Thursday, October 7, 2010
The Business of Recombinant Protein Production
Since the development of recombinant technology in the late 1970s, the use of recombinant proteins in therapeutics has become an attractive strategy for altering the biology of disease progression. In the early 1980s, recombinant human insulin from Escherichia colibecame the first recombinant pharmaceutical to enter the market. Development of several growth hormones produced in bacteria followed, as did production of monoclonal antibodies such as infliximab and ritxumiab from mammalian cell lines. By January of 2009, the number of protein-based recombinant pharmaceuticals licensed by the U.S. Food and Drug Administration and European Medicines Agency reached 151.1
Although recombinant protein technology provides a wealth of commercial opportunities, bringing a recombinant protein to the marketplace requires a substantial investment of time and resources. Because the synthesis and purification processes are technically complex and vary with each protein, estimating resources and timelines can be challenging at best. Yet for small companies, meeting these challenges is vital, says Vladimir Kostyukovsky, senior technical manager at Kymanox, Inc. “With start ups, you need to hit your milestones by a certain date, or you’re out of business.”
The most common expression systems for recombinant pharmaceuticals are derived from bacteria (usually E. coli), yeast (usually Saccharomyces cerevisiae), or mammalian cells. Key properties of individual expression systems affect convenience and quality of production. Characteristics inherent to a target protein also affect production capabilities. Making the transition from producing a laboratory stock of protein to commercial quantities also requires strategic planning and flexibility.
Protein synthesis and purification Microbial systems versus mammalian systems
Recombinant protein production in microbial systems (mainly bacteria or yeast) tends to be faster and cheaper than in mammalian systems. The robust cellular structure of bacteria and yeast make them amenable to culturing, but mammalian cells—derived from multicellular organisms—are not adapted to survive outside the body and are thus sensitive to external conditions like shear stress and osmotic shock. Bacteria and yeast replicate every 20 minutes to 2 hours, while mammalian cells do so every 24 hours to 2 days. Mammalian cells require complex—often proprietary—media with amino acids. Bacterial cell medium consists of simple carbon and nitrogen sources and inorganic salts. The cost for bacterial cell media is 90% lower than for mammalian Chinese hamster ovary (CHO) media. Fermentation or bioreactor runs take 24 to 72 hours in bacteria or yeast versus 14 days to 3 weeks in CHO cells.
Yeast and mammalian cell lines have inherent mechanisms for secreting properly folded, active proteins in culture medium. In E. coli, synthesized protein accumulates internally, and cell lysis is required to isolate the target protein. The process of lysis releases intracellular contents such as proteases or endotoxins, which can decrease yield and complicate purification. Recently, a strain of the gram-positive Corynebacterium glutamicum, which does not have endotoxins, has been engineered to express correctly folded, active recombinant proteins directly into the extracellular fermentation broth.
The following characteristics of target proteins influence their likelihood of being expressed and purified in a functionally active state:
Protein size. Eukaryotic cells, such as mammalian and yeast, have the advantage of being able to express proteins of 200 to 250 kDa, the size of most monoclonal antibodies. In some cases, expression of proteins as large as 400 kDa is possible. In E. coli, it is difficult to obtain proteins larger than 60 kDa in soluble forms.
Protein complexity. The number of protein subunits is inversely related to the likelihood of functional expression. Again, eukaryotic cells have a greater advantage in producing fully assembled, functional, multidomain proteins. Monoclonal antibodies, which consist of 4 subunits, can be secreted by eukaryotic cells as fully assembled complexes. E. coli can be used to express multidomain proteins, but they often lack activity.
Glycosylation. Posttranslational addition of sugar motifs to proteins profoundly affects biological activity, function, clearance from circulation, and antigenicity. Patterns of glycosylation are highly species-specific, and mammalian cell lines have glycosylation repertoires most similar to humans.
Common Challenges
Potential complications lie at every step of the process of recombinant protein expression and purification. The complications vary with each specific protein, but because proteins share common motifs, certain technical pitfalls are encountered frequently.
Protein aggregation. Suboptimal conditions during protein expression, purification, or storage can alter structure and result in aggregation or loss of activity. In bacterial expression systems, intracellular accumulation of protein can lead to formation of inclusion body aggregates.
Aggregation can sometimes be reversed by adjusting media composition, growth temperature, inducer concentration, promoter strength, or plasmid copy number. However, inclusion bodies formed by proteins native to eukaryotes but produced in bacteria tend to be resistant to solubilization. Even proteins that are successfully solubilized can become denatured and thus require potentially complicated in vitro refolding processes.
Refolding. The process of refolding is often preceded by a partial purification to remove host cell proteins that could aggregate with the target protein. Because refolding techniques vary and are often empirical, the online database REFOLD provides refolding protocols that have been successful for a wide range of proteins.2
Proteolytic degration. Host proteases, which can degrade the target protein, are commonly active during cell disruption, as intracellular contents are released. Genetic engineering can be used to remove a host’s more active proteases.
Disulfide bond generation. Disulfide bridges, which stabilize protein structure, are often abundant in secreted proteins. As with refolding, disulfide bond generation and maintenance are achieved through empirical processes. Possible strategies include targeting a specific extracellular excretion pathway or overexpression of chaperones or foldases.
Contamination. Contaminants can originate from host cells or from growth medium. Contaminants can interfere with protein function or cause adverse reactions in human consumers, such as through human pathogens harbored in mammalian expression systems or endotoxins in gram-negative bacteria. The process of removing contaminants can be extensive—often involving several rounds of chromatography—and each additional step diminishes yield.
Making the Transition to Clinical Production
The early steps in developing a recombinant pharmaceutical often require multiple iterations to optimize expression and purification of functionally active protein. As development moves closer to commercialization, schedules, pricing, and other aspects of managing a supple chain become paramount. This transition from focusing on technical concerns to the context of the clinic and broader marketplace can be challenging.
Shailesh Maingi, CEO and president of Kineticos Life Sciences, suggests there are key issues to consider throughout the process of production. First, are you going to make the protein yourself or outsource production? “From a business perspective, this decision is probably the most critical,” Maingi says. “If you want to produce it yourself, there is a huge investment required, not only in money, but in time and resources. If you’re a small, virtual company, you’re almost always going to outsource. If you’re a large company, you’re almost always going to insource because you have the capability and you have the technology.”
Smaller companies have the option of producing a lab supply of protein that can be used in preclinical toxicology studies. Outsourcing for larger-scale production can be done prior to initiating clinical trials.
If you decide to outsource, how do you choose a vendor? At the stages of protein expression and purification, working with a vendor that is flexible in its approach is important, because it is impossible to predict how complex the process will be for a given protein. Any vendor should be able to provide a clear proof of concept and performance history of the technology. Cost, quality, and convenience are important considerations as well. During the expression phase, proximity to the vendor can provide convenience for evaluating efficiency and yield of the process.
In summary, while the path to producing a functionally active and meaningful recombinant pharmaceutical can lead to great commercial opportunity, it can also be plagued with technical pitfalls and failures. Careful consideration of various strategies at every step of the process can optimize use of time and resources.
Although recombinant protein technology provides a wealth of commercial opportunities, bringing a recombinant protein to the marketplace requires a substantial investment of time and resources. Because the synthesis and purification processes are technically complex and vary with each protein, estimating resources and timelines can be challenging at best. Yet for small companies, meeting these challenges is vital, says Vladimir Kostyukovsky, senior technical manager at Kymanox, Inc. “With start ups, you need to hit your milestones by a certain date, or you’re out of business.”
The most common expression systems for recombinant pharmaceuticals are derived from bacteria (usually E. coli), yeast (usually Saccharomyces cerevisiae), or mammalian cells. Key properties of individual expression systems affect convenience and quality of production. Characteristics inherent to a target protein also affect production capabilities. Making the transition from producing a laboratory stock of protein to commercial quantities also requires strategic planning and flexibility.
Protein synthesis and purification Microbial systems versus mammalian systems
Recombinant protein production in microbial systems (mainly bacteria or yeast) tends to be faster and cheaper than in mammalian systems. The robust cellular structure of bacteria and yeast make them amenable to culturing, but mammalian cells—derived from multicellular organisms—are not adapted to survive outside the body and are thus sensitive to external conditions like shear stress and osmotic shock. Bacteria and yeast replicate every 20 minutes to 2 hours, while mammalian cells do so every 24 hours to 2 days. Mammalian cells require complex—often proprietary—media with amino acids. Bacterial cell medium consists of simple carbon and nitrogen sources and inorganic salts. The cost for bacterial cell media is 90% lower than for mammalian Chinese hamster ovary (CHO) media. Fermentation or bioreactor runs take 24 to 72 hours in bacteria or yeast versus 14 days to 3 weeks in CHO cells.
Yeast and mammalian cell lines have inherent mechanisms for secreting properly folded, active proteins in culture medium. In E. coli, synthesized protein accumulates internally, and cell lysis is required to isolate the target protein. The process of lysis releases intracellular contents such as proteases or endotoxins, which can decrease yield and complicate purification. Recently, a strain of the gram-positive Corynebacterium glutamicum, which does not have endotoxins, has been engineered to express correctly folded, active recombinant proteins directly into the extracellular fermentation broth.
The following characteristics of target proteins influence their likelihood of being expressed and purified in a functionally active state:
Protein size. Eukaryotic cells, such as mammalian and yeast, have the advantage of being able to express proteins of 200 to 250 kDa, the size of most monoclonal antibodies. In some cases, expression of proteins as large as 400 kDa is possible. In E. coli, it is difficult to obtain proteins larger than 60 kDa in soluble forms.
Protein complexity. The number of protein subunits is inversely related to the likelihood of functional expression. Again, eukaryotic cells have a greater advantage in producing fully assembled, functional, multidomain proteins. Monoclonal antibodies, which consist of 4 subunits, can be secreted by eukaryotic cells as fully assembled complexes. E. coli can be used to express multidomain proteins, but they often lack activity.
Glycosylation. Posttranslational addition of sugar motifs to proteins profoundly affects biological activity, function, clearance from circulation, and antigenicity. Patterns of glycosylation are highly species-specific, and mammalian cell lines have glycosylation repertoires most similar to humans.
Common Challenges
Potential complications lie at every step of the process of recombinant protein expression and purification. The complications vary with each specific protein, but because proteins share common motifs, certain technical pitfalls are encountered frequently.
Protein aggregation. Suboptimal conditions during protein expression, purification, or storage can alter structure and result in aggregation or loss of activity. In bacterial expression systems, intracellular accumulation of protein can lead to formation of inclusion body aggregates.
Aggregation can sometimes be reversed by adjusting media composition, growth temperature, inducer concentration, promoter strength, or plasmid copy number. However, inclusion bodies formed by proteins native to eukaryotes but produced in bacteria tend to be resistant to solubilization. Even proteins that are successfully solubilized can become denatured and thus require potentially complicated in vitro refolding processes.
Refolding. The process of refolding is often preceded by a partial purification to remove host cell proteins that could aggregate with the target protein. Because refolding techniques vary and are often empirical, the online database REFOLD provides refolding protocols that have been successful for a wide range of proteins.2
Proteolytic degration. Host proteases, which can degrade the target protein, are commonly active during cell disruption, as intracellular contents are released. Genetic engineering can be used to remove a host’s more active proteases.
Disulfide bond generation. Disulfide bridges, which stabilize protein structure, are often abundant in secreted proteins. As with refolding, disulfide bond generation and maintenance are achieved through empirical processes. Possible strategies include targeting a specific extracellular excretion pathway or overexpression of chaperones or foldases.
Contamination. Contaminants can originate from host cells or from growth medium. Contaminants can interfere with protein function or cause adverse reactions in human consumers, such as through human pathogens harbored in mammalian expression systems or endotoxins in gram-negative bacteria. The process of removing contaminants can be extensive—often involving several rounds of chromatography—and each additional step diminishes yield.
Making the Transition to Clinical Production
The early steps in developing a recombinant pharmaceutical often require multiple iterations to optimize expression and purification of functionally active protein. As development moves closer to commercialization, schedules, pricing, and other aspects of managing a supple chain become paramount. This transition from focusing on technical concerns to the context of the clinic and broader marketplace can be challenging.
Shailesh Maingi, CEO and president of Kineticos Life Sciences, suggests there are key issues to consider throughout the process of production. First, are you going to make the protein yourself or outsource production? “From a business perspective, this decision is probably the most critical,” Maingi says. “If you want to produce it yourself, there is a huge investment required, not only in money, but in time and resources. If you’re a small, virtual company, you’re almost always going to outsource. If you’re a large company, you’re almost always going to insource because you have the capability and you have the technology.”
Smaller companies have the option of producing a lab supply of protein that can be used in preclinical toxicology studies. Outsourcing for larger-scale production can be done prior to initiating clinical trials.
If you decide to outsource, how do you choose a vendor? At the stages of protein expression and purification, working with a vendor that is flexible in its approach is important, because it is impossible to predict how complex the process will be for a given protein. Any vendor should be able to provide a clear proof of concept and performance history of the technology. Cost, quality, and convenience are important considerations as well. During the expression phase, proximity to the vendor can provide convenience for evaluating efficiency and yield of the process.
In summary, while the path to producing a functionally active and meaningful recombinant pharmaceutical can lead to great commercial opportunity, it can also be plagued with technical pitfalls and failures. Careful consideration of various strategies at every step of the process can optimize use of time and resources.
Source: Joel White, Business Manager, Biotechnology; Ajinomoto AminoScience, Raleigh, North Carolina
Drug Discovery & Development - October 07, 2010
Ceremed's AOC® Awarded Best New Technology in Biomaterials for Spine Care in 2010
ORLANDO, Fla., Oct. 5 /PRNewswire/ -- Ceremed's patented implantable polymer material known as AOC® won Orthopedics This Week's annual award for Best New Technology for Spine Care in 2010 in the Biomaterials category. AOC® was selected winner by a panel of neurosurgeons, orthopedic surgeons and veteran clinical buyers, based on the technology's originality, clinical relevance, and the likelihood that it will improve current standards of care.
"I am proud of AOC®'s success," said Ceremed's chairman, Tadeusz Wellisz, M.D. "AOC® is a versatile technology that has been well received by physicians and scientists. This award serves as continued validation for AOC® as Ceremed strives to develop more products that aid the surgeon and improve the patient's quality of care."
About AOC®:
AOC® is Ceremed's proprietary implantable polymer material. It is composed of a blend of Alkylene Oxide Copolymers that are commonly used in the medical field. This unique blend is an ideal carrier because it dissolves without swelling and is eliminated from the body within 48 hours. Unlike most resorbable polymers, AOC® does not require metabolic or inflammatory processes to break down. AOC® is synthetic and can be formulated in a range of consistencies with a unique combination of properties, including anhydrous formulations, making it an ideal carrier for compounds that are not stable in aqueous solutions. The material is proving to be a versatile, soluble carrier that delivers a broad range of therapeutics to the surgical site without compromising the healing process.
AOC® is already used in spinal fusion products, as a soluble coating system for orthopedic and neurosurgical implants, and for bone hemostasis. Ceremed is able to custom-manufacture compounds using any OEM proprietary material in combination with the AOC® biomaterial.
About Ceremed:
Ceremed, Inc. is a privately held medical device corporation founded in Los Angeles, California in 2002. Ceremed's mission is to utilize its proprietary implantable polymer formulations to enhance the "Standard of Care" by replacing aging and possibly harmful materials with safe and effective materials and devices that provide for better patient outcomes by improving healing and reducing post-surgical complications. The company manufactures a variety of surgical implantable devices marketed both directly and through partnership licensing and manufacturing arrangements. Ceremed's signature product is the highly successful Ostene® Bone Hemostasis material (www.ostene.com).
"I am proud of AOC®'s success," said Ceremed's chairman, Tadeusz Wellisz, M.D. "AOC® is a versatile technology that has been well received by physicians and scientists. This award serves as continued validation for AOC® as Ceremed strives to develop more products that aid the surgeon and improve the patient's quality of care."
About AOC®:
AOC® is Ceremed's proprietary implantable polymer material. It is composed of a blend of Alkylene Oxide Copolymers that are commonly used in the medical field. This unique blend is an ideal carrier because it dissolves without swelling and is eliminated from the body within 48 hours. Unlike most resorbable polymers, AOC® does not require metabolic or inflammatory processes to break down. AOC® is synthetic and can be formulated in a range of consistencies with a unique combination of properties, including anhydrous formulations, making it an ideal carrier for compounds that are not stable in aqueous solutions. The material is proving to be a versatile, soluble carrier that delivers a broad range of therapeutics to the surgical site without compromising the healing process.
AOC® is already used in spinal fusion products, as a soluble coating system for orthopedic and neurosurgical implants, and for bone hemostasis. Ceremed is able to custom-manufacture compounds using any OEM proprietary material in combination with the AOC® biomaterial.
About Ceremed:
Ceremed, Inc. is a privately held medical device corporation founded in Los Angeles, California in 2002. Ceremed's mission is to utilize its proprietary implantable polymer formulations to enhance the "Standard of Care" by replacing aging and possibly harmful materials with safe and effective materials and devices that provide for better patient outcomes by improving healing and reducing post-surgical complications. The company manufactures a variety of surgical implantable devices marketed both directly and through partnership licensing and manufacturing arrangements. Ceremed's signature product is the highly successful Ostene® Bone Hemostasis material (www.ostene.com).
CryoLife Gets Japanese Regulatory Approval For BioGlue
(RTTNews) - CryoLife, Inc. (CRY: News) said its BioGlue Surgical Adhesive has received Shonin approval from the Japanese Ministry of Health, Labor and Welfare, or MHLW, for use in the repair of aortic dissections.
CryoLife's partner Century Medical, Inc., or CMI, will distribute BioGlue in Japan for use in this subset of cardiac surgery. Prior to distribution, MHLW will need to complete certain additional steps, most notably an on-site inspection of CryoLife pursuant to Japanese Quality Management System requirements and required product reimbursement paperwork for Japanese authorities.
As a result, management estimates that distribution in Japan will begin in the first half of 2011. CryoLife will remain the exclusive supplier of BioGlue to CMI.
CryoLife's partner Century Medical, Inc., or CMI, will distribute BioGlue in Japan for use in this subset of cardiac surgery. Prior to distribution, MHLW will need to complete certain additional steps, most notably an on-site inspection of CryoLife pursuant to Japanese Quality Management System requirements and required product reimbursement paperwork for Japanese authorities.
As a result, management estimates that distribution in Japan will begin in the first half of 2011. CryoLife will remain the exclusive supplier of BioGlue to CMI.
Tuesday, October 5, 2010
CryoLife Appoint D.P. Lang - VP Market Development
ATLANTA, Oct 04, 2010 /PRNewswire via COMTEX/ -- CryoLife, Inc. (CRY 6.17, +0.17, +2.83%)
A graduate of Harvard University with a degree in economics, Mr. Lang began his career at Medtronic in 1970 and has held sales and marketing positions of increasing responsibility throughout his medical device marketing and management career. From 2008 to 2010, Mr. Lang served as the president and was a consultant to Starch Medical Inc. He served as vice president of international sales and marketing for Medafor, Inc. from 2001 to 2008, where he established their European, Latin American and Asian distribution networks.
A graduate of Harvard University with a degree in economics, Mr. Lang began his career at Medtronic in 1970 and has held sales and marketing positions of increasing responsibility throughout his medical device marketing and management career. From 2008 to 2010, Mr. Lang served as the president and was a consultant to Starch Medical Inc. He served as vice president of international sales and marketing for Medafor, Inc. from 2001 to 2008, where he established their European, Latin American and Asian distribution networks.
Kraig Biocraft Laboratories Announces Application for Trademark of Spider Silk ...
LANSING, MI, Oct 05, 2010 (MARKETWIRE via COMTEX) -- Kraig Biocraft Laboratories, Inc.(KBLB 0.15, +0.03, +22.92%) announced today that that it has filed intent to use applications with the US Patent and Trademark office seeking registration of numerous marks for the purpose of branding recombinant silk fibers.
"The Company views branding of our recombinant silk to be just as important as it is with any other product line. It is anticipated that the proposed marks will enhance product marketability and distinguish our advanced technology from other fibers in the marketplace," said Kim Thompson, the Company's CEO and founder. "This is just the beginning of the Company's efforts to further distinguish itself in the market place as we move toward the commercialization of our technology."
The intent to use applications included seven separate proposed marks including Spiderpillar(TM) and Monster Silk(TM).
The Company recently announced the successful development of recombinant spider silk based fibers using genetic engineering.
The Company will also hold a shareholder press conference on Friday, October 8, 2010 at 4:30 p.m. EDT and will issue a reminder press release the morning of the conference call, which will include the phone number and access code instructions.
"The Company views branding of our recombinant silk to be just as important as it is with any other product line. It is anticipated that the proposed marks will enhance product marketability and distinguish our advanced technology from other fibers in the marketplace," said Kim Thompson, the Company's CEO and founder. "This is just the beginning of the Company's efforts to further distinguish itself in the market place as we move toward the commercialization of our technology."
The intent to use applications included seven separate proposed marks including Spiderpillar(TM) and Monster Silk(TM).
The Company recently announced the successful development of recombinant spider silk based fibers using genetic engineering.
The Company will also hold a shareholder press conference on Friday, October 8, 2010 at 4:30 p.m. EDT and will issue a reminder press release the morning of the conference call, which will include the phone number and access code instructions.
Nordson Corporation Enters Agreement to Acquire Micromedics, Inc.
WESTLAKE, Ohio, Oct 05, 2010 (BUSINESS WIRE) -- Nordson Corporation (NDSN 75.00, +3.31, +4.62%) today announced it has entered into a definitive agreement to acquire St. Paul, Minnesota-based Micromedics Inc., a leader in applying and dispensing biomaterials for controlling bleeding, healing wounds and other related medical procedures. Terms of the deal, which is expected to close within approximately 30 days, were not disclosed.
"The Micromedics acquisition fits Nordson's growth strategy of purchasing high performing market leaders with differentiated technology and a significant recurring revenue stream," said Nordson President and CEO Michael F. Hilton. "Micromedics extends Nordson's expertise in precision dispensing technology and helps grow our existing position in the rapidly expanding medical device industry. The market for biomaterial applicators in particular is expected to continue growing due to an expanding range of applications, the continuing introduction of new types of biomaterials, and more widespread reimbursement for procedures using these products."
"The functionality, ease of use and recognized performance advantages of Micromedics products provides significant differentiation in the market and drives customer loyalty," said Micromedics President Curt Miller. "Nordson's global presence, technology leadership and ability to invest should enable Micromedics to build on these strengths, expand its position as a leading provider in the global medical device market, and provide its employees with multiple opportunities for growth."
Micromedics bioapplicator products are marketed under the name FibriJet and include single and dual syringe applicators modified with interchangeable tips for the particular needs of specific surgical procedures. The products enable the controlled dispense of a single material or simultaneous dispense of two materials to a localized treatment site with simple, one-handed operation. The products are sold to a wide variety of end customers, including distributors, surgeons, OEMs, hospitals and outpatient clinics.
The acquired business will be integrated into Nordson's Advanced Technology Systems segment. Additional Micromedics product lines related to ear, nose and throat applications and surgical instrument protection are not being acquired by Nordson and will be spun out prior to close as a new company called Summit Medical Inc.
"The Micromedics acquisition fits Nordson's growth strategy of purchasing high performing market leaders with differentiated technology and a significant recurring revenue stream," said Nordson President and CEO Michael F. Hilton. "Micromedics extends Nordson's expertise in precision dispensing technology and helps grow our existing position in the rapidly expanding medical device industry. The market for biomaterial applicators in particular is expected to continue growing due to an expanding range of applications, the continuing introduction of new types of biomaterials, and more widespread reimbursement for procedures using these products."
"The functionality, ease of use and recognized performance advantages of Micromedics products provides significant differentiation in the market and drives customer loyalty," said Micromedics President Curt Miller. "Nordson's global presence, technology leadership and ability to invest should enable Micromedics to build on these strengths, expand its position as a leading provider in the global medical device market, and provide its employees with multiple opportunities for growth."
Micromedics bioapplicator products are marketed under the name FibriJet and include single and dual syringe applicators modified with interchangeable tips for the particular needs of specific surgical procedures. The products enable the controlled dispense of a single material or simultaneous dispense of two materials to a localized treatment site with simple, one-handed operation. The products are sold to a wide variety of end customers, including distributors, surgeons, OEMs, hospitals and outpatient clinics.
The acquired business will be integrated into Nordson's Advanced Technology Systems segment. Additional Micromedics product lines related to ear, nose and throat applications and surgical instrument protection are not being acquired by Nordson and will be spun out prior to close as a new company called Summit Medical Inc.
Saturday, October 2, 2010
The Mysterious Case of Kevin Xu - “businessman” Kevin Xu’s efforts to sell counterfeit pharmaceuticals including Plavix
Dan Rather and Pfizer expose a counterfeit drug dealer; IBM touts its technology in an anti-counterfeiting commercial.
Traditionally, fall ushers in a new season of television sitcoms and dramas. The ongoing drama of counterfeit drugs was again exposed in “Dan Rather Reports, The Mysterious Case of Kevin Xu,” an investigation into Chinese “businessman” Kevin Xu’s efforts to sell counterfeit pharmaceuticals including Plavix. PharmaManufacturing.com shows HDNet’s independent news organization’s video of the report, which credits Pfizer with exposing Xu.
A 34-page transcript of Rather’s 9/14/2010 report (Episode 528) is also available at HDNet. In it, John Clark, Pfizer’s global head of security, reports that China is often a source of counterfeit drugs and packaging.
Traditionally, fall ushers in a new season of television sitcoms and dramas. The ongoing drama of counterfeit drugs was again exposed in “Dan Rather Reports, The Mysterious Case of Kevin Xu,” an investigation into Chinese “businessman” Kevin Xu’s efforts to sell counterfeit pharmaceuticals including Plavix. PharmaManufacturing.com shows HDNet’s independent news organization’s video of the report, which credits Pfizer with exposing Xu.
A 34-page transcript of Rather’s 9/14/2010 report (Episode 528) is also available at HDNet. In it, John Clark, Pfizer’s global head of security, reports that China is often a source of counterfeit drugs and packaging.
Wednesday, September 29, 2010
It's Over...Medafor Terminates Disputed Drug Distribution Agreement With CryoLife
KENNESAW, Ga. -- CryoLife Inc. (NYSE: CRY) said it has received a notice from Medafor Inc. that terminates a contentious medical device distribution agreement between the two companies, the latest in a long-running dispute, according to an SEC filing.
CryoLife, the Kennesaw-based maker of medical products that enable heart and blood vessel reconstructive surgery, said it would challenge the validity of Medafor's termination of the agreement and pursue its rights and remedies in court.
CryoLife said Medafor's notice came after CryoLife challenged in court a determination in March by Medafor that it was "treating the agreement as terminated."
CryoLife had filed a case in the U.S. District Court for the Northern District of Georgia, Atlanta Division, to stop privately held Medafor, which develops drugs to help blood clotting during major surgeries, from proceeding with the termination of the agreement. The court agreed to hear the case but denied a preliminary injunction, last week.
CryoLife is the single largest shareholder in Minneapolis-based Medafor, with a 10.4 percent holding. CryoLife had sought to hold talks to buy the rest of the company but later withdrew the offer.
Medafor accuses CryoLife of violating an exclusive distribution deal by sellingHemostase, an absorbable blood-clotting agent manufactured by Medafor, in Spain for uses allegedly barred by the agreement. In a counter-suit, CryoLife accused Medafor of violating an agreement by allowing other companies to distribute the product in territories and medical fields reserved exclusively for CryoLife.
The termination of the deal will not materially alter CryoLife's guidance for Hemostase revenue of between $4 million and $4.5 million for the last two quarters of the year, the company said.
CryoLife, the Kennesaw-based maker of medical products that enable heart and blood vessel reconstructive surgery, said it would challenge the validity of Medafor's termination of the agreement and pursue its rights and remedies in court.
CryoLife said Medafor's notice came after CryoLife challenged in court a determination in March by Medafor that it was "treating the agreement as terminated."
CryoLife had filed a case in the U.S. District Court for the Northern District of Georgia, Atlanta Division, to stop privately held Medafor, which develops drugs to help blood clotting during major surgeries, from proceeding with the termination of the agreement. The court agreed to hear the case but denied a preliminary injunction, last week.
CryoLife is the single largest shareholder in Minneapolis-based Medafor, with a 10.4 percent holding. CryoLife had sought to hold talks to buy the rest of the company but later withdrew the offer.
Medafor accuses CryoLife of violating an exclusive distribution deal by sellingHemostase, an absorbable blood-clotting agent manufactured by Medafor, in Spain for uses allegedly barred by the agreement. In a counter-suit, CryoLife accused Medafor of violating an agreement by allowing other companies to distribute the product in territories and medical fields reserved exclusively for CryoLife.
The termination of the deal will not materially alter CryoLife's guidance for Hemostase revenue of between $4 million and $4.5 million for the last two quarters of the year, the company said.
AccessClosure Announces Distribution Agreement for Radial Compression Band
MOUNTAIN VIEW, Calif., Sept. 29 /PRNewswire/ -- AccessClosure, Inc., the market leader in extravascular closure devices, announced today an exclusive agreement with Benrikal Services to distribute the Bengal Radial Compression Band in the United States. The Bengal, uniquely designed for transradial procedures, will join the Mynx™ Vascular Closure Device in AccessClosure's portfolio of products.
"We felt that it was crucial to offer a solution for our customers who use the radial approach," said Gregory D. Casciaro, President and CEO of AccessClosure. "As a customer-focused company, we are striving to provide technologies for all approaches to access site management. The Bengal complements the key features of the Mynx, both of which were designed to minimize impact on the artery, to offer clinical versatility, and to deliver a comfortable experience for the patient. Including the Bengal in our closure portfolio allows AccessClosure to offer the same level of service and education to an even broader base of interventionalists."
The Bengal was designed in partnership with radial pioneer Olivier F. Bertrand, MD, PhD, FSCAI, an Interventional Cardiologist at the Quebec Heart-Lung Institute and Associate-Professor, Faculty of Medicine, at Laval University. "I designed this device to address unmet needs in radial closure. I wanted a simple tool that achieves quick and effective hemostasis, while protecting the ulnar nerve and providing a comfortable experience for the patient," said Dr. Bertrand. "I also wanted to simplify post-operative care for my nursing staff: in my practice, the Bengal requires less monitoring time as it can be removed immediately at the end of the hemostasis period."
Vascular closure devices help to close an artery after cardiovascular procedures. Interventional cardiologists may choose to access the coronary arteries through the radial artery in the wrist instead of the traditional approach using the groin. Use of the radial technique has increased in the United States in the past several years, due in part to the evolution of the technologies that enable the procedure.
The Bengal design offers a new approach to radial artery closure, combining a compression pad that delivers a unique pattern of targeted pressure with a soft polymer gel that ensures patient comfort while the band is on the wrist. "Our Canadian customers appreciate the simplicity and ease-of-use of this band," said Guy Bélanger, President of Benrikal Services. "As transradialists grow increasingly focused on avoiding radial occlusion after procedures, we have observed a natural inclination to a device that is very easy to adjust and optimize."
"We felt that it was crucial to offer a solution for our customers who use the radial approach," said Gregory D. Casciaro, President and CEO of AccessClosure. "As a customer-focused company, we are striving to provide technologies for all approaches to access site management. The Bengal complements the key features of the Mynx, both of which were designed to minimize impact on the artery, to offer clinical versatility, and to deliver a comfortable experience for the patient. Including the Bengal in our closure portfolio allows AccessClosure to offer the same level of service and education to an even broader base of interventionalists."
The Bengal was designed in partnership with radial pioneer Olivier F. Bertrand, MD, PhD, FSCAI, an Interventional Cardiologist at the Quebec Heart-Lung Institute and Associate-Professor, Faculty of Medicine, at Laval University. "I designed this device to address unmet needs in radial closure. I wanted a simple tool that achieves quick and effective hemostasis, while protecting the ulnar nerve and providing a comfortable experience for the patient," said Dr. Bertrand. "I also wanted to simplify post-operative care for my nursing staff: in my practice, the Bengal requires less monitoring time as it can be removed immediately at the end of the hemostasis period."
Vascular closure devices help to close an artery after cardiovascular procedures. Interventional cardiologists may choose to access the coronary arteries through the radial artery in the wrist instead of the traditional approach using the groin. Use of the radial technique has increased in the United States in the past several years, due in part to the evolution of the technologies that enable the procedure.
The Bengal design offers a new approach to radial artery closure, combining a compression pad that delivers a unique pattern of targeted pressure with a soft polymer gel that ensures patient comfort while the band is on the wrist. "Our Canadian customers appreciate the simplicity and ease-of-use of this band," said Guy Bélanger, President of Benrikal Services. "As transradialists grow increasingly focused on avoiding radial occlusion after procedures, we have observed a natural inclination to a device that is very easy to adjust and optimize."
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