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Skip to 0 minutes and 14 seconds So we talked about dosing factors. Now let’s summarize the Immunogenicity Factors The source. How close is the source to human?

Skip to 0 minutes and 35 seconds The contaminant the impurities of the formulation.

Skip to 0 minutes and 43 seconds The patient factor Some are very immunogenic, others are not. And other unknown factors that we don’t know yet. But, at the least we can work on the formulation.

Skip to 1 minute and 5 seconds For example, by glycosylation or by PEGulation. We can adjust the dose knowing that larger dose causes higher immunogenic response, and the smaller dose causes less immunogenic response. Route of drug application or administration. We know IV is most immunogenic and the sub-q is less immunogenic. So we can work on the factors that favor or disfavor the formation of immunogenicity. Reducing immunogenic response. So how do we work on that. We work on the source. We work on the origin of the biologics. We work on the structure. We talked about chimerization. We talked about glycosylation and we talk about PEG attachment of PEGulation. We work on impurity of the biologics. We work on the formulation.

Skip to 2 minutes and 32 seconds We pay attention to manufacturing process, for example, the freeze dry cycle or conditions. And we pay attention to storage conditions such as temperature, humidity, light or even pressure. And we work on the dosing factors. We don’t route the dose. And concomitant medication or affect immunogenicity. Now, let’s kind of summarize the clinical effect of immunogenic response. Generally speaking, it’s undesirable and therefore it results in the loss of efficacy or effectiveness. For example, the insulin the cotting factor, Interferon and monoclonal antibody. Generally speaking, immunogenicity result in loss of advocacy. Now, in very rare cases, you could result in enhancement of efficacy. For example, they’re both hormones but the case is rare.

Skip to 3 minutes and 56 seconds So, clinical effects of immunogenicity are generally undesirable, because they cause allergy; they cause anaphylaxis; and they even cause serum sickness or shock. So to speak. So how do we predict immunogenic response?

Skip to 4 minutes and 21 seconds We look at the degree of foreigness or degree of non-selfness. That is to say how foreign is the protein. And the degree of aggregation. Is it monomer or dimmer or has it been polymerized? Impurity and contamination.

Skip to 4 minutes and 51 seconds We can use the animal model to test the immunogenicity,

Skip to 4 minutes and 58 seconds or even with transgenic animal, we can test the immunogenicity of the biologics. Unfortunately, little is known for the hereditary factor but no prediction is 100% reliable. And that’s why biologic therapy still requires clinical monitoring to monitor the immunogenic response. And we have to deal with it clinically as they happen.

Immunogenicity Overview

The clinical consequences of antibody formation vary with the type and quantity of antibody present, and it may effect drug PK, PD, efficacy, and safety. Preclinical immunogenicity is not predictive of clinical immunogenicity in humans, but it helps to understand the findings in a toxicological venue. Assays for ADA detection are grouped into two categories: binding assays and neutralizing antibody assays, which result in different clinical implications.

Immunogenicity is presented in two perspectives: Product oriented attributes include structural variation, biologics formulation, manufacturing process and binding assay utilized. Patient oriented attributes include dose, route, dosing frequency, time length of administration, and idiosyncrasy. Preclinical and clinical assessments of immunogenicity are requited for biologics development.

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Pharmacotherapy: Understanding Biotechnology Products

Taipei Medical University