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Replies to post #677823 on NorthWest Biotherapeutics Inc (NWBO)
03/11/24 2:18 PM
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The demonstration of comparability does not necessarily mean that the quality attributes of the pre-change and post-change product are identical, but that they are highly similar and that the existing knowledge is sufficiently predictive to ensure that any differences in quality attributes have no adverse impact upon safety or efficacy of the drug product.
A determination of comparability can be based on a combination of analytical testing, biological assays, and, in some cases, nonclinical and clinical data. If a manufacturer can provide assurance of comparability through analytical studies alone, nonclinical or clinical studies with the post-change product are not warranted. However, where the relationship between specific quality attributes and safety and efficacy has not been established, and differences between quality attributes of the pre- and post-change product are observed, it might be appropriate to include a combination of quality, nonclinical, and/or clinical studies in the comparability exercise.
To identify the impact of a manufacturing process change, a careful evaluation of all foreseeable consequences for the product should be performed. In consideration of this evaluation, appropriate criteria to define highly similar post-change product can be established. Generally, quality data on the pre- and post-change product are generated, and a comparison is performed that integrates and evaluates all data collected, e.g., routine batch analyses, in-process control, process validation/evaluation data, characterisation and stability, if appropriate. The comparison of the results to the predefined criteria should allow an objective assessment of whether or not the pre- and post-change product are comparable.
Following the evaluation of the quality attributes, the manufacturer could be faced with one of several outcomes, including:
Based on appropriate comparison of relevant quality attributes, pre- and postchange product are highly similar and considered comparable, i.e., no adverse impact on safety or efficacy profiles is foreseen;
• Although the pre- and post change product appear highly similar, the analytical procedures used are not sufficient to discern relevant differences that can impact the safety and efficacy of the product. The manufacturer should consider employing additional testing (e.g., further characterisation) or nonclinical and/or clinical studies to reach a definitive conclusion;
• Although the pre- and post-change product appear highly similar, some differences have been observed in the quality attributes of the pre-change and post-change product, but it can be justified that no adverse impact on safety or efficacy profiles is expected, based on the manufacturer’s accumulated experience, relevant information, and data. In these circumstances, pre- and postchange product can be considered comparable;
• Although the pre- and post-change product appear highly similar, some differences have been identified in the comparison of quality attributes and a possible adverse impact on safety and efficacy profiles cannot be excluded. In such situations, the generation and analysis of additional data on quality attributes are unlikely to assist in determining whether pre- and post-change product are comparable. The manufacturer should consider performing nonclinical and/or clinical studies;
• Differences in the quality attributes are so significant that it is determined that the products are not highly similar and are therefore not comparable. This outcome is not within the scope of this document and is not discussed further.
The proposed method, including determining the relative amounts of IL-6, IL-8, IL-12 and TNFa and comparing them with threshold values, can be used to increase the immunotherapeutic activity of a population of activated dendritic cells and to determine the effectiveness of immunotherapy in a patient
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