical ingredient in the contaminated heparin received by Mr. Johansen and other Americans was obtained from Baxter/SPL's Chinese supplier, Changzhou SPL (a joint venture with SPL).  This crude heparin was referred to in the companies' own internal records as "the cheap stuff."  Baxter and SPL knew that the plant had never been inspected by the U.S. FDA (which the FDA later attributed to clerical error) or Chinese regulatory officials.  When the Chinese plant was finally inspected by the FDA after the heparin contamination crisis, multiple violations were found resulting in an import ban.  Additional evidence also brought to light during the trial established that Baxter and SPL failed to establish and comport with quality/purity specifications, including an impurity profile, and failed to trace and control their supply chain.  At trial, the Court granted partial directed verdict in favor of Mr. Johansen holding that the product sold by Baxter and SPL was defective as a matter of law.

According to the verdict, the award of compensation was for pain and suffering and was found against Baxter and the Chinese supplier, Scientific Protein Laboratories LLC.
Baxter spokeswoman Deborah Spak said the company is taking responsibility for legitimate cases of harm related to the contamination seriously, adding that Baxter will "vigorously defend claims that are not consistent with the definition established by public health authorities."
Baxter's therapies treat serious medical problems such as cancer, immune disorders and trauma. The company is coming off a challenging year due to economic weakness, costs pegged to the U.S. health-care overhaul and some product-quality and regulatory challenges.

Impact of Bleeding-related Complications and/or Blood Product Transfusions on Hospital Costs in Inpatient Surgical Patients

Inadequate surgical hemostasis may lead to transfusion and/or other bleeding-related complications. This study examines the incidence and costs of bleeding-related complications and/or blood product transfusions occurring as a consequence of surgery in various inpatient surgical cohorts. 
Methods: A retrospective analysis was conducted using Premier's Perspective hospital database.
Patients who had an inpatient procedure within a specialty of interest (cardiac, vascular, non-cardiac thoracic, solid organ, general, reproductive organ, knee/hip replacement, or spinal surgery) during 2006-2007 were identified. For each specialty, the rate of bleeding-related complications (including bleeding event, intervention to control for bleeding, and blood product transfusions) was examined, and hospital costs and length of stay (LOS) were compared between surgeries with and without bleeding-related complications.
Incremental costs and ratios of average total hospital costs for patients with bleeding-related complications vs. those without complications were estimated using ordinary least squares (OLS) regression, adjusting for demographics, hospital characteristics, and other baseline characteristics.
Models using generalized estimating equations (GEE) were also used to measure the impact of bleeding-related complications on costs while accounting for the effects related to the clustering of patients receiving care from the same hospitals. 

Results: A total of 103,829 cardiac, 216,199 vascular, 142,562 non-cardiac thoracic, 45,687 solid organ, 362,512 general, 384,132 reproductive organ, 246,815 knee/hip replacement, and 107,187 spinal surgeries were identified. Overall, the rate of bleeding-related complications was 29.9% and ranged from 7.5% to 47.4% for general reproductive organ and cardiac, respectively.

Overall, incremental LOS associated with bleeding-related complications or transfusions (unadjusted for covariates) was 6.0 days and ranged from 1.3 to 9.6 days for knee/hip replacement and non-cardiac thoracic, respectively. The incremental cost per hospitalization associated with bleeding-related complications and adjusted for covariates was highest for spinal surgery ($17,279) followed by vascular ($15,123), solid organ ($13,210), non-cardiac thoracic ($13,473), cardiac ($10,279), general ($4,354), knee/hip replacement ($3,005), and reproductive organ ($2,805). 

Conclusions: This study characterizes the increased hospital LOS and cost associated with bleeding-related complications and/or transfusions occurring as a consequence of surgery, and supports implementation of blood-conservation strategies.