Bioequivalence of Biologies

Likewise, generic drug makers are anxious to enter the lucrative arena of biologies. Yet, there is currently no means of easy access by the established regulatory 

Manufacturer Product Indication Market Exclusivity Expiration  

Genentech Nutropin (somatropin) Growth disorders Expired Expired 

Abbott Abbokinase (urokinase Ischemic events Expired Expired 

Eli Lilly Humulin (humin insulin) Diabetes Expired Expired 

---

In Vivo Bioequivalence Studies In vivo studies are conducted to establish the biological availability or activity of the drug from a topically applied semisolid formulation. Dermatopharmacokinetic studies, pharmacodynamic studies, or comparative clinical trials are generally conducted to assess the bioequivalence of topical products [16,17]. 

Bioequivalence assessments of drugs that are insignificantly absorbed into the systemic circulation are difficult. In some cases, for such drugs a biological marker has been established for the assessment of bioequivalence. Examples of biological markers used are skin blanching in the case of hydrocorticosteroids and neutralization of stomach acid for antacids. For certain cases a pharmacodynamic end point may be more appropriate for the assessment of bioequivalence. 

For medicinal products with large intra-individual variation (i.e. if the variation of a kinetic parameter exceeds 30 %) the 90 % confidence interval of Cmax should be between 69.84 % and 143.19 %, while the AUC-ratio should be within normal limits. Classical bioequivalence studies have limited value in indicating equivalent efficacy and safety for biosimilars (generic version of biological medicines). 

Bioavailahility studies are used to compare different formulations of the drug product, or different batches of the same formulation and, as discussed in Chapter 8, generic copies of a reference drug. Their comparative value is based on the premise that, if similar amounts of identical active substance are delivered to the site of action at similar rates, then a similar biological response can be expected, which leads to the conclusion that the two preparations are bioequivalent. 

It is interesting that the in vitro dissolution test (USP) was more sensitive to the piroxicam formulation variables than the biodata. The fast, moderate, and slow products were found bioequivalent to each other and to the lot of innovator product studied [100]. It is possible that either the formulation variables studied did not affect in vivo dissolution and/or the differences were not discernible because of the long biological half-life of piroxicam [146]. 

Part II Part II is the report concerning chemical, pharmaceutical, and biological documentation. The report details the composition, method of development of formulation, manufacturing processes under GMP, analytical test procedures, bioavailability, and bioequivalence. It should be noted that all analytical test procedures need to be validated, and the validation studies must be provided. 

Phannaceutical products must demonstrate and maintain established public standards for attributes that relate to their safety or effectiveness. In the United States these attributes are expressed as identity (e.g., chemical structure), strength (e.g., assay, content uniformity), quality (e.g., combination of certain physical, chemical, and biological attributes), purity (e.g., limits on impurities and degradation products), and potency (e.g., biological activity, bioavailability, bioequivalence) [10]. Public standards serve as one of several mechanisms for minimizing the risk of product-related injuries. In principle these standards should reflect the current state of scientific understanding and ensure and promote the development of high-quality products. 

---