Transdermal Drug Delivery

 

 

 

 

 

 

 

 

http://www.cambridgeconsultants.com

 

 

 

 

 

 

 

 

Tuesday 21st August, 2012

New eco-friendly breed of medical devices

Blood glucose monitor concept is easier to use and cuts environmental impact by two-thirds

A blood glucose monitor concept for diabetics that’s simpler to use, less cumbersome to carry and has a third of the environmental impact of traditional devices has been developed by Cambridge Consultants. The concept is the latest result of ‘Ecovation’ – an approach developed by the leading technology design and development firm to integrate environmental considerations into its radical concept generation process.
More than 346 million people worldwide have diabetes*, and monitoring glucose levels is a critical part of managing the condition and preventing long-term complications. Insulin-treated diabetics are advised to test blood glucose levels four times a day. Many existing blood glucose monitors require separate lancets, test strips, storage tubs for carrying these items, and sharps bins for disposal. This can mean the devices are fiddly to use, inconvenient to transport, and wasteful.
Applying the Ecovation process, Cambridge Consultants conducted a ‘life cycle assessment’ on a popular blood glucose monitor to identify which elements had the highest environmental impact and so should be the focus for innovation. It was identified that less than 5% of the environmental impact could be attributed to the monitor itself – with more than 70% due to the high number of single-use disposables that are consumed over the lifetime of the device.
Ideas generated to reduce the environmental impact ranged from efficient packing of unused and used components, to safe reuse of ‘single-use’ lancets and test strips. The winning concept achieved a 65% reduction in environmental impact by integrating the functionality of three previously discrete consumables and getting the device to do the handling – not the user. The final challenge was then to create a single consumable cartridge, which was both reliable and suitable for manufacturing.
For the user this novel concept has significant benefits. The integrated monitor design is easier to carry around, with fewer consumables requiring separate storage and transport. The cartridge design means the user only has to worry about loading the device once every 28 tests – and, by combining the lancets and test strips in the monitor itself, the glucose test is far easier to administer and more discreet for the user.
“What makes this concept so exciting is that, while it provides a sustainable alternative to the status quo, it also offers distinct usability advantages,” said Andy Pidgeon, of the Medical Technology division at Cambridge Consultants. “We have long championed combining the safety and reliability of the medical development framework with the broader lens of a consumer experience approach in order to create solutions that patients use both safely and willingly. Adding environmental considerations into the design process through Ecovation provides a framework for a new breed of superior medical devices.”
The approach employed in Ecovation can be applied to any type of product to reduce its overall environmental impact. For example, Cambridge Consultants previously demonstrated the methodology by producing an eco-vacuum concept that uses 43% less energy than the average vacuum cleaner.
“The Ecovation process, as demonstrated by our blood glucose monitor concept, has the potential to make a significant step change in reducing the eco-impact of almost any product,” said Gemma Evans, Senior Consultant in Innovation Management at Cambridge Consultants. “Applying Ecovation principles at the design stage needs to become standard practice if we are to reduce our carbon footprint. But making a product greener should never take away from its reliability or functionality and, as we have demonstrated, it can in fact improve its usability and the user experience while minimising its environmental impact.”

OBJ - factored in...

"Drug delivery devices have traditionally been viewed by many in the pharmaceutical industry as a low value and perhaps inconvenient part of the process of creating the pharmaceutical product. In recent years this view has changed to accommodate new healthcare policy, competition and the needs of new therapies such as biological molecules. The increasing pressure to improve patient compliance and reduce healthcare costs, amidst increasing competition from generic suppliers, has brought the need to differentiate drug products with new device forms more sharply into focus. We have moved so quickly and come so far that some new enabling technologies appear poised to revolutionise the market. These are exciting times for our industry..."

1.) The Aging Patient Population

The exponential rise in global population puts increasing strain on many aspects of our society, and healthcare is no exception. The dynamics of this increase are important too. For example, the increases in the elderly population will have a significantly disproportionate impact on our healthcare system, driven by a more rapid increase in patient need over the ability of our society to pay. Increasing numbers of patients, at a time when therapy costs are already high, puts strain on the management of disease in an often over-stretched system. Many delegates recognised that governments are beginning to view future treatments by outcome, in an attempt to find ways to reduce the overall cost burden. For example, agencies such as the National Institute for Health and Clinical Excellence (NICE) in the UK are pricing treatment options on just such a basis. Within this system, a number of drivers are being debated, including the trend towards home-based care to offset pressure on hospitals and local surgeries, and the efficiencies offered through better patient and outcome data management. The move towards home-based care raises the prospect of more simplified drug delivery devices, based on two characteristics of this new market. The first is that the prescribers and carers may no longer be doctors, so instruction on use/training should be simple and effective. The second is that the patient themselves or their non-professional carer may be required to administer drugs previously given in a clinic, requiring simple and low-risk mechanisms to ensure safety and efficacy.

2.) The Patent Cliff...
The patent cliff steepens
Many blockbuster drugs are facing expiry of their US patents in the next 2 years, which is expected to lead to plummeting sales owing to competition from generic versions of these drugs. “The patent cliff facing the industry is very real, with billions of dollars being stripped from companies' revenues," Michael Hay - Sagient Research Systems analyst.

Pharma tries to avoid falling off ‘patent cliff’ - May 2012
For four years Chris Viehbacher has been bracing himself for a nasty turn. Since being appointed Sanofi’s chief executive in 2008, he has been diversifying the French drugmaker to prepare for the moment it loses US patent protection on one of its most lucrative products. “It’s T-minus 3 weeks,” Mr Viehbacher says. Along with its US partner Bristol-Myers Squibb – Sanofi is set to see sales of Plavix, the blood-thinner that is the world’s top selling medicine, drop sharply this year from nearly €7bn in 2011. Along with many of his peers in the pharmaceutical industry, he faces a “patent cliff” of expiries that has pushed companies to adopt widely divergent responses and helps explain a recent flurry of licensing deals and acquisitions. Les Funtleyder, analyst and fund manager at Miller Tabak, says: “The cost of capital is pretty cheap and may not be forever. If you don’t have a good R&D engine, you have to find other ways to support the engine you do have.”

Pfizer this week was among the companies to report a drop in first-quarter sales and earnings as generic rivals diluted its sales of Lipitor, the cholesterol-lowering drug that was itself the world’s top seller until patent expiries began to bite. Late last month, similar gloomy forecasts at AstraZeneca on sales and earnings weighed heavily in the abrupt resignation of David Brennan as its chief executive amid growing investor pressure for change. The industry has faced expiries before, but Tim Anderson, pharmaceutical analyst with Bernstein, says: “Nothing like this has ever been seen before. A series of products are near simultaneously going off patent. In years past, the rates of erosion were substantially less.” - Source

3.) ...and the pursuing Generic Giants
OTC firms focus on new directions
Procter & Gamble is teaming up with Teva, GlaxoSmithKline is putting itself on a par with the best fast-moving consumer goods firms, and Merck & Co and Pfizer are considering their options. Relentless is a good way to describe merger and acquisition activity in the consumer healthcare industry over the past 12 months. Procter & Gamble, meanwhile, has taken a different direction to develop its OTC business. The US-based consumer-goods giant announced recently that it had signed a “master agreement” with the world’s largest generics company, Israel’s Teva Pharmaceutical Industries, to create a consumer healthcare partnership. Shlomo Yanai, Teva’s president and chief executive officer, insisted the tie-up had the “potential to reshape the entire global OTC market”. He explained that the partnership would enable “two global leaders” not only to combine their businesses and research and development portfolios, but also to bring together a set of “complementary capabilities” that were “unmatchable in the healthcare industry”. Yanai’s counterpart at Procter & Gamble, Bob McDonald, pointed out that Teva’s extensive portfolio in categories such as allergy, gastrointestinal and respiratory would provide a pipeline of potential prescription-to-non-prescription switches that could become either new lines or extensions to Procter & Gamble brands such as Metamucil, Pepto-Bismol and Vicks. When finalised, the deal will see Procter & Gamble retain full control of its North American OTC operations, while a joint venture – in which Procter & Gamble will hold 51% and Teva 49% – will combine the two companies’ non-prescription operations in all markets outside of North America. The joint venture will have annual sales of more than US$1 billion on formation, and Teva believes it could become a US$4 billion business within a few years. - OTC firms focus on new directions
Generics Rise Sparks Delivery Technology Need - May 2012

4.) The Need for Better Methods of Drug Delivery

TDDS and TMDS offer advantages over other dosage forms by delivering prolonged, systemic drug levels to allow for simplified dosing regimens and overcome limitations in oral bioavailability or first-pass metabolism.

NeedlesNeedles and syringes are the most common method of administering macromolecular drugs; an estimated 12 billion injections are given annually worldwide. Despite their common use, needles have several limitations, including needle phobia and accidental needle stick injuries. In addition, concerns have arisen about the unsafe use of needles, as exemplified by the overwhelming number of HIV, hepatitis C, and hepatitis B infections that are thought to originate each year from the re-use of needles and syringes.

Noncompliance with medical treatment regimes is also a significant issue. It has been estimated that most patients do not adhere to prescribed dosing regimens, even in developed countries. Non-compliance is linked to several factors, including pain, needle phobia, and forgetfulness, and can result in serious medical complications. In fact, noncompliance is a leading cause of hospitalizations when the carefully designed drug concentration profile is altered in a way that becomes harmful to the patient.

Typically, the blood concentration levels of both injectable and oral drugs that are administered repeatedly vary, depending on the schedule of their administration and the speed at which they are absorbed and distributed by the body. Deviations from the therapeutic range of blood concentrations cause undesirable effects. For these reasons, it is important that drug developers, in addition to considering the efficacy and safety of a drug, must also carefully consider how a drug-delivery system may affect patient compliance.

The limitations of conventional methods of drug delivery can be overcome by needle-free delivery of drugs through the skin or mucosal surfaces of the mouth, nose, or lungs. Although these represent viable alternatives to needle-based methods, these surfaces also present significant barriers to drug entry into the body, and breaching them in a safe, effective way is a major goal of drug-delivery research.

Oral Drug DeliveryOral drug delivery is the most common, and the preferred type of drug administration. A large number of small molecules, including those prescribed for the treatment of pain, heart disease, and blood pressure, are already delivered orally. Drugs delivered orally are typically absorbed across the intestinal epithelium into the bloodstream via two mechanisms. The trans-cellular route involves the transport of drugs through the cell membrane to cross the barrier, either by partitioning of the drug into cell membranes or through the generation of small pores in the outer cell membrane, which allows entry into the cell.

Alternatively, the drug may permeate through the paracellular pathway, which entails transport through the tight junctions between epithelial cells. A tight junction is a dynamic network of tightly packed proteins in the interstitial spaces of a cell monolayer. Tight junctions have been likened to gatekeepers, as their primary function is to maintain the barrier properties of the epithelium and only permit the transport of very small molecules (<4 nm in diameter).

The oral delivery of proteins and peptides has elicited a great deal of interest in recent years because of the availability of novel therapeutics through the advent of recombinant DNA technology. Proteins and peptides are macromolecules with a wide variety of functions in biological catalysis, the regulation of cellular processes, and immune-system protection.

Effective oral delivery of a protein or peptide requires that a therapeutic molecule be delivered to the site of interest and cross the intestinal epithelium barrier intact before being transported to the portal circulation system. Unfortunately, this process is difficult and results in only a small fraction of drug being absorbed in the bloodstream. The delivery of proteins and peptides is further limited by their susceptibility to enzymatic degradation in the gastrointestinal tract.

The scientific community has made a major effort in recent years to overcome the obstacles to oral delivery through the development of a large number of new, innovative drug-delivery techniques. These methods include enzyme inhibitors, permeation enhancers, mucoadhesive polymers, chemical modification of drugs, targeted delivery, and encapsulation.

Enzyme inhibitors are used to counteract the natural functions of the enzymes of the gastrointestinal tract that break down ingested proteins. Many studies have been performed in which inhibitors were co-administered with a drug, but these strategies have seldom been successful unless they included absorption enhancers.

Permeation enhancers have also been used, similar to the way they are used in transdermal drug delivery. Permeation enhancers, such as surfactants, fatty acids, and bile salts, either disrupt the epithelial membrane of the intestine or loosen the tight junctions between epithelial cells. While numerous studies have demonstrated that certain enhancers can be very potent delivery aids, safety concerns abound.

Mucoadhesives
Mucoadhesive strategies have also been used to localize drugs to a small, defined region of the intestine through attractive interactions between the carrier and the intestinal epithelium. This kind of localization results in a high concentration gradient of the drug across the epithelial barrier, which improves drug bioavailability. In addition, a strong adhesion force prolongs the residence time of the dosage at the site of drug absorption, which reduces the dosing frequency and, in turn, increases patient compliance.

Certain mucoadhesive polymers, such as polycarbophil and chitosan derivatives, have been shown to simultaneously act as permeation enhancers and enzyme inhibitors.

Encapsulation Technologies
Encapsulation technologies are another alternative for the oral administration of drugs. Using commercially available pH-sensitive polymers, it is possible to target particular regions of the intestine for drug delivery. Enteric coatings made from these pH-sensitive polymers enable drug-delivery devices to pass through the acidic environment of the stomach unscathed and rapidly dissolve in the intestine. Studies to evaluate these polymers for targeted oral delivery are ongoing in various laboratories.

Other techniques involve the targeting of M-cells in the intestine to improve mucosal vaccine delivery. M-cells, which are present in the Peyer’s patches of the intestine, have the unique ability to take up antigens; targeting can be achieved by using M-cell-specific lectins in combination with a drug-delivery formulation.

Other encapsulation strategies, including micro-particles, nanoparticles, and liposomes, have been developed. These strategies can protect proteins from enzymatic degradation in the intestine and/or facilitate protein uptake across the epithelium.

Transdermal Drug Delivery
Skin, the largest human organ, provides a painless, compliant interface for systemic drug administration. However, because skin evolved to impede the flux of toxins into the body, it naturally has low permeability to the movement of foreign molecules. A unique, hierarchical structure of lipid-rich matrix with embedded corneocytes in the stratum corneum (the upper strata [15 µm] of skin), is responsible for this barrier.

Corneocytes, cross-linked keratin fibers (about 0.2–0.4 microns thick and about 40 microns wide) held together by corneodesmosomes, provide structural stability to the stratum corneum. Lipids, which provide the primary barrier function in the stratum corneum, consist of several components; the primary constituents are ceramides, cholesterol, and fatty acids. The layer of lipids immediately adjacent to the corneocytes is covalently bound to them and plays an important role in maintaining the barrier function. The stratum corneum is continuously desquamated, with a renewal period of about one week, and is actively repaired by the secretion of lamellar bodies following the disruption of the barrier properties or other environmental insults.

Transdermal drug delivery involves placing a drug on the skin in the form of a patch, cream, or lotion wherein the drug permeates across the skin and enters the bloodstream. Key advantages of transdermal delivery include the easy accessibility of skin, which encourages patient compliance, avoidance of the gastrointestinal tract, and sustained release over extended periods of time.

A number of drugs, including scopolamine, nitroglycerin, nicotine, clonidine, fentanyl, estradiol, testosterone, lidocaine, and oxybutinin, are routinely delivered transdermally by skin patches. The patches, which generally last from one to seven days, depending on the drug, have enabled new therapies and reduced first-pass effects and severe side effects. For example, estradiol patches, which are widely used, have eliminated liver damage, which was a side effect of the drug when it was delivered orally. Transdermal clonidine, nitroglycerin, and fentanyl patches also have fewer adverse effects than the same drugs delivered orally. Nicotine patches have prevented, or at least reduced, smoking and increased lifespans.

Two classes of transdermal patches are currently available: (1) reservoir-type patches and (2) matrix-type patches. A reservoir-type patch holds the drug in a solution or gel, and the rate of delivery is governed by a rate-controlling membrane. Reservoir-type patches offer more flexibility in terms of drug formulation and tighter control over delivery rates than matrix-type patches. However, they are usually associated with greater design complexity. In matrix-type patches, the drug, adhesive, and mechanical backbone of the patch are combined into a single layer. Thus matrix-type patches are easier to fabricate, but they pose even more significant design constraints than reservoir-type patches.

Drugs that are currently administered transdermally have two common characteristics—low molecular weight and high lipophilicity. Opening the transdermal route to large hydrophilic drugs, a major challenge in the field of transdermal drug delivery, will require the development of technologies that enable the controlled, reproducible transdermal delivery of macromolecular drugs.

Passive Methods
Technologies that facilitate transdermal drug delivery can work either passively or actively, depending on whether an external source of energy is used to facilitate skin permeation. Passive methods include chemical enhancers, micelles, liposomes, and peptides. Examples of chemical enhancers include fatty acids, fatty esters, solvents, and surfactants. These enhancers facilitate transdermal transport by making drugs more soluble, increasing partitioning into the skin, fluidizing the crystalline structure of the topmost layer of skin, or dissolving skin lipids.

Various modes of transdermal drug delivery. (A) Liquid-jet injections deliver drugs into intramuscular, subcutaneous, or intradermal regions. (B) Permeability-based methods of transdermal drug delivery: (i) delivery through hair follicles; (ii) tape-stripping removes the stratum corneum and facilitates drug absorption; (iii) thermal or radio frequency wave-mediated ablation of the stratum corneum creates micropores that enhance drug delivery; (iv) colloidal carriers, such as microemulsions and transfersomes, enhance the dermal absorption of topically applied drugs; (v) low-frequency ultrasound increases drug delivery by making the skin more permeable; (vi) chemical enhancers or peptides for drug delivery; (vii) electroporation of the stratum corneum enhances drug delivery into the epidermis; (viii) microneedles penetrate into the epidermis to deliver drugs. (C) Powder injection delivers dry drug powders into superficial skin layers (epidermis and superficial dermis).

Although individual chemical enhancers have had some success, combinations of chemical enhancers are more effective. However, so far, the rational design of combinations of enhancers has been limited by the lack of information on interactions between individual chemical enhancers and the stratum corneum. The number of randomly generated formulations for binary mixtures is in the millions, and the number for higher order formulations (for example, ternary or quaternary mixtures) is even higher. Screening of these formulations is beyond the scope of traditional methods (e.g.,Franz diffusion cells).

High-throughput methods of screening transdermal formulations can open this bottleneck and may lead to the discovery of previously unknown mixtures. A new high-throughput method for screening transdermal formulations is >100-fold more efficient than Franz diffusion cells with this method, up to 1,000 experiments a day can be conducted, an experimental space well beyond the scope of traditional tools. Recent studies have also shown that peptides may effectively increase skin permeability. Specifically, peptides discovered using phage-display methodology have been shown to deliver macromolecules, such as insulin, in vivo (Chen et al., 2006).

Chemical enhancers are relatively easy to incorporate into transdermal patches and can be calibrated to deliver predetermined amounts of a drug by changing the application area. However, passive methods cannot dynamically control the drug dose.

Active Methods
Active methods can be controlled in real time by varying appropriate parameters. The device and application parameters can also be adjusted to match the patient’s skin properties. A growing number of researchers are now exploring transdermal devices with active mechanisms for skin permeation, such as microneedles, jet injectors, ultrasound, iontophoresis, and electrophoresis.

Microneedles are arrays of micrometer-sized shallow needles that penetrate only into the superficial layers of skin, thereby eliminating the pain associated with standard hypodermic needles. Microneedles have been made from a variety of materials, including metals, semiconductors, polymers, and glass, and have been shown to be effective in drug delivery. They have also been produced in solid and hollow forms. Solid microneedles are used to render skin permeable, whereas hollow microneedles actively deliver drugs into the skin at a controlled rate.

In contrast, jet injectors deliver a high-velocity liquid jet stream into the skin, delivering drugs into various skin layers, depending on the jet parameters. Jet injectors have a long history, particularly in the delivery of vaccines, insulin, and growth hormone. Ultrasound enhances skin permeability by cavitation, which temporarily disrupts skin structure. Iontophoresis and electroporation use electric fields to alter skin structure and/or provide additional driving force for drug penetration through the skin.

Combined Technologies
Although many individual technologies have been shown to facilitate transderml drug transport, combinations of technologies are often more effective than any of them alone. A combination of two or more technologies may not only increase the enhancement, but may also potentially be safer. Understanding the synergies between technologies and selecting the right combinations is a fruitful area for research that is still largely unexplored.

Summary
In the last decade, significant new insights have been developed into the structural organization and barrier formation of the skin. In the past, skin was considered primarily a barrier, but it is now known to be a smart material that controls its own structure and function in response to the environment. This new knowledge must be incorporated into the future development and evaluation of transdermal technologies.
Areas for Ongoing Research
Novel, painless, patient-friendly methods of drug delivery represent an unmet need in the field of health care. Discoveries in the last decade have demonstrated the feasibility of using several different methodologies for enhancing drug delivery through skin and other mucosal surfaces. These methods have shown the potential to deliver several molecules, including macro-molecules such as insulin and vaccines.

The development of mathematical models to describe and predict transport across the skin and mucosal barriers is another area of active research that has provided useful insights into the development of novel strategies. With the variety of engineering tools at hand, the future of drug delivery looks brighter than ever. The challenge is to convert these discoveries into useful products. - Source

5.) The Residual Drug Issue with currently marketed Transdermal Delivery Technologies
Currently marketed TDDS, TMDS, and topical patches may retain 10-95 percent of the initial total amount of drug as the residual drug after the intended use period. This raises a potential safety issue not only to the patient, but also to others including family members, caregivers, children, and pets. For example, adverse events due to a patient’s failure to remove TDDS at the end of the intended use period have been reported and are generally related to an increased or prolonged pharmacological effect of the drug. Also, some children have died from inadvertent exposure to discarded TDDS. - FDA Guidance for Industry: Q8(R2) Pharmaceutical Development
FDA Guidance for Industry: Residual Drug in Transdermal and Related Drug Delivery Systems

6.) The Regulatory Risk Factor - Drug Discovery Vs Drug Delivery
"The process of discovering and developing new medicines and vaccines is long and expensive and requires innovation and creativity. Industry development times are typically 10–15 years for new medicines and vaccines, with costs of up to £1 billion for each approved product. The R&D process often involves thousands of patients in trials to investigate the safety and efficacy of potential new treatments. Consumer Healthcare relies on product innovation, brand loyalty and trademark protection to be competitive and create value. Development timelines for new consumer healthcare products are significantly shorter than for pharmaceuticals and vaccines and the pace of innovation is rapid. The application of science and consumer insights are key to driving successful product innovation for consumer brands."

Collaborate to Innovate


7.) The Partnerships
GSK Consumer Healthcare
More than 600 people in the UK, USA, India and China are dedicated to our R&D efforts in Consumer Healthcare. We invested £153 million in 2011, up from £124 million in 2008. Developing a sustainable flow of new, scientifically differentiated products – our ‘innovation portfolio’ – is a critical element of our Consumer Healthcare strategy. These can include new technologies and formulations as well as product line extensions. We also carry out ongoing research to assess the efficacy and value of our products so that we can make validated claims to consumers.
Example of innovation in 2011:"In Oral healthcare, the business
launched a new breakthrough in
dental care through Sensodyne
Repair & Protect. The Repair & Protect
formulation is the first everyday
fluoride toothpaste to contain
patented NovaMin technology."

GSK Net Sales 2011
Pharmaceuticals £18.7 billion
Vaccines £3.5 billion
Consumer Healthcare OTC £2.5 billion
Oral healthcare £1.7 billion
Nutritional healthcare £1.0 billion"Sensodyne Repair & Protect, a strong contributor to growth in the Consumer Healthcare business, is the first everyday fluoride toothpaste to contain NovaMin technology, which is proven to repair sensitive teeth. Since its launch in February 2011, Sensodyne Repair & Protect has been available in 30 markets across Europe, Asia and the Middle East, with 20 additional launches planned for 2012. The Sensodyne franchise has registered double-digit growth for 11 consecutive quarters."

In May 2010 this article was first published about a small struggling biotech company which struck up a deal with GSK worth $135 million dollars for the NovaMin technology. GSK was keeping the deal confidential, but word slowly started leaking out in the local biotech community after the acquisition was mentioned in the company's 2009 annual report. A GSK spokeswoman would only confirm at the time that the deal was completed in December 2009.

Perhaps this allows one to consider what value GSK might place on innovative technologies which are found to enhance the performance of Oral Care products, and additionally what role confidentiality might play for GSK in regards to protecting new innovation in todays competitive fast moving consumer world

Imagine if GSK could find new innovative applications for enhancing product performance as well as reducing active chemical ingredients which would also reduce the chemical waste, lower the cost and increase profit margins.

GSK 2011 Annual Report

Would certainly be an interesting exercise to do a discounted cash flow analysis on OBJ when taking into consideration a company like P&G as their joint development partner, and the overwhelming evidence of powerful marketing leadership skills shining through in these sales figures...

P&G Net Sales 2011 ($ billions)

2011 Net Sales by Business Segment

Beauty $20.1 billion
Grooming $8.0 billion
Health Care $12.0 billion
Snacks and Pet Care $3.2 billion
Fabric Care and Home Care $24.8 billion
Baby Care and Family Care $15.6 billionP&G 2011 Notes to Consolidated Financial Statements

8.) Tools and techniques driving new innovation
Optical Coherence Tomography, multiphoton microscopy, Atomic force microscopy, and confocal microscopy, etc...

Nanoparticles and microparticles for skin drug delivery
Tarl W. Prow, Jeffrey E. Grice, Lynlee L. Lin, Rokhaya Faye, Margaret Butler, Wolfgang Becker, Elisabeth M.T. Wurm, Corinne Yoong, Thomas A. Robertson, H. Peter Soyere, Michael S. Roberts - Science Direct

Metabolic state of stratum basale treated with folic acid cream for 6 days. In vivo multiphoton images show untreated (left) and folic acid-treated (right, Product B) stratum basale. Free NAD(P)H lifetime contribution over protein-bound NAD(P)H contribution ratios (a1%/a2%)are inversely related to the metabolic rate. The τ1 component is related to free NAD(P)H in the cytosol, while the τ2 component changes when NAD(P)H protein-binding changes.

Atomic force microscopy (panels a and b) show two distinct size ranges of the SLN. The fluorescent nature of podophyllotoxin enables direct drug tracking by confocal microscopy (panel d). The drug appears to accumulate in the furrows (arrow) and hair follicles in addition to coating the surface of the skin.

Osprey Medical

Advanced Kidney Protection During Coronary InterventionsOsprey Medical is a medical device company incorporated in 2005 with operations based Eden Prairie, Minnesota, USA. The Company is focused on the development and commercialization of its propriety CINCOR™ System designed for the prevention of Contrast Induced Nephropathy (CIN). The CINCOR™ System originated from technology developed at the Baker Heart and Diabetes Institute in Melbourne, Australia.

Overview
Osprey Medical has been funded to date by Australian institutional funds managed by CM Capital Investments, Brisbane and Brandon Capital Partners, Melbourne and other Australian sophisticated or professional investors.

Following successful clinical trials across 6 sites in Australia, New Zealand and Europe, Osprey Medical obtained CE Mark and plans to commence a controlled market launch of the CINCOR™ System in Europe in 2012.

Osprey Medical has also obtained approval from the FDA in the US to conduct a registration-directed pivotal trial which is planned in 2012 and aims to obtain FDA approval to enable a US market launch of the CINCOR™ System in 2014.

Osprey Medical’s Board and Management is comprised of experienced and successful personnel with established track records covering medical device development, regulatory approvals, sales and marketing, and mergers acquisitions. Osprey Medical’s advisory board comprises world-recognised experts in heart and kidney disease.

CIN: A Large Addressable Market Opportunity
At least 3.5 million angioplasty and stenting procedures are undertaken globally each year. In just the US and Western Europe alone, approximately 2.2 million patients undergo angioplasty and stenting each year.

Osprey Medical plans to first target the CINCOR™ System in patients with chronic kidney disease and whose anatomy is suitable for dye capture, representing approximately 400,000 patients per year in the US and Western Europe.

Based on a price of US$1,500-US$2,000 per procedure in the US and Western Europe, the immediate CINCOR™ System market opportunity is estimated to be approximately US$600-US$800 million per annum. Additional large market opportunities exist in the rest of the world including Japan, Asia, and Latin America.

Highlights

* The CINCOR™ System is designed to capture dye from the heart before it can enter the kidneys and cause damage (CIN).

* There is a clear market need and a large addressable market opportunity for the CINCOR™ System.

* The CINCOR™ System has limited competition.

* CIN is costly to hospitals and payers.

* The CINCOR™ System has demonstrated safety, simplicity, and efficacy in clinical trials to date.

* The CINCOR™ System has obtained CE Mark and a controlled market launch is planned for Europe.

* The CINCOR™ System has obtained FDA approval in the US to conduct a registration-directed clinical trial.

* Osprey Medical is aiming to complete its pivotal trial and obtain FDA clearance in 2014.

* Osprey Medical has an extensive patent portfolio.

* There is strong industry acquisition demand for medical device technologies, products and companies.

* Osprey Medical has strong support from specialist Australian Institutional Investors.

* Osprey Medical has experienced board, management and advisors.

Management Team

MIKE McCORMICK - President & CEO
Mike McCormick was appointed President & CEO of Osprey Medical in March 2010. Mike has more than 20 years of experience in the medical device industry and president level experience with public and private medical device companies.

From 2003 to 2008, Mike was President and CEO of Anulex Technologies, Inc., a private company focused on developing proprietary technologies to support the healing of spinal soft tissues. Prior to this, Mike was President of Centerpulse Spine-Tech, a publicly traded full-line supplier of innovative spinal technologies with over 400 employees and US$125 million in annual revenues. Mike was involved in the successful sale of Centerpulse Inc. to Zimmer in 2003 for US$3.2 billion.

Early in his career, Mike worked at Boston Scientific Scimed for 10 years and Baxter Health Care where he served in a variety of sales and sales management roles. Mike received his Bachelor of Business Administration, Business Management from the University of Texas at Austin.

Mike is Chairman of the Board at OrthoCor Medical, Inc. a commercial stage private company in Minnesota and, is a member of the Board of Directors of Formae, Inc. a private company in the orthopaedics space.

RODNEY HOUFBURG - Vice President of Research & Development
Rod joined Osprey Medical in July 2010. Rod has over 18 years of experience in the research and development of medical devices. Prior to joining Osprey Medical, Rod served as Vice President of Research and Development for Anulex Technologies, a venture-capital backed spinal device company. Prior to Anulex Technologies, Rod served as Director of Product Development for Centerpulse Spine-Tech (now Zimmer Spine) and developed orthopedic products at Wright Medical Technology. Prior to entering the medical device field, he developed smart weapons at Alliant Techsystems.

Rod is the inventor or co-inventor on 10 issued patents and seven pending patents and is co-author on multiple medical device publications. He received a Bachelor of Mechanical Engineering from the University of Minnesota.

MIKE LARSON - Director of Operations & Quality
Mike joined Osprey in September 2010. Mike has over 25 years of experience in quality and manufacturing including 14 years in the medical device industry. Prior to joining Osprey, Mike was Quality and Regulatory Affairs Manager for Alexandria Research Technologies, a privately held orthopedic medical device company, where he was instrumental in gaining 510(k) clearance for two unicompartmental knee products. Mike has also held key quality and/or manufacturing positions with Enpath Medical, Anulex Technologies, ev3 and Centerpulse Spine-Tech (now Zimmer Spine).

Mike has extensive experience in setting up ISO 13485 and cGMP compliant quality systems, as well as developing supplier qualification and management programs. He also is experienced in regulatory compliance and complaint handling. Previous to his career in quality and manufacturing, Mike served in the US Navy for 16 years as a Non-commissioned Officer.

DAN MANS - Vice President of Clinical & Regulatory Affairs
Dan joined Osprey Medical in August of 2011. He has more than 20 years of experience in the medical device industry and has held senior executive level positions in both publicly held and private companies. Prior to joining Osprey Medical, Dan co-founded Voyageur Medical, a firm devoted to helping companies identify and resolve vital project uncertainties in the earliest stage of product development. From 2006 through 2009, Dan led Corporate Clinical, Regulatory and R&D functions for American Medical Systems, a global leader in pelvic heath. Early in his career, Dan worked for several successful start-up companies and at Medtronic where he held various clinical research and management positions.

Dan has contributed to over 25 product development teams producing products in electrophysiology, cardiac surgery, spinal orthopedics, urology and gynecology. He has testified twice before FDA advisory panels, both times gaining unanimous recommendation for approval for first-of-a-kind PMA devices. He has conducted clinical research and garnered product approvals in the US, Canada, Europe and Asia. Dan obtained a Bachelor of Science in Mechanical Engineering and graduate training in Biomedical Engineering, both from the University of Minnesota.

NANCY NESS - Vice President of Finance
Nancy joined Osprey Medical in May 2010 as acting Vice President of Finance. She currently serves as a Board Member and founder of Vatrix Medical and as an active chief financial officer for several medical device companies. Nancy has been providing key financial and fundraising services to over 28 medical device start-up companies in Minnesota, New York, and California. Nancy has also served in various financial positions for Anulex Technologies, Northwest Airlines (Delta) and Home Styles Publishing and Marketing, prior to focusing solely on the medical device and bio-pharma markets. In addition, Nancy spent five years as a certified public accountant. Nancy has more than 27 years of experience in the financial community.
Nancy has a B.A. in Accounting and Business Administration from the University of St. Thomas and a Certified Public Accountant license in 1984.

DOUG SCHOENBERG - Vice President Marketing, Education & Reimbursement
Doug joined Osprey Medical in April 2010. Doug has more than 14 years of experience in marketing in the medical device industry. From 2005 to 2009, Doug was Vice President of Marketing for Anulex Technologies, a venture-capital backed spinal device company. Doug was responsible for building Anulex's marketing, training, and reimbursement organization to commercialize two FDA 510(k) cleared products in a new market segment. He has also served in various marketing roles for St. Jude Medical, Zimmer Spine, and Schneider/Namic (now part of Boston Scientific).

Doug holds a B.A. from St. Cloud State University and an M.B.A in Marketing from the University of Minnesota. He also has co-authored a medical journal publication in the area of health economics

Board of Directors

JOHN ERB - Non-Executive Chairman
John Erb has 35 years of experience in the medical device industry.

John is currently Chairman of the Board of Vascular Solutions, Inc., a NASDAQ listed company and has served on this board for 8 years. Vascular Solutions manufactures medical devices for the cardiology and interventional radiology markets and has annual revenue of approximately US$100 million.

John previously served 8 years on the Board of Directors of CryoCath Technologies, Inc., a public company listed on the Toronto stock exchange. CryoCath Technologies developed, manufactured and distributed products to the electrophysiology cardiologist for the treatment of atrial fibrillation. CryoCath Technologies was acquired by Medtronic for US$350 million in 2008. John also served 8 years on the Board of Directors of SenoRx, Inc., a NASDAQ listed company. SenoRx developed, manufactured and distributed products used by oncologists treating breast cancer. SenoRx was acquired by C. R. Bard for US$250 million in 2010.

In 2007, John was Executive Chairman of the Board for CHF Solutions, Inc., a medical device company involved in the treatment of congestive heart failure. From 2001 to 2006, John was Chief Executive Officer of CHF Solutions. CHF Solutions was acquired by Gambro in 2010. From 1997 to 2001, John was President and Chief Executive Officer of IntraTherapeutics, Inc., a medical device company involved in the development, manufacturing, and distribution of peripheral vascular stents. IntraTherapeutics was acquired by Sulzer Medica for US$150 million in 2001. Previously, John was Vice President of Operations for Schneider Worldwide, a division of Pfizer, Inc. John spent 10 years with Johnson & Johnson's Iolab Division and started his career with American Hospital Supply Corporation.

John is currently on the Board of Directors of Jan Medical, a venture capital finance start-up focused on stroke. John has a bachelor's degree in business administration from California State University, Fullerton. John currently is the Chairman and Chief Executive Officer of Cardia Access, Inc., a start-up medical device company focused on innovative technologies for pacing the heart.

MARK HARVEY, Ph.D. - Non-Executive Director
Mark is a Partner and Director of CM Capital Investments. He has over 15 years experience in medical research, technology transfer and commercialization and has played key roles in the formation, fund raising, and management of numerous life science companies. He is currently on the Board of Directors of Sunshine Heart, Inc. (ASX:SHC), a medical device company developing a treatment for heart failure, and Pathway Therapeutics Inc., a clinical-stage company developing a small molecule, kinase inhibitor.

Prior to joining CM Capital Investments, Mark was the Managing Director of Symbiosis Group Limited, an early stage life sciences investment company, and was Group Manager, Life Sciences for UniQuest, the main commercialization company for the University of Queensland. Mark was also a member of the Investment Committee of UniSeed, a $60 million fund focusing on developing technologies from the University of Melbourne and the University of Queensland.

Mark has a PhD (Physiology) and a MBA, and is Adjunct Associate Professor of the University of Queensland.

CHRIS NAVE, Ph.D. - Non-Executive Director
Chris Nave is a founding partner of Brandon Capital Partners and Principal Executive of the Medical Research Commercialization Fund. Chris previously was Director of Commercialization at the Baker IDI Heart and Diabetes Institute, Melbourne Australia, where he was responsible for the commercialization of technologies developed at the Baker and the Alfred Hospital.

Prior to this, Chris was the Manager of the Biotechnology Team at Melbourne Ventures, the commercialization company of the University of Melbourne. Concurrently during this period, he was an investment manager for, and on the investment committee of, UniSeed Pty Limited. Chris has international business development experience with Leiras Pharmaceuticals in Finland, a wholly owned subsidiary of Schering AG.

Chris is currently a Director of Spinifex Pharmaceuticals, Fibrotech Therapeutics, and BACE Therapeutics. Chris has a first-class Honors degree in Science and PhD in Endocrinology and Physiology from the University of Melbourne. He recently completed the Private Equity and Venture Executive Program at Harvard Business School (Boston USA) and is completing a Graduate Diploma in Intellectual Property Law at the University of Melbourne. Chris a graduate of the Australian Institute of Company Directors. He is a member of Ausbiotech and the BioMelbourne Network.

Medical Advisors

Steve Bailey, MD
Dr Bailey is practicing interventional cardiologist. He is Professor of Medicine and Chief of Cardiology at the University of Texas Health Science Center in San Antonio. He teaches students, residents and fellows, and conducts research on many interventional cardiology related topics. Dr Bailey is past president of the Society for Cardiovascular Angiography and Interventions (SCAI) which is a professional organization for invasive and interventional cardiologists. He is board certified in internal medicine and cardiovascular disease.

David Kaye, MD
Dr Kaye is a practicing cardiologist, specializing in the areas of heart failure and transplantation. He is Head of the Cardiology and Therapeutics Division at the Baker Heart and Diabetes Institute in Melbourne, the largest cardiovascular research centre in Australia. The Company's core technology was developed by Dr Kaye and Dr John Power in their Heart Failure Research Group. Dr Kaye is known internationally for his work on the causes of heart failure and for the development of novel medical devices to treat cardiovascular diseases.

David Lee, MD
Dr Lee is a practicing interventional cardiologist. He is an Associate Professor of Cardiovascular Medicine and Director of Coronary Interventions and Cardiac Catheterization at Stanford University Hospital in California. His major research interests include new treatment strategies and delivery of care in STEMI, and device-based management of structural heart disease. Dr. Lee has published numerous cardiovascular research studies.

Gregg Stone, MD
Dr Stone is a practicing interventional cardiologist. He is Professor of Medicine and the Director of Cardiovascular Research and Education at New York-Presbyterian Hospital/Columbia University Medical Center, one of the most comprehensive university hospitals in the world with leading specialists in every field of medicine. He is the Co-Director of Transcatheter Cardiovascular Therapeutics (TCT), the world’s largest symposium on interventional cardiology and vascular medicine. Dr. Stone has served as the principal investigator for more than 60 national and international multicenter randomized clinical trials.

James Tumlin, MD
Dr. Tumlin is a practicing Nephrologist. He is Professor of Medicine at the University of Tennessee in Chattanooga. He is also the founder and Medical Director of the Southeast Renal Research Institute. He is widely acknowledged as a thought leader in acute kidney injury. He has conducted over 20 years of clinical research and has published numerous studies on contrast induced nephropathy. He is on the editorial board of the Journal of the American Society of Nephrology and reviews manuscripts for multiple medical journals.
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CIN: CONTRAST INDUCED NEPHROPATHY

What Is CIN?

Contrast Induced Nephropathy (CIN) is a form of kidney damage caused by the toxic effects of dyes (known as 'contrast media') used by cardiologists to x-ray the heart and blood vessels during commonly performed heart procedures such as angioplasty and stenting. The dye is toxic and can reduce the blood flow in kidneys which can lead to serious patient complications.

The dye can generally be tolerated in patients with normal kidney function. However, patients with poor or non-functioning kidneys may suffer from rapidly declining health, poor quality of life, and significantly shortened life expectancy.

Potential Consequences of CIN:
- Irreversible damage to the kidneys
- Longer hospitalization
- Increased risk of heart disease
- Long-term dialysis
- Rapidly declining health
- High risk of death

(Click here to watch how dye enters the kidney during a heart procedure)

Who's at Risk?

Patients that have compromised kidney function are at the highest risk of having a CIN event from heart procedures such as angioplasty or stenting. Typically, these are patients who, in addition to their heart problems, also suffer from either:

- Chronic kidney disease; or
- Diabetes

It is generally believed that a compromised kidney is less able to tolerate the toxic dyes and is slower in flushing toxic dye through the kidneys. As a result, the dye spends more time in the kidneys and has a greater chance of causing further kidney damage.

How is CIN Diagnosed?

Due to the toxic effect of dyes on the kidneys, cardiologists routinely assess patients' kidney function prior to conducting a heart procedure.

Kidney function is commonly assessed by a standard blood test, which measures the amount of substance known as serum creatinine, present within the blood. Serum creatinine is a waste product of the muscles of the body which, in a healthy individual, is filtered out of the body by the kidneys. Higher levels of serum creatinine in the blood indicate reduced functionality of a patient's kidneys.

The US National Kidney Foundation defines the five stages of kidney disease. These stages are determined primarily by serum creatinine measures.

What are the Outcomes of CIN?

High Risk of Death

Patients who acquire CIN can have an increased risk of death (mortality) before leaving the hospital after a heart procedure such as angioplasty or stenting. If CIN patients survive their hospital stay, their risk of dying remains high within a year of their heart procedure and is even higher within 5 years of their procedure.

High Cost to Health Providers

CIN has significant economic burden. The average additional length of stay in the hospital is 4 days and patients requiring dialysis can require much longer hospitalization. For patients surviving CIN, there is an increased risk of on-going heart and kidney problems, creating an added economic burden.

Can CIN be Treated?

It is generally accepted that there currently is no treatment available to reverse or improve damage to the kidneys, once a patient develops CIN. Once CIN develops, patients often stay in the hospital several additional days so fluid levels, kidney function, and potential complications can be monitored until their serum creatinine levels in the blood return to more normal levels. Even if serum creatinine levels return to more normal levels following CIN, patients may be at higher risk for accelerated kidney disease progression, future cardiovascular complications, and death after leaving the hospital.

Can CIN be Prevented?

Due to a lack of viable treatment options for CIN, cardiologists currently use preventative strategies including hydration and dye (contrast) management. However, to date, these strategies have had limited impact on reducing the frequency of CIN events. The table below describes the most common preventative strategies.

The CINCOR™ Contrast Removal System is designed to provide cardiologists with an advanced level of CIN protection in high risk patients undergoing heart procedures such as angioplasty and stenting.

The CINCOR™ System is a catheter and vacuum system that is designed to directly capture and remove a significant quantity of the dye as it leaves the coronary sinus (the heart's main drainage vein) before it makes its way to the kidneys. The CINCOR™ System can be activated multiple times throughout the heart procedure. At the conclusion of the procedure, the small amount of dye-laden blood is discarded.

Information in this post was sourced from these links:
CINCOR™
CINCOR™ Pivotal Trial
Media Sheet
Osprey Medical