Recent Ranbaxy citation (UCM382514) is worth the review as it gives us cause and effect relationship
between state of pharmaceutical manufacturing and regulations. Information can
be used to improve pharmaceutical manufacturing whether it is API manufacturing
or their formulations and how to avoid some of the common mistakes. It also
gives us perspective of the regulators. Views expressed here are my own and are
not any recommendations.
Involvement of Daiichi Sankyo as claimed may be coming but it may be too little too late.
Ranbaxy (Toansa) citation focuses on
the following.
1. Raw materials, intermediates and finished API failing
specifications.
2. Repeated analysis of the samples.
3. Lack of procedures and adequate record keeping
Not being associated with or visited
any of the Ranbaxy facilities, my first observation is that the manufacturing
and supply chain management are out of control. These are also manifestation of
a business model being practiced and are inadequate to meet the ever-changing
needs at a plant site.
Re-analysis of raw materials suggests
that the company’s supply chain process needs significant review and edits. My
conjecture is that the focus is on getting the cheapest raw materials that
might come close to the desired specifications. Since these raw materials are
converted to the desired API, process purification could be used to remove the
impurities. If this is the case it is suggestive that there are serious issues
and finally they have culminated in the current state.
Repeated sampling and analysis
suggests that the manufacturing processes are out of control and yields are a
variable. Product quality will be variable and in order to meet the desired
specifications batch cycles would be variable. With lower asset utilization the
overall plant capacity is lower than planned and costs will be higher than
desired. This suggests that plant or the company profitability is a variable.
Lack of procedures also suggests that
with changing raw materials, process conditions, methods and results plant
personnel do not know how to analyze samples and then it becomes a fly-by-night
operation and that is what the regulators found.
Since all such costs are absorbed, it
means that the selling price of the salable API and the formulated products, to
ensure profits, are much higher than what could be achieved by having optimum
processes. All this could have been eliminated if Ranbaxy had complete command
of their processes and they are repeatable. From a financial perspective this
would mean that the site profits would be much higher from the current levels,
a significant opportunity. In addition, asset utilization would improve
resulting in higher production capacity with no or minimal investment.
Regulators in their citation/s are
confirming that the processes are out of control. It is understandable that the
regulators cannot and will not suggest corrective measures to comply. However
there is an underlying question “Do the regulators know the cause and effect of
what is happening when they are visiting/inspecting API manufacturing and their
formulation facilities?”
Ranbaxy citation clearly indicates
that there is tremendous opportunity to lower pharmaceutical manufacturing
costs i.e. healthcare costs. Lower costs can mean larger customer base that can result in incorporation of better manufacturing technologies. Having command of the processes can be a global
win.
Ranbaxy and Daiichi Sankyo have given
significant lip service with every citation and consent decree suggesting they
are in control of the situation but it seems that neither of them has been able
to “walk the talk”.
Actually FDA citation of the API manufacturing facility is a heightened salvo and heads up warning to every API producer and
formulator in India not to overlook cGMP practices. cGMP can only happen when
companies will have command of the processes. Till that happens, with every
inspection every company should be looking out for potential citations.
Girish Malhotra, PE
EPCOT International
