Product Development - taking the high road or the low valley route

It goes without saying for all formulators that when we are presented with an NCE or NBE project to progress we have to bring out our basic pharmaceutics and pre-clinical toolkit and then select each tool carefully so as not to waste the usually very expensive compound in order to understand its physico-chemical properties and take each step with some care so it does not have to be repeated (tox studies etc.). This is neccessarily taking the high road as we know that one is generally going into uncharted territory. Of course, it gets easier if the compound is derived from an earlier compound series (then you have an outline map of the territory but you are still aware that you are in the middle of a mountain range). However no R&D Manager or Director would ask a formulator to start from scratch for a 10-15 year old marketed compound with a known physico-chemical and pre-clinical map generally readily available.

So what to do about the product formulation for the first generics developer? Which road to take? It is still quite surprising that most R&D departments treat this is as uncharted territory and want to take the difficult high road.

Any good IP Department will have already identified any relevant originator company's formulation patents or those of the speciality contract development company in question. The standard pharmaceutical excipients used in most products are well known and defined for safety reasons with unique excipients only very rarely being chosen (which are normally highlighed in a patent if it contributes a novel physical attribute or benefit). Nowadays we think nothing of entering the location address into a car's GPS system so we can be reasonably sure of at least getting within visual sight of our destination. Formulators have a similar role as the GPS. Ideally they need to get to the exact spot as the required pharmaceutical destination however QbD tells us that as long as we are in striking distance of the key attributes then we are in sight of our goal to be able to satisfy the regulatory requirements. Why do companies not ask for this QbD postcode or PIN to hand over to their formulators? Is it because they have so many qualified formulators within their organisation they want them to walk the various routes so that perhaps one of them will locate the destination and report back.

If your aspiring young children have never made a particular cake and they know that you have baked one before they may ask you for the recipe or alternatively check a cookbook or the internet. You would not expect them to decide 'you know I think I will just choose my own favourite ingredients and make it up as I go along'. You would gently guide them away from such unproductive activity. It is not unusual therefore for cooking programmes to have parallel online web content that give out this information for viewers to follow through after watching a programme.

When out-sourcing has been such a large part for the pharmaceutical industry for the past 25 years I would ask the question as to why so many formulation scientists, teams and their managers still remain so insular that they cannot look outside their own laboratory window. In must I think that in these matters our analytical colleagues are a little better in not trying to re-invent the wheel when someone else has previously already done the difficult work. Knowing at least one specific formulation point of the QbD design space would indeed be valuable in reducing the guesswork. Additionally it may give invaluable insights into ensuring that one avoids potential patent infringements.

In this case consider whether you want your formulators to consult a library book or to start writing their own book. I know which one is quicker, less expensive and more resource productive for your company and you can then use your formulators to do some of the more challenging work that is required to make your generic registrable. The choice is with those Managers who need to use company budgets efficiently, with those with project deadlines to meet (Project Managers), with Commercial and Business Development Managers who want to have a continuous stream of good products to generate future revenue. It is a often a sign of failure that these stakeholders only seem to get involved when projects are getting stuck in the mud. Ask yourself whether it is time therefore to consider visiting your friendly formulation library when you start your projects?