Because of the complex molecular structure of biological products, conventional analytical methods used for generic drugs may not be suitable for biological products. Following EMA and FDA, the CFDA has drafted a guideline for biosimilars. Here are some key points.
Biosimilar means that the biological product is highly similar to the reference product already approved by the CFDA. Biosimilars should have the same amino acid sequence of their reference products. PEG-modified products and antibody-drug conjugates should be consider carefully as biosimilar products. The reference products are limited to original drugs, excluding approved biosimilars.
To demonstrate biosimilarity, a sponsor must provide data from:
(a)quality studies (manufacturing process, physicochemical properties, biological activity, purity, impurities, immunochemical properties, stability, etc.). Data from quality studies should be provided on at least three batches of the drug substance;
(b) non-clinical studies (animal PD, PK, and immunogenicity). Animal toxicity data are not generally required;
(c) clinical studies (human PD, PK, immunogenicity, safety and effectiveness). A randomized, double-blind, controlled, equivalence or non-inferiority clinical trial is required.
For human PD/PK studies, CFDA recommends use of a crossover design for products with a short half-life (shorter than five days?) and a parallel study for products with a longer half-life. The acceptable limit for the confidence interval of the ratio may be 80-125%. This is not a default range.
One or more additional indications based on the same mechanism of action can be approved without additional clinical studies. A sponsor should consider whether the tested indication is the most sensitive one in detecting safety and effectiveness.
In short, CFDA’s biosimilar guideline is a piece of brief compilation of FDA’s guidelines. Many technical details and scientific considerations have been left out.