Furore over rise in fake drugs-induced deaths, treatment failures worldwide

A recent global report published in in the American Journal of Tropical Medicine and Hygiene alerted to a global pandemic of fake drugs killing children and adults worldwide.According to the report, falsified malaria drugs are responsible for death of over 150,000 children yearly and 10 per cent of all medicines worth over $200 billion (N72 trillion) that sold in developing countries including Nigeria are substandard.

Another new study published in the JAMA Network Open journal found that close to 19 per cent of all medicines in sub-Saharan Africa are either fake or substandard.The American Journal of Tropical Medicine and Hygiene research noted that the deaths of children are a cause for misery and one of the gravest perils comes in the form of falsified and substandard drugs for treating malaria, pneumonia and other diseases.

The report noted that hundreds of thousands of children each year are dying due to a surge of poor-quality or outright fake medicines especially anti-malarials, antibiotics and antihypertensive drugs.According to a study published in African journal of pharmacy and pharmacology titled “Counterfeit drugs in Nigeria: A threat to public health”, the production of counterfeit drugs is a broad and under reported problem particularly affecting poorer countries. It is an important cause of unnecessary mortality and morbidity, and loss of public confidence in medicines and health structures.

Empirical observations showed that there might be more counterfeit than genuine drugs in circulation. According to the study, major factors contributing to the prevalence of counterfeit drugs in Nigeria include ineffective enforcement of existing laws, non- professionals in drug business, loose control systems, high cost of genuine drugs, greed, ignorance, corruption, illegal drug importation, chaotic drug distribution network, demand exceeding supply amongst many others.

The study observed that counterfeit drugs pose great threats to the reduction in infant mortality, improved maternal health and combating human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), malaria and other diseases. It noted that due to the complexity of the counterfeit drug problem, no single technique could eliminate the public health threat posed by counterfeit pharmaceuticals. A multi-disciplinary and cross-functional approach will help combat the prevalence of counterfeit drugs in Nigeria.

The Pharmaceutical Manufacturers Group of the Manufacturing Association of Nigeria (PMG-MAN) said the economic and health implication of fake and falsified products cannot be over emphasised.Chairman PMG-MAN, Dr. Fidelis Ayebae, told The Guardian: “Health wise there is an increased treatment failure that ultimately lead to organ failures and then death, thus increased mortality rate, it is a huge public health threat, and a threat to achieving goal 3 of Sustainable Development Goals.

“Economically, opportunity cost of being out of work due to treatment failure and death is also a factor to be considered. Companies that their products are falsified are at the receiving end of the criminal act of these groups. Companies loose customer base and with the ridiculous prices they put the product in the market, genuine companies are at loss to compete with these products.”But stakeholders in Nigeria including the National Agency for Food and Drug Administration and Control (NAFDAC), the PMG-MAN, the Pharmaceutical Society of Nigeria (PSN) and the Association of Community Pharmacists of Nigeria (ACPN) are divided over the new reports.

History of fake drugs in Nigeria
In 1989, it was estimated that the percentage of spurious and falsified medicines circulating in Nigeria was nearly 70 per cent. In 1993, the World Health Organisation (WHO)/Federal Ministry of Health (FMoH) studies put the incidence of faking drugs in Nigeria at 33 per cent with a fatality rate of seven per cent. Ten years later in 1998, a study by researchers at the Faculty of Pharmacy, University of Lagos (UNILAG) Idi-Araba put the incidence of faking at 49.6 per cent with a fatality of 12.8 per cent and 10.6 per cent therapeutic failure. The UNILAG study group also confirmed that anti-malarials, analgesics and anti-infectives were the most counterfeited drugs.

The UNILAG study had even a damning report through its review which put the incidence of fake drugs traceable to open markets at 49.6 per cent and another significant 32.8 per cent to Patent and Proprietary Medicine Vendors’ License (PPMVL) holders. At a time The Lancet, the popular science journal put the incidence of faking at 48 per cent in the mid-2000 while late former Director General (DG) of NAFDAC, Prof. Dora Akunyili, held sway.

The late Akunyili at some point insisted that the level of faking dropped to 16 per cent and later less than five per cent. Under the watch of her successor, the Dr. Paul Orhil, the under five index was the reference point.In 2005, a study conducted by NAFDAC/WHO/British Department for International Development (DFID) showed that counterfeit medicines stood at 16.7 per cent.A National Survey on Quality of Medicines using Truscan showed that counterfeits stood at 6.4 per cent in 2012.

In 2014, NAFDAC, National Malaria Elimination Programme (NMEP) and United States Pharmacopeia (USP) collaborated on Monitoring the Quality of Antimalarial Medicines (MQM). The report of this survey, presented in August 2015, revealed the level of substandard and falsified antimalarial medicines in circulation to be 3.6 per cent (771 samples passed while 29 out of 800 samples failed).

The fifth and most recent round of the MQM survey was carried out in March 2018 and the report of the survey revealed that of the 907 antimalarial medicines sampled, 12 samples failed while 895 samples passed. This is a failure rate of 1.3 per cent.But more recent unpublished and unverified studies have put the recent figures for fake drugs circulating in Nigeria to be over 20 per cent.
NAFDAC disagrees

But Director General of NAFDAC, Prof. Christianah Mojisola Adeyeye, told The Guardian that there is a reduction in fake drugs in the country. She explained: “Prior to 2001, it was reported that 40 per cent of medicines circulating in the Nigerian pharmaceutical supply chain were either substandard, fake or counterfeited.

“As earlier stated, the first round of MQM survey conducted in 2014 revealed the level of substandard and falsified antimalarial medicines in circulation to be 3.6 per cent.“The Agency in collaboration with USP conducted Round Two MQM survey in 2016 and this revealed that 39 samples out of 900 samples had failed leaving the failure rate at 4.3 per cent.”Adeyeye said as a result of the increase in percentage of substandard and falsified anti-malarials from 3.6 per cent to 4.3 per cent in 2016, NAFDAC implemented strict regulatory measures before commencing Round Three of the study.

The pharmacist said Round Three MQM survey disseminated in December 2017 revealed that 14 samples failed out of 897 giving a failure rate of 1.6 per cent.She said Round Four MQM survey carried out in August 2017 and presented on December 12, 2018 revealed a failure rate of 1.9 per cent and Round Five MQM survey carried out in March 2018 and the reports, which were presented in March 2019, reveal that 12 out of 907 samples failed giving a failure rate of 1.3 per cent.

“Based on the above results, it can be inferred that the level of substandard and falsified antimalarial medicines in circulation has decreased,” the NAFDAC DG said.She added: “Although there has been no recent study on all classes of medicines, the five rounds of Monitoring of Quality of Antimalarials Survey carried out, reveal a reduction in the levels of substandard and falsified antimalarial medicines in circulation.”
What are the sources and causes of fake drugs in the country?

The NAFDAC DG identified: porous borders and under-declaration by importers. Adeyeye said Nigeria is a developing country and as such relies heavily on importation with large population (200 million and counting), large market size, low local production capacity, good purchasing power as an oil-producing country, vast and porous borders, and lack of stiff penalties for offenders.Former President of PSN, Olumide Akintayo, told The Guardian that the attraction to drug faking is grounded on the ease and indiscriminate access to fake drugs in Nigeria.

Akintayo explained: “The fact is anybody who has some infant thousands of naira and sells provision by the roadside dabbles into sales of drugs. The extremely weak regulatory control seals the contempt with which we handle drug sales and management. We contend with well over one million unlawful premises against less than 10,000 legitimate pharmaceutical premises (including manufacturers, importers, distributors and retailers). I am told we have about 20,000 registered PPMVL holders who ideally should sell only Over The Counter (OTC) drugs. With a poor funding mechanism, how does the Pharmacy Council of Nigeria (PCN), which registers pharmaceutical premises monitor and control 37 States of the Federation and Abuja with less than 100 full time pharmaceutical inspectors.”

Akintayo queried how can NAFDAC, presumably better funded, cope with enforcement of drugs and regulated products when these items are obviously disguised as non-regulated items which come in through ports of entry not officially designated for drug importation?

The pharmacist said one of the biggest areas of failure of the Health Minister led team at FMoH is the apparent mismanagement of the National Drug Distribution Guidelines (NDDG) philosophy he inherited from his predecessor. Akintayo said in some very inglorious output, the Health Minister has shifted the commencement of fundamental areas of the NDDG at least twice. He said a more proactive FMoH should have assisted the Coordinated Wholesale Centres (CWC), which was slated to replace the Open Drug Markets (ODM) in Lagos, Onitsha, Aba and Kano to secure necessary building approvals, which would have allowed the CWC concept blossom into realistic utopia.

Chairman PMG-MAN, Dr. Fidelis Ayebae, told The Guardian that the recent studies by NAFDAC and USP attributed the slight per cent of failure in quality to the poor storage of these products along the value chain of pharmaceutical drug distribution, which according to the report is poorly stored and managed, leading to instability of the products. This according to the report is observed mostly in open drug shops at rural areas.
Ayebae, however, said: “It will ignorant of me to say, falsified and substandard drugs are eliminated in Nigeria or is not still having its way to Nigeria market. Like every other developing and developed countries that are experiencing the same menace, we are also battling with the menace to reduce it to barest minimum. Africa being the next frontier for pharma investment, the pharma market according to Mckinsey consulting has jumped to $20 billion dollars and will grow to $65 billion by the year 2020.

“With our population boom and increase in disease burden. This data alone is enough to attract the ruthless criminals to exploit the market to cash into the vulnerable market with weak regulatory frame work, Of course with Nigeria being at population growth rate of 2.60 per cent being the largest population in Africa, and speculated worlds poverty capital of the world, we should expect to be at the receiving end of this falsified and substandard medicine, ours is to reduce it to barest minimum.”

Solutions
To address the issue the ACPN in a statement jointly signed by the National Chairman, Samuel Adekola, and the National Secretary, Bose Idowu, said they recognise some challenges that still needs to be dealt with.

The community pharmacists highlighted:
*Non-Adherence to designated ports of entries for drugs (both airports and seaports), which still encourages the distribution of falsified medicines in Nigeria.
*Continued sales of drugs in places where they are prohibited including bosses and other means of transportation. NAFDAC enforcement agents need to checkmate the influence of the night bosses and other illegal modes of freight forwarding deployed to move falsified medicines (fake drugs) in our country.
*It is our expectation that the new NAFDAC management will reduce lead-time employed in the registration of drugs and other products, which appears unduly long as far as the businesses of manufacturers, and importers are concerned.
In similar spirit, the ACPN expects progress in the quest for institutionalizing orphan and service drugs as well as the concept of community pharmacy Action Centres (COPA) to effectively coordinate self-regulation in community practice.
*We shall continue to engage NAFDAC on its cutting edge technology drive with special attention on product packs. Our deep conviction remains that dialogue remains a major pre-requisite to assuage feelings of some traumatized pharmacists who have been embarrassed based on what we presently have.

Akintayo said President Muhammadu Buhari and the National Assembly (NASS) must work together in national interest to facilitate a smooth passage of the Pharmacy Council of Nigeria Bill to an Act of Parliament. “The inherent blessings are too many but I will summarize it in one sentence by taking a position that the proposed Act has potentials to enhance regulatory controls and curb indiscriminate access to drugs by all shades of tainted interests. The Bill will entrench professionalism. It remains the way forward in our sector,” he said. Akintayo explained: “High morbidity and mortality rates. As at 1998, its therapeutic failure was 10.8 per cent and mortality rate was 12.8 per cent. You do not want to imagine the embarrassment at regional and global meetings when people ask what you are doing about fake drugs?

“Economically, you can see how diminished or out rightly insignificant the contribution of the pharmaceutical sector is relative to the Gross Domestic Product (GDP) in manufacturing and economy of the nation as a whole.” On penalty for offenders, the pharmacist said: “If I am right, I think the maximum penalty is a jail term of two years or fine of N500,000. Attempts have been made to renew this sanction but I am not aware that they have been successful albeit procedurally.“I do not believe in death sentence because human history has shown it does not serve much deterrence. The best way to deal with rich people is to deny them of their ill-gotten wealth. I would rather like to see the fall-guys in this criminal act forfeit all their assets to the Federal Government.”

The former PSN President urged the authorities to insist on professionalism, boost regulatory control, mobilise adequate funding and get the Government to exercise a political will in the totality of enforcement process.The PMG-MAN Chairman said: “It is interesting to note that PMG-MAN being gate keeper for all pharma manufacturing companies in Nigeria and a group that comprises of more than one hundred and twenty members, does have the capacity and skill to deliver on National Self Reliance and reverse the trend of 70:30 per cent ratio, if only Government policies are radically implemented to drive the industry in a very consistent path to industrialisation and growth.”

Ayebae recommended implementation of the National Drug policy, where Ministries Departments and Agencies (MDAs) are to patronise the local manufacturing companies in their procurement exercises, following through on Executive order 003 of Federal Government which grants preference to local manufactured products. He called for the closure of the windows of importation of basic essential medicines that local manufacturing companies does have capacity to produce and implementation of National Drug Distribution Guidelines. Ayebae added: “PMG-MAN we all know is a self-regulatory group. In the last few years we have been collaborating with organizations to build capacity. We have collaborated with USP, United Nations Industrial Development Organization (UNIDO), NAFDAC, West African Health Organisation (WAHO) in the bid to develop a road map for quality assurance in our companies. As such we look-forward to not just having capacity for Good manufacturing practice, but to be able to scale up our infrastructures to be globally competitive.

“Part of our ambitious goal is to seek for N300 billion Expansion and export intervention fund from our financial service institutions through Government initiatives and support, to support members as many as possible to engage in backward integration, the intervention will help members attain the international standards. If we access these funds and scale up our infrastructure, with the right policies we will be having a surveillance eye on Nigerian Market access landscape. If textile industries, Aviation industry, Agro-businesses and of recent in the news palm-oil producers qualify to access these funds for scaling up production. I think local pharmaceutical companies should also be a recipient of such intervention funds.

“The countries that we import from India and China they are highly incentivized to export to other countries, that their activities could be said to have made Nigeria a Pharma Dump. For us it is time to make Nigeria the largest pharma manufacturing hub in Africa, with financial support and incentives, we will have surveillance eye on the importers of fake and falsified medicines, using technology we will make it nearly impossible for the miscreants to access our landscape.”

Ayebae urged Mr. President, President Muhammadu Buhari to sign the new Pharmacy Council Bill, which has been passed by the 8th National Assembly, to have a supporting legal framework to fight this menace.He also recommended international convention, to come up with enforceable treaties at the global stage, while “we strengthen our laws to handle issues of falsified and substandard medicines, strengthen systems and capacity of the regulators for efficient surveillance and enforcement.”

The PMG-MAN Chairman said regulators should continue to engage stakeholders in the industry on self-regulatory model, adopt technology like blockchain model. He said government setting up a medicine security council to engage at the highest decision-making level will fast track policy formulation and implementation that will ultimately guarantee medicine security and keep these falsified and substandard medicine peddlers out of business over time.

Head of Party, United States Pharmacopeia (USP) in Nigeria, Dr. Chimezie Anyakora, told The Guardian that best way to address these issues is by ensuring steady supply of affordable, quality-assured medicines in communities across Nigeria. Anyakora said the importance and focus of the Promoting Quality of Medicines (PQM) programme in the country is from working closely with pharmaceutical manufacturers, to correcting for market failures and addressing supply chain issues.

Anyakora said the PQM programme is funded by the U.S. Agency for International Development (USAID) and implemented by the USP, a nearly 200 year-old American nongovernmental organisation whose mission is to improve global health through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods.

He said: “Finding and eliminating the sources of fake or falsified drugs is extremely important. And, it’s not easy. Increasingly complex global supply chains, along with sophisticated criminal networks, make the problem more challenging. Counterfeiters create almost indistinguishable copies of legitimate medicines that may have little or no therapeutic value, or may contain harmful substances. WHO also claims offshore foreign companies and bank accounts are used to facilitate the sale of falsified medicines.

“But, in the PQM programme’s patient-focused model, we don’t really distinguish between a medicine that has been willfully falsified and one that is substandard, either due to poor manufacturing or degradation along the supply chain. That is, we want to prevent all forms of poor-quality medicine from reaching patients. We thus ask ourselves mainly how we can strengthen regulation in Nigeria to better ensure that only quality-assured medicines come to market and we also ask ourselves what role pharmaceutical companies that follow good manufacturing practise can play.”