生物制药

建议你看看ICH Q8和ICH Q11。



园内都有中文版。



再看看中国药典凡例；



对了，ICH Q8Q9Q10的问答文件也看看。



在论坛搜搜我的帖子，思考一下，问题不就解决了吗？



说话不刺激你一下，你怎么进步？



告诉你这么多，你应该说-谢谢。

拜托，你看清楚，我不是提问题的那个人。好心不应该是你说话直接的理由。毕竟你是斑竹，是一个管理者

我看得很清楚，你不是提问的那个人，但是你是引用我帖子并质疑的人，因此才回复你了。



一句话就受不了？



就这样，还寻求进步，可能吗？

As a general rule, the use of overages of active substances in formulations is discouraged unless their use can be justified completely. The routine inclusion of overages by manufacturers of certain products without adequate justification is unlikely to be permitted. Similarly, the use of overages should not be an excuse for poor manufacturing, formulation, or analytical procedures. Where loss takes place during manufacture of the product, then the replacement might well be justified as a “manufacturing overage” because the amount present within the dose form at the time of release is likely to remain within the approved specification. However, large (for example 10%) overages used to compensate for poor product stability, in general, are not considered to be acceptable.

The presence in excess of inactive constituents in a formulation should also be explained and justified.

用关键词“Overages author:zhulikou431 ”搜索得：

cuturl('http://search.dxy.cn/?sm=1&words=Overages&mp=&mo=&mn=&username=zhulikou431&age=0&bid=0&t=0&c=0&limit=15&action_search=%E6%90%9C+%E7%B4%A2')



cuturl('http://analysis.dxy.cn/bbs/thread/15355195?keywords=Overages#15355195')

DRUG PRODUCT —EXCIPIENTS

Manufacturers may want to use an overage of an excipient in the manufactured product. There is a general antipathy toward this practice and any overages will need to be justified. The approach will depend on whether the overage is proposed based on losses during manufacture or the need to meet a requirement for the level of the excipient during the shelf life. Large overages—usually taken as those in excess of 10%—are unlikely to be allowed. This is because such large overages could present unacceptable hazards to users. It would be better to reformulate the product if such large overages are needed. Other overages will need to be justified in terms of the technical need for the overage and the potential for adverse events arising from their presence or the presence of the degradation products arising from them.


Manufacturing Overage

If the statistical analysis of stability data for different batches is carried out, there is a consistenttrend for the intercept of the assay of the drug product being below 100%; this may indicateinstability during the manufacturing stages and during the initial storage before the releaseassay. For products with marginal stability (i.e., with a calculated shelf life of 18 months orless), it may be worthwhile considering adding a manufacturing overage. This would need tobe justified in the stability report. Where the data on individual batches, packaging, strengths,etc., can be pooled to give a common estimate of the intercept; this can be used to calculate theoverage.The manufacturing overage can be calculated as follows:

Manufacturing Overage = [(100 × 100)/Intercept% Assay] - 100

上市品亦是如此我有啥办法呢

关于过量投料overage的问题，大家讨论的比较多了，我这里举一个实例，请大家讨论一下，特别是llb1978、zhoulikou431、luckiss几位版主。



过量投料的原因一般有二



第一、制剂不稳定，在货架期生命周期中主药有降解，为了弥补该损失，过量投料



第二、工艺中的损失，这个大家有提到，但是讨论的很少。



研发实例：



某注射液，采用活性炭吸附去除细菌内毒素，活性炭用量0.1%（w/v），主药大约吸附5%。辅料2种，一种是氯化钠。由于静脉推注给药，需要控制摩尔渗透压。



经过处方解析，处方如下：主药5mg/ml，辅料一 3mg/ml，氯化钠7mg/ml。摩尔渗透压 290 mOsmol/kg



研发时采用的工艺大抵有两种



工艺一、按照100%投料，浓配时加水量为设计批生产量的80%，经过活性炭吸附脱碳步骤，加注射用水按标示量100%定容，结果最终定容体积比设计的批生产量体积少8%左右。全检合格，但是带来一个问题，就是辅料的含量变相升高，导致摩尔渗透压升高，达到305 mOsmol/kg。



工艺二、按照105%主药投料，辅料按100%投料，浓配时加水量为设计批生产量的80%，经过活性炭吸附脱碳步骤，加注射用水按标示量100%定容，结果最终定容体积和设计批生产量一致，摩尔渗透压289 mOsmol/kg。



那么问题一、如果采用工艺一，有一个质量的变化，如何和小试还有标准处方衔接，CTD资料怎么写？如果要控制其中一个辅料的量，怎么办？如果要渗透压降下来，根据含量应为标示含量的90-110%范围，含量在95%时可以。



问题二、采用工艺二，有过量投料问题，但是质量方面能和小试很好的衔接，CTD怎么写呢？



麻烦大家参照具体实例来，针对实际问题，解决实际问题。谢谢。

这帖子又被顶上来了，那就再接着来，我的问题是选A还是选B还没人回答呢，假设非得多投料