The FDA's assessment of follow-on protein products: a historical perspective

Abstract

The scientific and regulatory issues that are associated with the possible introduction of 'follow-on' versions of protein drug products are the topic of considerable debate at present. Because of the differences between protein drug products and small-molecule drugs, the development of follow-on versions of protein products presents more complex scientific challenges than those presented by the development of generic versions of small-molecule drugs. Here, with a view to illustrating the Food and Drug Administration's (FDA's) scientific reasoning and experience in this area, we discuss past examples of the FDA's actions involving the evaluation of various types of follow-on and second-generation protein products and within-product manufacturing changes. The FDA believes its evaluation of the safety and effectiveness of follow-on protein products will evolve as scientific and technological advances in product characterization and manufacturing continue to reduce some of the complexity and uncertainty that are inherent in the manufacturing of protein products.

Challenges and Opportunities in Absorption, Distribution, Metabolism, and Excretion Studies of Therapeutic Biologics

“…Given their structural complexity, multifaceted manufacturing process, and, as a result, challenges for predicting impact of the manufacturing process changes on immunogenicity, biosimilars are not generic alternatives per se and generally are not interchangeable (90). Thus, unique regulatory pathways are required for biosimilars (91,92). PK and immunogenicity assessments, together with efficacy and toxicology studies, are key components in the development of biosimilars.…”

Biosimilar epoetins and other “follow‐on” biologics: Update on the European experiences

“…Previously, the FDA considered only more simple follow-on protein products. The biological medicines that have been approved under the abbreviated New Drug Application pathway (NDA 505(b)(2)) include recombinant human hyaluronidases, salmon calcitonin, human glucagons, and rhGH [25,28]. However, these products are not rated therapeutically equivalent to the innovators' medicines.…”

Aptamer: A Novel Therapeutic Oligonucleotide

“…Subsequently, these proteins are separated from the microorganisms and purified (as a downstream process) retaining its biological activity to inject in the human body. These complex proteins are difficult to cultivate, separate, characterize and reproduce [1,2].…”

“…Subsequently, these proteins are separated from the microorganisms and purified (as a downstream process) retaining its biological activity to inject in the human body. These complex proteins are difficult to cultivate, separate, characterize and reproduce [1,2].The basic mechanism of protein synthesis in any of the living organism involves transcription and translation of polynucleotide chain of Adenine, Guanine, Thymine, and Cytosine [3]. The sequence of the oligonucleotide is responsible for translating specific protein using a specific sequence of amino acid involved in the synthesis of protein.…”