生产日期

zhulfyt

美国或欧盟GMP，对注射剂生产日期的具体规定是怎么样的？对生物制品的生产日期是怎么规定的？

麦田.守望

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。

补充内容 (2018-10-8 16:34):
http://bbs.antpedia.com/thread-335523-1-1.html

麦田.守望

Guidance Document: Quality (Chemistry and Manufacturing) Guidance: New Drug Submissions (NDSs) and Abbreviated New Drug Submissions (ANDSs)

Drug product intermediate

A drug product intermediate is a material that is the result of a drug substance having undergone at least one processing step in the presence of any other substance (used in the manufacture of the drug product whether it appears in the finished dosage form or not) which must undergo further processing step(s) to become the finished dosage form.

That first processing step of the drug substance in the presence of any other substance would be considered a drug product manufacturing activity, subject to Part C, Division 2 of the Food and Drug Regulations, and would define the date from which the expiry date for the drug product would be established.

Mixtures of two APIs are considered a drug product intermediate and the date of manufacture would be considered the date that the two APIs are first mixed. If the drug product intermediate is not used immediately and an expiry date or retest date is set for the drug product intermediate, then the stability data to support the expiry date of the finished dosage form should be based on data from batches of drug product which have been manufactured using the drug product intermediate just before its proposed expiry date.

Sponsors having situations that might be an alternative to the above interpretation (e.g. inability to isolate the drug substance in a pure and stable form or mixing with excipients for safety or stability purposes, e.g. nitroglycerin, cholecalciferol) should discuss their case and scientific justification in advance with the pre-market approval bureau/office.

http://www.canada.ca/en/health-c ... ug-submissions.html（加拿大有清楚定义了）

kington

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）

孙艳红

生产日期为均质产品形成，对于注射剂一般从配料开始

krishna

fsyylf 发表于 2014-4-30 07:16
生产日期为均质产品形成，对于注射剂一般从配料开始

现在这么说不准确。生产日期不全是以均质产品形成。原料药是要求提前的。

一沙一叶

注射剂从主药溶解开始。

thwrqq

注射剂应是从配液操作开始，原辅料相互溶解在一起，才是化学反应的开始。

男儿当自强

学习了。。。

zhulfyt

谢谢，问题Yi经解决了

幻影

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。

hy1943

zhulfyt 发表于 2014-5-2 23:06
谢谢，问题Yi经解决了

请问下 你找到生产日期的法规定义了吗

zhulfyt

hy1943 发表于 2014-9-15 10:07
请问下 你找到生产日期的法规定义了吗

没有，我们按照国内GMP要求执行的

麦田.守望

How to assign a manufacturing date for API
https://www.rhotaupharma.com/rel ... ct-expiration-date/

补充内容 (2018-9-30 10:03):
http://www.ivtnetwork.com/printp ... latory-requirements

麦田.守望

菲律宾：Date of Manufacture -- The date indicating the start of processing of every batch.
埃塞俄比亚：Date of Manufacture -- A date fixed for the individual batch, indicating the completion date of manufacture.
WHO(1997)：Date of manufacture: A date fixed for the individual batch, indicating the completion date of the manufacture. It is normally expressed by a month and a year. The date of the release analysis may be taken as a date of manufacture, provided that the period between the beginning of production and the release of the product is not longer than one-twentieth of the shelf-life.

看起来我国与非洲兄弟更亲近



补充内容 (2018-9-30 14:00):
按WHO标准，2年有效期的药品在生产后2个月出COA的话，就可以报告发行日期为生产日期。：）

麦田.守望

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.

[ 81 FR 26691, May 4, 2016]

麦田.守望

新加坡2018：Date of Manufacture -- Date of manufacturing of a batch of product. （模糊不清）
IPEC2013：6.2 Date of Manufacture  The Date of Manufacture should be clearly defined by the original manufacturer and consistently applied for the particular excipient and process based on established policiesand procedures. （自己定）

麦田.守望

Guidance for Industry and FDA Staff
Medical Glove Guidance Manual Document issued on January 22, 2008
The “date of manufacture” refers to the date of completion of the final step of the manufacturing process (final packaging or sterilization).

麦田.守望

roadman 发表于 2018-9-30 14:30
Guidance Document: Quality (Chemistry and Manufacturing) Guidance: New Drug Submissions (NDSs) and A ...

2016年草案与此相同。2013年草案中有：
S.2.4 Controls of Critical Steps and Intermediates

In-process drug
A drug substance is considered be an in-process drug if it is mixed with any material or mixture of materials that must undergo further processing to become the drug in dosage form. If this activity is performed by the drug substance manufacturer/supplier as part of the raw material used in a drug product, then it is subject to the GMPs for manufacture of drug products (C.02 of the Food and Drug Regulations) and the expiry date of the drug product should be assigned based on the date of manufacture of the in-process drug. Any exception to this practice (e.g. inability to isolate the drug substance in a pure and stable form) should be justified.

意思相同。2016年草案和2017年正版中S.2.4下已无2013年草案的In-process drug定义，可见其被Drug product intermediate代替。


补充内容 (2018-10-5 16:15):
2001版草案中还没有此观念。

补充内容 (2018-10-5 16:25):
http://www.hc-sc.gc.ca/dhp-mps/a ... npadn_07-01-eng.pdf

小金库

看一下，谢谢分享