Waiting to Inhale
Once the drug is identified, it still has to be administered somehow, whether it’s sub-cutaneously, intramuscularly, intravenously, or perhaps orally or as a suppository. And there should be a reason behind the choice of delivery route. “Don’t do it just because you can—you really need to look at what is the unmet medical need, and then develop a target product profile,” said David Cipolla, senior director, pharmaceutical sciences, at Aradigm, which develops products for inhalation including macromolecular drugs.
“You need to make sure that the rationale for the product makes sense after considering all the stakeholders, to look at the competition in the marketplace that you’re competing with, and to keep your product profile updated as development progresses,” he added.
Cipolla discussed three principal scenarios for (re)positioning a drug for inhaled delivery. The first and most obvious is to treat lung-related disorders like asthma or lung cancer. The second is to find a lung-related indication for an existing drug, like using cyclosporine to prevent transplantation rejection. And the third is to use the inhalation route to treat a systemic disorder, to alter the pharmacokinetics (for pain relief, for example) or pharmacodynamics, or to avoid injection-related issues.
There are a variety of inhalation delivery systems to choose from, each with its own advantages and disadvantages that need to be weighed. Dry powder inhalers and metered dose inhalers are small, and quick and easy to use, for example. A nebulizer is bulky, inefficient, and requires long dosing times, but it’s a well-established technology that can be used off-the-shelf. Other, more advanced systems can assure more efficient and accurate delivery, with comparable or better performance for the latter versus injections.
Since biopharmaceuticals are manufactured in aqueous-based fermentation or cell culture systems anyway, Cipolla recommends going into initial safety and small proof of concept human studies using a standard jet nebulizer with a simple aqueous formulation.
“And then in parallel you can develop, if needed, another formulation that will give you the commercial specifications, such as the dose and long-term stability. And once you know that it works, that’s when you spend the time and money on whatever you want as a final delivery configuration.”