Which markets do pharmaceutical companies target for registration?
Registration is a key step to introducing a medical product into a country. Registration with national regulatory authorities enables distribution, marketing and, by extension, patient access to life-saving products across the country. In lower-income countries, the registration of newly launched products typically occurs less frequently and usually later than in higher-income ones with larger markets.
The Index assessed a sample of the 20 companies’ recently marketed products to gain an insight into their registration practices in the 106 low- and middle-income countries with high burdens of disease and/or high inequality. The companies submitted up to a maximum of 10 recently launched products to the Index for analysis, resulting in a total of 182 products.
Which countries do companies target?
The countries in scope with the most registration filings mainly include upper middle-income countries (UMICs) and low- and middle-income countries with a large volume of patients or higher possibility of revenue.
In contrast, the countries receiving the lowest number of registration filings include politically unstable countries, e.g., Somalia and South Sudan, or have small populations such as Tuvalu and Vanuatu. Twelve countries did not receive any registration filings. These countries are collectively home to more than 30 million people. Some of these countries have a high burden of non-communicable diseases (NCDs). For example, Kiribati, Micronesia, Fed. Sts., Tonga, Lesotho, Solomon Islands and Eswatini are featured in the top 10 high burden countries* for diabetes mellitus.
One product stands out: AbbVie’s HIV/AIDS product lopinavir/ritonavir (Aluvia®/Kaletra®) is the only product registered in Cabo Verde, Comoros, Djibouti, Guinea Bissau, Swaziland/Eswatini and São Tomé and Principe. There are two potential reasons for this: 1) the product has been on the market for a considerable period of time (2000); 2) HIV/AIDS has the highest level of intervention and prioritisation by global health stakeholders – treatments tend to be procured through supranational entities (i.e. pool procurement mechanisms).
Which diseases do most product registration filings concern?
A higher number of registration filings for NTDs and maternal and neonatal health conditions can be due to product development partnerships. These demand access provisions, including registration, and the existence of supranational procurement mechanisms. Such incentives do not exist for many NCDs except for products eligible for supranational procurement (donor-enabled pooled procurement).
Do companies rapidly register their products where the need is the greatest
Filing for registration in low- and middle-income countries within 12 months is not consistent and there is still a large time gap between the first global product registration and registration in these countries. Overall, companies do not always prioritise the countries with the highest burden of disease when filing for registration of their recently launched products. AstraZeneca, Boehringer Ingelheim, Johnson & Johnson and Novartis filed all their respective assessed products within a year from global registration in at least one of the countries in scope.
How some companies are overcoming registration challenges
Atezolizumab (Tecentriq®) is one of the most widely registered oncology treatments. Roche filed the innovative product for registration in 37 countries in scope, in 21 of which registration occurred within 12 months of the first global registration in the USA. This is noteworthy as often filing biological products for registration in low- and middle-income countries can be a disincentive as dossier submission for these products can be lengthy and burdensome. Some regulatory authorities may also lack the technical expertise to assess the dossier, resulting in significant delays.
Through emergency approval from regulatory authorities, Gilead first received emergency approval for remdesivir (Veklury®) in May 2020 from the US Food and Drug Administration (FDA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) as well as conditional approval by the European Medicines Agency (EMA) in June 2020. By partaking in the WHO prequalification process, the company can facilitate registration in low- and middle-income countries for this treatment. The products received full approval from the FDA in October 2020.
Opportunity for companies to prioritise countries with high burden of disease
Several new bodies and programmes have been established to help provide companies with support for product registration, for example, the African Medicines Agency (AMA). Companies should engage more systematically with these programmes, including WHO’s prequalification and collaborative registration procedures, to facilitate registration in low- and middle-income countries that might lack capacity to assess dossiers in a timely manner. Importantly, companies need to prioritise countries with the highest disease burdens when planning for registration, especially for products on the WHO Essential Medicines List (EML). This requires tactical planning. Such access planning throughout the research and development phase can help facilitate registration and rapid access to new products in a higher number of countries.
* Relevant top 10 high burden countries for diabetes(disease-specific subset of countries with the highest burden of disease) according to IHME global burden of disease study
