All opinions are my own.

Saturday, March 25, 2017

Can the Review and Approval Process for ANDA at USFDA be Reduced from Ten Months to Three Months?

Not having been involved with regulatory filing aspects of pharmaceuticals, reviewing Generic Drug User Fee Act Reauthorization (GDUFA II) (1) was educational. After review my process simplification instincts kicked in. If the current approval time line can be reduced from TEN months to THREE months, impact of the process will be lower drug costs.

Reading joint testimony of Drs. Woodcock, Marks and Shuren (2) and having had time to review the application process, reinforced my thinking that a time reduction is possible but to get there industry along with USFDA would have to practice what chemical engineers and chemists are taught and asked to practice for every manufacturing process they develop, design and commercialize i.e. produce quality first time and all the time. In terms of FDA’s vocabulary the filling and review processes would have to follow QbD (Quality by Design) practices. FDA will have to follow what it has been asking the industry to practice. Industry will also have to follow suit. I believe industry will also get hands on practice about QbD and it will trickle through the whole organization, a win-win.

Many associated and proficient with regulatory filings would categorically say that filings are not a manufacturing process and such a time reduction is impossible and cannot be done. Currently filing an application is a task that is repeated by many to create quality application. It will generate higher profits for the filer if they can reduce its approval time. It can be continuously improved and deserves our attention. We improve every repetitive task to facilitate our daily lives. So why not improve the FDA ANDA (abbreviated new drug application) application filing and approval process? Improvements here could have far reaching impact for other filings also.

I firmly believe that such a time reduction is possible but many things will have to change to get there. Our thinking and work philosophy has to change. In the current application process following challenges (1) have been identified. Each challenge is reviewed.

  • Submission completeness: It takes about four review cycles to approve ANDA.
  • Volume of applications
  • Other factors. Several factors delay timely consumer access.

a) Risk Evaluation and Mitigation Strategies are used by Brand companies to delay generic entry

b) Delaying or denying generic companies’ access to reference listed drug products, thereby preventing companies from conducting studies required for approval

c) Misuse of FDA’s citizen petition process as a means to block generic approvals. 

d) FDA generally cannot approve generics until patent and exclusivity on the innovator product expire. Patent litigation and other legal challenges can frustrate timely approval. 
Submission Completeness:
In March 2, 2017 testimony Pre-ANDA program is suggested. I believe that is the most brilliant idea for filing application and reducing time. It is a step QbD implementation of the application filing process.
“About four reviews” needed for FDA application is equal to FDA using four iterations to have a quality application. Current method to get to an acceptable product (application) is a QbA (Quality by Analysis) practice. I equate QbA to “Quality by Aggravation”.
FDA also has to practice what it is suggesting companies to follow. Quoting FDA “This guidance (3) describes the concept that quality cannot be tested into products; (ANDA application, to me is a product of FDA’s work), in other words, it should be built-in or should be present by design.”
Yes like manufacturing processes, applications for every product are going to be different when it comes to content but the information filing requirements are essentially going to be same. I believe a template application that covers better than 90% of the filing requirements can be designed. A standard application format could pare down four reviews to a single review and completeness. This would be a monumental accomplishment. If accomplished, we will automatically see the approval time reduction.
Currently it can take up to 45 days for the FDA reviewing team to determine completeness of the application. FDA would have to figure out how this time can be reduced to 15 days. Current review practices would have to be modified. Long delays suggest that the filing team does not understand FDA’s QbD expectations or FDA has not relayed them to applicants.
FDA has to create applications that clearly state what it expects from the companies. A standard template has to be created. It's possible that the current templates do not relay FDA expectations. A redesign may be necessary. Once these applications are designed, companies and FDA staff can be trained to follow the process. Workshops could be held on a regular basis to train industry to what is needed.
I know such processes work. We had similar processes at Illinois EPA in 1972 for various industry segments. We had timelines from submission to approval of equipment design and operating permits. Based on our questions, every industry submitted relevant information that facilitated review and approval. FDA may have to benchmark to see which government agency has the best application review and approval process. Elements can be incorporated.
Another important aspect of the filing process would be to involve the engineers and chemists who have created and commercialized the process so the filled application is complete and represents a quality (QbD) filing. It means that the companies have to do their homework. They know their processes the best.
Every effort has to be made to pare ten months to 90 days. It is a doable challenge.
Volume of Applications:
FDA can go with best basis planning scenario and deal with ups and downs of the numbers. Ability to deal with such changes will be its operational finesse strategy. Many businesses deal with such scenarios. Most likely I have oversimplified the situation.
Other Factors:
*    Risk Evaluation and Mitigation Strategies are used by Brand companies to delay generic entry. 

FDA has to develop a program or strategy to prevent such harassment. Roadblock could be set but there has to be a resolution that is acceptable to each side. Generics have to be on top of their game to counter such delay tactics. Legislatorial changes might have to be incorporated. In our political system that could be a challenge.
*       Delaying or denying generic companies’ access to reference listed drug products, thereby preventing the companies from conducting studies required for approval.

Congressional intervention might be needed. USP or others who have information should be able to share the information. Congress can create a scenario to assure necessary samples are available for the generics. This would be good for their constituents. I believe FDA can intervene also.
*       Misuse of FDA’s citizen petition process as a means to block generic approvals. 

If the brand companies are abusing citizen’s petition process, there has to be a counter strategy from the generics. I have not looked at this in detail but I am sure that there are ways and means to counter this challenge.
*      FDA generally cannot approve generics until patent and exclusivity on the innovator product expire. Patent litigation and other legal challenges can frustrate timely approval. 

Generic filers have to develop their strategies. I believe if the approval time is lowered from ten months to 90 days, companies could develop workable measures. Filing company has to have a complete grasp of the situation and strategies.
If the approval process is lowered from ten months to 90 days, need for priority review most likely could disappear.
Breakdown of 90 Day Time:
I would break the 90 days in three segments. Initial review has to be completed by FDA in 15 days from acceptance of the initial application. FDA has to provide the company deficiencies of the application. Incomplete application could be rejected. Companies will have 30 days to respond FDA’s requirements. FDA would have 45 days after corrections, more than sufficient time, to review and interact with the company and act on the application.
If for some reasons the company is not able to fulfill its obligation after the initial 15 day FDA review and complete its deficiencies 30 days, they could stand to loose its application and would have to start over again. With such a possibility, it would be in the best interest of all parties to have quality application from the get go. It will be a QbD win for all.
It is very possible that facility inspections could be an encumbrance in the approval process. However, having command of the designed process would be reflected in the application. If it were not that would mean that the designed and operating process is different from the filled information. It would be tantamount to falsification of information and it should be used to ban the company from shipping products to the US market. 
What I am suggesting might be a challenge but until we take on challenges progress is never made. By posting this blog I am not questioning authority of FDA or any other government body but just presenting an alternate perspective that would bring generics to the market quicker and lower healthcare costs. I might also be incorrect in my conjectures and expectations but it would be worth if we can make an improvement and lower drug costs.

Girish Malhotra, PE
EPCOT International 

  1.  Generic Drug User Fee Act Reauthorization (GDUFA II) Accessed March 16, 201
  2. Testimony of Drs. Woodcock, Marks and Shuren Accessed March 23, 2017
  3. Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base Guidance for Industry Accessed March 24, 2017

Monday, March 20, 2017

Strategies for Improving Batch or Creating Continuous Active Pharmaceutical Ingredient (API) Manufacturing Processes

This report was originally published in March 2011.  

It is being republished and is available to any person FREE of cost via my blog Profitability through Simplicity. Please request the report using CONTACT form. 

From time to time I will be adding to this report my perspective about chemistries of various active pharmaceutical ingredients and fine/specialty chemicals that are in the public domain.

Anyone can use the information to improve their processes. Information is a guide and its use is by their own choice and will not hold anyone liable for any damage, costs or expenses. 

Scope of this research

  • Enhance profitability by re-evaluating and re-engineering product development, manufacturing technologies, and commercialization methodologies.
  • Evaluate ways to simplify manufacturing technologies and implement sustainable processes.
  • Identify examples where process enhancements have had a substantial impact on yield and profitability.
  • Understand the need for review of current patenting strategies.
  • Assess the advantages of quality by design versus quality by analysis processes.

The commercialization of a new drug molecule should commence when the development of the molecule starts in the laboratory. This methodology gives the process chemist and chemical engineer familiarity with the chemicals and their properties, and allows them to share ideas and use the acquired knowledge for future projects.
An alternative business and manufacturing strategy has to be considered when catering to the drug needs of people in developing countries, who often cannot afford to pay prices of developed countries. These markets are showing 5–7% growth, compared to 2–3% in the developed countries.

Meeting regulatory needs takes precedence over having the most optimum process. In spite of companies’ efforts to meet regulations, there are often recalls due to poor practice. Recalls and citations are proof not only that the regulations are cumbersome to meet, but also that companies do not have control of their processes.

  • How can my company achieve economies of scale when manufacturing APIs?
  • What steps need to be taken to make it more difficult for generics companies to cannibalize market share once a drug's patent expires?
  • What process manufacturing lessons can be learnt from fine/specialty chemical companies?
  • Why does regulatory burden take precedence over optimizing API manufacturing processes?
  • Why should chemists and chemical engineers consider the commercialization of a product whilst it is still in laboratory development?

Friday, March 10, 2017

Process Simplification and The Art of Exploiting Physical Properties

Chemical additives, petrochemicals, plastics and pharmaceuticals are different reacted forms and formulations of organic (fine/specialty) and inorganic chemicals. We have mastered their use and continue to develop new uses to make our lives easier.

We are also familiar with or can find chemical and physical properties of the chemicals that are used in these applications. However, many of us have not totally understood or mastered their mutual behavior and/or how their mutual behavior can be used/manipulated/modified/exploited to simplify processes, especially the reactive processes. To some extent it is an art that can significantly improve profitability.  

Simpler processes streamline manufacturing. They are sustainable and assist in many other ways e.g. lower costs, higher profit, improve supply chain, give competitive edge through better product quality.

We have to ask ourselves a question “are we exploiting physical and chemical properties to their fullest extent?” If we are not, then the question is why not? Answer is very simple, at least to me. Values and virtues of physical and chemical are taught. However, we generally are not taught how to exploit them. I learnt from my mentors and colleagues. Shortcomings have been discussed in the past (1,2,3,4) and in many other publications. If we can understand and manipulate their mutual social behavior “sociochemicology” we should be able to create, design and simplify many of the reactive or formulation processes.

Collectively fault lies with us. Why? When developing a new process we don’t have the time to exploit these properties.
Opportunities are tremendous, however, getting from studying to practicing may not be the simplest. We do practice what we are taught, but not to the extent we could. Traditions also come in the way of exploitation. Most of the time textbook methods and laboratory practices are followed.

Everything has to be done yesterday and the pressure to have the process ready to be scaled up day before yesterday is omnipresent. With such constraints even the best, creative and imaginative chemists and chemical engineers can falter. Processes are commercialized and they may not be the most optimum. Generally such processes are accepted in the chemical industry. Continuous improvement opportunities allow us to better these processes. However, there are applications where commercializing a perfect process that has very stringent tolerances and meet certain regulatory needs are a must. Electronic chemicals and pharmaceuticals fit the higher tolerance regimen with pharmaceuticals due to regulations being even more demanding. Second chances in these areas can cost significant time and money.

Process Development Opportunities:

Process development is done in the laboratory and at times circumstances are not helpful to think BIG. By BIG, I mean how we will deal with commercial quantities of raw materials and intermediates. Our “Imagineering” falters somewhere when we are scaling up from the lab to a commercial process. We pay a price via higher product cost and at times with lack of first time product quality because we have not spent the time needed to create an efficient economic process.

Exploitation and imagineering of physical and chemical properties of the chemicals to create an economic process can be an art which depends on “eye of the designer”. Individual imprints come from our experiences and understanding of unit processes and unit operations.

I have used one of the physical properties as an example to illustrate how we can master/exploit sociochemicalogy to create and commercialize excellent and sustainable processes.

Liquids are Developer’s Best Friend: 

Every chemical comes in its natural state in one of the three forms: gas, solid and liquid.

At room temperature gas cannot be held in hand where as solid and liquid can be handled. When it comes to handling gases in the lab they are a challenge. Liquefied gas handling has use constraints in the lab. They can be a challenge in plants also. Special equipment would be needed if liquefied gas were to be handled. Since many labs are not equipped, gases are dissolved in a liquid and used in process development. Use of ammonia as ammonium hydroxide is an example. Process productivity can be lost when dilute gas solutions are used. Commercial handling of liquefied gases requires special attention and is product volume dependent.

In laboratory, solids are generally dissolved in appropriate solvent and used as a dissolved solution. Depending on solubility at room temperature process productivity can be significantly impacted. On commercial scale if the solid raw material can be used as a melt, it would be ideal, as the process will have high productivity. Again process economics and product demand come into play.

Raw materials, reaction intermediates and products as liquid are easiest to handle. Our ability to recognize the differences in density, mutual solubility, boiling point differences and other physical properties and exploit them to our advantage generally results in an economic and sustainable process (4,5,6). Exploitation of physical and chemical properties is not a cookie cutter exercise but is more like a precision surgery for each process, especially for the reactive processes.

There are many chemical reactions that can be commercially done in all liquid phase when the raw materials are solid or gas at room temperature. With sufficient residence time and using fundamental of chemistry and chemical engineering the produced product can be purified to produce global needs from a single plant. Latent advantages of such processes are very high productivity with minimal use of diluting solvents that are necessary in conventional processes. One has to imagine, explore and look. As explained earlier reason and rational for not looking in the lab is that we do not have the necessary equipment to explore such reactions. Many times such opportunities are never explored even after commercial success of such products.

Many books can be written about how sociochemicology of the chemicals can be used and improved to commercial advantage. It is best that such methods be left to the imagination of chemists and chemical engineers. Given a chance they are extremely creative, imaginative and resourceful and the results would magnificent.

Girish Malhotra, PE
EPCOT International

  1. Malhotra, Girish: A Radical Approach to Fine/Specialty API Manufacturing, Profitability Through Simplicity January 20, 2010
  2. Malhotra, Girish: Focus on Physical Properties To Improve Processes: Chemical Engineering, Vol. 119 No. 4 April 2012, pgs 63-66
  3.  Malhotra, Girish: Industry 4.0 (Digitization): Its Benefits to Pharma and Other Chemical Industries, Profitability through Simplicity, November 11, 2016
  4.  Malhotra, Girish: Chemical Process Simplification: Improving Productivity and Sustainability, ISBN: 978-0-470-48754-9, January 2011, John Wiley & Sons Inc.
  5.  US patents: 3,928,457; 4,945,184; 5,004,839; 3,564,001; 4,363,914
  6. McCabe, W. L. and Smith, J.C. Unit Operations of Chemical Engineering, McGraw-Hill, Inc. 1956; 40

Thursday, February 9, 2017

Pharmaceutical Sales Forecasts: Fiction, Facts or Alternate Facts

Every year many analysts and magazines publish their forecasts for the new drugs that have been approved by the US FDA the previous year. Every thing looks glorious and sales are projected in billions. An extremely rosy picture is painted. However, I have not found a “fact check recap” of the projected numbers three or five years after the sales projections have been made. In today’s new political lingo no one has presented “alternate facts”. Real numbers come from how many patients are benefitting from the new drugs and that is a missing piece of the reality.

It seems that the sales projections are always Up Up and Away (1), a wishful thinking. Even the yearly total global pharma sales are projected to grow about 5-7% per year ending around $1.3 -$1.5 trillion dollars by 2020-2022 (2,3). I have serious doubts about these numbers and wonder have these projections been questioned in a public forum. Most likely no one cares, at least that is my conjecture. Since businesses design their plants based on projected sales, I am comfortable in saying that we will consistently have “mega over capacity” at plants. In simple terms overspent capital, under-utilized assets and inefficient plants. This sentiment was recently echoed (4). I am afraid poor patients pay for this largesse through higher drug prices.

Trying to understand these forecasts, a recent article (4) was brought to my attention. Excerpts from the article enlightened me and reconfirmed my apprehensions. It seems to be telling us things many of the forecast pundits most likely do not want to know. 

“First, most consensus forecasts were wrong, often substantially.”
 “Furthermore, a significant number of consensus forecasts were overly optimistic by more than 160% of the actual peak revenues of the product.”
Although the conclusion that most forecasts are poor is not surprising in our view, the magnitude and extent of the error in forecasting is striking and troubling as it suggests a large-scale and systemic misallocation of capital and destruction of value in the industry. It also suggests that there is a substantial opportunity for companies and investors who develop a competitive advantage in forecasting.”
 “The ‘consensus’ consists of well-compensated, focused professionals who have many years of experience, and we have shown that the consensus is often wrong.”

A recent analysis of the projected global pharmaceutical sales (5) shows their irrationality, at least to me. 

If the world knows that these forecasts are “often wrong”, the question is what is the rationality and value of publishing such numbers year after year. Who benefits? Why are these supposedly “ostrichian” numbers published? Are these numbers just exuberance based or are telling us that the companies are doing great things when the reality is otherwise or is this a way to impress investors or much ado about nothing? Shouldn’t we be associating new therapies with people rather than dollars when we know these therapies have a very limited patient base?

The most important fact or a reality, which matters the most is never published or for that matter known to anyone and that is how many patients (+/-10%) are benefiting from the drugs or using it. Forecast numbers per drug can be checked, published and compared against forecast using various company Annual Reports.

I believe that number of patients would be an excellent indicator of each drug’s efficacy and ability to treat patients. Increasing numbers will tell us that drug’s mode of action is of value and could be modified to create better treatments for larger population. Future treatments could be based on this learning. If any new drug is just marginally better than an existing drug, lack of its sales will also be a deterrent for R&D investment in such therapies.

As I have not seen reality checks against forecasts and it begs the question “are we afraid to ask or know the reality?” My conjecture is that reality checks will allow the companies to have better R&D, manufacturing processes and offer us an opportunity for efficient asset utilization, a small step for making drugs affordable. In addition, these numbers will also be of value to the investors to discern and direct value of their investments.  

Girish Malhotra, PE
EPCOT International

  1. The 5th Fifth Dimension, Up Up and Away, Accessed February 8, 2017
  2. World Preview 2016, Outlook to 2022; Accessed February 8, 2017
  3. Global Medicines Use in 2020: Outlook and Implications, Accessed February 8, 2017
  4. Cha, Myoung, Rifai, Bassel and Sarraf, Pasha, McKinsey & Co.: Pharmaceutical forecasting: throwing darts? Nature Reviews, Drug Discovery: Volume 12, October 2013,  737-738, Accessed February 7, 2017
  5. Malhotra, Girish: Manufacturing technologies and their part, Chemica Oggi Chemistry-Today, September/October 2015 Vol. 33(5) pg. 28-31

Tuesday, January 10, 2017

Can Uniform Safety, Health and Effluent and Manufacturing Standards Create Process Technology Innovation and Competition in Pharmaceuticals?

Global warming, ecological damage, economic health, jobs, healthcare, cost of drugs and their affordability have become pulling and pushing issues for every country. I believe played right all of these concerns could be used to innovate, compete and can bring jobs back to the countries that have lost them. They can also create additional jobs in the countries that were willing to invest in innovative technologies. There can be tug of war but the fundamental question going forward is what kind of economic, social, environmental and moral legacy we want to leave. I am using Fine/specialty chemicals [pharmaceuticals are a subset] as the basis for my discussion. If we can do well in this reconfiguration, drug affordability and pharma revenues would improve. 

Since early seventies, when environmental protection laws were promulgated in the United States and other developed countries, many of the fine and specialty chemical operations [pharmaceuticals are the disease curing fine/specialty chemicals] started to migrate to then developing countries that had and still have comparatively lax environmental, health and safety laws. Bhopal (1) incident should be a reminder of these laxities.

I believe companies in the developed countries did not make a concerted effort to develop better and environmentally sustainable processes to retain jobs and operations in their countries (2). They were also price pressured by the companies from the developing countries. Ones who did innovate and developed better technologies benefitted financially to their credit.

Another change that accelerated move of fine/specialty chemical production to the developing countries was the need of the products that were used in the developed countries. Companies from the developed countries saw a business opportunity and production was moved. With lax regulations of the developing countries, it was cheaper to produce these products using proven processes. Many thought that such business strategies were farsighted at the time but the downside effects might not have been considered. Companies were giving away many aspects of intellectual property, which the developed countries had worked hard to develop. They also had to contend with unfamiliar business practices of the developing countries. Sometimes they posed challenges.

Local businesses in the developing countries capitalized and succeeded on the opportunities and expanded in producing active pharmaceutical ingredients and their formulations. Brands also capitalized. Generic producers in the developed countries were caught flat-footed.

Mid nineteen nineties brought changes due to World Trade Organization [WTO] agreements. They led to significant increase in imports of generic pharmaceuticals as well as fine/specialty chemicals to the developed countries. Stringency and laxity of environmental laws in the developed and developing countries respectively influenced decision-making. Culmination of the above was that the developed countries tilted the manufacturing landscape towards the companies from the developing countries. It might be time to rethink this landscape.

Current pharma supply chain landscape of the developed countries suggests that better than 50% of the drugs are coming from India and China. With globalization this is accepted and nothing wrong is considered with this scenario. However, strategic concerns have been raised. Recently the United States Department of Commerce has identified healthcare-related products where US have become reliant on other countries for certain critical items. This report (3) recommends U.S. industry should make renewed efforts to ensure supply chain resiliency by developing and maintaining multiple suppliers for critical components, materials, and finished products. These efforts could include development of new business strategies that give priority to domestic sources of supply, thereby reducing dependence on critical components and materials from suppliers based outside the United States. Additional steps should also be made to monitor the potential for supply disruptions before they occur.”

Some might recall the Heparin crisis. It led to increased FDA inspections (4) facilities in the developing country. We are seeing increased FDA citations. Developed country regulators are working with different governments to bring everyone on the same page but everyone is still not there. 

It is my belief that the following also resulted in lack of technology innovation in the developed countries and that led to the shift in jobs and businesses.

  1. Companies stayed with the mentality of treating API as fine/specialty chemicals and a local product. Their value as a global product was not realized. Had it been realized they would have seen the global opportunity. Value of economies of scale could have led to process technology innovation along with business model reconfiguration. Better technologies could have lowered manufacturing costs and kept drug manufacturing in the developed countries.  

  2. Companies stayed with and still practice manufacturing with after the fact product quality testing vs. produce quality products from the get go. This could have saved companies as much as 40% of the manufacturing cost resulting is higher profits. Again, better and innovative processes could have kept manufacturing in the developed countries.

In summation, developing countries capitalized on the opportunity and are fulfilling the pharmaceutical needs of the developed countries. Companies in the developed countries were and are delighted with the ensuing landscape of higher profits from lower cost imported products. Complacency sat in the developed countries and it is taken for granted that all generics will come from India, China and other countries. 

Can the Current Landscape be changed?

The current quasi-fervor of anti-globalization and protecting or bringing jobs back to the developed countries presents an opportunity to reconfigure the global pharmaceutical business, for that matter landscape of many other industries. “Global” could be considered an outreach but anything is possible in the changing political climate.

We are very well aware of the fact that the companies have to meet importing country’s product performance and quality requirements. Exporters have mostly done a good job of complying with such requirements. If they don’t, products are recalled and/or intercepted or banned from imports. Exporters are relied on their certifications and also expected to follow established good manufacturing practices. Even with that at times products slip through.

Pesticides, automobiles, fabrics and food etc. have to meet standards laid out by the importing country. Non-compliance can result in high financial losses. With protectionist sentiment on rise, trade policies are coming under worldwide scrutiny. With pharmaceutical prices on rise year or year, many a times without rationale, we should not be surprised if the current practices are put under the microscope sooner than later. We should note that pharmaceutical revenues are rising more due to price increases and high priced drugs for limited population rather than from affordable new drugs being discovered and offered to masses. If pharma companies can make drugs affordable and everyone on the planet is willing to spend a single penny per day per year pharma revenue will increase by about $26 billion per year.  

Companies in the developing countries don’t have to practice health, safety and environmental regulations of the developed countries. They might be complying with the local standards. They are generally less rigorous compared to the standards of the developed countries. Differences, as stated earlier, unlevel the playing field. 

It is well known that compared to other products pharmaceuticals have to meet much higher quality standards because less than quality products can result in lost of life. Pharmaceutical producers have to produce products following good manufacturing practices laid out by the importing countries. Constant vigilance and inspections have become necessary. Due to increased quality and procedural excursions, regulators in the developed countries are stretched. 

Playing field has to be leveled. My conjecture is that a leveled field will create competition because everyone will have to play by the same rules. There will be considerable resistance from the developing countries. Task is and will not be easy, but is doable. European Fine Chemicals Group (5) made a concerted effort to control quality of the pharmaceutical active ingredients.  

Establishing uniform global effluent, safety and health standards for the industries that produce and use chemicals (pharmaceuticals are chemicals) and petrochemicals should level the playing field. Current methods that are considered the best could be used as a starting point. This might not sit well with many countries because many companies will have to invest to revamp their operations. A discussion is necessary and it has to be hardnosed.

If agreements are not reached, countries could limit trade with non-complying countries and create jobs in their own countries. It is possible that the buyers could ask the producing plants to match effluent standards of the importing country or countries. A compliance phase-in time period e.g. five years could be established. Threat of potential loss of business will also lead to innovation and competition. Drug shortages could be a side effect.

Companies that have the most innovative culture, thinking and engineering talent will commercialize processes and methods that will make drugs affordable to 7.2 billion and growing inhabitants of the planet. Consolidation could take place. Benefit of economies of scale will result in better processes, in turn higher profits and revenues. Best will thrive.

The following could be part of the discussion. Companies that have registered offices or have an operating office/plant in the developed countries or elsewhere should meet effluent standards of the developed country that consumes their products. Every product would have to meet uniform safety, health, environmental and manufacturing standards. Example: If a company has its corporate office is in UK, India, China etc. sells products in US but produces API or formulated products in any developing or developed country or countries will have to meet safety, health, effluent and manufacturing standards of the United States. As stated earlier a time limit of five years could be used to revamp their operations. Most competitive and innovative will incorporate better technologies and methods and stay in business.  

Why propose uniform safety, effluent, health and product performance standards? Every industry especially pharma producers will have an even playing field. Best of the best technologies will produce quality products from the get go at the lowest cost. Global population will benefit. Companies that will have the best and most efficient methods to develop and commercialize products will produce medicines that are affordable to all. Drugs that are marginally better than the existing drugs will have to compete in the market place. Drug R&D would be streamlined.

Large buyers i.e. national healthcare buyers, Pharmacy Benefit Mangers (PBM) or any other buyers could also start a compliance discussion with their suppliers. Companies from the developing countries could take the lead and their success as we have seen in IT businesses could be a game changer. Governments and politics will intervene. They would have to kept out of the discussion.

Consensus even to start a discussion about uniform global health, safety and environmental when proposed could cause significant consternation and would be a challenge to many companies and countries. Developing countries will fight tooth and nail but they could win if they channel their energies and intellect it the right direction. Leveled playing field could be a global win and we will leave a better legacy. Drugs would become affordable to over 5 billion people. We will also lower impact toxins on mammalian, aquatic and avian inhabitants and our environment (6,7). Concerted effort will have to be made. Failure in establishing and complying with uniform safety, health and environmental regulations should not be an option. Under the current fervor to protect/regain jobs things could get unpleasant, if the global community fails to establish a uniform playing field.

It is my expectation that by having uniform drug quality, health and safety standards best of the companies will capitalize on economies of scale, as many might drop out, and have the best technologies that will produce products that are as much as 35-45% lower in cost and giving the producing companies the necessary profit margins and revenues from much higher patient base.

Girish Malhotra, PE
EPCOT International

2.     Malhotra, Girish: Why Have the Fine and Specialty Chemical Sectors Been Moving from Developed Countries?, Profitability through Simplicity, February 9, 2009, Accessed January 6, 2016
3.     Reliance on foreign sourcing in the healthcare and public health (HPH) sector: pharmaceuticals, medical devices, and surgical equipment, U.S. Department of Commerce Bureau of Industry and Security Office of Technology Evaluation December 2011, Accessed December 1, 2016
6.     Malhotra, Girish: Pharmaceuticals, Their Manufacturing Methods, Ecotoxicology, and Human Life Relationship, Pharmaceutical Processing, November 2007, Accessed December 1, 2016
7.     Fent, Karl, Weston, Anna A., Caminada, Daniel, Ecotoxicology of human pharmaceuticals, Aquatic Toxicology 76 (2006) 122–159, Accessed December 14, 2016