Revolution happens in every industry but some revolutions
are widely noted and others are not. Nucor Steel revolutionized the steel
industry through its ”mini-mills”. They are the largest steel producer in the
United States. Their electric furnaces overtook the traditional blast furnaces.
It was a perturbation. Many established biggies have been dwarfed.
A quiet but fast paced evolution is taking place in the
food industry. Berkshire Hathaway, Warren Buffett, and 3G Capital (Brazil) have
started a revolution in the food industry by acquiring Heinz, Kraft, Burger
King and Tim Horton (Canada). Nestlé Chairman
Mr. Peter Brabeck-Letmathe commented, “3G and
Buffett have pulverized the food industry market, particularly in America with
serial acquisitions” (1). Outsiders
are causing changes.
Pharmaceuticals
are going through their mergers and acquisitions but they are very unlike in
other industries. These are not based on manufacturing technology innovations.
Most are related to potential new drug or increasing market share.
Japanese
and European automobile companies led their evolution through product quality
and designs. On the other hand fine/specialty chemical industry, pharma’s older
cousin due to lack of technology innovation, has seen its shift from developed
countries to the developing countries.
Software’s influence:
Advances
in software have led evolutions all over. In recent years software has
progressively added conveniences for our comfort.
In
retailing, through on-line stores and social media, it has changed our
purchasing behavior. Google’s venture in driverless car is well known. Apple is
rumored to be looking at similar opportunities. Theranos, 23andMe, Nanobiosym
are using software technologies to simplify healthcare diagnostics. Google (2)
and 23andMe (3) are also involved in drug discoveries. There are
other companies like Verseon who are using software to reduce time for new drug
discoveries (4). I am sure NIH and pharma companies have
capabilities that are used to reduce drug development time. I expect that industry
outsiders might have higher success because they do not have many preconceived
notions and have a fresh look using latest software modeling methods.
I
conjecture that combination of software and miniaturization advances might soon
be available at doctor’s office. My speculation is that a routine blood
analysis would be done using a handheld device that has a sensor to read the
blood not requiring a blood sample. Results would be analyzed instantaneously
and patient given the most accurate treatment for her/his ailment.
We
are seeing significant and increasing influence of software’s prowess in our
lives. Can software’s influence percolate to innovate pharmaceutical and
chemical manufacturing technologies and software could be called pharma’s
“creative destructionist”? Answer would be positively yes. Pharma does need a
major evolution (5) and a spring.
We
need to recognize that every API and its formulation is a fine/specialty
chemical that has disease-curing value and has been formulated with inert excipients
and packaged for easy dispensation.
Current practices:
Fine/specialty
chemical manufacturing processes can be improved and changed after
commercialization. However, such changes do not happen easily for pharmaceuticals.
FDA regulation 21CFR314.70 has to be followed. Current practices produce the
desired drug but most of the processes are inefficient and unsustainable. Speed
to market is the major cause. There is significant room for improvements. Pharma’s
current manufacturing practices are about 30-40 years behind times especially from
fine/specialty chemicals, its older cousin. Pharma has not had the need to
change because of its assured profitability.
At
present, drug patented life is limited after the regulators have approved it
for commercial use. Most of the active pharma ingredients and their
formulations produced use methods and processes that are laboratory work based.
Laboratory practices are essentially duplicated as commercial manufacturing
practices even down to how the quality is checked of the intermediates. They add
to inefficiency. Generics follow similar practices. Whole business process becomes
and stays inefficient.
Future practices:
There
is considerable discussion about change/improvement of pharma’s manufacturing
practices. For it to happen paradigm shift in process development and their translation
to commercial practices is needed. Change has to be initiated and has to happen
within the companies. No regulatory body can force change. In addition, it has
to happen before clinical trials because change later is challenging, can be
expensive and has to follow regulations e.g. FDA 21CFR314.70.
Manufacturing
technology innovation change has to happen at the fundamental level and it starts
when any paper process chemistry is being reviewed and is going to be tested in
the laboratory for feasibility and commercial viability.
From
my perspective, before we start exploring/playing with the chemistry in the
laboratory, it is necessary to understand the sociochemicology of
all of the chemicals and that includes solvents, intermediates and produced
products. Sociochemicology is the relative behavior of individual and
collective behavior of chemicals. It is dependent on their physical and
chemical properties (6). Many can and will ask/say why we need to know
individual and mutual behavior of chemicals.
Answer
to this question is simple. Individual properties and behavior of many
reactants are available but mutual behaviors are not readily available. Physical
properties and behavior give us many processing clues. By knowing and
understanding individual and mutual behavior, we can develop great to excellent
processes. We can also manipulate and exploit sociochemicological behavior to
create simpler processes. Chemical engineers and chemists understand values
mentioned above. Safe handling information is also important.
Having
all of the above information before we go to the laboratory can significantly
cut short the laboratory process development and commercialization time. However,
there is big issue and it is “we do not have all of the above postulated
information about sociochemicology of every chemical involved and produced”.
Information
about many chemicals is available from different sites (7,8,9,10,11,12,13,14).
There are additional sources. Physical property Information is covered in e.g. Exxon’s
blue book and Hydrocarbon Processing (about 1960-1965) etc. and can be of
considerable value. If information about chemicals and their sociochemicalogy (their
mutual behavior) is not available, it will have to be generated in the
laboratory. Chemists and chemical engineers end up generating information what
they think is relevant but they may review all available options.
We
do exploit sociochemicological behavior of chemicals but to limited extent. Current
and ongoing advances in software technology, through modeling, could also be tapped
to create/predict sociochemicological behavior of chemicals. Modeled
information about behavior of chemicals would be of great value. It could give
us many different process design options that we had not considered. With this
information at hand, human genius using his/her creativity and imagination
along with training in chemistry and chemical engineering will facilitate development
and design of the best manufacturing processes in much shorter time. Such
processes will consistently produce quality products at the lowest cost. Well-designed
processes could significantly lower regulatory oversight from the current
levels. We could also leapfrog the process of “continuous improvement” before
the potential drug/s go to clinical trials. At some time in future 21CFR314.70
might not be necessary.
Some
benefits of understanding and using behavioral information of chemicals are
discussed. Physical state of reactants and intermediates can be used to improve
laboratory process development. We may be able to limit number of solvents used
to desired two and not to exceed three. Process productivity and conversion
yield will also be improved. Total number of conversion steps may be minimized.
Intermediate and final product solubility information can be used to develop a
better commercial process. Separation processes can be greatly improved. Reaction
process kinetics can be well understood and exploited to our advantage. Unit
operations and processes can be simplified. Supply chain and operations
scheduling can be significantly improved. Asset utilization and total business
process will also improve. Capital investment can be significantly reduced.
I
may be overoptimistic but having broader scope of information could catapult pharmaceutical
manufacturing processes (API and their formulations) from QbA (quality by
analysis) to QbD (quality by design) from inception and eliminate “B” bureaucracy
(government and internal) and “C” consternation (should we think about continuous
improvement) from pharma vocabulary. Processes thus developed would have many
of the following benefits.
- Longer patent life for new molecules due to shorter drug discovery
and development time
- Lowest product cost for brand and generic drugs
- Consistent and uniform product quality
- Use of best technologies
- Reduced time to market
- Highest profits
- Highly sustainable processes with minimum environmental impact
- Much higher customer base allowing economies of scale advantage
- Potential of continuous API manufacture
- Highest possibility of continuous formulations
Outlined
benefits clearly suggest that it is time to accelerate change in pharma’s process
development and commercialization practices. However, if we are content with
the existing practices nothing will change.
Software
powerhouses can create the needed information if it has not been created and/or
is in private domains. Created information will definitely improve API and
chemical manufacturing and their formulation methodologies. Success here would
have widespread benefits for billions and pharma landscape would be changed
forever. In addition, every industry that uses chemicals will also benefit.
I
firmly believe that software enhancing our understanding of chemical behavior can
be a REAL “creative destructionist”. Process of continuous innovation will become
way of life and change many landscapes.
Girish Malhotra
Girish Malhotra
President
EPCOT
International
- NESTLE CEO: Warren
Buffett just 'pulverized the food industry market http://www.businessinsider.com/r-nestle-says-taking-action-to-keep-top-slot-in-food-industry-2015-4
accessed August 25, 2015
- Large-Scale Machine Learning for Drug Discovery, http://googleresearch.blogspot.com/2015/03/large-scale-machine-learning-for-drug.html
accessed August 26, 2015
- In Big Shift, 23andMe Will Invent Drugs Using Customer Data http://www.forbes.com/sites/matthewherper/2015/03/12/23andme-enters-the-drug-business-just-as-apple-changes-it/
accessed August 26, 2015
- Malhotra, Girish: Are Software
Technologies Going to be Pharma’s Creative Destructionists? Profitability
through Simplicity, http://pharmachemicalscoatings.blogspot.com/2015/07/are-software-technologies-going-to-be.html
accessed August 25, 2015
- Malhotra, Girish: Does the Pharmaceutical Industry Need A Steve Jobs? Profitability through Simplicity. http://pharmachemicalscoatings.blogspot.com/2011/11/do-pharmaceuticals-need-steve-jobs.html November 8, 2011
- Malhotra, Girish: Focus on Physical Properties To Improve Processes: Chemical Engineering, Vol. 119 No. 4 April 2012, pgs 63-66
7.
Chemblink
11.
Merck
Index
13.
Sigma-Aldrich
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