Botulinum toxin type A products are not interchangeable: a review of the evidence

Abstract

Botulinum toxin type A (BoNTA) products are injectable biologic medications derived from Clostridium botulinum bacteria. Several different BoNTA products are marketed in various countries, and they are not interchangeable. Differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. These differences result in a specific set of interactions between each BoNTA product and the tissue injected. Consequently, the products show differences in their in vivo profiles, including preclinical dose response curves and clinical dosing, efficacy, duration, and safety/adverse events. Most, but not all, published studies document these differences, suggesting that individual BoNTA products act differently depending on experimental and clinical conditions, and these differences may not always be predictable. Differentiation through regulatory approvals provides a measure of confidence in safety and efficacy at the specified doses for each approved indication. Moreover, the products differ in the amount of study to which they have been subjected, as evidenced by the number of publications in the peer-reviewed literature and the quantity and quality of clinical studies. Given that BoNTAs are potent biological products that meet important clinical needs, it is critical to recognize that their dosing and product performance are not interchangeable and each product should be used according to manufacturer guidelines.

Keywords: abobotulinumtoxinA; glabellar lines; incobotulinumtoxinA; non-interchangeability; onabotulinumtoxinA.

Figure 1

Comparison of clinical response of two hypothetical BoNTA products. Notes: (A) Graph showing hypothetical response at months 1 and 4 for two different products. Assessed at only month 1 and 4, the products may appear equivalent. (B) Graph showing hypothetical response at months 1, 2, 3, and 4 for the same two products. The products clearly exhibit different pharmacodynamics, as evidenced at months 2 and 3.

Figure 2

Progressive differentiation of four hypothetical BoNTAs. Notes: BoNTA products are biologics derived from Clostridium botulinum bacteria. For each product (denoted as example Products 1–4; not meant to correspond exactly to currently approved products), the manufacturing process, formulation, and method of determining units differ. These factors result in differences in product in vivo profiles, including preclinical dose–response curves and clinical dosing, efficacy, duration, safety/adverse events, and immunogenicity. The products are subject to further differentiation based on confidence in and knowledge of the product gained through regulatory approvals, the number and quality of clinical studies that are conducted and published in peer-reviewed journals, research into the mechanism(s) of action, long-term evidence, and anti-counterfeit measures. Abbreviation: BoNTA, botulinum toxin type A.