I was reminded a few days ago of the inspirational story of Jasper Kane and John McKeen who completed a scale-up of penicillin production in just six months to meet the demand created by the second world war ( www.tcetoday.com/changedtheworld ). Kane and McKeen must surely have taken enormous pride in the fact that of the 150,000 soldiers treated at the D-day landings alone, 90% were dosed with penicillin produced in their plant.
The difficulties of scale-up
“The mould is as temperamental as an opera singer, the yields are low, the isolation is difficult, the extraction is murder, the purification invites disaster and the assay is unsatisfactory”
The words of factory manager John Smith about penicillin will doubtless bring a wry smile of recognition to those involved with the tough challenge that is process scale-up. Spanning the gulf between the excitement of discovery – “We can do it” – and the necessity of commercial production – “We can make money” – the importance and difficulty of scale-up tend to be underestimated.
But it is in good process development that cash yielding, commercially successful processes have their roots, especially for the pharmaceutical industry, where process change may often be discouraged by the requirements of validation.
Plus ca change
While timelines in the pharmaceutical industry are no longer, thankfully, driven by an ongoing world war, relentless economic pressures, coupled with one-off events such as the need for a new flu vaccine, mean that little changes in terms of the demands placed on scale-up teams.
That said the industry is currently investing huge resource in learning and understanding processing, in ways that it hasn’t before. Quality by Design and the Process Analytical Technology wrap around the central idea that we need to design robust processes, on the basis of secure knowledge and control them effectively. In the future faster, more efficient scale-up should become the norm.
A call to arms
Appropriate analytical technologies will underpin the transformation that the FDA and many practitioners envisage for pharmaceutical manufacture. The pharmaceutical industry is now actively seeking new analytical techniques – instrument manufacturers need to rise to the challenge of meeting its requirements: technologies that deliver richer data streams and/or allow for effective monitoring in a timeframe consistent with the process dynamics.
In certain areas, such as laser diffraction particle size analysis, we already have technology that spans the lab – line divide. In others – the combining of spectroscopic techniques with imaging for example, the potential is still to be explored.
These are challenging but exciting times but it would be encouraging to think that should Kane and McKeen be called upon to repeat their astounding success today they would be able to get the information they needed faster, and move to full-scale production more confidently, than they did all those decades ago.