The aim of this post is to explain how a biosimilar is developed. It has to be said that the process involves a certain amount of complexity and may last a number of years, with the development period depending on the molecule, the company and the country, among other factors.
The development and registration process for a biosimilar
We shall try to explain this as simply as possible. Are you with us?
As a starting point, it should be noted that the development process consists of producing the cell line, defining the manufacturing process and the formula, verifying the similarity and conducting the required pre-clinical and clinical analysis, prior to registration.
It is a process that goes through various phases:
First, the limits of the biosimilarity need to be established. This consists of analysing various batches of the reference product. This process will provide us with the quality acceptance criteria that the biosimilar product must meet.
Once in possession of said criteria, we can proceed to product development. This phase, in turn, is divided into a further seven sub-phases, which are as follows:
- Selection and transfection of the host cell. This process, however technical it may appear, essentially consists of introducing the desired genetic material into a cell.
- Selection of the clone. The cells that already contain the genetic material corresponding to the desired protein are cultivated. From these, the cell line that produces the desired protein at the highest level of quality is selected. To give you an idea of what is involved, this step may involve up to 18 months of research.
- Creation of cell banks. A sufficient quantity of cells are taken to be able to manufacture the biosimilar product throughout its entire marketing period.
- Development of the manufacturing process:
- Cell expansion and protein production: part of the cell bank is thawed and the cells contained are placed in a culture medium to reproduce and thus increase in number.
- Protein purification: once the cells have synthesised the protein, it is then subjected to a process for eliminating impurities and other unwanted substances.
- Once purified, the formulation in which the protein is most stable must be selected. Generally, this formulation will contain one or more compounds that act as buffers and keep the pH stable, guaranteeing the protein solution’s stability throughout its shelf life.
- Lastly, the protein is dosed into vials through a filling process. With this procedure, the desired medicinal product is obtained. After the quality control analysis, the product is ready for use.
- Testing similarity. The biosimilar obtained through the manufacturing process designed is analysed to compare it with the reference medicine on the market through a series of physico-chemical and bio-activity tests to confirm the product’s similarity to the reference medicine.
After the previous test, the next phase is pre-clinical product development. The medicinal product obtained in the previous phase is studied in animals in comparison with the innovator product to demonstrate that they behave in the same manner. This phase is followed by clinical product development, by way of which the medicinal product is also studied in humans in comparison with the innovator product.
All the data obtained during product development are reported adhering to a specific format in what is called a registration dossier; i.e., a compilation of all the information from the product development stage.
The registration dossier is then submitted to the heath authorities for evaluation and, where applicable, approval, using the regulatory guides and pathways for biosimilars available in each country.
We hope we have managed to provide a clear, step-by-step explanation of the process for developing and registering a biosimilar. It is a lengthy process that can take, on average, between six and twelve years, and that, as we shall see in the next post, is followed by the manufacturing process. If you have any questions, please do not hesitate to ask our experts.