Insulin Imports Fail to Meet Many Countries’ Needs

Despite being a 100-year-old medicine, insulin remains inaccessible to millions around the world– owing to limited availability and its high price.

Why did you conduct this study?

Our previous in-country research shows that often insulin is not available on pharmacy shelves in low- and middle-income countries.

While the actual and physical availability of insulin for use by the patients depends on the myriad of processes that are involved in-country, we wondered if the many countries that cannot manufacture insulin and depend on imported insulin – are actually importing enough in the first place.

What did you do?

We used two sets of data – i.e. the United Nations global commodity trade data and available country-specific diabetes prevalence estimates – to see if the insulin quantities imported into import-dependent countries are adequate to meet insulin treatment needs of the local population.

From our previous research, we know that only 20 countries have insulin manufacturing capacity– meaning all the other countries would be dependent on imports for insulin. Some import- dependent countries also export insulin (i.e. they are passing some of it through to other countries) probably for business/foreign-exchange reasons, so we studied only those countries that exported small amounts, no more than needed to treat ~500 patients in a year. Our study sample was 82 countries (plus 22 ‘test’ countries) and the study time-period was 2000-2018.

We converted imported insulin kilograms into insulin International Units (IUs) and also estimated the annual patient need in IU using the diabetes prevalence data and data on how many persons with diabetes are using insulin. Dividing these two estimates, we calculated insulin ‘supply-needratio’, where an annual ratio of >= 1.00 means the insulin imports in a given year are adequate to meet the need for at least that one year.

What did you find?

Imports of insulin in many countries with no local insulin production – most especially in Africa and Asia – are simply not enough to get it to all those persons with diabetes who need it.

Import-dependent countries rely mostly on Denmark, France and Germany to source insulin for their patients. These three countries host manufacturing or corporate headquarters of Novo Nordisk, Eli Lilly and Sanofi.

•   The fact that only 20 countries in the world are known to produce insulin domestically has to do with the complex insulin manufacturing process, the complex regulatory processes and the fact that only a handful of corporations own the intellectual property rights on the many aspects of insulin manufacturing process.
•   Exports of insulin from other companies/countries (like those located in India, Mexico, and Brazil) are limited in terms of their export outreach and export relatively smaller quantities.

  The good news is that the gap between countries’ insulin imports and the domestic need hasnarrowed down in all regions since 2000. The bad news is that this is NOT true for countries in Africa and Asia. Indeed, even in recent years (2012-18), there are countries in almost all parts of the world where insulin imports are just not enough to treat all those who need it.

  62.2% of all study countries had supply need ratio < 1 during the majority of years between 2012 and 2018. Percent countries with ratios less than 1.00:

•   Africa: = 87.5%
•   Asia: = 88.9%
•   Caribbean & Oceania: = 46.2 %
•   Americas: = 20.8%
•   Eastern Europe: = 37.5%
•   Middle East: = 28.6%

  Reasons for under-importation compared to in-country diabetes patients’ insulin need (i.e. supply-need ratio < 1) in many countries

  Many reasons are possible:

•   The problem of missed patients
  o Patients with diabetes remain undiagnosed and/or those who need insulin are not

  prescribed it

•   Insulin import forecasts may be artificially lowered because access barriers may be

  preventing patients from getting insulin

•   Perhaps more of those on oral hypoglycemics should really be getting insulin but are not

Reasons for over-importation compared to in-country diabetes patients’ insulin need (i.e. supply-need ratio > 1) in many countries

Yes – we do see that (according to our calculations) some countries, especially in the Middle East and Eastern Europe, imported higher volumes that what would be needed by the patients with diabetes. Several reasons are possible:

•   First, it is possible that the actual number of patients with diabetes in those countries are higher than what the published estimates say.
•   The actual need often is much higher than what we assumed in our calculations – thus higher imports.
•   Several studies have shown that pharmaceutical marketing plays a major role in the utilization of the type and quantity of insulin that physicians prescribe and patients use. Such phenomenon may result in higher that needed insulin imports.

  Our Insulin study and the COVID pandemic & future implications & potential solutions

  This year the WHO Director General Tedros A. Ghebreyesus raised concerns about poor COVID-19 vaccines availability in lower income countries by noting “the world is on the brink of acatastrophic moral failure ─ and the price of this failure will be paid with lives and livelihoods in the world’s poorest countries”. This global North-South inequity in vaccine availability is unfortunately echoed by our study for insulin – an essential medicine that was discovered 100- years ago!

 This irony should not be lost on anyone. Medical sciences today is making breakthroughs by developing newer vaccines, medicines and gene therapies for horrible diseases. And –at the same time – we are failing to ensure that those who need insulin actually get this century old life-saving medicine. The development of a vaccine or medicine is only as good as our ability to ensure equitable access to it. Insulin is but one ‘poster child’ for this.

We have found that African nations are importing insulin from countries that themselves cannot make it, suggesting that African imports are made through intermediaries that must be first buying from insulin manufacturing countries and them shipping it to Africa.

This has implications for insulin supply security. Most importantly, Africa currently lacks a regional insulin manufacturing “champion”. Until such time, smaller manufacturers in India, Brazil and China must step up!

Any message from your study for the American readers?

There is likely more than enough insulin produced in the United States to supply insulin for all those who need it here. Yet the problem of poor insulin access is not alien in the US and other high-and-middle-income countries that actually do manufacture insulin. Several US presidential

candidates have talked about the issue of the high and ever-increasing insulin prices in recent years. The cost of insulin has nearly tripled in the past 15 years, and that the lack of transparency generally around price and supply makes it difficult to figure the root cause of price increases.

A January 2021 US Senate Report – following a bipartisan investigation – noted that manufacturers and the pharmaceutical benefits managers act synergistically to inflate the price of insulin.

The issues that constrain patient access to insulin are complex in any country. At the same time, we know that legislative developments in America are followed and often adopted in other parts of the world, so it is high time we attempt to end inequities in insulin access here in the US andsend a positive “insulin for all” message to rest of the world. One hundred years should be enough time to provide access for everyone to this life saving medicine.

What do you suggest as Ways forward/Recommendations?

•   First, national and regional governments should develop mechanisms to generate better information about their diabetes population and their treatment needs – and also on how the provision of diabetes treatment and access barriers vary within a country and across socio- economic strata. This is essential for improving insulin needs forecasting.
•   Allocate sufficient funding and resources (e.g., inclusion of insulin in national benefit packages) for adequate insulin sourcing and in-country distribution.
•   To optimize insulin sourcing and get better value for their money, governments and insulin buyers could benefit from a global or regional pooled procurement mechanism. Market commitments that promise large purchase orders over time at established prices can also create healthier market dynamics.
•   Governments and medical organizations – especially in resource poor settings – should encourage the use of less expensive human insulin and only switch patients to more expensiveinsulin analogues when it’s clinically needed. Regulatory support for smaller manufacturers tofacilitate the review of their biosimilar insulin products along with efforts to improve physician and patient perceptions those products will help increase market competition and may lead to lower prices.

o The World Health Organization (WHO), in November 2019, included insulin in its“prequalification” program. Smaller manufacturers in Asia, South America, and the UAEcould benefit from this program that can facilitate their products’ entry and adoption inmarkets with unmet need (e.g., Africa) and both supplier and importing countries can benefit through high-volume low-price business model.