Assurance of Clonality: a key regulatory requirement for biotherapeutics

Since the FDA’s approval of the first recombinant protein in 1986, the number of approved biopharmaceuticals has grown constantly over the years, reflecting their increasing relevance in modern medicine. By 2021, the FDA approved the 100th monoclonal antibody product together with nine other new biologic drugs, accounting for 16% of the total number of drugs approved that year. One major factor that could potentially impact process consistency and product quality is the clonal derivation or clonality of the cell line. A well-characterized clonally-derived cell line is not only a fundamental component of the biopharmaceutical manufacturing process but also a requirement for regulatory submission, most typically at the Investigational New Drug (IND) application stage.