The method history report: an adaptable tool for communicating immunogenicity assay development and validation.

Over the developmental lifetime of a therapeutic protein, the immunogenicity assay validation history can become substantial, frustrating review of clinical immunogenicity within the biologics license application. In our experience, this can lead to questions by regulators, resulting in numerous information requests during the review process. To address this, we propose a new document, the method history report (MHR), which can comprehensively present the history of the immunogenicity assay for regulators, including assay development and validation. The flexibility of the MHR allows for adaptation to the specific needs of each therapeutic program, while maintaining a consistent template. Here, we detail the rationale, general outline and template for the MHR and recommend others consider adopting it for their biologics license application-related activities.

Response to Tetanus and Pneumococcal Vaccination Following Administration of Ixekizumab in Healthy Participants.

BACKGROUND: Ixekizumab (IXE) is an interleukin (IL)-17A antagonist approved for the treatment of adults with moderate-to-severe psoriasis. OBJECTIVE: The objective of this study was to determine if the immune response to tetanus and pneumococcal vaccines in healthy subjects administered IXE was noninferior to control. METHODS: In a randomized, open-label, parallel-group study, adult subjects received vaccinations alone (N = 42, control) or in combination with 160 mg IXE subcutaneously 2 weeks prior to vaccination and 80 mg IXE on the day of vaccination (N = 41, IXE). Response to tetanus vaccination was defined as anti-tetanus antibodies ≥ 1.0 IU and a ≥ 1.5-fold increase if baseline was ≤ 1.0 IU or a ≥ 2.5-fold increase if baseline was > 1.0 IU. Response to pneumococcal vaccination was defined as a ≥ 2-fold increase from baseline in anti-pneumococcal antibodies against > 50% of the 23 serotypes. The primary outcomes were the percentages of patients with a response to the tetanus and pneumococcal vaccines 4 weeks after vaccination. A noninferiority analysis of IXE to control using a 40% margin was evaluated for the primary outcomes. Safety and pharmacokinetics were also assessed. RESULTS: IXE (38 completers) was noninferior to control (41 completers) based on the difference in the proportion of responders to tetanus [1.4%; 90% confidence interval (CI) - 16.6 to 19.2] and pneumococcal (- 0.8%; 90% CI - 12.9 to 11.0) vaccines. Twenty subjects (14 IXE, six control) reported 43 mild treatment-emergent adverse events. CONCLUSION: IXE does not suppress the humoral immune response to non-live vaccines and was well tolerated in healthy subjects. ClinicalTrial.gov identifier: NCT02543918.

A study of the synthesis of triazoles using microwave irradiation.

Herein we describe the conversion of a known [3+2] cycloaddition reaction between an azide and an acetylene from a thermally promoted reaction to a microwave assisted process. Modification of conditions including concentration, temperature, solvent type and time were investigated. This methodology study led us to use high concentration and high temperatures to achieve the desired fast reaction times and high yields.