Diabetes mellitus is a public health challenge due to its high and increasing prevalence and associated morbidity and mortality that have health and economic impact on individuals and societies. It has been estimated that about 15% of people with diabetes require insulin, but currently only about half are treated with insulin. Access to insulin remains inadequate, and its unaffordability and unavailability have been well documented in LMICs and in some high-income countries as well. The number of suppliers is very small and the market of biosimilars is very limited. It is critical to ensure the affordability and availability of quality-assured human insulin if the Global SDG target of a 30% reduction in premature mortality due to non-communicable diseases is to be achieved.
As part of the ongoing efforts to increase availability of quality-assured human insulin products, WHO PQT/MED is launching the first human Insulin Master File (h-IMF) pilot procedure for the prequalification of human insulin, modelled after its Active Pharmaceutical Ingredient Master File (APIMF) procedure for small molecules.
The APIMF procedure is a well-established procedure that is used to preserve the confidentiality of API information when the API is procured by several finished product manufacturers. The approach using an APIMF is generally not considered applicable to biological products because of risks resulting from their complex molecular characteristics, manufacture and control. However, human insulin is a relatively simple molecule and well understood in terms of molecular characteristics and clinical effects. The h-IMF pilot procedure allows confidential intellectual property or “know-how” of the drug substance (DS) manufacturer to be protected, while at the same time ensuring that the finished product applicant has access to adequate information on the DS and therefore can take full responsibility for the quality of the finished drug product (DP). It is hoped that this procedure will contribute to increased access to human insulin in LMICs.
The h-IMF pilot procedure is an opportunity offered to h-IMF holders and applicants for prequalification of h-insulin finished products:
- h-IMF holders: the DS information (CTD module 3.2.S) should be already approved within the context of the marketing authorization of a DP by an SRA, WHO PQT/MED will rely on the assessment and inspections conducted by the SRA to assure the quality of the DS. The module 3.2.S information will therefore not be reassessed by WHO.
- Applicants for prequalification of h-insulin: WHO PQT/MED will assess the DP dossier according to the principles laid down in “WHO Pilot Procedure for Prequalification of Biotherapeutic Products: human insulin”, while cross referring to the h-IMF if the DP submission is supported with a letter of access and a copy of the open part of the h-IMF