REGULATORY AFFAIRS – Rethink the Regulatory Dynamic: A Better Approach for Being Your Product’s Best Advocate


Technology is always moving forward, its momentum main­tained by a series of inorganic micro- and macroevolutions. While 100 years ago, patients were likely to receive medication by ingesting a tablet or getting an injection, alternative routes of administration have ballooned, greatly increasing the complexity of drug-device combination products, defined for our purposes here as products composed of both a drug and a device that fa­cilitates its delivery. The pressurized metered-dose inhaler (pMDI) and the autoinjector, two of Kindeva Drug Delivery’s early indus­try-leading innovations, are prime examples of this increased complexity. In both instances, the need to safely deliver the right dose of a drug to the right place necessitated the creation of very complicated, very precise devices.

Understandably, this complexity will continue to grow as each innovative idea branches to the next. And for combination prod­ucts, even as the devices become more complex, so too do the drugs themselves, including the development of features that allow more control over the release timing and positioning of a drug substance. This side-by-side evolution in dosage form and device functionality raises both engineering and chemistry chal­lenges.

As drug-device combination products grow more complex, regulations increase commensurately. However, to implement and enforce appropriate regulatory standards and truly ensure prod­uct safety, regulators must understand what it is they are regulat­ing. Given that both halves of drug delivery combination products are concurrently evolving on an incline, this is a tall task. How do you address it? That involves a lot of collaboration and education.


With combination products, there are regulatory require­ments related to the drug, and there is another set of require­ments for the device. In many regions of the world, these two regimes are often incompatible, rarely communicating with one another. On the drug side of the regulatory equation, safety and efficacy take focus. With device regulatory review, a key focus is on manufacturing quality systems and ensuring adequate control of highly engineered components. While there are standards for quality and effectiveness on both sides, these differing outlooks can lead to conflicting guidance.

For drug delivery combination products, which fit squarely in both regulatory regimes, there is a need to untangle and work through potential complications. As a simplistic hypothetical ex­ample, imagine that a medicinal regulator is requiring a warning on your product’s label while the device regulator is requesting contradictory language. By clearly understanding the regulations of both agencies, you can help align this sort of diverging guid­ance.


Remember that you are the expert on your technology, not the regulators. There is no way for anyone to appreciate the de­tails of a novel device prior to its explanation. A key focus of any regulatory agency is protecting patient safety while ensuring effi­cacy, so appropriately explaining how a new device meets those requirements can keep all parties on the same page.

For many developers, the issue is re­ally one of terminology, as an entirely new device improperly explained offers false or insufficient understanding for regulators. Providing thorough and complete details about the new device helps ensure regu­lators apply the appropriate guidelines and standards. While drawing compar­isons may be important to illustrate your product’s functionality, it is vital you also explain everything that makes your prod­uct different from others. By relaying those unique elements, you help ensure regula­tors judge the device as truly innovative.

Highlighting the safety and patient-centric features of any new device gives regulators a solid foundation from which to review the product. Regardless of your final approach, be sure to consider the best way to explain the product in advance of needing to do so. The clearer the expla­nation, the easier it is for regulatory agen­cies to review and hopefully approve the new product.


Don’t miss an opportunity to sit down with regulators. Many regulatory bodies have pre-submission or pre-development meetings, which are excellent venues in which to explain your new technology or new drug and highlight the potential pa­tient benefit. This is a surefire way to strengthen the regulatory partnership. Even if you don’t get the exact results you hope for, discussing study design, device manufacturing, or the intricacies of sub­mission itself offers insight into the thought process of regulators, as well as an under­standing of how you can better communi­cate with them. This early and regular engagement also gives you a seat at the table in the discussion of how to protect public health while bringing the most ef­fective product to patients as quickly as possible. You will have further opportuni­ties to educate regulators throughout the process, but it is best to begin the process prior to the submission of data or, even better, before the generation of that data, so start early.

This is a practice particularly recom­mended for combination products be­cause regulatory bodies worldwide tend to impose regulations that may not apply to the product or technology in hand. By dis­cussing your product with regulators throughout development, you increase the odds of it being understood and regulated accurately with the correct set of regulatory requirements appropriate to its functional­ity and use.


From ideation to commercialization, the entire process of creating a drug-de­vice combination product is risky. Will the device work? With the drug formulation? Can it be scaled? In fact, the risk of not addressing an unmet patient need is often the drive behind discoveries. So, the risk is baked into each step, and as your product proceeds along the pipeline into patient use, those risks quickly become regulatory concerns.

Among the most important aspects of healthcare is minimizing the risk to the pa­tient, so in the struggle to balance conflict­ing requirements, the soundest position from which to start is with a patient-centric approach. If you can justify a deviation from a stated requirement because you can show it is in the best interests of the patient to do so, you stand a much better chance of getting a regulator agreement and, in turn, aligning the stated require­ments for your combination product more closely with its actual use.

In the face of guidance that often seems based more on history than on a patient-centric evaluation of the specific combination product at hand, it is vital the regulators understand why your viewpoint is the right one for the patient. The expla­nation of this falls to you. As discussed, there is no way for the regulatory regime to completely understand your combina­tion product if you do not provide that in­formation. Developing your patient-centric rationale for regulators requires you to ask yourself some questions: Am I creating a quality product? Will it be safe for pa­tients? Will it be effective?


Once you’ve examined these ques­tions for yourself, you can better determine how far away what you are doing is from what regulators are expecting. Then the question becomes, “How do I justify that difference?” Commencing from this van­tage point gives you a place from which to start developing a patient-centric rationale that helps regulators better understand your product and which guidance to apply. Given the high level of many regulations versus the more specific guidelines that try to explain how to meet the regulation, there is often room for interpretation so long as you provide sound reason for it. This is a strategy that is particularly neces­sary for combination products because of the dual regulatory bodies overseeing the invention, for which a justified shift in ef­fective guidance could remedy any clash­ing requirements. Your role in keeping your combination product on track is en­suring it is understood, which means bringing a clear, patient-centric discussion to the regulatory table.

Nick Smalley is Vice President, Regulatory Affairs, where he leads Kindeva Drug Delivery’s Global Regulatory Affairs Organization. He has held previous positions in regulatory at 3M Health Care, Perrigo, UCB, and Norton Healthcare Limited. He earned his BSc (Hons) in Chemistry from Loughborough University.