Accelerating the go-to-market of nasal combination products with integrated solutions

Ear, Nose, Throat market trends outlook

The overall Ear, Nose, and Throat (ENT) market was heavily impacted by Covid-19 pandemic due to masks-wearing, lockdown, and less social interactions, exposing people less to respiratory virus as well as allergens. People also tend to avoid going to the drugstores for non-vital treatment during the pandemic, leading to a significant 9,5% drop in Over the Counter (OTC) volume demand in 2020. When we start returning to our normal life post-pandemic, the market need is clearly observed to rebound in 2021, reaching an increase of 5,7%, requiring an agile and fast turnaround from the pharmaceutical industry to secure supply for patients in need of medications. The ENT market is estimated at 1,9 billion devices, with the majority of drug products for nasal applications. [1]

The topical therapies still dominate the nasal market to treat allergic rhinitis, sinusitis, and nasal congestion. Allergic rhinitis is mostly seasonal and is usually relieved by nasal spray containing topical-acting medications. Corticosteroids are today the first line treatment for allergic rhinitis as they reduce swelling, inflammation, and mucus secretion in the nasal cavity. This long-standing historic market is still very dynamic following incoming pipelines from the generic players, representing opportunities for growth. In fact, today 65% of the topical treatments are generics. [2]

Most of these topical treatments are available Over the Counter (OTC). In many developed countries, OTC regulations have come a long way becoming more and more stringent, approaching Rx drugs dossier requirements, strengthening barriers to entry, ensuring patient’s safety. For instance, recent Medical Devices Regulations (MDR) for European Market opens opportunity to upgrade the required standard on raw material compliancy, control strategy and documentations on products as well as processes for the registration of OTC drug products, implying similar exigence level as per prescription bound solutions.

The nasal route is non-invasive and does not require healthcare professionals’ intervention. Unlike injectables, patients can self-administer their medication with a rapid onset. It offers better bioavailability as nasal administration avoids hepatic first-pass effect which could be encountered when taking medications orally. Nasal devices are needle-free hence increasing patient acceptance level, leading to positive therapy outcomes following improved patients’ adherence and compliance.

More recently, there has been a growing interest and further exploration in delivering drugs through the nose for systemic-acting drugs, by targeting nasal turbinates. Turbinate occupies a large surface area of the nasal mucosa and is highly vascularized, offering a convenient pathway for a systemic delivery.

A rising number of prescribed systemic-acting drugs originally administered in injectable forms have been successfully repurposed and made available as unit-dose nasal sprays. Patients and/or their caregivers are now able to administer a one-shot spray easily and rapidly to manage emergency and crisis situations, such as overdoses, seizures, and migraines. This allows a broader patient population targeting, increasing its accessibility to different end-user groups. To ensure patient’s safety, the regulatory bodies impose strict regulations on this alternative route to optimize its drug efficacy with equivalence as per injectables, especially for life-saving drugs. The reliability of the device plays as a key role to ensure success in saving patients’ lives.

A full range of pumps solutions for topical, multidose administration

Nemera has a long-standing experience in developing and manufacturing complex nasal devices. Our journey since several decades has proven our capabilities in bringing a wide range of successful market references across the globe, both in regulated and low-regulated countries, to ultimately improve patients’ quality of life. Every year, our state-of-the-art GMP manufacturing facility produces millions of multidose nasal spray pumps. Our market-proven devices have been commercialized for diverse formulations delivery, bringing our customers’ combination products to serve patients. Our expertise in spray characterisation and bioequivalence have made it possible to commercialize a number of combination products. Today, millions of patients rely on our devices to relieve symptoms from chronic conditions such as allergic rhinitis, sinusitis, or nasal congestion.

Single-metered dose for systemic-acting drug administration

Multi-dose nasal spray pumps find their place in chronic therapies, but not in acute applications. When the device use is punctual, repriming might be needed before use; also, a large volume of a drug content could be wasted as it’s a one-off usage. Consequently, novel therapies are starting to emerge with a precise, ready-to-use unit-dose nasal spray for emergency and crisis treatments.

Nemera’s UniSpray delivers a single-metered 100µL dose spray and can be used for new, repurposed, or generic drugs. UniSpray has gone through different human factor studies, design verification and processes to ensure device reliability and robustness, assuring patients’ safety and ease-of-use, complying to the regulatory requirement.

This single dose nasal spray is a ready-to-use primeless device with 360° functionality, enabling one-handed activation. To ensure the correct use of the device, it offers an ergonomic and intuitive design. Once the device is activated, the plunger is locked in its position, preventing premature activation which is extremely critical in emergency use, visually telling users a clear message that the dose has been administered. The final locking also prevents device disassembly after activation.

UniSpray is a customizable platform, offering flexibility for spray adjustment for new formulations and generics. To accelerate time to market, UniSpray is compatible with the existing marketed primary drug containers and is also adapted to fit conventional filling lines. In line with this objective, for generic drugs, the preliminary bioequivalence of selected molecules is performed by Nemera which generate initial documentations, assuring spray characteristics equivalence and consistent performances; this foundation therefore must be completed by customers based on their formulation. For new or repurposed drugs, spray performance adjustment can also be done to ensure drug administration efficacy.

Innovative solutions to explore novel therapies

The vaccine research and delivery are accelerated amid Covid-19 pandemic. The nasal route is seen as an alternative for vaccine delivery to conventional injectable forms, benefitting from Nasal Associated Lymphoid Tissue (NALT), a region associated to the lymphatic network that can induce a mucosal and systemic immune response. By obtaining mucosal immunity in the nasal cavity, our immunity response will be able to combat respiratory pathogens as soon as they enter the upper respiratory tract, preventing further infection. It is also more accessible for patients with needle-phobia, especially for younger age groups.

With our extensive experience in intranasal delivery and injectables, we are developing a reliable, easy to use and safe nasal vaccine solution. The concept device is compatible with existing prefilled luer lock syringes and is constituted with a nozzle and a dose divider. It contains two-doses, allowing vaccine delivery for each nostril.

Another promising route being explored nowadays is the nose-to-brain pathway, presenting opportunities to offer efficient drug delivery particularly for central nervous system (CNS) therapies. Direct brain delivery would mean lower doses therefore less toxicity and less off-target effects as the medications mitigate the first-pass metabolism. However, anatomically, our brain is protected by the blood brain barrier (BBB) which prevents >95% of molecules from entering the CNS from the blood stream. Nose-to-brain delivery poses a real challenge in targeting the olfactory region in the nose, which is extremely difficult to reach as it represents a small surface area.

Electronic components are also being explored to foster patient’s safety, for instance to secure potent drug administrations. There is a wide range of drugs that are used for painkillers. As an example, opioid treatment such as fentanyl is used to relieve pain with its rapid onset of action through unit-dose or multidose nasal drug delivery.
Indeed, fentanyl is a potent drug, used to treat severe pain that has become the main driver of recent increases in synthetic opioid deaths. The fentanyl painkiller is used on a regular basis by patients with cancer. For multidose nasal spray presentations, this may lead to opioid overdose when it is not used according to the treatment posology. Given this, it is crucial to consider the mode and way of administration to ensure the patients’ safety.

On that account, Nemera explores how to manage drug overdosing using a smart nasal spray device. Nemera developed a smart electronic concept device with child-resistant, dose counting and locking features, Safe’n’Spray, offering solutions to prevent overdosing of potent drugs. It is an integrated device with a reusable electronic locking unit and fingerprint identification, to monitor drug dose delivery in a defined period to ultimately ensure patient’s safety.

Holistic end-to-end partner for the combination product journey

“We put patients first” is Nemera’s bottom line principle. Our development team works actively to understand patients’ needs through discussions and tests with patients individually or within groups and round tables with Key Opinion Leaders. Our early-stage development concepts are evaluated through the user test studies to ensure a profound understanding of patients’ unmet needs. This is to ultimately optimize the intuitiveness, ease-of-use, and usability of the device with the aims of reducing the occurrence of misuse and optimizing the device performance when handled by patients.

Delivering drug products to the targeted site is challenging in the case of nasal delivery. Nemera continues to work on nasal delivery system concepts aiming the delivery to specific areas of the nasal cavities for optimum drug efficacy. To illustrate, we use in-vitro testing on nasal casts which replicate human anatomy to predict in-vivo deposition. To support our internal projects, we have developed our own nasal cast, which can also support the joint development effort with customers towards a successful combination product.

The expertise on spray technology is also key to nasal drug delivery. Understanding the physics of the atomization and achieving good control of the spray characteristics are two of the R&D pillars for nasal drug delivery. We actively work on design processes and tools to support our spray development and reduce the number of design iterations required.

We offer design services and customized development starting from a design brief, an idea, and a concept. This design phase is finalized through a validated design which can be followed by stability and clinical samples all the way further down the road to industrial volumes.

Furthermore, we capture a clear growing interest of pharmaceutical companies in working with partners who foster a holistic approach, to support and help them navigate through their combination product development. By this, not only do we offer our expertise for robust device design and state-of-the-art manufacturing capacity, yet do we also accompany our customers throughout their development phases with our integrated front-end solutions. Thanks to our high-end laboratory facilities, we propose device plus formulation test services as well as test methods development for our customers’ needs. Besides, to navigate through a dynamic regulatory landscape, our regulatory experts are ready to help guide the projects.

In the case of establishing bioequivalence, following regulatory guidance is extremely crucial. Thanks to our in-vitro test capabilities, we can support specific generic projects through a complete set of tests that meets the authority’s prerequisite. This data generation will be statistically analysed regarding USA and EU guidelines for eventual customers’ IVBE dossier registration filing.

Speaking of the fundamental idea of integrating patients within the combination product development, Nemera also provides a full understanding of the patient journey and recommends user-related activities to further optimize patients’ experience for a specific drug/device combination product. Thanks to our extensive human factor capabilities, the pharma company could ensure that their selected device, in combination with their drug, is appropriate, safe and effective for the target population. For instance, our support encompasses making a specific Instruction For Use (IFU) adapted to certain target population, as well as supporting Human Factor activities in alignment with pharma company’s chosen regulatory path including ANDA versus NDA, or else.

Incorporating patients’ insights as early as possible to feed in our platform advancement is crucial. This is done by leveraging the patients’ journey throughout our drug delivery device research and development internally, to ensure our device answer the unmet needs of the end-users.

Through capabilities in human factors engineering, user experience design, engineering, lab services, statistical expertise, and regulatory support, Nemera is uniquely positioned to offer all the support that customers require through an integrated device platform and service program.

Conclusion

In line with the growing interest across local- and systemic-acting treatments within the nasal route, our device platforms coupled with the integrated end-to-end approach enable us to support and bring drug/delivery combination solutions to the patients. Nemera is the utmost holistic partner and helps its customers succeed in the sprint to market. From early device strategy to state-of-the-art manufacturing, Nemera is committed to the highest quality standards. Agile and open-minded, Nemera works with our customers as partners. Together, they go the extra mile to fulfil their mission.

1. IQVIA market data, total of devices sold, 2019-2021, worldwide
2. IQVIA market data, total of multidose devices sold, 2021, worldwide

Find out more about drug delivery pulmonary & nasal: https://www.ondrugdelivery.com/accelerating-the-go-to-market-of-nasal-combination-products-with-integrated-solutions/

About Nemera

As a world-leading drug delivery device solutions provider, our purpose of putting patients first enables us to design and manufacture devices that maximize treatment efficacy.

We are a holistic partner and help our customers succeed in the sprint to market of their combination products. From early device strategy to state-of-the-art manufacturing, we’re committed to the highest quality standards.

Agile and open-minded, we work with our customers as colleagues. Together, we go the extra mile to fulfil our mission.