Companies have a collectively broad regulatory reach in LMICs, yet many essential products are not widely registered

• Collectively, across their product portfolios, the five companies have registered at least one product in 90 of the 108 low and middle-income countries (LMICs) in scope, demonstrating a broad existing regulatory reach.

• However, an analysis of a subset of ten off-patent essential medicines per company* shows that registration practices vary significantly, with one company failing to file any of its ten assessed products in any low-income country.

Registering products with a country’s national regulatory authority (NRA) is an essential first step in making quality-assured products available in that country’s market. Registration alone does not guarantee that a product will be accessible to all patients, and factors including commercialisation, affordability, marketing and supply are also critical to ensuring equitable access. Nonetheless, registration is key, not just in terms of product availability, but also because registering a product plays a critical role in strengthening regulatory capacity of NRAs, market surveillance and quality control of products, in pharmacovigilance activities, and ultimately ensuring that patients have access to safe, effective and high-quality medicines.

Where have companies previously filed for registration?

Cipla, Hikma, Sun Pharma, Teva and Viatris collectively have a broad existing regulatory reach. However, an analysis of a subset of products from each company reveals that they do not always register these products in countries where they have previously registered other products – for example, in countries where they have the proven capability to work with NRAs.

The companies’ existing regulatory reach was assessed by analysing whether they had filed any products from their entire product portfolios within any of the 108 countries in scope. Collectively, the five companies have filed at least one product for registration in 90 of these countries. Among these companies, at least one product is registered in 25 out of the 27 low-income countries, 42 of the 55 lower-middle income countries, and 23 of the 26 upper-middle income countries in scope.

While this does not necessarily mean that the companies are all registering a wide range of the products in these countries, it does highlight the essential role generic and biosimilar medicine manufacturers already play in supplying medicines in LMICs. It also demonstrates the companies’ ability to register products with these NRAs, and may therefore indicate where they have the capability to register more products, including those within scope of this analysis, which are essential medicines identified as priorities for access.*

_{*Of the products within the scope of the Generic & Biosimilar Medicines Programme, ten off-patent medicines from each company’s portfolio were selected for specific analysis.}

How was companies’ existing regulatory reach assessed?

The Generic & Biosimilar Medicines Programme assessed companies’ registration efforts by analysing their previous registration filings, specifically looking at instances where each company registered at least one product within a country in scope. This assessment was based on the registration of products from companies’ entire portfolios, including those beyond the 102 products in scope. If a company has previously registered any product in a particular country, it demonstrates their capability to register other products within that same country.

Where are products registered?

While various factors can influence companies’ registration strategies, such as commercial potential and market competition, companies have the capability to improve access and reach populations in need. One approach is for companies to strategically leverage their existing regulatory reach by registering more of their products in countries where they have previously registered other products. To determine if companies were already adopting this approach, registration filings for a subset of off-patent essential medicines – ten products from each of the companies’ portfolios – were analysed. Overall, the companies have registered these products in 77 countries in scope, despite having previous regulatory activity in 90 countries. Among the 77 countries, this includes registrations in 38 of the 55 lower-middle income countries, 19 of the 27 low-income countries, and 20 of the 26 upper-middle income countries in scope.

Furthermore, companies do not need to limit themselves to countries where they have existing regulatory reach, but can look at extending their footprint to more LMICs. By registering their products in markets where they do not have an existing or established presence, companies can promote better access to essential medicines for a broader population.

Registration data was also collected for a sample of in-licensed products manufactured under licensing agreements with innovator companies, which can facilitate access to innovative medicines in LMICs. Data about eight licensed compounds** reveals that, while all of the licenses would allow the sub-licensee to register their generic or biosimilar version of the product in at least 90 countries, the number of registrations per product spans a wide range. For example, there were minimal to no registrations for COVID-19 therapeutics, while registrations for HIV treatments covered approximately 40% of the countries within the licences’ scope.

_{**Licenses cover the compounds needed to manufacture specific products.}

Majority of companies include low-income countries in their registration strategies

Among the 27 low-income countries in scope, the five companies collectively demonstrate their capability to register their products in 25 countries. Narrowing down from the companies’ entire portfolios to look specifically at the ten products per company selected for analysis,* companies have filed for registration or successfully registered these products in a collective total of 19 low-income countries. This can be considered a positive achievement as some of these countries have limited regulatory capacity or are perceived as having lower commercial potential.

Despite the overall promising picture, there is a disparity between companies’ registration efforts in low-income countries for the subset of products selected for assessment; one company has not registered any of these products in any low-income countries, while another has registered products in 16 low-income countries.

_{*Of the products within the scope of the Generic & Biosimilar Medicines Programme, ten off-patent medicines from each company’s portfolio were selected for analysis.}

Mechanisms to facilitate registration are used, but not extensively

Three out of the five companies assessed are engaged in mechanisms to facilitate registration. However, these mechanisms are still underutilised, despite their potential to facilitate timely access to products. These companies have made use of mechanisms including the WHO Collaborative Registration Procedure (CRP) for WHO prequalified products, as well as regional joint assessments including ZaZiBoNa and ECOWAS.** When countries utilise these facilitated mechanisms, this aids in improving their regulatory preparedness and capacity. It also accelerates the registration of quality-assured products in their markets, while easing some of the challenges faced by companies in registering their products in LMICs – thereby incentivising them to register their products.

_{**The ZaZiBoNa process is a work-sharing initiative between NRAs in Zambia, Zimbabwe, Botswana, Namibia, South Africa, Democratic Republic of Congo, Tanzania, Malawi and Mozambique. ECOWAS is the Economic Community of West African States.}

What needs to happen next?

Companies can broaden the registration of essential products through two key steps: firstly, by registering more of their products in the LMICs where they already have existing regulatory reach; and secondly, by expanding their reach to additional countries. As part of their registration strategies, they can prioritise products already registered by SRAs or prequalified by WHO, using mechanisms such as CRP or regional joint assessments that can facilitate and accelerate registration. They can also prioritise registration in countries with a high burden of disease, focusing on medicines with access gaps in LMICs, including cancer, cardiovascular diseases, HIV, diabetes and mental health conditions. This effort can include in-licensed products supplied through voluntary licensing agreements. Some companies have registered several of their assessed products in low-income countries, and they can now expand these efforts to ensure all products in their portfolio are registered in low-income countries.