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Franck Pavan, CDMO Department Manager, Injection products, Pierre Fabre

A: From my perspective, new enhancing bioavailability technologies will move forward in the future. Most of the new active ingredients that are discovered have physical and chemical characteristics that are not compliant with, let’s say, a clear solubility in water and that’s why it’s more and more difficult to maintain the bioavailability of those active ingredients. I’m quite confident that new technologies like the ones you’re asking about will be improved in the future, but the technology will be highly expensive and will then be used for high-added-value products. This is the purpose of the new generation of products: to have a better bioavailability and to be more specific for the pathologies they need to treat.

 

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Luca Mantovani, CEO, INFA Group

A: Bioavailability is of concern not only to pharma but also to other industries very close to pharma. I think [controlled release is] one of the most interesting opportunities for life science companies because you can leverage a combination of drug substances with specialty products. I have in mind some natural polymers that play a role in slowing the release of the drug into the tissues, so that’s an extreme­ly normative and interesting oppor­tunity. Also, there’s a lot of work on particles engineering and solubiliza­tion of products to enhance bioavail­ability. All in all I think the industry is making good progress.

 

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Cyrus Mirsaidi, President and CEO, BioDuro

A: It’s clear that reformation know how is a critical skill for contract service providers. Advanced API chemistries, for example, are requiring sophisticated processing capabilities to overcome solubility and bioavailability issues. The market is evolving, and many of pharma’s global players are exploring ways in which to leverage reformulation and advanced API processing skills to create new opportunities and markets for their products. That is, opportunities that can exploit and enhance the market reach of newer compounds losing patent protection, or leveraging advanced development and manufacturing capabilities in an effort to breathe new life, efficacy and market appeal into common medicines.

Demand for high-quality pharmaceuticals for the Chinese population is growing as fast as China’s consumer-oriented middle class and China FDA is working to regulate the industry to meet global quality standards. BioDuro’s experience in China is telling. We are working with some 20 Chinese firms, many pursuing the development and manufacture of New Abbreviated New Drug Application candidates. What’s interesting is that many of these compounds are being reformulated, designed to more closely match the particular physiological and societal needs of China’s sprawling, diverse population.

 

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Wes Wheeler, CEO, Marken

A: Solubility and subsequent issues of bioavailability have long been an issue for Pharma, especially for poorly water-soluble compounds. For both branded Pharma and contract manufacturing organizations alike, “solving” a compound’s solubility issues is often the key to unlocking either its full therapeutic benefits, processing efficiency or its market potential – but more likely, all of the above. Contract manufacturers in particular are seek­ing market success improving their technical acumen and operations to assist drug innovators in developing formula­tions and other oral solid-dose and delivery technologies to overcome issues related to solubility and enhancing bio­availability. One strategy for success Pharma is adopting has to do with extending the patent protection and market life of an approved drug via the FDA’s 505(b)(2) regulatory pathway, which for many is a strategic response to the pending loss of patent protection. Manipulating the formulation and bioavailability aspects of existing drugs to prepare them for new patient classes or disease catego­ries is a major aspect of this trend. Drugs approved under 505(b)(2) rely on data from existing reference drugs and require only a fraction of the number of clinical trials for approval compared to a brand-new candidate. Ultimately this means a “new” and patent-protected drug can achieve FDA approval in as little as two and a half years. Ultimately, these market dynamics will continue to ener­gize the industry’s supply chain and that includes the need for well-managed, secure clinical supply logistics to assure clinical trial success.

 

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Tim Tyson,Chairman, CEO, Avara Pharmaceutical Services

A: Many of the new chemical molecules under consideration are very difficult to formulate from a solubility standpoint. Innovators with new molecules are looking for their supply chain partners to deliver the technologies and different types of capabilities to make chemicals more soluble. There are certainly a number of things that can make a product more bioavailable; technologies like nano-crystallization that cre­ate smaller, more soluble particle sizes is just one of several effective methods. Increasing the time a compound spends in the body and controlling release can be accomplished through different coatings technologies and techniques that manipulate dissolution profiles. Avara’s fielding some interesting technology. One is a drilling technology that al­lows two different APIs in one tablet. We also have a polymer-coating technology that allows the product to stay in the body longer and dissolve over a specified rate over a longer period of time, and an enteric coating technology that only releases once it’s in the intestine. One of the most important things to remember is there are a significant number of molecules in development that could potentially be more effective thera­peutically if the industry can apply the research and development it’s going to take to innovate and make medicines more bioavailable. In the near term I think we’ll see a signifi­cant increase in the amount of time and effort that the industry spends towards developing technologies to make prod­ucts more bioavailable.

 

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Marianne Spaene, Executive Vice President Global Business Development, Marketing & Sales, Siegfried USA

A: One of the most promising strategies for enhancing bioavailability is to apply the API in an amorphous form that is more soluble than crystalline forms. Spray drying — a novel, flex­ible bridging technology that can be applied to most poorly soluble drugs — allows the API to first be dissolved with tailor-made polymers in an organic solvent so that it can be isolated and stabilized in the amorphous form. With the API encapsulated in the polymer matrix, crystal­lization cannot occur and the final product becomes more soluble and, ultimately, more bioavailable. Essentially, by improving bioavail­ability, new drugs can be made available for patients and the daily dose per patient can be effectively decreased, thereby reducing prob­able side effects. Siegfried as an integrated drug substance and drug product partner offers spray drying from lab development to large-scale manufacturing.