Director-General's Office

WHO Director-General addresses UK medicines regulatory authority

Dr Margaret Chan
Director-General of the World Health Organization

Annual lecture of the Medicines and Healthcare Products Regulatory Agency
From health care products to trust and reliance: the expanded role of regulatory authorities in an era of global health perils. London, United Kingdom

1 March 2016

Distinguished staff at the Medicines and Healthcare Products Regulatory Agency, distinguished guests, ladies and gentlemen,

Thank you very much for the invitation. It is an honour and a pleasure to deliver the 2016 MHRA annual lecture.

The infrastructures, mechanisms, and agencies that protect public health on a daily basis often go unnoticed until something terrible goes wrong, like drinking water contaminated with lead, melamine in infant formula, counterfeit cough syrups and fever medications that kill hundreds of children, or falsified yellow fever and meningitis vaccines.

The reasons for these breakdowns are multiple: human error, a slip-up in good manufacturing practice, the greed that motivates criminal behaviour, or the sheer lack of regulatory capacity that dominates much of the developing world.

The recent catastrophe with the water supply in Flint, Michigan is a tragic reminder of what can happen when the need to cut costs takes precedence over the duty to keep the public safe. It also shows how quickly a mishap can topple politicians and health officials and destroy public confidence in government.

Work done by the UK’s Medicines and Healthcare Products Regulatory Agency, or MHRA, quietly and effectively protects public health on a daily basis. More specifically, it protects millions of people every day, in multiple ways.

Public confidence in the quality and safety of medical products translates into confidence in national health services and confidence in the government’s commitment to protect its people.

I wonder how many members of the general public know all the things you do to gather product-related intelligence and build systematic and broad-based barriers to harm.

Your drug and device alerts and your marketing authorization and licensing work are well-known components of the regulatory framework.

I am thinking of other functions that give the public such a wide and sturdy safety net, while also creating space for innovation.

I am thinking about the new toolkit for pregnant women that will make them better informed about the risk of developmental disorders and birth defects associated with certain prescription drugs. About promising innovative medicines that may be eligible, based on early clinical data, for inclusion in your scheme for early access to medicines.

About the way you keep watch over the content of websites, addressed to consumers, that promote prescription-only medicines.

The support you provide to WHO and world health is immense. The reporting forms used in our 50-year-old programme for international drug monitoring are adapted versions of the UK Yellow Card Scheme.

Your labs have helped us unravel some deadly cases of contaminated medicines in several countries

With your support, we will soon issue an international good practice for regulatory authorities and inspectors that can help reduce incidents of incomplete presentation of data by manufacturers or deliberate data falsification.

Our joint work on international nonproprietary names for pharmaceutical products benefits patients everywhere in the world.

Within the Agency, the National Institute for Biological Standards and Control, or NIBSC, is a global leader in assuring the quality of vaccines and other biological medicines, in developing standards and reference materials for worldwide use, and in carrying out applied research.

You are the leading WHO International Laboratory for Biological Standards and a designated WHO collaborating centre for polio and influenza.

For the R&D community, having biological standards is equivalent to what postal codes do to speed up the mail and how country codes standardize international telecommunications.

As another added value for world health, your work on biological standardization makes it possible for new high-quality competitor products to enter the market on an equal footing with those from established manufacturers.

Doing so has changed the market for public health vaccines, increasing predictable supplies and getting prices down.

Working with your European Union and global partners, including WHO, MHRA responds to the challenges created by an increasingly globalized world. Biological and pharmaceutical products and medical devices keep growing in number and complexity.

Supply chains are becoming ever more complex. Products are often produced by several companies. They may move through multiple countries and distributors before finally reaching the patient.

WHO welcomes the meeting you will hold in May to look at the future of biological medicines, including ways to keep the vaccine pipeline flowing.

New vaccines can be breakthroughs for global health, but they can also help address the problem of antimicrobial resistance, which is moving the world ever closer to a post-antibiotic era in which common infections will once again kill.

While all of these functions of the Agency and Institute may be out of the spotlight on a daily basis, they certainly become highly visible, and vitally important, during public health emergencies of international concern, like the recent outbreaks of Ebola and Zika virus disease.

To support the WHO response to Ebola, MHRA fast tracked the review of clinical trial applications for Ebola vaccines. NIBSC fast tracked the development and production of five reference reagents for use in the calibration of PCR tests and serological assays.

The reference reagent for serology assays helps standardize methods used to measure antibodies in epidemiological studies and in clinical trials of candidate vaccines and immune therapies.

Endorsed by WHO last year, these five reagents are the global gold standards used by anyone undertaking Ebola R&D. All of this work leaves the world better prepared for the next Ebola outbreak.

The new collaborative mechanisms that brought scientists, national health officials, pharmaceutical companies, and regulatory authorities together during the Ebola response establish pathways that can expedite product development during other health emergencies.

This is happening right now with Zika.

MHRA have offered to support WHO, as needed, in the evaluation of candidate Zika products. NIBSC responded immediately to the WHO request to develop and evaluate reference preparations for anti-Zika antibodies.

These reference preparations will provide researchers, product developers, and regulatory authorities with a single standard that can be used to benchmark the multiple diagnostic tests for Zika that are currently under development.

Better diagnostic tools are urgently and desperately needed. The current PCR test can detect the virus only during the brief window of viraemia. This weakness is further compounded by the fact that the illness is so mild. Many people infected with Zika will not be prompted to seek a test during this brief window of just a few days.

Moreover, the Zika virus frequently co-circulates with dengue and chikungunya viruses. These viruses cross-react in tests for IgM antibodies against Zika virus, making them imprecise.

Imagine the anguish of a pregnant woman living in or returning from an affected country, with no way of knowing whether she and her fetus have been affected. Ultrasound detection of microcephaly is possible only late in pregnancy.

As with Ebola, Zika has caught the medical and scientific communities largely empty-handed, with WHO left to promote mosquito control as the most immediate line of defence.

For both of these diseases, we are in the 21st century and yet cannot immediately tap the power of modern medical tools.

For Ebola, it was early detection, contact tracing, quarantine, and infection control. For Zika, right now, it is mosquito control at a time when more and more insecticides have been rendered ineffective by the development of resistance.

Zika is a tricky virus that continues to astonish scientists. Who could have imagined that a mosquito bite would be linked to severe birth defects and other serious neurological complications?

More than half of the world’s population lives in an area where Aedes aegypti mosquitoes are present. Who knows what the next nasty surprise will be?

We know there will be more nasty surprises, if not from the volatile microbial world, then from some of the other complex threats in this era of global perils.

Ladies and gentlemen,

The world has changed dramatically since the start of this century, when the Millennium Development Goals became the focus of international efforts to reduce human misery.

At that time, human misery was thought to have a discrete set of principal causes, like poverty, hunger, poor water and sanitation, several infectious diseases, and lack of essential care during pregnancy, childbirth, and childhood.

The results of that focus, and all the energy, resources, and innovations it unleashed, exceeded the wildest dreams of many. It demonstrated the power of solidarity and brought out the best in human nature.

Last year, the United Nations General Assembly finalized the new 2030 agenda for sustainable development. The factors that now govern the well-being of the human condition, and of the planet that sustains it, are no longer so discrete. The new agenda, with its 17 goals and 169 targets, will try to shape a very different world.

More and more we are seeing the worst in human nature: international terrorism, senseless mass shootings, bombings in markets and places of worship, ancient and priceless archaeological sites reduced to rubble, and seemingly endless armed conflicts that have contributed to the worst refugee crisis since the end of the second World War.

Our world is profoundly interconnected and this, too, has consequences. The refugee crisis in Europe shattered the notion that wars in faraway lands will stay remote.

The Ebola outbreak shattered the notion that a disease of small African nations will have no consequences elsewhere.

The explosive spread of Zika virus disease throughout Latin America and the Caribbean shattered the notion that a disease long considered a medical curiosity will stay that way.

And there are other perils. Inequalities, in income levels, opportunities, life expectancy, and access to health care have reached their highest levels seen in more than half a century. Some wealthy nations are losing their middle classes, the backbone of stability for democratic societies.

The climate is changing, with numerous consequences for health. These consequences are also profoundly unfair. The countries that contributed least to greenhouse gas emissions will be the hardest hit.

Chronic noncommunicable diseases have overtaken infectious diseases as the number one killers worldwide. Treatment for chronic conditions vastly increases the need for medical products and raises questions about their constantly rising prices.

With most newly approved cancer treatments costing more than $120,000 per patient per year, treatment is becoming unaffordable even for the wealthiest countries in the world. In some developing countries, the management of diabetes alone absorbs more than a third of the entire health budget.

We are losing our vital but fragile antimicrobials. The detection last year by Chinese scientists of a new resistance mechanism, the mcr-1 gene, sent shockwaves through the medical and scientific communities.

The gene is located on a mobile plasmid that transfers easily from one bacterial strain to others. This is a horizontal transfer of resistance, and it is frightening.

In the Chinese study, the mcr-1 gene conferred resistance to colistin, the last-resort antibiotic used to treat several life-threatening infections caused by Gram-negative bacteria.

Colistin is a 50-year-old antibiotic that was shelved in the 1970s because of its toxic effects on the kidneys. It was brought back into clinical use when all newer antibiotics began to fail.

As colistin had not been widely used, it was still effective. It was also cheap, which encouraged its massive use as a growth promoter in food production in several countries, including China.

The Chinese findings, which have been replicated in several other countries, solidify the links between the agricultural use of antibiotics, resistance in slaughtered animals, resistance in food, and resistance in humans. All of the dots are connected.

If we lose colistin, as several experts are predicting, we lose our last medicine for fighting a number of serious infections.

Last month, British treasury minister Lord Jim O’Neill, who heads the UK panel reviewing antimicrobial resistance, likened current trends to a “slow-motion car crash” and singled out vaccines as a crucial part of the solution.

As noted, widespread vaccination against bacterial infections would reduce the need for antibiotics, thus reducing a key driver of resistance at source.

The panel will publish its final report in May. I am very pleased to know that your Prime Minister, David Cameron, is committed to pushing its recommendations through the UN General Assembly and the G7 group of countries.

Ladies and gentlemen,

The health targets in the new 2030 sustainable development agenda are supremely ambitious.

They aim at nothing less than the elimination of AIDS, tuberculosis, and malaria and an end to preventable maternal and childhood deaths. They also explicitly call on governments to support R&D for new vaccines and medicines.

Yes, we can aim for the moon and, yes, we will have to have new tools to get there. All global strategies, approved by our Member States, for reaching the 2030 health targets stress that success depends on specific R&D breakthroughs.

Many of these breakthroughs are broadly beneficial. For example, having reliable and affordable point-of-care diagnostics is another way to make prescribing more precise and thus reduce the overuse of antimicrobials.

The MenAfriVac vaccine, developed and priced specifically for use in Africa, provides a good example of the impact a new vaccine can have.

Since 2010, more than 230 million people in 16 countries in Africa’s meningitis belt have been vaccinated against meningococcal meningitis serogroup A, with support from GAVI and the Bill and Melinda Gates Foundation.

Given the added impact of herd immunity, the recurring outbreaks of meningitis A that have devastated 26 African countries for decades have been virtually eliminated.

Aiming for the moon at a time when most budgets for domestic and international health are shrinking also calls for approaches that use what already exists more wisely. Finding more creative uses for existing vaccines can change patterns of use, with multiple spillover benefits for health.

In July 2013, WHO created a stockpile of oral cholera vaccines in response to a critical situation. Cholera epidemics were raging, yet the demand for vaccines was low and manufacturers had little incentive to increase supplies.

Establishing the stockpile, WHO made a commitment to buy and use 2 million doses a year in order to stimulate demand and convince industry that a stable market exists.

Although the cholera vaccine stockpile is essentially a vaccine procurement and distribution mechanism, it has generated multiple health benefits well beyond saving lives.

It improved reporting. In public health, the promise of assistance is one of the strongest incentives to report epidemic-prone diseases immediately and transparently.

As long experience shows, the temptation to cover up a cholera outbreak is great, given the potential impact on trade and tourism.

It improved the speed needed for an emergency response, especially in the context of humanitarian crises. Following receipt of a request, vaccines arrive in the country within a maximum of 10 days.

It increased supplies. Three producers have now been prequalified by WHO, with vaccine supply set to double this year. These vastly increased supplies have opened the first opportunity for pre-emptive campaigns in “hot spots” with repeated outbreaks.

It increased access in underserved populations. More cholera vaccines have been deployed to affected areas over the past two years than in the previous 15 years combined.

It decreased costs as more producers entered the market.

It generated data on vaccine safety, efficacy, and the duration of immunity, thus strengthening the case for further investment.

And it has stimulated the development of better vaccines offering greater protection, a longer shelf life, and fewer logistical challenges.

In short, a seemingly simple thing, like creating a stockpile, has transformed a vicious cycle of low demand, low production, high price, and inequitable distribution to a virtuous cycle of increased demand, increased production, reduced price, and greater equity of access.

A stockpile of rabies vaccine is a logical next step to follow.

Ladies and gentlemen,

The tremendous contribution that this Agency and Institute make to the quality and safety of existing medical products and the development of new ones will make little difference in the absence of systems for delivering these products to those in greatest need.

Let me conclude with a visionary example.

The government of Rwanda is implementing a product delivery programme that will use drones to deliver medical supplies, such as blood bags, to remote rural areas that cannot be reached by roads.

Since post-partum haemorrhage is the leading cause of maternal mortality, the life-saving potential is vast.

Drones can deliver many other health interventions. Post-exposure treatments for rabies and snakebites are especially important, as most deaths from these conditions occur in rural areas.

Studies conducted by Ugandan and US researchers have shown that transportation by drone does not impair the quality of lab samples and medicines.

The first test flights in Rwanda, known as the “land of a thousand hills”, are scheduled to begin in August.

Plans for the future include the building of three drone-ports that will be able to cover almost half of Rwanda’s countryside. You will be pleased to know that British architect Norman Foster is one of the partners supporting this project.

Just as mobile phones overcame the lack of landlines, the use of drones to deliver life-saving medical products can overcome the lack of road infrastructure seen in much of rural Africa.

Though it is early days, experts have been quick to recognize the extraordinary potential of this delivery innovation.

It could transform the capacity of rural health facilities to save lives.

It could revolutionize the ability to retain qualified staff by assuring them they will not have to stand by, helpless, and watch people die from treatable causes.

In an era of global health perils, we need to let our imaginations soar when looking for ways to get quality medical products to those in greatest need.

That will, indeed, help us reach the moon.

Thank you.