關(guān)鍵質(zhì)量屬性
A Critical Quality Attribute (CQA) is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. CQAs can be associated with drug substances, drug products, excipients, intermediates (in-process materials), and container/closure components. At an early stage of process development, the information available on product attributes may be limited. For this reason, the first set of CQAs may come from prior knowledge obtained during early development and/or from similar products rather than from extensive product characterization. The degree of criticality assigned to quality attributes is derived using risk-based tools and the potential impact of the attributes on safety and efficacy. Following comprehensive assessments of scientific evidence and risk, quality attributes are ranked according to the degree of criticality, which may be a continuum that more accurately reflects the complexity of structure-function relationships and varying levels of uncertainty around attribute classification. Attributes not assigned as CQAs should also be considered in the development of the process.
關(guān)鍵質(zhì)量屬性（CQA）是為了保證預(yù)期藥品質(zhì)量需要保持在適宜的限度、范圍或分布范圍內(nèi)的物理的、化學(xué)的、生物的或微生物的性質(zhì)或特性。CQAs 可能與原料藥、制劑產(chǎn)品、輔料、中間產(chǎn)品（中間物料）和容器/密封系統(tǒng)有關(guān)。在工藝開(kāi)發(fā)的早期可以限定為可用的產(chǎn)品屬性信息。為此，起初設(shè)定的關(guān)鍵質(zhì)量屬性可能來(lái)自早期開(kāi)發(fā)和/或類(lèi)似產(chǎn)品獲取的先前的知識(shí)而不是大量的產(chǎn)品性質(zhì)。質(zhì)量屬性的關(guān)鍵程度來(lái)源于利用基于風(fēng)險(xiǎn)的工具和質(zhì)量屬性對(duì)安全性與有效性的潛在影響。在對(duì)科學(xué)證據(jù)和風(fēng)險(xiǎn)進(jìn)行了綜合評(píng)估之后，根據(jù)關(guān)鍵性程度對(duì)質(zhì)量屬性排序，這樣可能更能反映結(jié)構(gòu)-功能關(guān)系的復(fù)雜性和屬性分類(lèi)不確定性的變化程度。與CQAs 無(wú)關(guān)的屬性在工藝開(kāi)發(fā)中也應(yīng)加以考慮。
CQAs are not synonymous with specifications. In addition, there is not necessarily a one-to-one relationship between CQAs and specifications. Specifications are a list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the tests described. Several product attributes identified as CQAs may be detected by a single test method, and therefore, built into a single test specification (e.g., API solubility, hardness, porosity are CQAs evaluated using a single test: dissolution). Some CQAs may not be included in the specifications if they are very well-controlled and consistently achieved within the process (e.g., viral clearance is not tested for every batch), while some attributes not considered critical may be included in the specifications.
CQAs 與質(zhì)量標(biāo)準(zhǔn)不是同義詞。另外，也沒(méi)有必要將CQAs 與質(zhì)量標(biāo)準(zhǔn)一一對(duì)應(yīng)。質(zhì)量標(biāo)準(zhǔn)是檢驗(yàn)、參照的分析程序和用數(shù)值限度、范圍描述的適當(dāng)?shù)目山邮軜?biāo)準(zhǔn)或描述的測(cè)試的其他標(biāo)準(zhǔn)的列表。被確定為CQAs 的幾個(gè)產(chǎn)品屬性可以用單一方法檢查，因此，可以建立單一的測(cè)試標(biāo)準(zhǔn)（例如：API 的溶解度、硬度、孔隙度是可以用一個(gè)試驗(yàn)-溶出度來(lái)評(píng)價(jià)的CQAs）。有些在工藝過(guò)程中容易控制和達(dá)到的CQAs 可以不包含在質(zhì)量標(biāo)準(zhǔn)中（如病毒清除不是每批檢查），而一些不是關(guān)鍵性的屬性也可能制定在質(zhì)量標(biāo)準(zhǔn)中。
The identification of potential CQAs is an ongoing activity initiated early in product development. It makes use of general knowledge about the product and its application, as well as available clinical and non-clinical data. CQAs are subject to change in the early stages of product development, and thus require a quality risk management approach that evolves as knowledge about the product and process is generated (for discussion, see Section 6.1 “Application of Risk Management”). CQAs for commercial products should be defined prior to initiation of Stage 2 activities.
潛在CQAs 的確定是一個(gè)始于產(chǎn)品開(kāi)發(fā)早期的持續(xù)性活動(dòng)。它需要利用產(chǎn)品及其應(yīng)用以及臨床和非臨床數(shù)據(jù)等一般知識(shí)。在產(chǎn)品開(kāi)發(fā)的初期，CQAs 是易變的，所以需要質(zhì)量風(fēng)險(xiǎn)管理方法來(lái)轉(zhuǎn)化產(chǎn)生的產(chǎn)品和工藝的知識(shí)（有關(guān)討論見(jiàn)6.1 節(jié)“風(fēng)險(xiǎn)管理的應(yīng)用”）。商業(yè)產(chǎn)品的關(guān)鍵質(zhì)量屬性應(yīng)在第二階段活動(dòng)開(kāi)始前被定義。
聯(lián)系客服
