A biosimilar is a biological therapeutic product very similar to an approved originator biological drug. These two therapeutic products have similar clinically inactive ingredients, with no significant differences in potency, purity, and safety. Besides, it includes detailed functional and physicochemical evidence of similarity between the two drug products. Assessing biosimilar drugs involves systematically assessing nonclinical, clinical, and analytical features.
Biosimilar studies are similar to biomarker analysis. Clinical biomarker services and biomarker validation services establish the reliability and efficacy of the test biomarkers. Similar to biomarker labs, bioanalysis services focus on conducting robust biosimilar programs. The biosimilar product must demonstrate similarity in biological activity, physicochemical properties, efficacy, safety, pharmacokinetics, and immunogenicity. The current article dives into strategies CROs can consider for biosimilar analysis.
Strategies for Biosimilar Programs
Immunogenicity is a critical component of biosimilar validation and development initiatives. The US FDA and EMA guidelines recommend conducting immunogenicity clinical studies for biosimilar drug products. These guidelines further highlight the principle and challenges faced during biosimilar programs.
Immunogenicity is the body’s response to a biological drug product. Most drug biotherapeutics or biological products induce immune responses. These host immune responses can be disease, patient, or product related triggered responses. Depending on individual cases, immunogenicity host response can cause effects varying from little consequences to loss of efficacy and life-threatening events. Hence, testing undesirable immunogenicity is crucial for all biosimilar drug products. Let us understand the requirement of one assay and two assay approaches in immunogenicity testing.
Biosimilar drug development studies compare two drug products in head-to-head comparative studies. In some cases, the biosimilar drug product can be compared to an originator drug from the US and another originator drug from the EU. Researchers can use two independent assays or a single assay to assess immunogenicity between the originator and biosimilar drug. The one-assay approach employs one screening and one confirmatory assay to evaluate clinical samples.
Regulatory guidelines recommend that ADA assays determine antibodies against the originator and the biosimilar drug. In the one assay study, the biosimilar must act as the capture and detection reagent and ensure the detection of all immunogenic epitopes. Besides, confirmatory assays must have excess biosimilar as competing antigens. This approach eliminates intra-assay variability, as it will have one confirmatory and one screening cutpoint. Moreover, the same assay can analyze both dosed biosimilar and reference products. In addition, it saves valuable assay reagents.
On the other hand, the two-assay approach ensures that novel ADAs of both the reference product and the biosimilar are detected independently. However, both these assays must have adequate drug tolerance and sensitivity. Moreover, a two-assay approach can detect antibodies against the innovator drug and provide an accurate comparison of immunogenicity rates.
However, the one-assay technique is preferred over the two-way approach. Although the one-assay method may underestimate the likelihood of evaluating the immunogenicity of the reference drug product, it minimizes intra-assay variability. And most importantly, the immunogenicity of the biosimilar is crucial, as the immunogenicity of the reference product is already assessed and validated.