These days, everyone in pharma has been closely watching the ‘Patent Cliff’ that so many Innovative pharma companies is facing. This wave of expirations has created a huge demand for alternative ways to squeeze life out of existing molecules by getting many other indications approved for the same molecule through different dosing or through other forms of the molecule. More importantly, significant efforts are taking place in adapting the same molecule through a novel drug delivery system(s) by contracting formulation research to Drug Delivery System (DDS) Companies. The major advantage could come through various means, such as improved patient compliance, better bioavailability, or product differentiation through rapid release profile such as a Orally dispersible tablet which dissolves in five seconds or less than a conventional ‘Immediate Release (IR) dosage form, which was on the market for many years.

This could potentially also lead to a faster onset of action, if the absorption is enhanced sublingually. There are contract research companies such as CURE Pharmaceutical that have the capability to develop novel drug delivery technology to put a fixed dose combination of drugs sandwiched in two layers of thin polymeric films, as a fast dissolve oral dosage form. They also have successfully created an electrolyte-containing ‘energy strip’ that would be utilized for ‘instant energy’ rather than taking a drink which contains carbohydrates and electrolytes.

Similar to the life of an innovative pharmaceutical molecule, drug delivery companies have a finite patent life for their technologies in which to establish the value of the technology and the company. Various models exist to demonstrate how these companies best exploit the value of their intellectual property and how they plan to continue to grow after key patents expire. A large number of companies target the formation of partnerships with major pharma companies to apply their delivery technologies. As these technologies mature, drug delivery companies can look to develop or acquire new or improved technologies or to transition to the internal development of products followed either by licensing or marketing. In recent years, the growing acceptance of the use and value of drug delivery technologies, together with the maturing of many technologies and the increasing trend of mergers within the pharma industry, has resulted in a changing relationship between the two industries.

This column presents the perspective of the pharma industry on how technologies are being evaluated and utilized. There are some key factors that are considered when selecting a partner DDS company. Leading pharmaceutical companies have grown significantly in size through the M&A activities. This increase in scale has an impact on how technologies are utilized and therefore has implications on the interactions with DDS companies. This has led to greater competition for business with the top pharma companies, but also offers significant opportunities for the drug delivery companies that can demonstrate the advantages of their technologies and value the technology appropriately to allow completion of research contracts and eventual commercial agreements. The impact of increasing scale with the leading pharma companies creates huge organizations with wide-ranging expertise and skills in different technologies and large portfolios of compounds. To utilize the advantages of this scale effectively, pharma companies need to operate on a global scale with integrated organizational structures, various sites, departments and operating procedures. Efficient application and understanding of drug delivery technologies is a vital necessity to allow their scientists to develop large numbers of small and large molecules efficiently despite diverse and challenging properties.

Many DDS technologies will be employed to improve or modify the pharmacokinetics. Traditionally, some drug delivery technologies have been reserved for line extensions but, providing there is sufficient confidence in the ability to deliver a technology without significantly impacting on the development times, drug delivery technologies are increasingly being utilized for early stage research candidates to enable bioavailability or a specific delivery of a drug or to launch the optimal formulation thereby increasing the probability of obtaining a best-in-class final drug product. To capitalize on scale, pharma companies must share and transfer knowledge efficiently between projects and across sites to develop best practices for key DDS technologies.

Access to technologies is through a combination of internal and external initiatives. Internal access is preferred for core technologies that are likely to be utilized frequently, providing there is freedom to operate. Critical IP for DDS technology normally defines the value. For example, this is how Pfizer could broadly utilize Bend Research’s Spray Dried Dispersion (SDD) technologies to various early stage molecules to enable those at the early research stage to be able to put into a dosage form for enabling the API to show enhanced bioavailability.

Expiration of patent life, over recent years has resulted in some technologies being internalized by pharma companies, whereas previously the only option would have been to enter into some kind of collaboration to access the technology. External collaborations are still an option in these areas, although the switch to outsourcing as opposed to licensing is reflected in the value assigned to the technology.

High priority projects at times are adapted for application of internal technology solutions if an appropriate external technology is not available or if the price or contractual terms are regarded as unacceptable. In order to reduce the impact of technology failures, multiple approaches may be adopted in parallel up to proof of concept before selecting the preferred approach through technical and commercial considerations. Increased M&A activities within pharma, coupled with the patent expirations of some drug delivery technologies, have caused a major impact on the interactions of drug delivery companies with leading pharmaceutical companies.

A number of strategies and approaches can be adopted by the drug delivery companies to increase the probability of signing fresh deals. Providing sufficient data to demonstrate the advantages of the technology — or what it may be capable of doing — is vital. The amount of information required will also vary depending on the technology. If there are some good proven technologies already available, there has to be a major advantage in considering development of a novel technology with all the associated costs and risks. Similar to the aims of the pharma industry — developing products with improved properties over currently marketed dosage forms and focusing on areas of unmet medical need — the aims of the drug delivery industry should be the same to develop best-in-class or first-in-class technologies or focus on areas of unmet need.

DDS technology valuation depends upon the status of development, the IP position and a comparison with alternative approaches that could be used. The impact of the technology on the product is also vital. Some technologies enable delivery of a compound, and a product would not be possible without employing that approach, whereas others allow development of an enhanced formulation with an increased commercial value. For an unproven technology, the risk of failure is more, and therefore access costs should be significantly lower. The drug delivery company also benefits from a collaboration that shares some of the risk and supports development activities on the technology that may then be applied to other projects.

IP protection is essential to add value to a technology compared with know-how, but the impact or value of the intellectual property to the specific product also needs to be assessed. A specific technology may have broad patent protection; however, there may also be alternative approaches that could be capable of achieving a similar result.

R&D Contracts
The type of initial R&D and subsequent commercial agreement needs to be determined on an individual basis to best meet the needs of both parties. These can range from outsourcing agreements to feasibility studies on new technologies or a license and development (L&D) agreement aiming to advance a product to the market. In some instances, a broad platform deal may be attractive to both parties to allow access to the technology for multiple candidates, leading to the formation of a longer-term partnership between the two companies. Generally, these would provide non-exclusive access to the drug delivery technology. Working with a familiar company and technology also avoids the learning curve associated with any novel technology where new or different technical hurdles could be encountered together with risks around negotiating acceptable commercial terms with a new partner. Defining ownership of IP is always a key part of any agreement. Protection of IP around the compound is critical to the pharma company, whereas ensuring control of ownership of the technology is the main driver for the DDS company.

Ultimately, effective use and understanding of drug delivery technologies is a key requirement to allow scientists to develop molecules efficiently and effectively in a timely manner. Each individual pharmaceutical company will have different technology requirements driven by their portfolios, discovery strategies and existing internal capabilities. There will always be limitations with existing technologies and gaps to be exploited — allowing incremental improvements — but broad areas of unmet need do exist. Certain areas that can be problematic for pharma scientists and where new technologies may have an expanding role include:

• Delivery of biologics such as peptides, proteins and DNA,
• Enabling solubility and thereby enhancing oral bioavailability,
• Improving capabilities for the delivery of a drug (for example, inhaled insulin), and
• Reduction of drug side effects and interactions.

For early development candidates, reliance on a novel drug delivery technology to improve pharmacokinetics or efficacy can add significantly to the cost, risk and time involved in the development process. There have been successes through application of drug delivery technologies, but there are also many failures where the combination of a drug with a delivery technology does not achieve the desired outcome. Preliminary feasibility studies to assess the key factors for a technology and to reach a proof of concept decision point rapidly are essential.

Further data to fully characterize and understand the capabilities and limits of the technologies is valuable to build confidence, increase the likelihood of a technology being utilized and reduce the technology attrition factor. One needs to clearly understand the objectives of such an application of a novel technology to a drug molecule. Ultimately, it needs to bring unique value to the patient in terms of patient safety, compliance and efficacy!

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Makarand (Mak) Jawadekar most recently served as Director, Portfolio Management and Performance at Pfizer Global R&D, until February 2010, when he opted for an early retirement after 28 years at Pfizer Inc. He currently serves on several companies’ advisory boards and also consults with bio/pharmaceutical companies for global outreach in emerging market regions. He can be reached at mjawadekar@yahoo.com.