Features
Ethical drugs, unethical practices
by Geewananda Gunawardana, Ph.D.
Ensuring the quality, safety, and efficacy of pharmaceuticals requires a high level of constant vigilance. A good example is the four deaths caused by contaminated eye drops in the USA last May despite the well-regulated and best prepared monitoring of the drug supply by the US Food and Drug Administration. Unfortunately, the consumers in places where regulations as well as their implementations fall short of ideals can fall victims much more frequently: A World health Organization (WHO) report finds that about 10% of the world’s drug supply is either subpar or fake. Global deaths among children alone due to subpar drugs is over 150 thousand annually while the economic cost is estimated to be about US $ 200 billion.
While loss of life is a tragedy, the failure to ensure the quality of medicinal products can have far reaching and long-lasting consequences of much larger magnitude. The emergence of drug resistant infections and parasitic diseases and genetic disorders due to subpar drugs will only come to light in the long run.
To get some idea about the vulnerability of pharmaceuticals, it is important to know the way the regulatory process works. Almost 90% of the new drug development takes place in North America and Europe. The rest is divided among Japan and Israel. India and China, leaders in generic drug manufacture, are only beginning to enter this field through collaboration with American and European pharmaceutical companies. When a drug is invented, the inventor obtains a patent, which is an exclusive right to market it for 20 years. However, a patent only keeps the competition away, and it does not give the authority to market the drug, which must be obtained from the regulatory agency of the respective country.
To get the marketing authority, a vast amount of data must be produced showing efficacy, safety, and manufacturability of the drug. This process takes 10 to 12 years on average and over US $ 1.5 billion in R&D costs. As the development takes up to 8 to 10 years, the actual patent life left when it goes to market is reduced to 10 to 12 years, during which time the company must recoup all the costs and make a profit. A drug marketed under patent is known as a brand name drug. These initial R&D costs make the brand name drugs expensive.
The manufacturer of the brand name drug must follow all the current good manufacturing practices (cGMP) as specified by the regulatory agency of the marketed countries. The International Conference on Harmonisation (ICH) has standardised these guidelines and are followed by the major pharmaceutical manufacturing countries. Adherence to the cGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations.
The consequences of failing to meet guidance can be harsh. For example, the UK based Glaxo Smith Kline was fined US$ 3 billion in 2012, the highest in history for cGMP violations. The brand name drug manufacturers avoid taking any risks as the stakes are very high. There are some companies that were forced to shut down for failing to follow cGMP. A common problem with brand name drugs is the manufacture of counterfeit drugs sold in small markets despite the best efforts of the patent owner to avoid such piracy. The commitment to quality and the stringent regulatory vigilance makes brand name drugs less susceptible for quality issues.
Once the patent expires, anyone with the right capabilities can manufacture the drug and seek marketing authorisation in selected countries. These drugs are referred to as generic drugs. Since the generic manufacturers do not have to bear the billion-dollar R&D costs, they can afford to lower the price. The competition for market share also drastically reduces the cost of generic drugs, often by over 80% of the original price. The costs can be further reduced by moving the manufacturing into places where the labor and operating costs are lower and occupational safety and environmental regulations are lax or lacking altogether. The affordability and wide availability are the beneficial outcomes of generic drugs. For example, 91% of the drugs prescribed in the USA in 2022 were generic drugs. Except for a rare event, the US drug supply remains safe and reliable, mainly thanks to the diligence of the US Food and Drug Administration.
The bulk of these cost-effective generic drugs are destined for low- and middle-income countries. Unfortunately, that is where the troubles begin. The WHO has formulated international regulatory standards to ensure the safety and efficacy of the drugs in places where ICH guidance is not implemented. They also have a program for pre-qualification of drug manufacturing facilities when requested. While international organisations require WHO prequalification for drug purchases, individual governments can follow their own regulations. Knowing the presence of potential buyers who are willing to forgo cGMP requirements, some manufacturers tend to ignore the need for costly qualification or certification programms. This practice is also encouraged by the premise on the buyers’ side that testing alone can ensure the quality of drugs. However, the truth is that failing to follow cGMP can lead to unintended release of subpar drugs to markets even if the standard testing procedures are followed.
Two processes where this can happen easily are sterilisation and achieving content uniformity. Failure to ensure that every single unit of the drug, be it a pill or a vial of many thousands manufactured, is compliant could result in subpar drugs reaching the market. In the case of uneven sterilisation, microbial contamination can occur as was seen with eye drops. Failure to ensure uniformity can result in drug units containing either higher or lower doses than shown on the label.
Most of the generic drugs are manufactured in Asia. Drug manufacturing is a multistep process conducted in multiple locations under varying levels of regulatory control. A routine drug manufacture can have the following basic steps: procurement of raw materials, synthesis of starting materials and/or intermediates, synthesis of the active pharmaceutical ingredient (API), procurement of excipients, and formulation of the API into the drug product – capsule, tablet, syrup etc. This can vary for biologics such as vaccines and recombinant proteins etc., which make up only about 2% of all drugs used. In either case, at every step, the product must be stored in proper containers under the right conditions as determined based on its stability to prevent degradation and contamination.
Except for biologics, almost all drugs are produced by chemical synthesis. A small portion are either plant or microbial origin. The generic drug manufacturers come up with alternate synthetic routes that are cost effective. This creates a major problem: Any synthetic process generates impurities or side products in addition to the desired product. These impurities could have unknown properties, including toxicity, and must be removed or kept to a minimum using various purification steps. The processes and analytical methods used for this purpose by the brand name manufacturer are optimized to monitor and control any impurities specific to the raw materials, starting materials, and excipients they used. However, if the generic manufacturers introduce any changes, the standard quality control methods may not work, and undesired impurities will end up in the drug causing potential adverse events. Another potential problem, particularly in the warm and humid tropics, is microbial contamination, as happened with eye drops when handling and storage conditions are deviated.
With complicated supply chains, it is very difficult for the drug purchaser to track if all processes used in the manufacture of the drug were conducted under cGMP. Either they do not have the wherewithal or have no impetus altogether as happens when questionable drug procurement methods are followed. There are other ways the purity of drugs can be compromised. All drugs have a limited lifetime as specified by the expiration date. The expiration date is set assuming the storage of the drug under certain conditions and in designated containers. Any deviation, which can happen easily when transported between tropical locations, the drug can degrade reducing the potency or efficacy and introducing impurities. Without proper cGMP, it is not possible to know if such deviations have occurred.
If the drug is degraded, the desired therapeutic effect may not be achieved. In addition to that, in the case of antimicrobial and antiparasitic drugs, the administration of lower doses can lead to the development of drug resistant varieties. Infections caused by resistant organisms can be difficult, and sometimes impossible, to treat. Antimicrobial resistance is an urgent global public health threat that killed around 1.27 million people worldwide in 2019. If not controlled, this could render the current anti-infective drugs virtually useless and makes it one of the world’s most urgent public health problems.
The impurities or contaminants in drugs can have numerous undesired results including death. The deaths of 66 children in Gambia last year caused by taking contaminated cough syrup, imported from India, is just one example. A serious problem is contamination with genotoxic compounds. If not detected promptly, the consequences would not be known for many generations. The genotoxic impurities can be harmful when present in as low as parts per million amounts in the drug. The analytical techniques for detecting such low amounts require specific instruments not readily available in most laboratories. Recently, a whole family of hypertension drugs were found to contain genotoxic impurities and were withdrawn from the US markets.
These are the problems that can arise under normal operating procedures, and fortunately, the ones that can be eliminated if proper cGMP are observed. To worsen things, there are added problems that go beyond manufacture and cGMP. Unscrupulous drug companies and corrupt administrations contribute to the problem by knowingly allowing substandard drugs into healthcare systems with total disregard for life and limb. Pharmaceutical industry is notorious for its “gift” system for buying or prescribing their drugs. In one reported incident, a company sold 45 years’ worth of antibiotics to a developing country when the shelf life of the drug is only 2 years. Unloading drugs that are nearing expiration or not suitable for their own countries into low-income countries is a common practice.
The subpar drug related adverse events are predictable but also preventable. Generic drugs in general are safe and effective as international organizations have provided the means to ensure their safety and efficacy. Every step from the supply of starting materials to the dispensing of the drug to the patient must be controlled according to the guidance to receive the full benefits of drugs and avoid adversities. Sri Lanka has incorporated most of those rules and regulations to their own. However, their complete implementation remains questionable. Purchasing drugs without knowing its complete history is inviting trouble. Neglecting to do so puts future generations at risk in addition to wasting hard-earned foreign exchange.
by Dr Gotabhya Ranasinghe
Senior Consultant Cardiologist
National Hospital Sri Lanka
When we sought a meeting with Hon Dr. Ramesh Pathirana, Minister of Health, he graciously cleared his busy schedule to accommodate us. Renowned for his attentive listening and deep understanding, Minister Pathirana is dedicated to advancing the health sector. His openness and transparency exemplify the qualities of an exemplary politician and minister.
Dr. Palitha Mahipala, the current Health Secretary, demonstrates both commendable enthusiasm and unwavering support. This combination of attributes makes him a highly compatible colleague for the esteemed Minister of Health.
Our discussion centered on a project that has been in the works for the past 30 years, one that no other minister had managed to advance.
Minister Pathirana, however, recognized the project’s significance and its potential to revolutionize care for heart patients.
The project involves the construction of a state-of-the-art facility at the premises of the National Hospital Colombo. The project’s location within the premises of the National Hospital underscores its importance and relevance to the healthcare infrastructure of the nation.
This facility will include a cardiology building and a tertiary care center, equipped with the latest technology to handle and treat all types of heart-related conditions and surgeries.
Securing funding was a major milestone for this initiative. Minister Pathirana successfully obtained approval for a $40 billion loan from the Asian Development Bank. With the funding in place, the foundation stone is scheduled to be laid in September this year, and construction will begin in January 2025.
This project guarantees a consistent and uninterrupted supply of stents and related medications for heart patients. As a result, patients will have timely access to essential medical supplies during their treatment and recovery. By securing these critical resources, the project aims to enhance patient outcomes, minimize treatment delays, and maintain the highest standards of cardiac care.
Upon its fruition, this monumental building will serve as a beacon of hope and healing, symbolizing the unwavering dedication to improving patient outcomes and fostering a healthier society.We anticipate a future marked by significant progress and positive outcomes in Sri Lanka’s cardiovascular treatment landscape within the foreseeable timeframe.
by Fr. Emmanuel Fernando, OMI
Jesuit Fr. Aloysius Pieris (affectionately called Fr. Aloy) celebrated his 90th birthday on April 9, 2024 and I, as the editor of our Oblate Journal, THE MISSIONARY OBLATE had gone to press by that time. Immediately I decided to publish an article, appreciating the untiring selfless services he continues to offer for inter-Faith dialogue, the renewal of the Catholic Church, his concern for the poor and the suffering Sri Lankan masses and to me, the present writer.
It was in 1988, when I was appointed Director of the Oblate Scholastics at Ampitiya by the then Oblate Provincial Fr. Anselm Silva, that I came to know Fr. Aloy more closely. Knowing well his expertise in matters spiritual, theological, Indological and pastoral, and with the collaborative spirit of my companion-formators, our Oblate Scholastics were sent to Tulana, the Research and Encounter Centre, Kelaniya, of which he is the Founder-Director, for ‘exposure-programmes’ on matters spiritual, biblical, theological and pastoral. Some of these dimensions according to my view and that of my companion-formators, were not available at the National Seminary, Ampitiya.
Ever since that time, our Oblate formators/ accompaniers at the Oblate Scholasticate, Ampitiya , have continued to send our Oblate Scholastics to Tulana Centre for deepening their insights and convictions regarding matters needed to serve the people in today’s context. Fr. Aloy also had tried very enthusiastically with the Oblate team headed by Frs. Oswald Firth and Clement Waidyasekara to begin a Theologate, directed by the Religious Congregations in Sri Lanka, for the contextual formation/ accompaniment of their members. It should very well be a desired goal of the Leaders / Provincials of the Religious Congregations.
Besides being a formator/accompanier at the Oblate Scholasticate, I was entrusted also with the task of editing and publishing our Oblate journal, ‘The Missionary Oblate’. To maintain the quality of the journal I continue to depend on Fr. Aloy for his thought-provoking and stimulating articles on Biblical Spirituality, Biblical Theology and Ecclesiology. I am very grateful to him for his generous assistance. Of late, his writings on renewal of the Church, initiated by Pope St. John XX111 and continued by Pope Francis through the Synodal path, published in our Oblate journal, enable our readers to focus their attention also on the needed renewal in the Catholic Church in Sri Lanka. Fr. Aloy appreciated very much the Synodal path adopted by the Jesuit Pope Francis for the renewal of the Church, rooted very much on prayerful discernment. In my Religious and presbyteral life, Fr.Aloy continues to be my spiritual animator / guide and ongoing formator / acccompanier.
Fr. Aloysius Pieris, BA Hons (Lond), LPh (SHC, India), STL (PFT, Naples), PhD (SLU/VC), ThD (Tilburg), D.Ltt (KU), has been one of the eminent Asian theologians well recognized internationally and one who has lectured and held visiting chairs in many universities both in the West and in the East. Many members of Religious Congregations from Asian countries have benefited from his lectures and guidance in the East Asian Pastoral Institute (EAPI) in Manila, Philippines. He had been a Theologian consulted by the Federation of Asian Bishops’ Conferences for many years. During his professorship at the Gregorian University in Rome, he was called to be a member of a special group of advisers on other religions consulted by Pope Paul VI.
Fr. Aloy is the author of more than 30 books and well over 500 Research Papers. Some of his books and articles have been translated and published in several countries. Among those books, one can find the following: 1) The Genesis of an Asian Theology of Liberation (An Autobiographical Excursus on the Art of Theologising in Asia, 2) An Asian Theology of Liberation, 3) Providential Timeliness of Vatican 11 (a long-overdue halt to a scandalous millennium, 4) Give Vatican 11 a chance, 5) Leadership in the Church, 6) Relishing our faith in working for justice (Themes for study and discussion), 7) A Message meant mainly, not exclusively for Jesuits (Background information necessary for helping Francis renew the Church), 8) Lent in Lanka (Reflections and Resolutions, 9) Love meets wisdom (A Christian Experience of Buddhism, 10) Fire and Water 11) God’s Reign for God’s poor, 12) Our Unhiddden Agenda (How we Jesuits work, pray and form our men). He is also the Editor of two journals, Vagdevi, Journal of Religious Reflection and Dialogue, New Series.
Fr. Aloy has a BA in Pali and Sanskrit from the University of London and a Ph.D in Buddhist Philosophy from the University of Sri Lankan, Vidyodaya Campus. On Nov. 23, 2019, he was awarded the prestigious honorary Doctorate of Literature (D.Litt) by the Chancellor of the University of Kelaniya, the Most Venerable Welamitiyawe Dharmakirthi Sri Kusala Dhamma Thera.
Fr. Aloy continues to be a promoter of Gospel values and virtues. Justice as a constitutive dimension of love and social concern for the downtrodden masses are very much noted in his life and work. He had very much appreciated the commitment of the late Fr. Joseph (Joe) Fernando, the National Director of the Social and Economic Centre (SEDEC) for the poor.
In Sri Lanka, a few religious Congregations – the Good Shepherd Sisters, the Christian Brothers, the Marist Brothers and the Oblates – have invited him to animate their members especially during their Provincial Congresses, Chapters and International Conferences. The mainline Christian Churches also have sought his advice and followed his seminars. I, for one, regret very much, that the Sri Lankan authorities of the Catholic Church –today’s Hierarchy—- have not sought Fr.
Aloy’s expertise for the renewal of the Catholic Church in Sri Lanka and thus have not benefited from the immense store of wisdom and insight that he can offer to our local Church while the Sri Lankan bishops who governed the Catholic church in the immediate aftermath of the Second Vatican Council (Edmund Fernando OMI, Anthony de Saram, Leo Nanayakkara OSB, Frank Marcus Fernando, Paul Perera,) visited him and consulted him on many matters. Among the Tamil Bishops, Bishop Rayappu Joseph was keeping close contact with him and Bishop J. Deogupillai hosted him and his team visiting him after the horrible Black July massacre of Tamils.
Sri Lanka-Singapore Free Trade Agreement
By Gomi Senadhira
senadhiragomi@gmail.com
“You might tell fairy tales, but the progress of a country cannot be achieved through such narratives. A country cannot be developed by making false promises. The country moved backward because of the electoral promises made by political parties throughout time. We have witnessed that the ultimate result of this is the country becoming bankrupt. Unfortunately, many segments of the population have not come to realize this yet.” – President Ranil Wickremesinghe, 2024 Budget speech
Any Sri Lankan would agree with the above words of President Wickremesinghe on the false promises our politicians and officials make and the fairy tales they narrate which bankrupted this country. So, to understand this, let’s look at one such fairy tale with lots of false promises; Ranil Wickremesinghe’s greatest achievement in the area of international trade and investment promotion during the Yahapalana period, Sri Lanka-Singapore Free Trade Agreement (SLSFTA).
It is appropriate and timely to do it now as Finance Minister Wickremesinghe has just presented to parliament a bill on the National Policy on Economic Transformation which includes the establishment of an Office for International Trade and the Sri Lanka Institute of Economics and International Trade.
Was SLSFTA a “Cleverly negotiated Free Trade Agreement” as stated by the (former) Minister of Development Strategies and International Trade Malik Samarawickrama during the Parliamentary Debate on the SLSFTA in July 2018, or a colossal blunder covered up with lies, false promises, and fairy tales? After SLSFTA was signed there were a number of fairy tales published on this agreement by the Ministry of Development Strategies and International, Institute of Policy Studies, and others.
However, for this article, I would like to limit my comments to the speech by Minister Samarawickrama during the Parliamentary Debate, and the two most important areas in the agreement which were covered up with lies, fairy tales, and false promises, namely: revenue loss for Sri Lanka and Investment from Singapore. On the other important area, “Waste products dumping” I do not want to comment here as I have written extensively on the issue.
1. The revenue loss
During the Parliamentary Debate in July 2018, Minister Samarawickrama stated “…. let me reiterate that this FTA with Singapore has been very cleverly negotiated by us…. The liberalisation programme under this FTA has been carefully designed to have the least impact on domestic industry and revenue collection. We have included all revenue sensitive items in the negative list of items which will not be subject to removal of tariff. Therefore, 97.8% revenue from Customs duty is protected. Our tariff liberalisation will take place over a period of 12-15 years! In fact, the revenue earned through tariffs on goods imported from Singapore last year was Rs. 35 billion.
The revenue loss for over the next 15 years due to the FTA is only Rs. 733 million– which when annualised, on average, is just Rs. 51 million. That is just 0.14% per year! So anyone who claims the Singapore FTA causes revenue loss to the Government cannot do basic arithmetic! Mr. Speaker, in conclusion, I call on my fellow members of this House – don’t mislead the public with baseless criticism that is not grounded in facts. Don’t look at petty politics and use these issues for your own political survival.”
I was surprised to read the minister’s speech because an article published in January 2018 in “The Straits Times“, based on information released by the Singaporean Negotiators stated, “…. With the FTA, tariff savings for Singapore exports are estimated to hit $10 million annually“.
As the annual tariff savings (that is the revenue loss for Sri Lanka) calculated by the Singaporean Negotiators, Singaporean $ 10 million (Sri Lankan rupees 1,200 million in 2018) was way above the rupees’ 733 million revenue loss for 15 years estimated by the Sri Lankan negotiators, it was clear to any observer that one of the parties to the agreement had not done the basic arithmetic!
Six years later, according to a report published by “The Morning” newspaper, speaking at the Committee on Public Finance (COPF) on 7th May 2024, Mr Samarawickrama’s chief trade negotiator K.J. Weerasinghehad had admitted “…. that forecasted revenue loss for the Government of Sri Lanka through the Singapore FTA is Rs. 450 million in 2023 and Rs. 1.3 billion in 2024.”
If these numbers are correct, as tariff liberalisation under the SLSFTA has just started, we will pass Rs 2 billion very soon. Then, the question is how Sri Lanka’s trade negotiators made such a colossal blunder. Didn’t they do their basic arithmetic? If they didn’t know how to do basic arithmetic they should have at least done their basic readings. For example, the headline of the article published in The Straits Times in January 2018 was “Singapore, Sri Lanka sign FTA, annual savings of $10m expected”.
Anyway, as Sri Lanka’s chief negotiator reiterated at the COPF meeting that “…. since 99% of the tariffs in Singapore have zero rates of duty, Sri Lanka has agreed on 80% tariff liberalisation over a period of 15 years while expecting Singapore investments to address the imbalance in trade,” let’s turn towards investment.
Investment from Singapore
In July 2018, speaking during the Parliamentary Debate on the FTA this is what Minister Malik Samarawickrama stated on investment from Singapore, “Already, thanks to this FTA, in just the past two-and-a-half months since the agreement came into effect we have received a proposal from Singapore for investment amounting to $ 14.8 billion in an oil refinery for export of petroleum products. In addition, we have proposals for a steel manufacturing plant for exports ($ 1 billion investment), flour milling plant ($ 50 million), sugar refinery ($ 200 million). This adds up to more than $ 16.05 billion in the pipeline on these projects alone.
And all of these projects will create thousands of more jobs for our people. In principle approval has already been granted by the BOI and the investors are awaiting the release of land the environmental approvals to commence the project.
I request the Opposition and those with vested interests to change their narrow-minded thinking and join us to develop our country. We must always look at what is best for the whole community, not just the few who may oppose. We owe it to our people to courageously take decisions that will change their lives for the better.”
According to the media report I quoted earlier, speaking at the Committee on Public Finance (COPF) Chief Negotiator Weerasinghe has admitted that Sri Lanka was not happy with overall Singapore investments that have come in the past few years in return for the trade liberalisation under the Singapore-Sri Lanka Free Trade Agreement. He has added that between 2021 and 2023 the total investment from Singapore had been around $162 million!
What happened to those projects worth $16 billion negotiated, thanks to the SLSFTA, in just the two-and-a-half months after the agreement came into effect and approved by the BOI? I do not know about the steel manufacturing plant for exports ($ 1 billion investment), flour milling plant ($ 50 million) and sugar refinery ($ 200 million).
However, story of the multibillion-dollar investment in the Petroleum Refinery unfolded in a manner that would qualify it as the best fairy tale with false promises presented by our politicians and the officials, prior to 2019 elections.
Though many Sri Lankans got to know, through the media which repeatedly highlighted a plethora of issues surrounding the project and the questionable credentials of the Singaporean investor, the construction work on the Mirrijiwela Oil Refinery along with the cement factory began on the24th of March 2019 with a bang and Minister Ranil Wickremesinghe and his ministers along with the foreign and local dignitaries laid the foundation stones.
That was few months before the 2019 Presidential elections. Inaugurating the construction work Prime Minister Ranil Wickremesinghe said the projects will create thousands of job opportunities in the area and surrounding districts.
The oil refinery, which was to be built over 200 acres of land, with the capacity to refine 200,000 barrels of crude oil per day, was to generate US$7 billion of exports and create 1,500 direct and 3,000 indirect jobs. The construction of the refinery was to be completed in 44 months. Four years later, in August 2023 the Cabinet of Ministers approved the proposal presented by President Ranil Wickremesinghe to cancel the agreement with the investors of the refinery as the project has not been implemented! Can they explain to the country how much money was wasted to produce that fairy tale?
It is obvious that the President, ministers, and officials had made huge blunders and had deliberately misled the public and the parliament on the revenue loss and potential investment from SLSFTA with fairy tales and false promises.
As the president himself said, a country cannot be developed by making false promises or with fairy tales and these false promises and fairy tales had bankrupted the country. “Unfortunately, many segments of the population have not come to realize this yet”.
(The writer, a specialist and an activist on trade and development issues . )
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