Q&A with Kindeva Drug Delivery: Putting patients at the centre of drug development

EPM speaks to Steve Wick, vice president of R&D and chief technology officer at Kindeva Drug Delivery about changes in formulations and how patients are being put at the centre of development.

How are drug delivery systems changing to become more patient-centered?

Over the past decade, there has been a transformation within the pharmaceutical industry surrounding the integration of drug delivery system technologies and devices. Historically, the pharmaceutical industry focused on the drug and how to most effectively and safely deliver this drug to the patient. Although safety and efficacy remain paramount, healthcare providers and patients are increasingly interested in an improved overall patient experience. We’ve seen a focus on factors such as dosing regimen, remediation of side-effects, human factors, ease of use, and form factor convenience.   Within this transformation, numerous technologies have been developed to improve the overall patient experience: sustained release technologies, implantable technologies, pen-injectors, self-regulating systems, and mobile health/wearable technologies.  The future of drug delivery will incorporate expanded patient-centric technologies such as bio-feedback systems, tissue targeted drug delivery, long-term drug delivery (months), and an expansion of mobile health solutions. While the exact nature of innovation is difficult to predict, the next generation of drug delivery innovation will come through aligning technological solutions to patient needs.

With respect to inhaled medicines, how do you anticipate formulations will evolve over the next five to 10 years?

The delivery of higher doses (multiple milligrams and higher) is the challenge that limits the future of inhalation therapies. I suspect that expansion of the dosage limits will continue to be an area of focus over this five-10 year time horizon. The development of novel Dry Powder Inhalation (DPI) technologies and devices will likely play a significant role in our ability to deliver higher doses to the lungs. DPI technologies with higher efficiency in terms of respirable dose or carrier-free formulation technologies will enable higher doses.

The delivery of higher doses from a pressurised metered dose inhaler (pMDI) using conventional valve technologies is extremely challenging. The attainable dose is limited by pMDI valve capacity (typically limited to 100 microliters or less) and drug solubility limitations in propellant systems. In the future, we will start to see new valve systems and new propellant systems which both will enable higher doses from pMDI systems.

Certainly, worth noting is that future active pharmaceutical ingredients (APIs) are likely to become more complex with unique chemical properties and increasingly challenging solubility characteristics. These complex APIs will likely require complex formulation technologies to achieve stability. The use of surfactants or suspending agents along with stabilising agents is likely to become routine. As we move from monotherapies to drug products containing two or three APIs, the formulation challenges become exponentially more complex, requiring novel formulations and world-class scientists to deliver stable product performance profiles. 

Sustained release inhalation dosage forms achieving less frequent dosing regimens is also an area of interest. Recent product launches have routinely achieved once-per-day dosing requirements and this is likely optimal from an inhalation perspective. Dosing less frequently than daily will require a combination of increased residence time in the lung and sustained release formulation technologies. Although perhaps achievable, the therapeutic value of such a solution must be carefully measured against the risks in terms of potential lung toxicity.

Reflecting on the Covid-19 pandemic, is there value in exploring alternative formulations or delivery systems for vaccines?

First, consider the route of administration. Vaccines are often delivered intramuscularly. However, there is reason to believe that vaccines will elicit an enhanced immune response when delivered intradermally. Historically, there have not been reliable devices that can reproducibly and consistently deliver to the intradermal layer. With more of these delivery systems in development, I believe intradermal delivery can play an important role in the delivery of certain vaccines.

Moreover, vaccines can be effectively delivered through the inhalation route – both via the lungs and the nasal cavity. Most of the work reported in the literature focuses on single dose DPI delivery systems. Single dose systems are cost-effective and enable the introduction of innovative approaches to achieve a stable drug product. Vaccines are deactivated through denaturing and conventional particle engineering technologies often result in vaccine deactivation. If a respirable particle size can be achieved without deactivation of the vaccine and the vaccine itself is stable, then achieving a stable formulation with either a DPI or a pMDI system should be possible.

So, the bottom line is depending on the stability profile of the vaccine itself, the dosage requirements, and the dosing regimen, cost-effective, self-administered vaccine systems could be achieved for Covid-19 to enable rapid distribution and repeated self-administration.

How can the industry apply data, analytics, and predictive modelling to formulation and product development?

The drug delivery industry is already applying data analytics and predictive modelling to the development of both formulations and novel device technologies. In-vitro modelling has become a routine tool in the development of formulations for inhalation drug delivery and advances in predictive modelling have dramatically improved our ability to predict in-vivo performance of a formulation.

This same approach has recently been taken by Kindeva within the development of novel device technologies including breath-actuated systems, nasal delivery systems, and intradermal delivery systems. This approach requires a fundamental understanding of the underlying route of administration, experience with multiple drugs, and the drug-device interaction expertise to properly design and utilise predictive modelling. This expertise is typically developed only by leveraging decades of drug delivery experience.

When your customers approach you with their formulation and development challenges, what are the factors that increase the degree of technical difficulty?

The most frequent challenge we encounter is a customer looking to achieve higher doses. The primary consideration in addressing this challenge is solubility of the API. If the API has limited solubility in the propellant, adhesive, or formulation, the drug product can be assembled as a suspension. However, achieving a stable suspension can be problematic and may require more complex formulations with co-solvent systems. These complex formulation excipients can in turn lead to increased stability challenges.

Beyond the technical challenges with formulation, another challenge in the development lifecycle is understanding the regulatory requirements for approval. There are country-specific and region-specific requirements and they can often evolve quickly. For novel products, these pathways are often more complex and require a greater degree of coordination and communication with the regulatory bodies. CDMOs will be more successful if they maintain in-house regulatory expertise and engage them early and often in the development process.

In the end, experience with a multitude of APIs combined with a thorough understanding of the drug-device interaction and regulatory capabilities enables Kindeva scientists to tackle these complex formulation and development challenges.