In order to obtain a biosimilar product that is comparable to the reference drug, it is essential that both molecules have the same amino acid sequence.
To confirm this, we use a technique known as "peptide mapping", which cuts the protein into smaller peptides and separates them using a chromatographic method. The peptide profile obtained is specific to the protein and allows us to confirm that the biosimilar product has the same sequence as the innovative reference drug.
Various batches of the reference product are selected and analysed. This provides us with the quality acceptance criteria for our product.
We normally use mammalian cells, which we transfect by means of genetic engineering in order to insert the manipulated genetic material and thus cause the cell to synthesise the desired protein.
The transfected host cells are cultured in order to select the monoclonal cell line (they all grow from one stem cell) that produces the desired protein with the highest degree of quality.
Once the optimal monoclonal cell line has been selected, it is necessary to increase the number of cells in order to manufacture the biosimilar throughout the product's entire marketing process.
This group of cells is called a cell bank.
The manufacturing process is split into two main stages: upstream and downstream.
This involves finding ideal culture conditions (medium, temperature, oxygen, etc.) so that the cells grow and reproduce to optimum effect. The cells are cultured in order to obtain the necessary quantity for industrial-scale production.
The cells are left in ideal culture conditions for 12 days in order to produce the desired mAb or protein, which will then be expelled into its culture medium.
This takes place in bioreactors, with single-use technology.
It is one of the most critical stages in the process.
Once the production process is complete, it is necessary to discard the cells using filtration and/or centrifugation, as well as to eliminate salts and nutrients etc., through purification. This is how we obtain a liquid that is free from unwanted remnants and which contains our molecule.
Using our synthesised protein, we then carry out a series of basic steps which allow us to eliminate any impurities and obtain our pure active substance while minimising losses.
The product is checked to ensure it is virus-free using viral inactivation (pH modification) and filtration.
Affinity: using a resin related to our molecule, which retains it and separates it from other substances.
Cation and anion exchange: using a suitable resin, the molecule is separated from other substances based on its load.
Also known as ultrafiltration-diafiltration The key elements of this part of the process are the chromatography columns and their control equipment, as these constitute a complex network of valves, interconnected lines and pumps controlled by a computer program. They are able to run complex flow sequences and volumes of great precision and accuracy.
The protein is dosed into vials, which are subsequently analysed according to specification using validated analytical methods to ensure their quality.
The biosimilar obtained from the manufacturing process is compared to the reference drug using a series of state-of-the-art physicochemical and bioactivity analyses.
The medicine obtained in the previous phase is studied in animals in comparison to the innovative reference drug, in order to demonstrate that both products behave in a similar way.
The medicine is also studied in humans in comparison to the innovative reference drug, in order to demonstrate that both products behave in a similar way.
We have obtained the peptide map for our biosimilar product, and it is "fingerprint-like" with regard to the reference drug.
All of the data obtained during product development (biopharmaceutical, preclinical and clinical) are collected in the registration dossier, which will constitute a compilation of all the information relating to the product's development.
This confirms the quality, safety and efficacy of the product, as well as its biosimilarity with the marketed reference drug.
The registration dossier is submitted to the Health Authorities for its assessment and approval in accordance with the regulatory guidelines and channels available for biosimilars in each country.
Once the regulatory bodies approve the registration, we can proceed to market our biosimilar product.
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