As mentioned in the previous article, the biotechnological challenge of the national pharmaceutical industry has already started and companies that do not prepare themselves can be stuck with the generic and similar model with increasingly tight margins.
But what steps must be taken in the development of a biosimilar? What is the comparability study?
· Characterization of the comparator medicine: Drawing a parallel with the development of a generic medicine, it all starts with the in-depth study of the comparator medicine (“reference medicine”), but for biologicals it is necessary to analyze several batches to characterize it correctly since variations between batches are intrinsic to this type of medicine. At this stage it is essential to determine what are the critical attributes of product quality (CAPQ), which are the biological, structural and physicochemical properties critical to the safety and efficiency of the medication and, in parallel, define the acceptable ranges of variability for each chosen parameter. This is a fundamental step for the development of a biosimilar because it is from these determinations that the “Design Space” is defined so that the future product always remains within the limits of variability observed for the innovator.
· Biosimilar development: as in any product that aims to be a copy, this step aims to obtain a product as close as possible to an innovative medicine using technology, substrates and excipients similar to the new biological.
· Comparative physical chemical tests: in the development of synthetic medicine, the test medicine is compared with the innovative medicine with pharmaceutical equivalence studies. In the case of biological products, these tests are not applicable, and the comparability exercise must be carried out, which needs to be carefully structured, in order to demonstrate that the product under development has quality attributes highly similar to the comparator medicine in terms of structure and biological activity. The physical-chemical tests, ideally, should be carried out by different analytical techniques for each parameter studied because, as biological molecules are extremely complex, a single method cannot demonstrate full understanding of the analyzed property, and should elucidate the similarities in relation to primary structure (amino acid sequence), secondary structure (resulting from hydrogen connections that occur between the hydrogen of the group - NH and the oxygen of the group C ═ O), tertiary (resulting from folds over themselves of the primary structures of proteins giving rise to a spatial arrangement) and, in some cases, quaternary (when the proteins come together through non-covalent protein-protein interactions to form a protein aggregate).
· Comparative functional characterization: biological activity, binding to the target of the recipient, and the impurity profile of the production process and the product.
· Comparative pre-clinical tests.
· Comparative clinical study.
Good quality analytical data is essential to make it possible to reduce the requirements of non-clinical and clinical data, remembering that it is necessary to submit the data set of items 3 to 5 in the DDCM (Clinical Drug Development Dossier) together with the proposal clinical development for ANVISA to analyze and authorize the execution of the clinical stage.
The comparability study includes pre-clinical and clinical studies and at the end it must demonstrate high similarity between the product under development and the comparator, and any discrepancy must be justified, while demonstrating that there is no significant impact on safety and efficacy.
The development of a biosimilar requires specialized technology and labor, and it obviously has a relatively higher cost than that of a generic (at least 10 times higher), but in contrast, it competes with a lower number of competitors and the prices are much more attractive.