Optimized physical properties (e.g., bulk, surface/interfacial, and mechanical properties) of active pharmaceutical ingredients (APIs) are key to the successful integration of drug substance and drug product manufacturing, robust drug product manufacturing operations, and ultimately to attaining consistent drug product critical quality attributes. However, an appreciable number of APIs have physical properties that cannot be managed via routes such as form selection, adjustments to the crystallization process parameters, or milling. Approaches to control physical properties in innovative ways offer the possibility of providing additional and unique opportunities to control API physical properties for both batch and continuous drug product manufacturing, ultimately resulting in simplified and more robust pharmaceutical manufacturing processes. Specifically, diverse opportunities to significantly enhance API physical properties are created if allowances are made for generating co-processed APIs by introducing nonactive components (e.g., excipients, additives, carriers) during drug substance manufacturing. The addition of a nonactive coformer during drug substance manufacturing is currently an accepted approach for cocrystals, and it would be beneficial if a similar allowance could be made for other nonactive components with the ability to modify the physical properties of the API. In many cases, co-processed APIs could enable continuous direct compression for small molecules, and longer term, this approach could be leveraged to simplify continuous end-to-end drug substance to drug product manufacturing processes for both small and large molecules. As with any novel technology, the regulatory expectations for co-processed APIs are not yet clearly defined, and this creates challenges for commercial implementation of these technologies by the pharmaceutical industry. The intent of this paper is to highlight the opportunities and growing interest in realizing the benefits of co-processed APIs, exemplified by a body of academic research and industrial examples. This work will highlight reasons why co-processed APIs would best be considered as drug substances from a regulatory perspective and emphasize the areas where regulatory strategies need to be established to allow for commercialization of innovative approaches in this area.

中文翻译：

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协同处理的API的最新进展以及实现这些转化技术商业化的提案。

活性药物成分（API）的最佳物理性质（例如，体积，表面/界面和机械性质）是成功整合原料药和药物产品制造，稳健的药物产品生产运营以及最终获得一致的药物产品的关键关键质量属性。但是，相当数量的API具有无法通过诸如形式选择，结晶工艺参数调整或研磨之类的途径进行管理的物理属性。以创新方式控制物理性质的方法提供了为批量生产和连续药物生产提供更多和独特的机会来控制API物理性质的可能性，最终导致简化和更可靠的药物生产过程。具体而言，如果在原料药生产过程中允许通过引入非活性成分（例如，赋形剂，添加剂，载体）来产生协同处理的API，则会创造各种机会来显着增强API的物理性能。目前在原料药生产过程中添加非活性助剂是共晶的一种公认方法，如果可以对其他具有修饰API物理性质能力的非活性成分给予类似的补贴，那将是有益的。在许多情况下，共同处理的API可以实现小分子的连续直接压缩，并且从长远来看，可以利用此方法来简化从小分子到大分子的连续端到端原料药到药品生产过程。与任何新技术一样，尚未明确定义对共处理API的监管要求，这给制药行业对这些技术的商业实施带来了挑战。本文的目的是强调实现协同处理API的好处的机会和日益增长的兴趣，以大量的学术研究和工业示例为例。这项工作将从监管的角度突出说明为什么最好将协同处理的API视为原料药，并强调需要制定监管策略以使该领域的创新方法商业化的领域。本文的目的是强调实现协同处理API的好处的机会和日益增长的兴趣，以大量的学术研究和工业示例为例。这项工作将从监管的角度突出说明为什么最好将协同处理的API视为原料药，并强调需要制定监管策略以使该领域的创新方法商业化的领域。本文的目的是强调实现协同处理API的好处的机会和日益增长的兴趣，以大量的学术研究和工业示例为例。这项工作将从监管的角度突出说明为什么最好将协同处理的API视为原料药，并强调需要制定监管策略以使该领域的创新方法商业化的领域。