DECEMBER 2024LIFE SCIENCES REVIEW 19The presence or generation of particles and leachables from administration materials can also represent patient safety and immunogenicity risks. This should be tightly controlled during in-use administration. Particles can be introduced when handling and administering the DP and can also be generated due to incompatibility of the drug during in-use procedures. Dose accuracy and analytical challengesDose escalation studies are often performed in First-In-Human (FIH) and early clinical trials. In addition, highly potent biotherapeutics are often effective at extremely low doses. These scenarios pose challenges when performing clinical in-use testing as protein-based therapies may adsorb to administration material interfaces, leading to potential product loss and subsequent under-dosing of patients. Another issue around dose accuracy is that the available analytical methods may face limitations in accurately quantifying the lowest effective dosing solution, making it difficult to precisely predict potency and purity levels. An evaluation of the concentration of the dosage levels during simulated in-use testing is therefore paramount because no analytical assessment is typically performed in the clinic to ensure correct dose delivery to the patient. Clinical and regulatory challenges The complexity of the clinical set-up is difficult to control, as multiple procedures are available to administer drugs in clinics, and there is no universal global standard for clinical in-use testing. Regulatory authorities may accept various approaches during simulated administration testing as long as there is a clear technical and scientific rationale to support the approach. As such, relying on the experience and knowledge of an experienced Contract Development and Manufacturing Organization (CDMO) to propose suitable material and procedures to help ensure suitable clinical in-use data for regulatory submissions is key. Conclusions Clinical in-use testing is a regulatory requirement of health authorities worldwide to ensure patient safety and accurate dose delivery. Providing high-quality guidance, information, and testing is key to enabling safe in-use administration procedures for patients and healthcare personnel and ensuring a successful regulatory filing with health authorities to support the conduct of clinical trials and market applications. Partnering with a CDMO that has vast experience with in-use simulated administration testing can help support better decision-making on the appropriate study set-up, which could result in more effective and faster preparation of the relevant chemistry manufacturing and controls (CMC) sections of regulatory submissions. Clinical in-use testing is a regulatory requirement of health authorities worldwide to ensure patient safety and accurate dose delivery
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