Analytical Similarity Assessment in Biosimilar Product Development

Shein-Chung Chow

• Publisher: Chapman and Hall/CRC
• Year: 2018
• ISBN:
  9781351339452
• Edition: 1
• Topic: Matemáticas
• Subtopic: Probabilidad y estadística

This book focuses on analytical similarity assessment in biosimilar product development following the FDA's recommended stepwise approach for obtaining totality-of-the-evidence for approval of biosimilar products. It covers concepts such as the tiered approach for assessment of similarity of critical quality attributes in the manufacturing process of biosimilar products, models/methods like the statistical model for classification of critical quality attributes, equivalence tests for critical quality attributes in Tier 1 and the corresponding sample size requirements, current issues, and recent developments in analytical similarity assessment.

1Introduction

1.1Background

When a brand-name chemical (small molecular) drug product is going off patent protection, pharmaceutical/generic companies may file an abbreviated new drug application (ANDA) for generic approval. In 1984, the United States (US) Food and Drug Administration (FDA) was authorized to approve generic drug products under the Drug Price Competition and Patent Term Restoration Act. For approval of generic drug products, the FDA requires that evidence in average of bioavailability in terms of rate and extent of drug absorption be provided through the conduct of bioavailability (BA) and bioequivalence (BE) studies. The assessment of bioequivalence as a surrogate for evaluation of drug safety and efficacy is based on the Fundamental Bioequivalence Assumption that if two drug products are shown to be bioequivalent in average bioavailability in terms of drug absorption, it is assumed that they will reach the same therapeutic effect, or that they are therapeutically equivalent. Under the Fundamental Bioequivalence Assumption, regulatory requirements, study design (e.g., a two-sequence, two period or replicated crossover design), criteria (e.g., 80/125 rule based on log-transformed data), and statistical methods (e.g., Shuirmann’s two one-sided tests) for assessment of bioequivalence are well established and accepted by most regulatory agencies worldwide (see, e.g., Shuirmann, 1987; EMEA, 2001; FDA 2001, 2003a, 2003b; WHO, 2005; Chow and Liu, 2013).

Unlike small molecular (chemical) drug products, the concept for development of generic versions of biologic products is different. The generic version of biologic products is usually referred to as follow-on biologics by the US FDA, biosimilars by the European Union (EU) European Medicines Agency (EMA), and subsequent entered biologics (SEB) by the Public Health Agency (PHA) of Canada. The generic versions of biologic products are viewed as similar biological drug products (SBDP). The SBDP are not generic drug products, which are drug products that contain identical active ingredient(s) as the innovative drug product. Webber (2007) defines follow-on (protein) biologics as products that are intended to be sufficiently similar to an approved product to permit the applicant to rely on certain existing scientific knowledge about safety and efficacy of an approved reference product. Under this definition, follow-on products are not only intended to be similar to the reference product, but also intended to be interchangeable with the reference product. As defined in 351(k) of Public Health Service (PHS) Act, the term biological product means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings. Th...