Pharmaceutical companies including
API (active pharmaceutical ingredient) manufacturers have an uphill battle to
achieve manufacturing perfection that will deliver quality products without
regulatory oversight. I believe that the industry has created this regulatory
juggernaut due to its inability to produce consistent and repeatable quality
The recent case of Johnson and
Johnson was a failure of manufacturing and financial controls that are the
fundamentals of good business. There are other similar incidents where the
products were contaminated. Due to such repeated occurrences, the regulatory
noose gets tighter. Since industry created the juggernaut, it can and has the
ability to loosen the noose provided it “rights” its practices.
Since drugs are for human consumption,
manufacturers have to be reined in to assure quality. This has led to the
establishment of “do and don’t” guidelines i.e. analysis paralysis. The industry,
besides inventing new molecules, is more focused on how to meet and comply with
guidelines and regulations rather than developing and commercializing processes
that are based on “best of the best” physical and social sciences (chemistry,
physics and economics) i.e. chemical engineering.
Brand companies have lived with
speed to market. Since they can make their financial margins and generics will
take over the business, their thinking has been to invent new molecules and not
to invest in new and better manufacturing technologies for the products that
are short lived in their stable.
There are other factors that
inhibit pharmaceutical companies to have the “best of the best” manufacturing
processes for the manufacture of drugs. They are:
Drug pricing is based on the highest price
customer will pay. Since companies can achieve their financial goals, there is
no economic incentive to improve manufacturing technologies.
Due to drug dosage, annual volume of the drug
per plant per year can be very low.
Companies have relied on fitting the process in
the existing equipment. This has not resulted in having an optimum process for
the products and can result in variable product quality. This is one of the
causes that have lead pharmaceutical companies to the current state.
Ability to pass on the costs associated with
inefficient processes to the customers.
Lack of competition during the patent period and
also after the patent expiration. Later is due to the regulatory and other
economic challenges companies have go through to commercialize drugs. Unless
the volume is very large few venture the field.
Ability of the companies to recall any
“off-spec” products from the market without much retribution.
All of the above collectively and
individually can be overcome if the companies create excellent processes based
on good physical sciences for the “new products only”. If done right they will
improve the total business process such as inventory turns, minimize in-process
testing and accumulation of intermediates.
Regulatory and financial investment
is a deterrent to manufacturing technology innovation for the existing
products. However, generics can innovate manufacturing technologies for
existing products as well as the products that are transitioning out of patent,
i.e. new generic products. They have incentive as they are there for the long
There are possibilities and
opportunities. We have to look at them individually and collectively. Some of
them are listed as follows.
Improving raw material inventory turns by
ensuring raw materials do not have to be tested and can be used “just in time”.
There are ways this can be accomplished.
Improving and/or eliminating intermediate
isolation and storage by completely eliminating in-process sampling and testing,
i.e. the process will have to be perfect and repeatable at every step.
Use of high-powered analytical instrumentation
during development of API and drug formulation is necessary. However, we need
to develop tests that are simple to give us the necessary answers in the
shortest time. We do not need a rocket launch procedure when we can walk ten
feet or need to use a Lamborghini when a bicycle would suffice.
Many of the puritans might not
agree with my simplifications and perspective. Unless we try to simplify and
take command of the processes and produce repeated quality product, regulations
will prevent us from manufacturing innovation and simplification. Many of us
may remember the jingle “Try it, You’ll
A systematic and well-orchestrated
methodology can be developed and incorporated for pharmaceutical manufacturing.
All of the elements exist. If done properly we can move from regulation-based
manufacturing to science based and driven manufacturing. Science based
technologies will produce consistent and repeatable quality product that will
become the norm rather than the exception. Total business process (inventory
turns, cash flow and capital investment) will improve and be simplified. In
addition, processes will be economic and sustainable.
Malhotra, Girish: The Path Towards
Continuous Processing, Pharmaceutical Processing, August 2010, pgs
Malhotra, Girish: Process
Centricity is the Key to Quality by Design, Profitability through Simplicity April 6, 2010
Malhotra, Girish: Pharmaceutical Costs, Technology Innovation,
Opportunities and Reality, Pharmaceutical Processing February 2010 pgs
Malhotra, Girish: Alphabet Shuffle: Moving From QbA to QbD – An Example
of Continuous Processing, Pharmaceutical Processing, February 2009 pg 12-13
Will Chemical Engineers Save Pharma? Pharmamanufacturing.com
April 10, 2009
Malhotra, Girish: API Manufacturing: A Road Map for Green Chemistry and Processes;
pharmaQbD.com October 14, 2008
Malhotra, Girish; API Manufacture-Simplification and PAT; Pharmaceutical Processing, November 2005,