nature most companies in manufacturing, distribution and service industries use QbD methods for their operations. However,
pharmaceuticals, which have to sell consistent quality product
by law, have not fully incorporated QbD in their business routine. Had this been done, this QbD discussion would not have
been on the forefront. My conjecture is that since the inefficiency costs can be recouped, achieving quality on the first go
is not part of the business practice. This is manifested by quality by analysis “QbA” practices.
Regulators have in the last ten years been cajoling the pharmaceutical industry to adopt and implement quality practices
and move away from QbA methods. However, the industry
is still in discussion phase as evidenced by the considerable
conversation in the chat rooms. When questions like “What is
QbD” come up, it clearly suggests that many involved in pharmaceuticals are not familiar with the terminology, its fundamentals and value. When experienced people raise the question of
“quality by design” it is suggestive of lack of implementation
consideration at their companies.
WHY SHRUG OFF QBD?
Money is of great value to all of us. The simplest way to
comprehend the value of QbD is “making more money” than
pre-QbD environment. If a QbD philosophy is incorporated in
business practices from the onset it will result in companies
having the best technology and supply chain platform for its
processes resulting in much higher profits ( 4). I have revised
the savings to about $150-$200 billion dollars. These savings
come from process yield improvement, better asset utilization,
supply chain management and reduced regulatory paperwork.
With QbD in place, time to market can be reduced and production capacity can be improved with no or minimal investment.
Such savings would not only improve company profits but will
also lower drug prices and lighten the pressure from governments and NGOs. Money saved by various NGOs and foundations could expand their programs to assist additional people.
It would be a win-win.
With benefits outlined a question remains. Why is there no
mob rush to incorporate QbD? The answers are simple and in
front of us.
We all know that the current manufacturing processes are
not the most efficient and sustainable and that the supply chain
can be significantly improved. If companies are able to make
profits in today’s environment, the need to improve technology is not a priority. If a company does decide to improve
their technology, they have and will make sure that the drug
performance has not changed. Still regulatory bodies, for public
safety, might want re-approval. I am sure that no one including
the regulatory bodies has monetized the cost of time and effort
that is needed for the re-approval. Regulatory bodies are pushing new quality related directives. They can be applied for new
processes and products only.
Patent life dictates product life, brand/ethical companies
have very little or no interest in improvements during a prod-
uct’s short life. However, with the best technology from the
onset, brand companies can ward off generic entries.
IS THERE HOPE?
Definitely yes! Justification for QbD ( 5) exists and the
benefits are significant. However, it will take a very different business model, approach and thinking to get there.
Creative disruption ( 6, 7) might be the way. QbD is an effort, a way of life and not a magic wand. Effort is needed to
cure the ills of process inefficiency. We can exceed regulatory expectations, simplify supply chain management and
improve asset utilization.
Regulators and product safety advocates have to understand
that it will take a concerted effort to incorporate QbD in API
manufacturing and formulations. It has to be incorporated by
the companies from the start of the product development process. In order for QbD to be adopted for existing products and
processes, regulatory bodies will have to facilitate the process.
Checks and balances will have to be put in place. Regulatory
bodies working with the industry to improve product quality
through manufacturing technology innovation might not sit
well with the media and industry watchdogs. Any quality related incident, due to public outcry, could become an obstacle
and result in legislative intervention.
An API manufacturing company can be the dark horse and
show the world how QbD can be incorporated from the start.
There is no cookbook recipe for QbD. It is dependent on socio-chemicalogy of the chemicals involved. Design of experiment
( 8) strategies will assist to have the best process that will produce quality product not needing repeated in process analysis.
Lack of QbD can be illustrated through the following example. Pricing information is a tell tail sign of how the process
is being managed.
Six different companies producing Nevirapine, part of the
HIV/AIDS drug regimen, were contacted by the WHO to quote
their API price ( 9). The Boehringer Ingleheim price of $1400.00
per kilo compares to $200.00-$275.00 per kilo from Chinese
and Indian companies. This difference is significant. Boehringer
held the original patents and they have expired. Had the company incorporated process improvements and QbD their price
would have been in line or lower than their competitors unless
Boehringer’s profit margin is extremely high or the process is
extremely inefficient. With their price being so high I wonder
how they still have Nevirapine customers.
Based on my knowledge of the chemistry and how I would
manufacture the product, the selling price after reasonable
profit should not exceed $120-$130 per kilo. Demand is sufficient to suggest that the global need could be satisfied from
not more than two plants with possibly one being enough.
Having six plants is suggestive that the processes are inef-