“I am a co-founder and currently the Director for Regulatory Bioanalysis at A4P Consulting Limited (Sandwich, UK), a bioanalytical and bio-logistic company formed in 2011 and based at Discovery Park, Sandwich.
A4P provides expert resource and knowledge for the management and oversight of outsourced activities in bioanalysis and bio-logistics for the life science sector.
Utilizing our considerable drug development experience and knowledge formed within pharmaceutical, biotechnology and CROs we deliver value added, cost effective, scientifically robust and regulatory compliant solutions for outsourced and third-party provider requirements.
We cover bioanalysis used for pharmacokinetic purposes and in the biomarker discipline. Our management of bioanalytical projects can cover the evaluation and selection of suitable bioanalytical providers, the specialist supervision of assay development, validation and study sample analysis, expert management of biomarker data and peer review of bioanalytical reports and summaries.”
Our provision of expert resource and knowledge in delivering the management and oversight of contracted bioanalysis predominantly runs from the early pre-clinical regulatory space through the clinical development phases to the post marketing product development arena where this is impacted by regulatory considerations. We also have in-house experience of early discovery bioanalytical support and the interface of clinical development programs and diagnostic solutions required in biomarker development and deployment.
Achieving effective and documented oversight of outsourced activities is a paramount objective for us to achieve. Sponsors have to pay increasing attention to their accountabilities for outsourced generated data. Thus, considering and assessing how to deliver the extent of oversight and management of each project is a key factor. We suggest that requires an insight and a perspective on drug development across a number of therapy areas and appropriate expertise coupled to flexibility in approach.
We also believe a vitally important factor in bioanalysis outsourcing is being able to place the primary technical objective into context. Simply being able to measure something does not necessarily mean that the generated data is relevant or will be of value to the wider development activities and objectives. Furthermore, the application of regulatory guidelines in an arbitrary manner irrespective of their context relative to the objectives of the data is also an area of that can be wasteful of effort or worse potentially misleading. Indeed, this has begun to be addressed for example in a recent White paper from the EBF on towards decision-based acceptance criteria for bioanalytical method validation .
The need for more diverse bioanalytical data is now commonplace. This is markedly increasing the complexity of how to operate within a regulatory environment. The line between investigative data and primary data is increasingly blurred in programmes, in studies and even within the same sample where multiple analytes are being measured.
Data are accumulated increasingly by and through multiple owners of the asset. This often leads to significant continuity issues with previously generated data where these are held in various locations and organizations. Often simply locating these data needs a significant expenditure of effort and time. This also increases the time required in understanding and interpreting the context of the data and the supporting meta data that underpins the data’s validity and acceptability.
An interesting challenge is where the outsourcing is seen as the solution to where issues in particular geographical locations confront sponsors. If local supply is not immediately available for various reasons such as technological, regulatory or cultural then a significant amount of effort needs to be undertaken to find solutions that can still try to meet expectations that can initially be unrealistic. From a bioanalytical regulatory perspective, the global initiatives around harmonization and communication across and between jurisdictions being fostered by the bioanalytical community are invaluable.
The challenges that have become apparent are that the nature of clinical trials are changing as they reflect the disease types and the manner and subject populations that that are being researched. One significantly increasing area is the number of therapies directed towards orphan and rare disease states. From an operational perspective this has an impact on the number of subjects, the progress of recruitment and the geographical areas where the trial centers are located. Whilst there can still can significant amount of consolidation of sample logistics, there is an increasing trend that the size of particular analytical batches available to be matched against the data feedback that sponsors are requesting is diminishing. From an operational bioanalysis perspective this is going to present challenges to both costing models and allocation of bioanalytical resources.
An additional factor is in the nature of trial designs, such that it is now relativity commonplace for multiple bioanalytical endpoints to be required to be measured. Here the challenge can be one of a limited amount of biological sample available for these measurements from each subject. Furthermore, if the technologies required to be used to make the measurements are not available in a particular location or at a particular provider, the need for co-ordination and collaboration across and between vendors is an area of potential growth and transformation.
The complexity and the fiscal challenges in obtaining marketing authorizations for new therapies is apparent in what is perceived as a resultant downward trend in the industries productivity is surely going to have an impact on outsourcing trends. The aim of many organizations will still continue to be to control research and development costs, particularly in managing capital expenditure.
Undoubtedly it still remains that a prime motive for any organization to outsource is to maintain productivity where internal resource gaps occur. This may be in personnel, expertise, technology or demands caused by local geographical regulatory and business factors. The model of drug development organizations having all technologies and the concomitant resources and expertise they may require at sometime within their ’in house‘ establishment has gone and are very unlikely to reinstated. These two factors alone will surely drive an increase in amount of outsourcing.
CROs are already responding to this by becoming more innovative, offering services in areas such as discovery support, widening their technology platforms and looking to deliver added value in offerings that stretch wider than traditional bioanalytical support models. Obviously, they will need to remain focused on quality, productivity and cost factors but innovative opportunities clearly exist.
The range of therapeutic agents being developed and researched is clearly much more diverse than in the past. Thus, bioanalytical requirements are now much less predictable. It is no longer the case that the only bioanalytical requirement is to quantify an exogenously dosed small molecule from fixed time point samples. Bioanalysis is now expected and required to cover a range of types of therapeutic agents which are much more diverse than have even been previously. Thus, to meet this diversity, new technology developments are currently and will continue to be made available. However, access to these new technologies and the expert resource required to manage and operate them are as likely to be held in contract organizations as in innovator organizations. Experienced resource with appropriate attributes and expertise is in significant demand.
Operating models adopted by various organizations towards outsourcing still fundamentally fall into ‘tactical’ or ‘strategic’approaches. The tendency for larger organizations, such as the multi-national pharma companies, to build strategic alliances with similarly sized CROs is continuing to increase rather than decrease. Similarly, the size and diversity of the larger CROs is driving their need to increase the number of strategic alliances to protect and secure their capital investments.
This may well place a greater tension for smaller entities such as biotech start-ups or organizations with niche therapy technologies, particularly where these are in very early development or as more conceptual ideas. These organizations are also much more unlikely to have the breadth of expertise or technology access to cover all elements of even very early therapy developmental needs. The amount of capital expenditure that these innovators can deploy is much more likely to be limited and focused to achieve milestone goals that are more limited. For example, many smaller companies will have business objectives to take therapies only to certain stages of development such as achieving a Phase II proof of concept and then being able to partner or divest the asset. Thus, it is very possible that these organizations will tend to gravitate towards smaller niche providers to solve particular problems rather than build very strategic alliances where much of what could be provided is not of immediate or short term relevance.