However, TDCs usually are lack of reference product classes, market data, and other necessary inputs data.
Both of them fell within the bioequivalence interval (80%125%%) of reference product, proving that experimental product is bioequivalent to Kaleorid®.
On the other hand, a considerable amount of referrals were due to causes that may have been prevented by the applicant through early communication with the competent authorities, such as the choice of reference product or dosage strength.
Lastly, based on current data, biosimilars cannot be considered simple substitutes of reference products in IBD, unless demonstrated by well-designed randomized controlled trials.
However, in Italy, the position paper of the AIFA excludes automatic therapeutic substitution of reference products with biosimilars [ 4].
Debate is still ongoing about the substitution of reference products with biosimilar ESA therapy in patients already in treatment.
Several scientific societies have issued position papers on biosimilars, highlighting that, after many years since the introduction into the market of the first biosimilars, these drugs are to be considered as therapeutic equivalents of reference products.
Most require that the reference product should have been approved in the same regulatory jurisdiction, although the use of reference products approved by regulatory authorities with similar scientific and regulatory standards would be considered by some authorities (in the European Union [EU], Saudi Arabia, Jordan, Egypt, South Korea, and India).
Additional factors can influence clinical safety and effectiveness requirements, including the degree of understanding of the mechanism of action of the reference product and disease pathology, together with the extent of clinical experience with the reference product and its therapeutic class.
According to the dosage information and published reports of the reference product, the administration of trastuzumab to women of reproductive potential is not recommended [ 10, 19, 20].
This evaluates whether the probability of concluding average biosimilarity (corresponding to ABE) in a contrast of the biosimilar test and the reference products (T vs R) is similar to the "reproducibility" probability obtained in a comparison of two applications of the reference product (R vs R).
