Detailed worldwide manufacturers and product information on Transdermal Patch:

http://www.pharmiweb.com/News/Pressreleases/PressRelease.asp?PRID=358 has the following information: The transdermal market is dominated by HRT patches, but patches are also used for delivery of testosterone, nicotine, nitroglycerine, and analgesics. 3M markets Minitran, which is the smallest daily nitroglycerin patch in the world Noven's Vivelle-Dot is the world's smallest estradiol transdermal system (ERT) patch. One of the pioneers in this field is Alza, which developed the first patch in the US. Its brands include Duragesic, Estraderm, Transderm-Nitro, Transderm-Scop, and Catapress-TTS. The OTC market also has transdermal patches, including those used for delivery of nicotine, analgesiscs and cold and sinus remedies. One of the technological challenges to extending this delivery mode to other products is that proteins and peptides are too large to pass through the skin. One way to get round this is to use electricity or ultrasound to help push the molecules through. Iontophoresis involves passing a direct electrical current between two electrodes on the skin surface. Phonophoresis uses ultrasonic frequencies to help transfer high molecular weight drugs through the skin. ALZA is developing E-Trans technology Design options include disposable E-Trans systems for delivering drug over hours or days, and reusable systems with replaceable batteries and drug pads. E-Trans systems can be programmed for continuous (zero-order), patterned, on-demand or feedback-controlled drug delivery. Fentanyl delivered by the E-Trans method is currently in Phase III. Imarx is developing ultrasound assisted transdermal insulin system. 3M is currently evaluating a wide range of low solubility compounds and developing transdermal systems that have smaller size and prolonged wear periods. Buspirone patch being developed by Elan holds tremendous potential in the transdermal drug delivery market. Other products potentially suitable for this sort of development include alprostadil, minoxidil, hormones, analgesics, contraceptives, and antifungal agents. Here are details of the companies mentioned above: 1. 3M 3M Pharmaceuticals is renowned for its inhalation technology and transdermal drug delivery systems, 3M Pharmaceuticals drew on 3M's long-standing expertise in Scotch Tape and Post-it Notes to create the innovative "drug-in-adhesive" technology for transdermal patches. 3M's Minitran (nitroglycerin) Transdermal Delivery System is the smallest and thinnest transparent nitroglycerin patch. And today, most transdermal patches, from hormone replacement therapies to smoking cessation products, include components from 3M. http://www.3m.com/us/healthcare/pharma/pharma_about.jhtml 3M is a $16 billion diversified technology company with leading positions in consumer and office; display and graphics; electronics and telecommunications; health care; industrial; safety, security and protection services; transportation and other businesses. Headquartered in St. Paul, Minnesota, the company has operations in more than 60 countries and serves customers in nearly 200 countries,

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We began selling our products outside the United States in 1929, and established an International Operations organization in 1951. More than half of 3M's sales come from outside the United States.

http://www.3m.com/about3m/facts/CorpFacts.jhtml Home page http://www.3m.com/ from which you can move to the 3 web sites in various countries. 2. Noven Noven Pharmaceuticals, Inc., headquartered in Miami, Florida, is a leader in the development of transdermal and transmucosal drug delivery technologies and products. Together with Novartis Pharmaceuticals, Noven owns a women's health products company called Novogyne Pharmaceuticals. Noven's existing products include advanced estrogen transdermal delivery systems (including Vivelle and Vivelle-Dot, licensed to Novogyne, and Estradot, licensed to Novartis) and combination estrogen/progestin transdermal delivery systems (including CombiPatch, licensed to Aventis, and Estalis, licensed to Novartis). With a range of additional products in development, including once-daily MethyPatch for Attention Deficit Hyperactivity Disorder, Noven is committed to becoming the world's premier developer, manufacturer and marketer of transdermal and transmucosal drug delivery systems. http://www.noven.com/PR032201.htm Home page: http://www.noven.com/default.htm 3. Alza ALZA Corporation introduced the concept of controlled transdermal delivery to the world through seven different patches, each of which was the first transdermal formulation on the market in its therapeutic category. That tradition of innovation continues today, as ALZA continually refines and improves the technology used in its D-TRANS transdermal systems. ALZA Experience: Bringing the First Patches to Market in Seven Therapeutic Categories. Transderm Scop (scopolamine)This product introduced the therapeutic patch concept to the world in 1981. Transderm-Nitro (nitroglycerin) an alternative to the brief effects of sublingual nitroglycerin and the messiness of nitroglycerin ointment. Catapres-TTS (clonidine)ALZA's rate-controlled system allows hypertensive patients to wear one patch for a week Estraderm (estradiol) Because transdermal delivery avoids the problem of liver metabolism, the estradiol dose of this patch is only a fraction of that in oral estrogen replacement and provides twiceweekly, convenient therapy. Duragesic (fentanyl) CIIIntroduced in 1991 NicoDerm CQ (nicotine) and Clear NicoDerm CQ Testoderm (testosterone) and Testoderm TTSIntroduced in 1994 and 1998, respectively http://www.alza.com/wt/how.zoo?page_name=dtrans Macroflux systems can be drug-coated for direct administration or can be used in combination with passive transdermal or electrotransport systems to significantly expand the delivery opportunities for synthetic drugs, therapeutic proteins and vaccines. technology incorporates a thin titanium screen with precision microprojections that, when applied to the skin, creates superficial pathways through the skins dead barrier layer

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allowing transport of macromolecules. provides the option of dry-coating the drug on the Macroflux microprojection array for bolus delivery or using a drug reservoir for continuous passive or electrotransport applications. allows for better control of drug distribution throughout the skin patch treatment area and reduction in skin irritation potential. http://www.alza.com/wt/how.zoo?page_name=macroflux Home page http://www.alza.com/ 4. Imarx SonoDerm Technology Ultrasound Assisted Transdermal Transport Many drugs, particularly large molecules such as insulin, are not absorbed by the oral route and have to be injected frequently. As an outgrowth of the Companys work on ultrasound contrast agents and ultrasound mediated drug delivery (SonoRelease Technology), ImaRx has developed novel ultrasound enhanced transdermal drug delivery systems. Patent: Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles US 5733572 3/31/98 http://www.imarx.com/sonoderm.asp Home page: http://www.imarx.com/default.asp 5. Elan Not very much information available on the Elan web site, and nothing about the buspirone patch. Transdermal delivery systems Validated through successful launches of a number of smoking cessation products in Europe and the United States Number of patch products in late stage development for the US market http://www.elan.com/drugdelivery/expertise/default.asp Elan Transdermal Technologies, Inc. 3250 Commerce Parkway, Miramar, FL 33025. TEL (954) 430 3340, FAX (954) 430 3390 http://www.elan.com/aboutus/facilities/default.asp Home page http://www.elan.com/ Spring Valley, New York, October 3, 2001 Pharmaceutical Resources, Inc. ("PRI") (NYSE:PRX), today announced that its subsidiary, Par Pharmaceutical, has entered into a licensing agreement with Elan Transdermal Technologies (NYSE: ELN) to market a generic clonidine transdermal patch. An ANDA for the product was filed earlier this year with the FDA. A paragraph IV certification was filed along with the application, certifying that the product did not infringe the branded product's formulation patent, which expires May 2003. The product launch is expected to occur in either late 2002 or early 2003. The patch is a generic version of Boehringer Ingelheim's Catapres TTS, which is indicated for the treatment of hypertension. Brand sales are approximately $160 million. http://www.parpharm.com/html/nf/PR-LicensingForClonidineTTS.html However, this seems to be the only transdermal product by Boehringer. We also market the only transdermal antihypertensive in the U.S. CATAPRES-TTS (clonidine), an adhesive patch that delivers blood-pressure medication directly through the skin. http://us.boehringer-ingelheim.com/businessunits/bipi/bipi.html Parent company: http://www.boehringer-ingelheim.com/corporate/home/home.asp

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And some other companies below: 6. Novosis AG Devices, adhering to skin that deliver drug through intakt skin into the body for systemic action. Transdermal Drug Delivery Systems (TDS, often named Patches) come in two "flavours": * thin flexible coloured or nearly invisible matix patches * flexible coloured or transparent liquid or semi-solid filled reservoir patches. Whereas the more elegant filmlike matrix patches in general can deliver only relatively small amounts of drug, reservoir patches are preferred systems, when higher drug amounts (> 5mg/day) should be delivered. Reservoir systems may contain significant amounts of liquid absorption promotors that may be neccessary for sufficient absorption. Incontinence TDS Indication: Urinary urge Incontinence Licensing opportunity: Worldwide License available Drug substances: Oxybutynin Intellectual property: Patent Application Opioide TDS Indication: Moderate to severe Pain Licensing opportunity: Worldwide rights available with Cooperation Partner Drug substances: not disclosed Intellectual property: Patent Application Back Pain TDS Indication: Back Pain Licensing opportunity: Worldwide Rights with Cooperation Partner Drug substances: Local Anaesthetic Intellectual property: Patent Applied http://www.novosis.com/ennf/products/list/1/ There are links on this page to further information about each of these TDS products. Novosis AG's conceptual and practical expertise is established in: * development and manufacturing of transdermal drug delivery systems (TTS, TDS, patches), * development and manufacturing of epidermal drug delivery systems (EDS, patches), Novosis AG is located in MIESBACH, Germany, a Bavarian Alpine town 30 km south of Munich. http://www.novosis.com/ennf/company/ 7. Lavipharm Corp Lavipharm is a leading developer and manufacturer of the 3rd generation transdermal systems. For instance, our 3rd generation transdermal nitroglycerin patch (sold under a variety of trade names) is popular with patients and physicians worldwide http://www.lavipharm.com/us/business/transdermal-1.html BTW, Lavipharm also develops buccal delivery systems: Lavipharm's unique Intra-Oral Delivery System (IODS) lets you control oral delivery with extraordinary precision. The IODS films allow you to precisely control the release of the drug by delivering active components, which dissolve over a defined time period, to a specific site. http://www.lavipharm.com/us/business/intraoral-1.html 8. New Jersey Center for Biomaterials The main focus of the research group headed by Dr. Bozena B. Michniak is in the area of topical and transdermal drug delivery. A major part of the work is devoted to the tissue engineering of skin, and a human skin co-culture of fibroblasts and keratinocytes using collagen as a dermal matrix, has been developed and been shown to possess similar drug permeability to human skin. This novel model surpasses those available to date Other major projects in the laboratory include optimization of formulations for topical and transdermal delivery, such as ketoprofen gels, microsphere and unimolecular polymeric

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micelle formulations, and liposomal creams. In addition, projects include the development of transdermal patches for the U.S. Army, development of a topical antipapilloma formulation containing a novel antisense oligonucleotide, and iontophoretic delivery of drugs with and without additional chemical enhancement. Drug permeability pathways and effect of agents as well as iontophoresis on skin membranes are being investigated using confocal microscopy as well as SEM and TEM. Structure-activity relationships have been investigated for over 200 newly synthesized compounds with both dermal enhancing and retarding properties. The work includes chemical modeling of both the enhancer/retardant compounds as well as the modeling of lipid layers of the stratum corneum. http://www.njbiomaterials.org/research/drugdelivery.htm As a formal consortium of New Jersey's premier public institutions of higher education working closely with industry, the Center coordinates academic, technical and clinical resources http://www.njbiomaterials.org/about/index.htm 9. Ultrasonic Technologies Ultra-Sonic Technologies, LLC was founded in May of 2002 by Karl R. Zurn and Dr. Ludwig Weimann. MED Associates Inc. of Georgia and St. Albans, Vermont, is a business partner in this venture. Ultra-Sonic Technologies, LLC's main goal is to develop an ultrasonic device for painless transdermal drug delivery based on Dr. Ludwig Weimann's patented design. In addition, Ultra-Sonic Technologies, LLC provides custom services for the development of transdermal and topical drug delivery patches with controlled release of the active substance from the device. The company's laboratory is located in the St. Albans Industrial Park of St. Albans, Vermont. http://www.ultra-sonictechnologies.com/about.htm Method and Apparatus for In-Vivo Transdermal and/or Intradermal Delivery of Drugs by Sonoporation Patent Number: 6,487,447 B1 An apparatus for performing in-vivo sonoporation of a skin area and transdermal and/or intradermal delivery of a drug solution includes a container having an end covered with a porous membrane and containing the drug solution and an ultrasound horn having a tip submerged in the drug solution. The ultrasound horn applies ultrasound radiation to the drug solution. http://www.ultra-sonictechnologies.com/patent.htm TRANSDERMAL DELIVERY OF POLY-L-LYSINE BY SONOMACROPORATION A feasibility study of using high amplitude ultrasound to deliver large molecules transdermally Ultrasound in Medicine & Biology Volume 28, No.9, pp.1173-1180, 2002 http://www.ultra-sonictechnologies.com/transdabstract.htm (includes link to download a reprint) 10. Anatares Pharma Antares Pharma is the acknowledged leader in the delivery of drugs using gel technology. Gels are generally well known although developing a gel to provide for the penetration of a drug in therapeutic amounts through the skin represents a significant challenge. Antares Pharma developed a proprietary gel technology platform with two main goals: one is the systemic delivery of potent compounds such as hormones, the other is the local dermal delivery of active substances for treatment of psoriasis, softtissue infections and local infections, management of hair loss, etc. Antares Pharma believes that gel technology has compelling advantages compared with patch technology.

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http://www.antarespharma.com/content/products/transdermal/gel.html Transdermal patches: The systems designed by our Company are of the drug-inadhesive type and consist of transparent and flat units, which contain the active principles in a matrix composed of acrylic pressure-sensitive adhesive, and excipients such as permeation enhancers, co-solvents and antioxidants. These drug-in-adhesive systems give the Company the potential to work with drugs in several therapeutic fields like HRT, anti-inflammatory / analgesics and Central Nervous System agents. Products using this technology are marketed throughout Central and South America and registration's approval is currently awaited in Italy. http://www.antarespharma.com/content/products/transdermal/patch.html Antares Pharma has developed a proprietary technology for the Transdermal Administration of Estradiol. This transdermal system belongs to the Drug-in-Adhesive type. Antares Pharma's Transdermal Delivery Systems (TDS) are designed for continuous release of 17 beta-Estradiol following application to the skin, during a 7-day period. http://www.antarespharma.com/content/products/estradiol/index.html 11. Altea Therapeutics Altea Therapeutics has developed a proprietary noninvasive method to achieve the delivery of therapeutic proteins, conventional drugs and vaccines through the skin. Based on experience with over a hundred human subjects, the Company believes that use of its technology can provide a painless, convenient and effective method to deliver drugs and vaccines that previously have been limited to administration by injection. The method rapidly and painlessly causes tiny openings or 'micropores' that are tens of microns in diameter, to form through the stratum corneum, the dead outer layer of the skin. No mechanical probes or skin puncturing devices are used. Therapeutic molecules of all sizes and physicochemical types are able to diffuse through these micropores for local action within the viable skin tissue or for systemic action after uptake by the circulatory system. The 'skin microporation' technology can be configured to achieve a variety of drug delivery profiles including: sustained, pulsatile, rapid and on-demand dosing. The Company's corporate and research facilities of 25,000 square feet are located in the greater Atlanta area, with additional business offices in Europe (Stockholm) and Salt Lake City http://www.alteatech.com/ 12. Birch Point Medical The company's initial commercial product is the IontoPatch. The IontoPatch is a medical device application of Birch Point Medical's WEDD technology platform. It is an electronic transdermal drug delivery device designed for the Physical Medicine and Rehabilitation market. It is used primarily by physical therapists, occupational therapists and sports medicine professionals to deliver drugs to specific anatomical sites. http://www.birchpoint.net/markets_products.html An innovative self-contained battery produces an electric current to carry drug molecules non-invasively across the skin and to underlying tissue. Drug delivery is shut off automatically when the prescribed dosage has been administered. The IontoPatch is single use and disposable. Since there are no external batteries or wires, patients are able to return to their daily activities while receiving time-released iontophoresis. http://www.birchpoint.net/markets_iontopatch_device.html 13. Iomed Produce electrode systems for transdermal delivery For example The TransQFlex electrode gives you an added advantage over other transdermal drug delivery systems.

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This new shape with gel technology increases the conformability of drug delivery, especially to areas of the body that make traditionally shaped electrodes more difficult to use. TransQFlex GelSponge will increase your ability to treat patients more comfortably, while increasing the ease-of-use for you. http://www.iomed.com/products/transq_flex.htm Numby Stuff electrodes teamed with IONTOCAINE (brand of lidocaine 2% HCI with 1:100,00 epinephrine topical solution) provide clinically effective dermal anesthesia up to 10mm depth in as little as 10 minutes. http://www.iomed.com/products/numby_stuff.htm IOMED's Phoresor Iontophoretic Drug Delivery System is indicated for the administration of soluble salts and other drugs into the body for medical purposes as an alternative to hypodermic injection The Phoresor Iontophoretic Drug Delivery System is also indicated for production of local dermal anesthesia using IONTOCAINE brand of lidocaine hydrochloride 2% and epinephrine 1:100,000 topical solution). http://www.iomed.com/products/phoresor.htm IOMED, Inc. is a leader in the development, manufacture, and sale of active drug transport systems. We are pursuing opportunities to utilize our non-invasive drug transport systems in combination with specialty pharmaceuticals to offer unique products designed to satisfy substantial unmet medical needs in large pharmaceutical markets. Based in Salt Lake City http://www.iomed.com/index.htm 14. MacroChem, The Transdermal Drug Delivery Company MacroChem's SEPA absorption enhancer is capable of delivering a wide range of drugs transdermally that are otherwise absorbed only minimally or not at all when applied to the skin. SEPA is an acronym for "Soft Enhancement of Percutaneous Absorption," where "soft" refers to the reversibility of the skin effect, and "percutaneous" means "through the skin." MacroChem synthesizes SEPA by condensing ethylene glycol and decyl aldehyde (decanal). SEPA enhances skin penetration by altering the fluidity of the lipid layers in the stratum corneum. Those lipids surround the skin cells of the stratum corneum the way mortar surrounds bricks in a wall. SEPA temporarily alters the alignment of those lipids allowing drug molecules to slip through. However: The FDA has advised MacroChem that further clinical trials of SEPA-based investigational drug products have been placed on clinical hold until potential safety issues regarding a transgenic mouse carcinogenicity study have been resolved. MacroChem is working with FDA to resolve these issues. http://www.macrochem.com/site/content/research/sepa.asp 15 Sontra Sontra has developed a novel; non-invasive and painless skin permeation technique that uses ultrasound to permeate the skin. Sontra's SonoPrep skin permeation device provides a convenient way to enhance permeability through a short (15 seconds) wellcontrolled burst of low frequency (compared to diagnostic imaging) ultrasonic energy to the skin that allows sustained permeability for up to twenty four hours. The transport properties of the outermost layer of the skin (the stratum corneum) are greatly improved after skin permeation and the technique opens up the potential for non-invasive transdermal diagnostics and the enhanced delivery of drugs through the skin. http://www.sontra.com/technology/skinpermeation/ ontra's initial studies in the area of transdermal drug delivery, suggest that ultrasoundmediated skin permeation can enhance transport rates across the skin up to 100-fold for both small and large compounds. Sontra is investigating the delivery of several large

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proteins and peptides by incorporating the use of the SonoPrep device in combination with transdermal patches to deliver the drug transdermally. http://www.sontra.com/company/companyoverview/ 16. Vyteris Our technology uses iontophoresis to deliver drugs painlessly through the skin without needles or other mechanical devices. It works by inducing a low-level electrical current that repels or drives a drug with a natural ionic (electric) charge through the skin. This delivery method is intended to offer an alternative to oral, injection and infusion pump delivery and to avoid problems associated with these delivery methods http://www.vyteris.com/ 17 BioChemics BioChemics, Inc. is a drug delivery company based in Danvers, MA. BioChemics has developed and patented a unique, powerful and broadly applicable form of patch-less, gel-based transdermal drug delivery technology. This technology called PENtoCORE , may be thought of as a "liquid needle" which is able to deliver drugs through the skin and into the bloodstream. PENtoCORE is a platform technology which is directly applicable to prescriptive, over-the-counter, and veterinary drugs. Between 1994 and 1997, BioChemics received FDA marketing approval on 13 pharmaceutical products (3-Human over-the-counter medications and 10-Veterinary products). successfully test-marketed its 3 new transdermal products: Osteon (an arthritis pain blocker), Athlete's Relief (a sports injury pain blocker), and deFEET (an anti-fungal medication). http://www.biochemics.com/c1.html 18. L.A.M. Pharmaceuticals LLC In 1994, L.A.M.'s scientists discovered a phenomenon that when lower molecular weight hyaluronic acid was combined with other polymers of specific electric charge, it was capable of penetrating all layers of the skin. In addition, this polymer matrix was able to surround or encapsulate other molecules, including therapeutic drug molecules, carrying them through the skin for systemic absorption. This transdermal molecular transport phenomenon is known as the L.A.M. Ionic Polymer Matrix technology and is proprietary to L.A.M. Pharmaceutical, Corp. http://www.lampharm.com/about.htm 19. A.P. Pharma A.P. Pharma, Inc. (NASDAQ NM: APPA) is a specialty pharmaceutical company focused on the development and commercialization of innovative medical treatments utilizing its proprietary polymer-based drug delivery systems. The Company's primary emphasis is on advancing its Biochronomer technology platform for site-specific and systemic drug delivery. Designed to release drugs over a period of hours, days, weeks or even months, Biochronomer systems can be fabricated into a wide range of forms, ranging from solid strands to free-flowing gels which erode away as they deliver the drug. http://www.advancedpolymer.com/ Collaborative activities include: Site Specific Pain NSAID Film; Analgesic Anesthetic Gel. http://www.advancedpolymer.com/products/development.html

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20. MIKA Pharma, Limburger, Germany MIKA Pharma GmbH was established in 1994 in order to develop and produce primarily dermal, transdermal, and buccal application systems for pharmaceuticals on the basis of sprayable liposomes, pre-liposomal solutions and proprietary micellar solutions. The products developed and manufactured by MIKA Pharma GmbH are distributed by independent pharmaceutical firms. MIKA Pharma GmbH has patented its "MIKA spraygel-technology" and has filed its "MIKA -SILEC-technology" for international patent. http://www.mika-pharma.de/company/gesamt.htm 21. Nex Med Inc NexMed, Inc., is an emerging pharmaceutical and medical technology company, with a product development pipeline of innovative topical drug treatments based on the NexACT transdermal drug delivery technology. Its two lead NexACT products under development are the Alprox-TD and Femprox creams for ED and female sexual arousal disorder, respectively. http://www.nexmed.com/ 22. Encapsulation Systems Inc. Transdermal patches are unable to deliver as many as 175 currently FDA approved medicinal compounds simply because the skin pores are too small to accept the molecule. If a transdermal patch could be made to transfer the larger molecule drugs through the skin the market opportunity would not only include the projected 175 currently listed drugs but many new formulations in development Enhancement of drug transport via a modified transdermal patch to enable it to deliver large molecule drugs through the skin. We accomplish this by using ultrasound to transport the large molecule drugs, via a wearable, portable and programmable drug sonic applicator device. http://www.encsys.com/ustrip.html 23. Acrux Acrux Ltd is a new Australian-based company with a unique vision and skills in transdermal drug delivery systems - ways of administering a range of drugs for a range of needs directly through the skin. http://www.acrux.com.au/home.shtml Together, Acrux's ACROSS and MDTS systems represent a platform technology with immediate ability to deliver therapies such as hormone replacement therapy (HRT), nicotine replacement, pain control and treatments for angina, erectile dysfunction, urinary incontinence, anxiety states and other central nervous system (CNS) disorders. Acrux's initial focus for the validation of its transdermal technology is in the development of products for female HRT, in which ACROSS enhancers are combined with the MDTS spray applicator to provide a new metered-dose transdermal delivery system. http://www.acrux.com.au/technology.shtml 24. Adhesives Research Inc Adhesives Research has supported the development of transdermal drug delivery systems (TDDS) since 1984 and has become a leading component developer and supplier. Advanced pressure-sensitive adhesive technologies are integral transdermal system components for the effective delivery of prescribed medications. We develop and manufacture customized adhesive polymers and adhesive/film laminations to meet clinical as well as commercial requirements. Ask about our new dissolvable films

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technology for the delivery of pharmaceutical prescription and OTC ingredients in a different, consumer friendly, easy-to-use platform. http://www.adhesivesresearch.com/pharm/indexphr.htm 25. Jenapharm GmbH The Jenapharm Center of Competence for Transdermal Drug Delivery Systems (TDDS) is dealing with patches, gels, sprays and powders with transdermal efficacy. TDDS have many advantages and benefits in therapy. Jenapharms experts in TDDS are also playing a major role in Scherings global chemical manufacturing control (CMC) development process as * worldwide communication partner for CMC aspects of transdermal systems * development, assessment and testing center of transdermal formulations * authority for handing over TDDS projects to contract manufacturers, and for site changes * provider of clinical supplies (conforming to GMP) The extensive experience in TDDS provides improvement of product properties regarding performance and tolerability. The capabilities for successful development of TDDS are based on intensive cooperation with e.g. Scherings specialist department or the silicone knowhow at Leiras Oy (Turku, Finland). http://www.jenapharm.de/eng/research/pharm/exp1.html 26. Norwood Abbey, Australia Transdermal - laser assisted delivery - laser technology is designed to painlessly and temporarily alter the stratum corneum, or outer layer of skin, to enable a wide range of drugs to be delivered effectively and without the gastric side effects associated with oral drug administration. Our research has indicated that a very large range of drugs can potentially be better delivered via the use of Norwood technology. Transdermal microneedle arrays - by opening micron-scale holes in the skin, drugs that are either too large or too hydrophobic to diffuse through intact skin may be delivered effectively. Because micro-needles penetrate only into the upper layers of skin (where the primary transport barrier resides), they avoid contacting nerves and capillaries, which means they can be painless and bloodless. Micro-needle arrays could improve administration of existing medications, allow development of new therapeutic compounds and ultimately be used in microprocessor-based systems for delivering drugs continuously or in response to body needs. http://www.norwoodabbey.com/indexcompro.htm 27. Novavax Micellar Nanoparticles (MNPs) are proprietary, submicron-sized, water miscible, nonphospholipid structures derived from amphiphilic molecules. Novavax scientists have demonstrated that MNP's are able to incorporate alcohol soluble drugs, pesticides, vaccine adjuvants, proteins, whole viruses, flavors, fragrances and colors. MNP's also have the ability to entrap ethanol or methanol soluble drugs, and to deliver certain of these drugs transdermally through intact skin. Novavax's first target indication with MNP technology is the Hormone Replacement Therapy (HRT) market. http://www.novavax.com/delivery_micellar.html 28. Genetronics Electroporation technology has proved to have many more applicationsthan can be pursued simultaneously. Genetronics has identified many of these opportunities and developed prototypes or product concepts. A prototype for the Genetronics Transdermal Delivery Device was created and testing has been initiated for applications from drug delivery to cosmetics. Genetronics is currently engaged in a collaborative

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research agreement with a pharmaceutical partner to investigate the use of transdermal drug delivery. http://www.genetronics.com/productsother.htm 29. Adherex Technologies, Ottawa Current research in transdermal drug delivery is directed toward methods and mechanisms of overcoming this low permeability. A protein called E-cadherin is involved in the regulation of skin cell adhesion and the maintenance of the skin permeability barrier. We have developed several synthetic compounds that target E-cadherin to disrupt the skin barrier. Tests show that our compounds increase the penetration of both charged and uncharged dyes through human skin in the laboratory. http://www.adherex.com/transd.htm 30. AlphaRx AlphaRx's proprietary technology, known as Bioadhesive Colloidal Dispersion (BCD), overcomes drug insolubility problems of hydrophobic drugs through enhanced oral and transdermal drug delivery and is protected by one issued and five pending U.S. patents and corresponding international patents pending. BCD consists of two different platforms: Colloidal Lipid Dispersion System ("CLD") for trans-dermal delivery and Self Emulsifying Controlled Release Tablet System ("SECRET") for oral delivery. .. CLD can be incorporated into cream, gel, liquid or "patch" vehicles. http://www.alpharx.com/website/products_dd.htm You might also be interested in a report by Jain Pharmabiotech Transdermal Drug Delivery - Technologies, Markets, and Companies May 2003. 135 Pages, US$ 750 * Up-to-date one-stop information on transdermal drug delivery * Description of 59 companies involved and 46 collaborations in this area * Market analysis 2002-2007/ * Market values in major regions * Strategies for developing markets for transdermal drug delivery * A selected bibliography of 85 publications http://pharmabiotech.ch/reports/tdd/