When developing a drug delivery device, fast development is of the essence. Jay Bhogaita, head of emerging markets at Bespak, explores the complex relationship between formulation- and device-providers and looks at how it can be optimised
The general principles and benefits of Accelerated Feasibility Testing (AFT) are well known to many pharmaceutical companies, those being: an efficient and timely assessment of the appropriate drug delivery method for your formulation; accelerating the device development phase; and ultimately, minimising time to market
.What is perhaps less well recognised, and is the focus for this article, are the particular benefits that an experienced specialty medical device manufacturer can bring to the development process in terms of timely objective advice, a cost effective methodology and critically, real world expertise in managing the complex relationship between the formulation and the device. For example, the interactions between a pressurised metered dose inhaler (pMDI) valve, actuator, formulation and container pack.
The successful pairing of a drug and delivery device is critical to the safety and efficacy of the product and usually its commercial success. Harmonising these elements can be complex, requiring several iterations and consuming time and money.
In both established and emerging markets, AFT is helping pharmaceutical companies develop alternative methods of delivery using inhalation technologies, and this article will explore the particular benefits that AFT can bring to help speed the progress of such innovation.
Traditionally, the concept of outsourcing any element of the development process has been perceived by pharmaceutical companies as bringing risk and complication. There are naturally concerns around sharing commercially sensitive information; a sense that ownership of the project will be lost; that the company entrusted with that element of development may not meet all the regulatory requirements for launch; or simply that the cultural differences and working practices of the two companies mean that outsourcing is a less than straightforward affair.
The reality can be quite different but there are criteria by which potential partners should be measured. Their facilities, experience, technical capability, their procedures and track record are all factors that should be considered. There must also be a meeting of minds both culturally and scientifically and a mutual commitment to developing and building a strong relationship. Such a close relationship can deliver many benefits: much faster development time; perhaps enhancements to formulations; and often a much more robust product.
"Lack of resource" is often cited as a reason to outsource a development project or an element of the programme. Although perfectly legitimate, the consideration to outsource should not be confined to times when internal resources are limited. Most expertise comes with experience and companies should reasonably expect to see evidence that the selected outsourcing partner has successfully developed other devices from a similar phase as their own before committing to any part of a programme. Bespak, a leader in medical devices for inhaled drug delivery and anaesthesia, for example, has the facilities and, perhaps more importantly, the real world expertise to optimise the complex relationship between the valve, actuator, can and formulation. Only by truly understanding each element can the overall device be expected to meet the appropriate regulatory standards to reliably and effectively treat patients. When the value of such domain specific knowledge is appreciated, the justification to outsource becomes much stronger.
Compared to in-house development, the services of a specialty medical device manufacturer can provide particular benefits for those organisations that wish to develop an inhalable form of an existing Active Pharmaceutical Product or that wish to rapidly transition between dosage forms.
Often with in-house development programmes the Container Closure System (CCS) and actuator are considered in isolation of the formulation. This can lead to a 'trial and error' approach when it comes to optimising the valve and actuator for the specific formulation; an iterative process which has been known to extend development times by months or even years. As an illustration, a number of standard valves could be tested with a particular formulation in series and yet none of them prove to be compatible. Yet by developing the formulation in parallel with a delivery device and with a thorough understanding of the characteristics of the formulation, the manufacturer's AFT scientists can optimise valve and actuator within a much shorter timescale.
Device designers can also benefit from a manufacturer's AFT process, from initial material specification to the overall efficacy of the medicinal product. It is a recognised feature of the US Food and Drug Administration (FDA) regulatory approval process that the decision to select materials made in the early years of a device's development are expected to be fixed for the lifetime of that device. If a specific material is used in device development and the critical safety and efficacy studies have begun, a change in any part of the specification may necessitate additional testing and delay the product development, launch and potentially result in fewer sales. A device manufacturer should have experience of working with medical grade materials, preferably ones that have been used before. The manufacturer can then help the marketing authority select the most appropriate material for their formulation and device.
Successful and profitable commercialisation is best fulfilled if the device can be produced cost effectively over time. By working closely with AFT specialists who are closely aligned with manufacturing engineers, any foreseeable problems that may otherwise hinder successful industrialisation and commercial production of the device can be addressed at the start, saving valuable time and money later.
Whilst much of the AFT offer is focussed on optimising existing therapies and devices, manufacturers with AFT capabilities can also help speed the development of novel device concepts.
Nasal drug delivery is one example where a manufacturer with specific knowledge can help customers take advantage from a new delivery technology. The nasal cavity provides several benefits as a target for drug delivery including the rapid onset of therapies, and the capability to deliver delicate or complex molecules such as peptides and proteins. The efficient delivery of drugs to the nasal region however is highly complex and benefits from a thorough understanding of the nasal anatomy, as well as AFT in order to optimise a device.
Bespak has invested in the development of a nasal cast designed to replicate the structure and complexities of the nasal cavity. The nasal cast can then be used to characterise how aerosolised particles are deposited within the nasal region as device features, fire points and formulation characteristics are varied.
Though pMDI technologies typically offer cost effectiveness benefits and generally pass through the regulatory approvals process relatively quickly, there may be occasions, particularly in the generics market, where the transfer of a pMDI therapy into a Dry Powder Inhaler (DPI) may enable customers to create a point of difference through enhanced device design or a clearly differentiated brand. A device manufacturer with credibility in optimising both kinds of device can offer real benefits in terms of delivering modern DPI designs that provide much sought-after design and patient compliance features.
Accelerated Feasibility Testing is a well-established methodology, with clear benefits to pharmaceutical partners and device designers in terms of identifying an appropriate drug delivery method and then accelerating the device development phase. The use of an experienced specialty medical device manufacturer, in particular one with real world expertise in managing the complex relationship between valve, actuator, formulation and drug pack, has additional benefits. Whilst much of the AFT process is focussed on optimising existing therapies and devices, device manufacturers can also help speed the development of novel, conceptual devices.
Key criteria to consider when outsourcing AFT projects
1. What kind of relationship are you looking for?
2. How complex is the device?
3. Do you have the necessary Container Closure System expertise in-house?
4. Do you have the required resource in-house?
5. Do you have expertise in marrying formulations with devices in-house?
6. Has the supplier got a track record in your delivery device?
7. Can they demonstrate success with similar products?