Landscape-shifting pressures

The Challenge

The research & development based pharmaceutical sector is grappling with a series of landscape-shifting pressures. The strong and increasing threat from generics drug manufacture continues to erode its market share. In its 2009 'Generic Drug Roundup Report' the FDA noted that generic drugs, costing between 20% and 70% of their branded equivalents, save consumers some $8-10BB per annum.

Downward pressure on pricing and the implications of, for example, healthcare reform in the United States; the National Institute for Clinical Excellence in the United Kingdom; and the requirement to develop and market therapies at affordable prices in developing countries are combining to diminish margins. Cost effectiveness is emerging as a key driver and, behind this, the implications for the efficiency and effectiveness of the management of product development and operations is driving behavioural change.

All of the above is compounded by the lack of productivity of the historic pharmaceutical R&D model. In the ten years from 2000-2009, an average of 24 new molecular entities per annum was approved by the FDA - a high of 36 in 2004 and a low of 17 in 2002. This is part of a continuing downward trend by decade. And all of this in an environment which promised to be target-rich!

Regulatory requirements demand an evidential basis of product and manufacturing process understanding. Whilst this is partly in response to some high profile product failure and liability instances over the last several years, it also reflects a more sophisticated feel for effective ways in which products can be designed, developed and manufactured in order that they are both safe and efficacious when brought to market.

The challenge for the R&D based pharmaceutical sector is clear. It is this: to improve quality and productivity simultaneously and sustainability thereby reducing the cost of a safe and efficacious therapy to the patient.

The Response – a Case Study

Lessons are being learned from other technology sectors that have successfully addressed such challenges, such as electronics. There is currently much discussion around ICH Q8 and ICH Q9. Respectively, these address Pharmaceutical Development - Quality by Design, and Risk Management. These guidelines are intended to stimulate the appropriate adoption of best practice tools and techniques, practices which have been extensively applied in those other technology sectors over the years. Collectively they have been described as Lean, Six Sigma, Design for Six Sigma, Operational Excellence. The philosophies and practices associated with Q8 and Q9, and their very language - 'Quality by Design'; 'Design for Manufacture'; 'Quality Risk Management' - are about applying these best practices in pharmaceutical R&D.

Having benchmarked the performance of its peers amongst the top dozen pharmaceutical companies, our client engaged SI Associates to help them reduce the cycle time of their Late Development process by 50% within 18 months.

Using a structured approach to process re-design and optimisation aligned to the principles and practices of ICH Q8, ICH Q9 and ICH Q10 the initial project activity involved working with the global, multi-cultural senior team of the client both to confirm the goals for the activity and to commence the process of building the 'To Be' model for the product development operation.

Importantly, this team included senior representation from the peer processes of Late Development, specifically Early Development, Operations and Supply Chain. Equally, other relevant functional representation was engaged (for example, QA Regulatory and Information Technology).

The approach included a considered appraisal of where the best practices associated with Q8, Q9 and Q10 would most beneficially be deployed in the optimised operating model. This precipitated the natural extension of best practice adoption into those peer processes of Late Development.

This team agreed the architecture of the 'To Be' model and defined an Implementation Plan for its development and deployment across the business. This Plan addressed not only the 'technical' elements of the transition to the improved model, but also those significant considerations associated with Change Management (communication; skilling; structures etc). This involved direct engagement with the majority of personnel impacted by the change.

Direct support to a range of sub-teams associated with the implementation of the optimised Late Development model was provided. A pilot implementation was identified (using a particular drug dosage form). The successful implementation of the pilot led to the roll-out of the model across the entire R&D operation.

Benefits

The benefits associated with the implementation of the optimised Late Stage Development model were transformational and the original goals exceeded.

Late Development Cycle Time was reduced by 65%. Associated Time-to-Market and pipeline capacity benefits were realised.

The Cpk's associated with Technical Transfer to manufacturing sites have witnessed step-change improvements to previously unattained levels, 5 and 6 sigma.

All of the above was achieved (developed, deployed and institutionalised as the accepted 'way of working') globally across multiple cultures within 18 months.