Making A Patch

Making A Patch

Investors frequently ask if any pharmaceutical company can develop and manufacture a patch as advanced and wearable as Vivelle-Dot^®. We appreciate the significance of that question, and we believe the simple answer is "No". Noven possesses a range of resources – among them proprietary know-how, highly-experienced personnel, specialized equipment and leading science – that favorably distinguishes us from other transdermal companies and that makes it difficult for others to make comparable products.

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Noven's most significant distinguishing characteristic is our intellectual property. Noven's patch process is proprietary; we hold over 30 U.S. and 100 international patents that protect it. And while Noven will develop patches for license to others (Novartis AG and Aventis for example), we prefer to seek out higher margin projects that we can market ourselves before we consider development projects for third parties.

Formulation

Noven's formulation scientists and capabilities distinguish us as well. All of Noven's patches use an advanced drug-in-adhesive matrix, meaning that the drug is mixed with the adhesive that holds the patch on the skin. Each completed patch is an ultra-thin, three-layer laminate comprised of the patch backing, the drug/adhesive mix and the release liner (the part peeled away and disposed of upon application) (Fig. 1).

The design and development of the ideal combination of drug, adhesive and backing is where our technical know-how and proprietary technology first come into play. Proper formulation ensures that the product will deliver a safe and effective dose and adhere for the intended wear period. Our research and development group includes chemical engineers who are formulation experts. In fact, both Noven's founder and its Chief Technical Officer are chemical engineers by training.

The greatest technological challenge at this stage is preventing drug crystallization, skin irritation and failed adhesion as the patch approaches the small size and high efficiency of Vivelle-Dot^®. Our DOT Matrix^® technology is the solution to this challenge and is subject to several patents that do not expire until 2014.

Manufacturing

Manufacturing presents its own challenges. We believe we have one of the most advanced patch manufacturing facilities in the world. Located on our 10-acre corporate headquarters in Miami, Florida, Noven's facility occupies about 80,000 square feet and has the capacity to produce 400 million patches per year. Quality control and quality assurance systems check and double-check every step in the process.

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Our facility is approved by the U.S. Food and Drug Administration and the Medicines Control Agency of the United Kingdom, and is certified by the U.S. Drug Enforcement Administration for the production of patches that contain controlled substances. Our facility is busy and efficient, currently producing Vivelle^®, Vivelle-Dot^®, CombiPatch^®, Estradot^®, Menorest^®, Estalis^®, Femiest^® and DentiPatch^® for commercial sale around the world.

We enjoy excellent production flexibility and are not reliant on third parties for machinery engineering. Our in-house engineers can design, build and maintain most production equipment, including special purpose and replacement parts. They can also support R&D by rapidly fabricating or modifying equipment essential to that function's specialized needs.

Step-By-Step

The machines required to manufacture a patch like Vivelle-Dot^® are generally large, expensive and customized. This is especially true for our primary coating machine, which is over 45 feet long and has been tailored to Noven's products.

The first step in manufacturing a Noven patch is blending, where we mix active drug compounds with our custom adhesives in large, specialized kettles (Fig. 2). After blending is complete, the drug/adhesive mix is pumped to the next machine for coating.

In the coating process, a thin, precise drug/adhesive layer is applied within tolerances of about one-tenth the thickness of a human hair to long, broad sheets of release liner material. The blending solvent is then removed in the large arch tunnel oven (Fig. 3), then the final layer of the three-layer patch – the backing – is laminated. Although initially applied to the release liner, the adhesive matrix permanently bonds to the patch backing. Using our continuous web technology, the completed laminate is then rolled for the next production step (Fig. 4).

The laminate rolls are then sent through punching, pouching and cartoning machines specially configured for each product. Dosing is controlled in part by patch size, and patches of precisely the proper size are punched from the laminate sheet (Fig. 5). The release liner side of the patch is scored for easy removal, and then the completed patch is inserted and sealed into air-tight protective pouches.

Machines place the pouched units into their final carton (Fig. 6) and unit counts are carefully verified. In the final step of the process, completed product boxes are put into shipping cartons for distribution. Carton and insert designs are country-specific. In the case of Estalis, for example, Noven has packed and shipped product with trade dress intended for over a dozen different countries, and Menorest is marketed through Novartis AG to an even broader audience, meeting the needs of patients – quite literally – around the world.