Friday, October 15, 2010

Pharmaceutical Companies Can Innovate If They Want To

Pharmaceutical companies including API (active pharmaceutical ingredient) manufacturers have an uphill battle to achieve manufacturing perfection that will deliver quality product without regulatory oversight. I believe that the industry has created this regulatory juggernaut due to its inability to produce consistent and repeatable quality products.

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, 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 the drugs are for human consumption, the 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. Industry besides inventing new molecules is more focused on how to meet and comply with the 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:

1. 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.

2. Due to drug dosage, annual volume of the drug per plant per year can be very low.

3. 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.

4. Ability to pass on the costs associated with inefficient processes to the customers.

5. 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.

6. 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 haul.

There are possibilities and opportunities. We have to look at them individually and collectively. Some of them are listed as follows.

1. 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.

2. 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.

3. 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 Like It”.

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.

Girish Malhotra, PE
EPCOT International

Related Articles:

1. Malhotra, Girish: The Path Towards Continuous Processing, Pharmaceutical Processing
2. Malhotra, Girish: Process Centricity is the Key to Quality by Design, Profitability through Simplicity April 6, 2010
3. Malhotra, Girish: Pharmaceutical Costs, Technology Innovation, Opportunities and Reality, Pharmaceutical Processing, February 2010 pgs 20-24
4. Malhotra, Girish: Alphabet Shuffle: Moving From QbA to QbD - An Example of Continuous Processing, Pharmaceutical Processing, February 2009 pg 12-13
5. Will Chemical Engineers Save Pharma? April 10, 2009
6. Malhotra, Girish: API Manufacturing: A Road Map for Green Chemistry and Processes; October 14, 2008
7. Malhotra, Girish; API Manufacture-Simplification and PAT; Pharmaceutical Processing, November 2005, Pages 24-27


raman said...

a really interesting article!

patent litigation said...

It seems to me that the "regulation-based" approach results necessarily from the fact that the pharmas are predominantly market-driven. One expects that, of course, from corporations. However, an unfortunate side effect is that, almost necessarily, the science and R&D get short shrift. That being the case, perhaps the Bayh-Dole bill provided precisely the needed counterpoint in patent law, in that it has encouraged relationships between research institutions and manufacturers. That may be the best that we can do, as long as pharmaceutical companies place more value on profit than on science.