We need to re-write the rules and regulations surrounding pharmaceuticals
Writing about drug policies in Bangladesh is easy and difficult at the same time. You may wonder how that is possible -- let me explain. It is easy, because one can quickly draw a conclusion by just reading through the policies and some of the information available on the country’s drug regulatory authority’s website.
One easy conclusion could be: “How did the country end up like this?” Or: “Who is controlling the pharmaceutical businesses in the country?” At least, that is what my own reactions have been. The difficult part comes when I talk to pharmaceutical company executives and visit their very impressive manufacturing facilities.
They are so professional and articulate, the buildings and equipment so impressive, that it is “hard” not to believe their claims that the medicines produced at their facilities are safe, effective, and of good quality. The other difficulties are due to a lack of clear information from those in the upper echelon of the industry, and the fear of “losing” my life the next time I visit Bangladesh. I hope you realize after reading this to the end, why I highlighted a few words in quotations.
Early intentions were good
The first drug policy was adopted in 1982. Among several reasons, the primary one was to make the essential drugs recommended by the World Health Organization (WHO) available to all within an affordable price and to provide incentives to local pharmaceutical industries to grow. Intentions were good, no doubt, and the country’s local pharmaceutical industry has witnessed a significant, continual growth.
Also, all essential drugs (initially 170 of them) were made available at or below the affordable price that the government set. There were two other drug policies adopted in 2005 and 2016. The impact of these policies are visible and look good overall. There are over 250 pharmaceutical manufacturers now in Bangladesh.
That many companies in such a small country is unexpected, and may not be comparable to that of any other developing country of similar size. The growth of ready-made garment manufacturing companies in Bangladesh was expected, because of the lower labour cost and a huge worldwide market.
The incentives for growth of pharmaceutical companies in Bangladesh may be different than what an outsider thinks. Cheaper labour cost has limited contribution to the growth of pharmaceutical companies in Bangladesh.
Before readers draw any conclusions regarding my intention of writing this article, let me make one thing clear: I am neither suggesting that the growth of Bangladesh’s pharmaceutical industry should not have taken place, nor do I object to further growth in the future. In fact, I believe that the Bangladeshi pharmaceutical industry could become even larger and play an important role in global drug business, if planned and executed carefully.
The drug policy, laws, and regulations of a country should be based on the principles of securing, maintaining, and improving public health, and not just the health of the pharmaceutical industry. One may claim that making the most essential drugs affordable and available, as a result of the drug policy, met the principles of public health. I agree, and that was essential. Unfortunately, the devils are in the details.
In order to make essential drugs affordable to all in Bangladesh, the government of Bangladesh sealed the upper limits of prices for active pharmaceutical ingredients (API) that local pharmaceutical companies could import, as well as the prices of finished drug products that the pharmaceutical companies sell to the public. Most of the APIs are imported from either India or China. Sealing the upper limit of the prices for both the APIs and the finished products of essential drugs may compromise the quality of the drugs.
Again, I am saying this based on the policies available on the Bangladesh Drug Administration’s website. All of the 250 pharmaceutical manufacturers in the country are competing for a share in the market for these drugs. The pricing of the finished products plays a major role in penetrating and securing market share. Therefore, the incentive is to lower the cost of goods to maintain a reasonable margin, since the upper end of the price is sealed.
The lowering cost of goods is basically lowering the quality, in most cases. The quality of medicines is fundamental to ensure the safety of the product and thus, the public health. I am not even talking about the efficacy of drugs (and biologics) manufactured and distributed locally in the absence of evidence.
I am questioning whether these drugs are safe for use. We need answers to these and many other related questions:
• Are the APIs imported at a cheaper price by the local pharmaceutical companies of good quality?
• Are these API manufacturers in India and China exporting the same APIs at the same price to the generic companies in the regulated countries in the West? If not, how do they sell APIs to Bangladeshi pharmaceutical companies at a lower price? What quality aspects are being compromised in order to lower the cost?
• Do they sell these APIs to Bangladeshi pharmaceutical companies before fully purifying and eliminating all potentially toxic process impurities?
• Do local pharmaceutical companies conduct full USP/BP monograph testing upon receipt of these APIs? If they do, do the USP/ BP monographs cover tests for all the potential process impurities?
• What are the health consequences of taking these medicines -- with possible impurities -- to the public, especially when taken chronically?
• Why is the prevalence of kidney and other organ failure diseases so high in Bangladesh? What contribution could toxic impurities in the medicines have on the prevalence of these diseases?
There are many more criteria to be examined to make a full assessment of the situation. Similar quality assessment should be done for excipients (inactive ingredients) used to formulate dosage forms. I am sure there are differences between larger and smaller manufacturers in terms of how they procure APIs and test for their quality.
I do not have direct experience. However, I have heard from some employees of even larger pharmaceutical companies that they do not always care for quality. Bangladesh’s consumer market, to whom the medicines are sadly subjected, go by the glossiness of the products and the manufacturer.
On the other hand, one can import quality APIs and other raw materials at a much higher price than the government-imposed price limits to produce better quality and expensive medicines to export to other countries.
Safety and efficacy
All the drugs produced in Bangladesh are unproven “generic” versions of drugs approved in the regulated countries. Innovative pharmaceutical companies do years of animal and human clinical studies to demonstrate the safety and efficacy of their drugs before regulatory approvals.
This is a rigorous process of drug development that takes up almost 10 of the 20 years of patent life. Because Bangladesh enjoys the freedom from international intellectual proprietary regulations (patent) until 2032, local pharmaceutical companies can make the innovator’s drugs almost immediately by procuring APIs from India or China.
Formulation of these drugs are developed locally by individual pharmaceutical companies. With few exceptions, most of these copycat drug formulations should be tested for bioequivalence with the innovators’ drugs. It is important to ensure that the generic versions of the innovator’s drugs get absorbed and distributed inside the body similarly. This is basically a surrogate test to ensure the safety and efficacy of generic drugs.
Formulation development and pharmacokinetics (including bioequivalence) are complex and require expertise from serious academic programs, including post-graduate level education. These bioequivalence studies are not required for registration by the Bangladesh Drug Administration. In the absence of any evidence of bioequivalence, there is no guarantee that the generic versions of the drugs produced in Bangladesh are safe or effective.
After more than five decades of establishing pharmacy education in Bangladesh, the country still has not defined the role of pharmacists. A pharmacist’s primary role is to dispense drugs by filling a prescription from a physician. This dispensing is a critical step in the overall health care system. This requires six years of education, leading to a Doctorate of Pharmacy (PharmD) followed by intensive licensing procedures in developed countries.
The pharmacist profession has been consistently declared by the general public as the most honourable job in the US. In Bangladesh, pharmacies are run by pharmacists with inadequate education and little knowledge of drugs. They sell prescription drugs without any prescriptions. One can even buy narcotics over the counter, ie, without any prescription.
I have no doubt that there have been many deaths and injuries over the past years (which will continue), when patients either self-medicate without seeing a doctor, or buy medicines as recommended by incompetent pharmacists and administer “treatment” with potentially dangerous drugs and drug combinations. I could be wrong, but this benefits the pharmaceutical industry and they don’t want to make any changes.
This was discussed at many forums in Bangladesh for many years, including myself on multiple occasions with the key stakeholders. Nothing was able to change the needle.
Making medicine is a science, and science is based on evidence. In absence of evidence of safety, efficacy, and quality, it can’t be science and hence should not claim to be medicine. This may sound harsh. But when it is about the health, life, and death of people, there should not be any compromise on the evidence of safety, efficacy, and quality of medicines.
Concern about the lack of evidence applies to all medicines manufactured by pharmaceutical companies in Bangladesh, at least for the local market. As you can see, the pharmaceutical business is complex and it’s hard for most of the general public to understand what is good and what is bad for them when they buy medicines from drug stores.
So, they have to rely on the prescribing physicians to select the right medicines for them, and for pharmaceutical companies to deliver safe, effective, and quality medicines. Due to the nature of the business, both physicians and pharmaceutical companies have to maintain the highest ethical standards, because public health, along with the life and death of patients, depends on how honest physicians and pharmaceutical companies are.
There should be public demand to re-write the rules and regulations, and for their full enforcement. There should be an expert committee -- not the one the Bangladesh Drug Administration currently has which is heavily represented by the industry -- to review and identify the flaws and limitations of the rules and regulations, and develop a comprehensive one that defends public health.
We also need to define the profession of pharmacist in Bangladesh. There should be another committee to develop a drug dispensing system where graduate pharmacists (BPharm/PharmD) will control dispensing. This is absolutely doable and I bet graduate pharmacists will prefer to be a dispensing pharmacist instead of looking for a job in the pharmaceutical industry. If there is a will, there is always a way.
It is important to make the Bangladesh pharmaceutical industry a sustainable global business. Larger companies are probably trying to achieve this independently. But, this is likely to take a longer time unless regulatory infrastructure and governance become efficient and the industry associations join hands to establish credibility globally, most importantly in regulated countries.
I grew up in Bangladesh and finished my education there, including a Bachelor’s and Master’s in pharmacy from Dhaka University. I am one of the founders of Bangladeshi American Pharmacists Association (BAPA) and was president of the association for a term.
I have tried individually, as well as representing BAPA, to pay my debt to Bangladesh by providing something meaningful. I am at the end of my career in the pharmaceutical industry after being a regulatory professional for the last 35 years. This is probably my last effort to make the general public of Bangladesh aware of the situation.
Murad Husain, RPh, MS, is the Senior Vice President of PTC Therapeutics, a pharmaceutical and biotechnology company based in the US. Prior to PTC, he was heading regulatory function at Savient, and was Director of Regulatory Affairs at Pfizer, Hoffmann-La Roche, and a few other multinational pharmaceutical companies.