Looking back, looking forward

IN THE mid-1990s the leading products were small molecule, oral solid dosage (OSD) forms. Most products were developed in house within pharma R&D and, while success rates were not high, the profitability of pharmaceuticals made the shotgun approach feasible.

The last 21 years have seen dramatic changes to this landscape: mega mergers and consolidation of companies have resulted in consolidation of manufacturing and R&D. There has been increasing dependence on outsourcing – both for manufacturing and R&D – which has led to integration challenges and increased focus on a diverse and vulnerable supply chain.

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Patent expiry for the majority of leading small molecule products, with dramatic loss of market share, has focused the industry on cost controls and rationalisation. Decline in top-line revenue adds pressure on pharma companies to reduce expenses to maintain bottom line revenue. This has caused rationalisation of overcapacity, lack of recapitalisation, and pricing pressure on materials and cost of goods.

Government pricing pressure is increasing worldwide and this same period has also seen tremendous growth in globalisation, with recognition of the growing importance of ‘pharmerging’ markets, as global companies increasingly focusing on manufacturing and sales in these locations. The rationalisation of manufacturing capacity is occurring while global demand for pharmaceuticals continues to rise.

This period has also seen the emergence of biologic therapies, which now account for most of the leading products on the market today. For a period, this reduced the impact of the ‘patent cliff’, but the growing acceptance of biosimilars is beginning to have a similar effect. Many of these biologic products are more expensive, renewing the debate about cost/benefit and the focus on pricing.

Manufacturing

The technology to manufacture OSD is very different from manufacturing sterile products – and the manufacture of the drug substance (API) is even more complex. The rise of biopharmaceuticals has led to new challenges and innovations. We have seen an increased proportion of ‘cold chain’ products, which, in addition to concerns about supply chain security, has given new focus to distribution.

Higher yields have meant continued reduction in the size of equipment and increasing use of single-use technologies that have allowed dramatic reduction in facility footprint and associated costs. We have witnessed the change from manually intensive aseptic processes to highly automated equipment with advanced environmental controls. Analysis of product has moved from laboratory to advanced instruments, including some uptake of in-process analytics. Most dramatically, however, is the shift from paper records to terabytes of electronic data. Richard M Johnson, President/CEO, Parenteral Drug Association

The increase in development of combination products – drug/biologic and device – has been rife but new integration with diagnostics and software are promising even more benefits as well as challenges. New therapies are emerging from enhanced understanding of the genetic and individual contributors to disease, which brings the possibility to customise treatment in a more focused way. Each of these advances challenge the existing paradigm of manufacturing and control.

Regulation

Our regulatory framework is a further aspect that’s changed. Twenty years ago we saw the beginnings of EU integration and international harmonisation. The understanding of GMP has steadily harmonised, but the legal and regulatory framework has unfortunately not kept pace, with some markets using regulation as de facto trade barriers. We are seeing greater cooperation and exchange of information among global regulators, as they recognise the need to adapt to the changing global supply chain, but this still primarily focuses on GMP enforcement. The licensing of products is still highly fragmented, and the impact on manufacturing and post-approval changes has continued to be a barrier to innovation.

The future of therapies to solve medical needs is exciting, but will inevitably create challenges to business, manufacturing and regulation. The pace of change will only increase. It falls to all of us to embrace these changes and deliver better outcomes to the patients we serve.

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