20/21 April 2021
Unlike recombinant products whose APIs are derived from a defined cell bank, so-called biological medicinal products are characterised by large variability in sourcing and intermediate steps. Biological medicinal products are derived from human or animal organs, tissues or body fluids. As a rule, the sources are very diverse (i.e. several suppliers, multiple slaughterhouses, various donors); the same applies to the intermediates foreseen to further processing manufactured in diverse forms, e.g. as resin adsorbat or paste. All in all, the manufacturing process of biological medicinal products is highly complex and questions about the definition of starting materials, intermediates and document requirements for the marketing authorisation application arise again and again.
The EMA has recently published a Guideline entitled "Guideline on the use of starting materials and intermediates collected from different sources in the manufacturing of non-recombinant biological medicinal products" which helps clarifying the questions above. The definition of the starting materials concerned is based on typical medicinal products of biological origin (heparin and urine derived urokinases and sex hormones (gonadotropins). Pooled porcine intestinal mucosae are defined as the starting material from which any heparin is extracted. Pooled human urine is defined as the respective starting material for urine derived urokinases and hormones.
The Guideline describes the requirements for the quality documentation of module 3 of the marketing authorisation dossier. Here, the complete manufacturing process including all sources as well as the relevant safety aspects (i.e. donor controls, virus testing and veterinary investigations) has to be carefully documented.
Allergens and blood plasma derived medicinal products as well as advanced therapy medicinal products aren't covered by the scope of this Guideline.