Current issues
The outsourcing of device development
The pharmaceutical industry has undergone some radical changes during the 1990s with extensive consolidation through mergers, take-overs and strategic friendly acquisitions. This trend is set to continue and it has been predicted by some stockmarket observers that by the year 2010 around 50% of the world pharmaceutical market will be taken by only five or six 'mega' companies, each with a market share approaching 10%.
The consolidation that has already occurred has led to some significant re-thinking on the role of research and development in the pharmaceutical industry, and in particular on how the R&D budget can be managed effectively to provide substantial value-adding developments. The discovery part of pharmaceutical R&D will continue apace with the development of ever increasingly sophisticated techniques for compound formation, identification and screening. This fuelling of the development pipeline will place additional burdens and stresses on the early stage development groups whose task is to provide evidence of efficacy and safety in man.
The resource necessary to support the wide-ranging research activities can be defined using a number of simple criteria (for example, the perceived importance of a given therapeutic area to the business). However, the resource required for the drug product development activities is less predictable and less able to be planned with precision. New compounds can fail in both early and late stage development, irrespective of the quality of the decision-making processes, and thus there can be significant peaks and troughs in the level of resource needed over the longer term.
The pharmaceutical industry has traditionally preferred to maintain a large part of its R&D activities in-house but is now increasingly looking to outsourcing as a means of better balancing its internal core groups and providing for better management of the peak demands for resource. An additional driver for outsourcing is the increased focus on 'core competencies' - do what the business is good at and get others to do what they are good at.
The need for novel drug delivery systems to administer new compounds has led to companies building new groups in-house and to look to outside organisations to complement their in-house activities. The development of drug delivery devices is a particular example where the strategy of outsourcing can be successfully applied.
Device development for the pharmaceutical industry requires a range of skills not generally seen within the drug product development division of a large pharmaceutical company. The range of skills necessary for device development includes:
- Design engineers
- Mechanical engineers
- Industrial designers
- Materials specialists
- Packaging engineers
- Electronic engineers
- Physicists/chemists
- Formulation scientists
- Skilled fabrication technicians
In addition to this unusual skill base there is also the issue of specialised facilities and equipment that are essential for the efficient development of a delivery device. The range of facilities and key equipment includes:
- 3D computer aided design (CAD) with the ability to provide complex surface construction, interfaced to computer controlled lathes and mills (Figure 1)
- Other rapid prototyping techniques such as stereolithography, early mould tool construction and injection moulding equipment
- Well equipped and versatile workshops to provide precision engineered components and test rigs (Figure 2)
- Laboratory facilities for performance testing with specific or representative formulations (Figure 3)
- Access to user groups to guide the 'human factor' aspects of the device development.
In addition, the ability to carry out theoretical modelling of, for example, flow paths through the metering chambers of dry powder inhalers, and sensor technology expertise to allow precise on-line testing, are invaluable in providing added support to the device design process.
Figure 1: Computer controlled engineering at PA
There are many apparently compelling reasons why pharmaceutical companies should either keep drug device developments in-house or acquire the skills and technical capabilities to carry out internal device developments:
- Better integration of device development with pharmaceutical product development
- Rapid response to device/drug formulation interaction issues as they arise
- Better control over the entire product development process
- Ability to maintain intellectual property rights (IPR) in-house
- Progressive build up of the skill base, knowledge and know-how during the development process.
Figure 2: PA's versatile workshops
A well-resourced and appropriately skilled group with extensive experience in device development can no doubt fulfil the needs of a drug product development programme. Whether this can be accomplished in the timeframes demanded by the drug product and clinical development plans, and within an aggressive regulatory strategy framework for a pharmaceutical company that does not have full in-house capabilities, is a very different matter.
There are equally compelling reasons why device development can, and in many cases should, be outsourced particularly when no, or only limited, in-house capability exists:
- The time and costs (ongoing revenue and capital) associated with establishing a critical mass of resource, skill base, facilities and equipment
- The time and commitment for the integration and training of the new disciplines in the ways of the pharmaceutical industry (GMP, GLP, Pre-Approval Inspections, product and process validation, the addressing of regulatory issues during the approval process)
- For many companies, device development may be a one-off activity with no long-term need for the range of skills that need to be applied.
Figure 3: Part of PA's extensive laboratories
Even in the case of those companies with an experienced, well-resourced and equipped device development group there will always be occasions when additional resource is required to smooth out the peaks - unless the group has the luxury of being able to accommodate all peak workloads.
The requirements for a successful outsourced device development are numerous but the key to success is to identify an appropriate 'development partner' rather than a 'supplier' of the device development service. For the duration of the device development programme, the development partner becomes an integral part of the drug product development team and must assume the same level of commitment to the programme, and responsibility within it, as is expected of the other core team members.
As a minimum the development partner must have the range of skills, facilities and equipment described above. It must not only be capable of talking the same language as the other members of the team, but also to 'mirror' the same development processes that the team demands for a successful drug product development. In short it must have an in-depth understanding of drug product development and how to integrate device development into the overall programme.
The device and drug product development must be carried out in a manner compatible with the ever-increasing demands of the regulatory authorities, and in particular, the device must be at an appropriate stage of development for each phase of the clinical programme. It is essential that the drug product evaluated in a pivotal Phase 3 clinical programme is truly representative of the product to be marketed, and this applies equally to the delivery device as it does to the drug product formulation.
The establishment of the right development partnership with the right device development organisation can ensure that the device development process is well integrated into the drug product programme and that there is responsiveness to the needs of the drug product development team. Additionally, as the development partner is a key team member, it is the team that exercises 'control' over each of the key elements of the process.
The development partner must understand that device IPR is an important consideration for many pharmaceutical companies. A good device IPR position can effectively provide added drug product protection well beyond the patent expiry of the drug compound itself. Thus, an acute awareness of the need to create patent and design protectable elements of the device is required. This need to develop added drug product protection is assuming increasing importance in the era of active pharmaceutical product life-cycle management.
It is well appreciated that a significant knowledge base and extensive know-how are developed during the process of design and development of delivery devices. There must be a commitment to the effective transfer of this knowledge and know-how from the development partner to the pharmaceutical company from the outset - this is not a process that should be planned for the end of the development, it is a continuous process through the lifetime of the development.
The apparent barriers to outsourcing drug delivery device development described earlier can be somewhat illusionary. Through selection of the right development partner, the pharmaceutical company can access the required and specialised expertise to add to its own internal drug product development team and save considerable time in the overall device development process. By establishing the right commercial and technical relationship with the development partner, the pharmaceutical company can benefit enormously.
The key to the successful outsourcing of a drug delivery device development is in achieving mutual trust and respect between the partner organisations and to build and develop a fully integrated development team. Successful development partners view the relationships they develop with client organisations as long-term relationships, lasting long after the successful completion of a single development programme.
Pharmaceutical companies do have many options on how best to carry out a drug product development programme, the use of a development partner is increasingly being seen as the most appropriate and cost-effective means of developing the device component of the drug product. The success of this approach is also becoming increasingly apparent.
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