Interesting Thrombin Slides

https://drive.google.com/file/d/0B6J8c60Kq5rVekNoT0sxcEVmbzg/view?usp=sharing

Revealed - UK NHS tests for Transfusion related vCJD. US California new cases.

In More Bad news for purveyors of Bovine derived products and transfusion supporters, thousands of NHS patients could be secretly monitored by the Government for symptoms of the human form of mad cow disease amid concerns that there could be another wave of infections.

Experts advising the Department of Health believe patients who have received more than 80 blood transfusions are most at risk of developing the fatal brain disease because it can be passed on through infected blood.

They say monitoring these patients could give vital clues about the way the disease develops and is transmitted from person to person and could help work out whether there are likely to be further deaths. 

Thousands of NHS patients could be secretly monitored by the Government for symptoms of the human form of mad cow disease amid concerns that there could be another wave of infections

It could also inform officials whether the risk from blood donations needs to be treated more seriously.

But they are considering conducting their surveillance secretly because they fear that informing patients they are at risk and are being monitored will cause unnecessary alarm.

The proposals have been discussed by a powerful panel of leading scientists and doctors, which advises the Government on the disease, known as variant CJD.

More...

• Blood test for mad cow disease used in UK for the first time
• Flesh-eating bug that you can catch on the bus or train is spreading in the UK

The panel's report, published online, suggests conducting 'covert health surveillance' of around 30,000 patients known to have received a high number of blood transfusions.

Experts would expect to see at least 150 cases of vCJD in this group of patients, based on scientific evidence that between one in 4,000 and one in 20,000 of the population may be infected.

Experts believe patients who have received more than 80 blood transfusions are most at risk of developing the fatal brain disease as it can be passed on through infected blood

But this has so far not been seen and may either mean the risk is lower than previously thought, or that it is taking longer for cases to develop.

The 'highly transfused' group includes people suffering life-threatening illnesses including acute leukaemia, aplastic anaemia and the blood disorder thalassemia - as well as those with multiple injuries due to road accidents, or heavy blood loss from aneurysms. 

The report acknowledges that following patients without their consent is 'ethically problematic'.

But the panel, a subcommittee of the Advisory Committee on Dangerous Pathogens, has asked the Health Protection Agency to set out the various options for monitoring these patients based on seeking their consent or not. 

Chris James, chief executive of the Haemophilia Society, said: 'We are shocked to learn there was ever any suggestion of non-consensual monitoring. 

'Given the history of contaminated blood in the 1970s and 1980s, the maintenance of medical ethics is especially important to the haemophilia community.

'Any proposed framework must be reviewed by an ethics committee and open to challenge from individuals and organisations such as ourselves through a formal consultation process.' 

Latest official figures show seven NHS patients have died from vCJD after having blood transfusions.

Four are known to have been given blood from people who were infected with fatal vCJD, and the other three had previously had transfusions although it is not known whether the blood was contaminated.  

Since the first vCJD cases emerged in the mid-1990s, 175 people in Britain have died from the brain wasting disease, which is linked to eating beef infected with BSE.

Experts predicted that hundreds more could die after receiving blood infected with the disease. But they now admit they are baffled as to why these cases have failed to emerge. 

One theory is that some people have a genetic advantage and may only carry the disease without developing symptoms. However, they can still infect others if they give blood.

In one case, a patient is known to have been exposed to vCJD in a blood transfusion and is still alive 24 years later. 

A memorial plaque to victims of Human BSE on the Riverside Walk near Westminster Bridge, London

At the moment, patients are only informed that they are at increased risk of developing vCJD if they have been exposed to blood from more than 80 donors and if they are about to have brain, spinal or complex eye surgery.

But this threshold may now be raised to only inform patients if they are exposed to 300 or more blood donors because the lack of vCJD cases so far may indicate that the risk of catching vCJD in blood may be lower than previously suspected. 

Judy Kenny, of the CJD Support Network, whose husband Deryck died aged 69 in 2003 after being given contaminated blood, said: 'If the authorities are going to do any monitoring, patients should be aware of it. 

'There is no grey area - if they are thinking about unconsented monitoring, then it is wrong.'

CJD occurs when nerve-tissue proteins called prions (illustration above) turn 'bad' and gradually destroy the brain

Professor Chris Bunce, science director of charity Leukaemia and Lymphoma Research, said: 'The extent of the risk [of vCJD] to patients who receive regular blood transfusions as part of their treatment is as yet uncertain. 

'One way to ascertain the risk would be to monitor the distribution of the pathogen among people in this group. 

'But with that comes the moral question of whether patients should be informed or not, and this is the dilemma of the Health Protection Agency.'

A Department of Health spokesman said: 'No decisions have been taken on any unconsented follow-up of highly transfused patients.

'No unconsented follow-up has taken place and none would without appropriate ethical approval and on the basis of legal advice.


Meanwhile Stateside...
(Sacramento, CA) 
Friday, February 10, 2012

The Marin County Public Health Officer, Dr. Craig Lindquist, says one person who was diagnosed with a brain disorder similar to Mad Cow Disease has passed away, but that the person did not contract the disease from contaminated beef.  That makes it the classic form of the disease and not the varient form.   

There is another resident still living with Creutzfeldt Jacob Disease or CJD.  Lindquist says there is no evidence it is of the varient variety either. 

CJD is very rare, but always fatal.  It attacks the memory, hand eye coordination and vision before killing the victim within a year. 

The Mad Cow variant of the disease can be spread only by contact with the brain tissue or nervous system tissue of someone or something that is afflicted.  Twenty five years ago, nearly 170 people died of the variant form of the disease in Europe.

Doctor Richard Breitmeyer runs the lab at UC Davis that  tests  Mad Cow disease in sheep and cattle.  

BREITMEYER:  "The current science believes in the United Kingdom that was the cause of Varient CJD in people in that they had consumed meat products that were contaminated with the bovine form."

Breitmeyer's lab is one of six in the nation.

Cattle fed with bovine bone meal was found to be a significant cause of the spread of the disease in Europe.  Of the 40,000 animals tested each year in the United States since, only two tested positive.

In humans, 85 percent of those afflicted with classic CJD had no known risk factors.  Five to ten percent had a genetic history of the disease.

CRY Q3 10Q, FDA Disapproves Perclot IDE.....Perclot China Trial underway......

10Q - PerClot and HemoStase
Revenues from the sale of hemostats, consisting of PerClot and HemoStase, decreased 71% for the three months ended September 30, 2011 as compared to the three months ended September 30, 2010. Revenues from the sale of PerClot and HemoStase decreased 40% for the nine months ended September 30, 2011 as compared to the nine months ended September 30, 2010. The revenue decreases in the three and nine months ended September 30, 2011 were primarily due to a decrease in hemostat sales volume in domestic markets, partially offset by an increase in sales volume in international markets. The revenue decrease in the nine months ended September 30, 2011 was also impacted by a decrease in average selling prices, which decreased revenues by 6%.
International hemostat revenues increased 24% for the three months ended September 30, 2011 and 55% for the nine months ended September 30, 2011 as compared to the three and nine months ended September 30, 2010, respectively. This increase is primarily due to an increase in international sales of PerClot in the 2011 periods over the international sales of HemoStase in the corresponding 2010 periods. Management believes that international PerClot revenues have been favorably impacted by the Company’s ability to market PerClot for all surgical specialties, expanding the direct European sales force into Austria, and PerClot’s product performance when compared to other hemostatic agents.
The decrease in domestic sales volume for the three and nine months ended September 30, 2011 was due to the Company’s planned discontinuation of sales of HemoStase in late March 2011. The Company recognized no domestic hemostat sales in the second or third quarters of 2011, subsequent to the discontinuance of HemoStase sales, as PerClot is not yet approved for commercial distribution in domestic markets. The Company anticipates this loss of domestic hemostat sales to result in a decrease in total hemostat sales for the remainder of 2011 when compared to the corresponding 2010 periods.


The Company will not be able to sell PerClot in the U.S. in future years until U.S. Food and Drug Administration (“FDA”) approval is granted. On March 31, 2011 CryoLife filed an Investigational Device Exemption (“IDE”) with the FDA seeking approval to begin clinical trials for the purpose of obtaining Premarket Approval to distribute PerClot in the U.S. On April 29, 2011 the FDA disapproved CryoLife’s IDE filing with numerous comments and questions. CryoLife is currently addressing those comments and questions and anticipates refiling its IDE for PerClot in the fourth quarter of 2011.


Q3 Report - Brackets have been added-
Ashley Lee...

We experienced some delays in getting PerClot approved in certain international markets and some competitive issues in the EU, which leaves us to slightly lower our guidance.

Worldwide BioGlue revenues were up 10% for the third quarter and up 5% for the nine month period. These increases were predominantly driven by volume increases, particularly in Japan, due to the recent launch of the product. This was the largest year-over-year quarterly increase for BioGlue revenues, since third quarter of 2008, and we continue to remain enthusiastic about the opportunity in Japan.

Total sales in the third quarter in Japan were $651,000 and year-to-date in Japan were approximately $1.2 million. To-date, approximately 250 surgeons have been trained and over 160 accounts have ordered product. We expect another large order from Japan before the end of the year.

PerClot sales for the third quarter were $620,000 and were $1.9 million year-to-date. We experienced some delays in getting PerClot approved in certain international markets and some competitive issues in the EU, which leaves us to slightly lower our guidance. However, despite these delays, our international revenues from the sale of powdered hemostats in the third quarter still increased 24% compared to the prior year, and 55% for the nine month period compared to the prior year.

Steve Anderson...As Ashley has discussed earlier in third quarter of 2010, we announced our first technology acquisition and that we have signed a worldwide manufacturing and distribution agreement for a unique powered hemostatic agent PerClot with Starch Medical of San Jose (Shanghai), California (China).
(Chinese) PerClot is an ideal replacement for the hemostatic powder that we had been distributing worldwide. The primary difference is that PerClot’s gross margin will be 80%.....we filed our IDE for PerClot with the FDA in March of this year. The FDA had questions about our submission that we have been addressing. We will be reaching our IDE to the FDA in mid November. We expect to begin the clinical trial for PerClot (Link to current trial Xijing Hospital of Digestive Diseases, Xi'an, Shaanxi, China) during the second quarter of next year. The clinical trial will probably involve about 300 patients, 150 PerClot patients and 150 control patients. We expect that with six months enrollment and three months follow-up of these patients that we will file our PMA in the second quarter of 2013.

• In which circumstances does the FDA disapprove or withdraw an IDE?
  FDA may disapprove or withdraw approval of an IDE application if FDA finds that:
• 1. The sponsor has not complied with applicable requirements of the IDE Regulation, any other applicable regulations or statutes, or any condition of approval imposed by an IRB or FDA.
  2. The application or a report contains untrue statements or omits required material information.
  3. The sponsor fails to respond to a request for additional information within the time prescribed by FDA.
  4. There is reason to believe that the risks to the human subjects are not outweighed by the anticipated benefits to the subjects or the importance of the knowledge to be gained, that informed consent is inadequate, that the investigation is scientifically unsound, or that the device as used is ineffective.
  5. It is unreasonable to begin or to continue the investigation due to the way in which the device is used or the inadequacy of:
     (i) the report of prior investigations or the investigational plan; (ii) the methods, facilities, and controls used for the manufacturing, processing, packaging, storage, and, where appropriate, installation of the device; or (iii) the monitoring and review of the investigation.

Q & A...

Matt Dolan - Roth Capital Partners

Great. First question on the guidance, just looking at the revenue at this point it implies maybe around 10% sequential uptick in Q4. So how far below $122 million should we expect or what gets you to that type of sequential uptick, meaning, is there a category that improves something on the macro level that rebounds?

Ashley Lee

We think that the upside is in the Cardiogenesis product line and the PerClot product line as well as potentially BioGlue in Japan.

Matt Dolan - Roth Capital Partners

Okay. But given your guidance on those categories it still requires a pretty big sequential uptick?

Ashley Lee

Yeah well the possibility exists again that we could do better and then we expect to do better in Cardiogenesis, PerClot, and BioGlue in Japan. And that -- we think that that’s, we have more upside in those three areas than the rest of the business.

Matt Dolan - Roth Capital Partners

Okay. And then on the earnings guidance just to clarify, I think the delta between adjusted and GAAP last quarter was $0.05 as supposed to an $0.08 differential at mid year. So I wanted to make sure that that’s the reason for the increase in the earnings guidance? And secondly the implied guidance for Q4 cuts EPS basically in half. So I’m just trying to understand why that would be?

Ashley Lee

The primary driver in non-GAAP, the increase in non-GAAP EPS as compared to the end of the second quarter is primarily due to the shifting of some R&D expenses due to some delays and getting some studies started, as those will be shifting out of 2011 into 2012. As it relates to the fourth quarter we provided for some additional expenses in the fourth quarter this year to account for the ongoing discovery and the acceleration of the discovery in our litigation with Medafor.

Raymond Myers - Benchmark

And that was going to be my next question. So let’s get right to that. Roughly how much Medafor litigation expense should we expect?

Ashley Lee

If you go through the end of the third quarter we had spent about $1.4 million and we’re expecting a similar amount in the fourth quarter of this year about $1.4 million.....

Cryolife announce first patients enrolled for BioFoam (Bovine) trial.

ATLANTA, Oct. 24, 2011 /PRNewswire via COMTEX/ -- CryoLife, Inc., CRY +2.52% , a leading tissue processing and medical device Company focused on cardiac and vascular surgery, today announced that it has enrolled the first patient in its U.S. Investigational Device Exemption (IDE) clinical trial for its BioFoam® Surgical Matrix protein hydrogel technology. In connection with the trial, BioFoam will be used as an adjunct to conservative measures of achieving hemostasis on newly resected liver parenchyma.
The approved IDE is for a prospective, multicenter, randomized feasibility study evaluating safety outcomes of BioFoam as compared to a standard topical hemostatic agent. The feasibility investigation will be conducted at up to three investigational sites and will enroll 20 eligible subjects with 10 subjects in each treatment group.
"We are pleased to begin enrolling patients in our IDE study, which is a milestone in our efforts to obtain BioFoam approval for distribution in the U.S.," said Steven G. Anderson, CryoLife president and chief executive officer. BioFoam is based on the same protein hydrogel technology platform from which BioGlue Surgical Adhesive was developed read more HERE.

Late wound healing problems after use of BioGlue® for apical hemostasis during transapical aortic valve implantation

Dural repair with four spinal sealants: focused review of the manufacturers' inserts and the current literature.

Abstract

BACKGROUND CONTEXT:

Deliberate or traumatic dural fistulas are typically augmented by a "sealant" or "fibrin glue" to enhance the strength of dural closure.

PURPOSE:

Little is known about the risks and complications associated with two specific "sealants" and two specific "fibrin glues" used for dural closure.

STUDY DESIGN/SETTING:

Review of the manufacturers' inserts and a focused review of the literature concerning the pros and cons for two "sealants" (DuraSeal [Confluent Surgical Inc., Waltham, MA, USA] and BioGlue [Cryolife, Kennesaw, GA, USA]) and two "fibrin glues" (EVICEL [Johnson and Johnson Wound Management, Ethicon Inc., Somerville, NJ, USA] and Tisseel [fibrin sealant; Baxter International Inc., Westlake Village, CA, USA]) were assessed.

PATIENT SAMPLE:

A focused review of the literature using four different "sealants" or "fibrin glues" was performed.

OUTCOME MEASURES:

Documentation of persistent/recurrent postoperative cerebrospinal fluid fistulas was an end point for failure for the four different "sealants" and "fibrin glues."

METHODS:

Manufacturers' inserts and a focused review of the literature concerning the relative safety and efficacy of two "sealants" (DuraSeal and BioGlue) and two "fibrin glues" (EVICEL and Tisseel) used to augment dural closure were assessed.

RESULTS:

Although DuraSeal is approved by the Federal Drug Administration (FDA) for intracranial and spinal application, two instances of paralysis are described in the literature. BioGlue is classified by the manufacturer as neurotoxic. EVICEL, one of the "fibrin glues," appeared in just two animal studies, whereas Tisseel, the other "fibrin glue," has been used in many large clinical series without adverse events.

CONCLUSION:

Despite the lack of FDA approval, Tisseel (fibrin glue) has seen wide adoption in "off-label" use. DuraSeal, which is FDA approved, was associated with two instances of paralysis. Alternatively, BioGlue was described as neurotoxic even by the manufacturer.

Exhibit Caution with Bovine Thrombin

Patient Safety in Surgery

EU Protocol for the use of CryoLife BioFoam

CryoLife protocol for EU rollout of BioFoam, Click Thumbnail to view.

ARCHIVE
On 10/27/09, CryoLife (NYSE: CRY) announced that the FDA has granted approval for the company's Investigational Device Exemption (IDE) to conduct a human clinical trial for its BioFoam Surgical Matrix protein hydro-gel technology. BioFoam will be used to help seal liver parenchymal tissue when cessation of bleeding by ligature or other conventional methods is ineffective or impractical. The approved IDE is for a prospective, multicenter, randomized feasibility study evaluating safety outcomes of BioFoam as compared to a standard topical hemo-static agent. The feasibility investigation will be conducted at two investigational sites and will enroll 20 eligible subjects with 10 subjects in each treatment group.
CryoLife now will seek approval from the U.S. Department of Defense (DoD), which will be the final step necessary to begin this trial. CryoLife is currently conducting a 60-patient controlled clinical launch of BioFoam at up to six centers in the United Kingdom, Germany, France and Italy. Upon successful completion of the feasibility study, and subsequent FDA and DoD approvals, a follow-on prospective, multicenter, randomized, controlled pivotal study will be conducted. It is currently anticipated that the pivotal investigation will enroll a total of 164 eligible subjects, 82 subjects in each treatment group across a maximum of 10 investigational sites.

U.S. FDA advisory meeting - TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE

On Oct. 28, the committee will discuss FDA's risk assessment for potential exposure to the variant Creutzfeldt-Jakob disease(vCJD) agent in U.S.-licensed plasma-derived Factor VIII and labeling of blood and blood components and plasma-derived products, including plasma-derived albumin and products containing plasma-derived albumin, to address the possible risk of transmission of vCJD.
On Oct. 29, the committee will hear informational presentations related to FDA's geographic donor deferral policy to reduce the possible risk of transmission of CJD and vCJD by blood and blood products and human cells, and tissue and cellular and tissue based products. The committee also will hear updates on the development of devices to remove transmissible spongiform encephalopathy agents from blood components and chronic wasting disease.

DATE: Oct 28-29, 0830/1230

LOCATION: Holiday Inn, 2 Montgomery Village Ave., Gaithersburg, Md.

CONTACT: Bryan Emery or Rosanna Harvey, 301-827-0314

King Pharmaceuticals - Edited

Net sales of THROMBIN-JMI were $37 million, unchanged from the sales level of the first quarter of this year and were below last year’s second quarter sales of $49 million.

...THROMBIN revenues were flat versus the first quarter, we continue to diligently work with the hospital sales force to manage the lifecycle of this highly competitive and commoditized market.

William Tanner – Lazard Capital Markets

Brian, I know you had a couple 483 letters, at least, certainly this year. I wonder if you could give us a rundown on any outstanding issues that there may be at any of your plants or others relevant to King? Just a second question on the Purdue settlement, was there an attempt to encompass the oxycodone NT with that or is that something likely you have to revis in the future?

Brian Markison

Bill, thank you for the question on the Purdue settlement, but we really can’t and will not add much too it than what we’ve already said, but I appreciate the question. With the 483s, I’ll let Joe speak to that.

Joe Squicciarino

As you point out, we had two of our plants underwent inspection earlier this year, one in Rochester, Michigan, where we manufacture Bicillin, and the other is in Middleton, Wisconsin, where Thrombin-JMI is manufactured. So the outcome of the Rochester, Michigan 483s, we had relatively low number of observations. All of the corrective actions pertaining to those observations have been completed. We submitted the final report to the Detroit office of the FDA about a month ago. So nothing earth shattering there and we feel good about that audit and the outcome.

In Middleton Wisconsin, we had slightly higher number of observations; many of them or some of them I should say pertaining to process validation and a couple of other issues. We have addressed about half of the observations in Middleton. So they’re complete and the remaining observations that are yet to be addressed pertain to future production run, so we won’t be able to address those until those future production runs take place, but in both cases we’re in a good shape.

William Tanner – Lazard Capital Markets

Then just nothing else subsequent to those?

Joe Squicciarino

When you say, no, nothing…

William Tanner – Lazard Capital Markets

In terms of the other 43 letters?

Joe Squicciarino

No, no, we have not received any.

Brian Markison

Keep in mind, the Rochester facility is a single purpose plant for Bicillin only, and as Joe mentioned the Middleton facility is a single purpose plant for THROMBIN-JMI. Again, we believe that the Company’s management or the process is going to accept those steps well.