生物制品原液的生产日期制定原则
QA生产管理

1.原液的生产批号应为菌种活化的时间，还是以中间体生产时间还是以原液的分子构成时间为生产日期。

2022-08-03 10:54 龙涵     
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EMA规定：Note for Guidance on Start of Shelf Life of the Finished Dosage Form

The expiration period of a production batch should be calculated from the date of release of that batch.
生产批次的有效期应从该批次的放行日期开始计算。
The date of such a release should, under normal circumstances, not exceed 30 days from the date of production of that batch.
在正常情况下，此类放行日期应不超过该批次生产日期30天。
If batches are released exceeding 30 days from the production date, the date of production, as defined below, should be taken as the start of the shelf-life.
如果批次放行超过生产日期30天，则生产日期（如下定义）应作为保质期的开始。
The date of production of a batch is defined as the date that the first step is performed involving combining the active ingredient with other ingredients .For medicinal products consisting of a single active ingredient filled into a container, the initial date of the filling operation is taken as the date of production.
批次的生产日期定义为涉及将活性成分与其他成分混合的第一步操作的日期。对于由分装到容器中的单一活性成分组成的医药产品，分装操作的开始日期被视为生产日期。
EU GMP、cGMP及ICH Q7中无均没有明确的生产日期规定，中国GMP规范中规定“除另有规定外，生产日期不得迟于产品成型或灌装（封）前以最后混合的操作开始日期，不得以产品包装日期作为生产日期”。
对于普通制剂（产品），含无菌，其生产日期的确定可以适用以上原则。原料药生产日期很多资料上说可以以最终混合日期为生产日期，但个人认为使用最后一步精制日期作为生产日期更为合理。

生物制剂产品的配制日期即为生产日期（中国药典三部）
21 CFR 610.50 - Date of manufacture for biological products.

§ 610.50 Date of manufacture for biological products.
(a)When the dating period begins. The dating period for a product must begin on the date of manufacture as described in paragraphs (b) and (c) of this section. The dating period for a combination of two or more products must be no longer than the dating period of the component with the shortest dating period.

(b)Determining the date of manufacture for biological products other than Whole Blood and blood components. The date of manufacture for biological products, other than Whole Blood and blood components, must be identified in the approved biologics license application as one of the following, whichever is applicable: The date of:

(1) Potency test or other specific test as described in a biologics license application or supplement to the application;

(2) Removal from animals or humans;

(3) Extraction;

(4) Solution;

(5) Cessation of growth;

(6) Final sterile filtration of a bulk solution;

(7) Manufacture as described in part 660 of this chapter; or

(8) Other specific manufacturing activity described in a biologics license application or supplement to the biologics license application.

(c)Determining the date of manufacture for Whole Blood and blood components.

(1) The date of manufacture for Whole Blood and blood components must be one of the following, whichever is applicable:

(i) Collection date and/or time;

(ii) Irradiation date;

(iii) The time the red blood cell product was removed from frozen storage for deglycerolization;

(iv) The time the additive or rejuvenation solution was added;

(v) The time the product was entered for washing or removing plasma (if prepared in an open system);

(vi) As specified in the instructions for use by the blood collection, processing, and storage system approved or cleared for such use by FDA; or

(vii) As approved by the Director, Center for Biologics Evaluation and Research, in a biologics license application or supplement to the application.

(2) For licensed Whole Blood and blood components, the date of manufacture must be identified in the approved biologics license application or supplement to the application.
2022-08-15 16:28 圣人有点冷     
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回答：

       生物制品中传代细胞种子复苏开始或者原代动物细胞投产那天就是原液生产的起始日期。毒种种子传代建立三级库记录单独保存，不纳入生产记录。这个是我们以前工作中的规定。成品生产日期就是半成品配制那天的日期，这个是在药典中有规定。

以上希望对你有帮助。

2022-08-09 10:56 漆白雪黑     
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