原辅料留样期限

beiwei5du

1433240751 发表于 2015-7-14 11:32
我们文件规定保留至原、辅料有效期后1年，通常物料采购量会根据生产计划确定，采购量不会太大，近效期还使 ...

操作是有一点问题的，但是还是先要合规

beiwei5du

jmmarui 发表于 2015-7-14 13:04
对于这个问题，曾经也思考过：
    说起留样，那就要从留样的目的说起，留样的目的主要是为了追溯用的 ...

实际的按照规定，A物料应该留应该是12+36=48个月，但是针对你说的这些问题，确实也是一个困扰。我查查国外是否有相关的规定或解释。

beiwei5du

TITLE 21--FOOD AND DRUGS

CHAPTER I--FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES

SUBCHAPTER C--DRUGS: GENERAL

PART 211 -- CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

Subpart I--Laboratory Controls

Sec. 211.170 Reserve samples.

(a)（原料留样） An appropriately identified reserve sample that is representative of each lot in each shipment(这里说的是每一次运输都需要留样，当然前提是批次，而不仅仅是每一个批次留） of each active ingredient shall be retained（没有提及到留样的包装、环境控制）. The reserve sample consists of at least twice(至少两倍全检量，而在中国只是留样量只是说到至少满足鉴别的需要） the quantity necessary for all tests required to determine whether the active ingredient meets its established specifications, except for sterility and pyrogen testing.（也提到无菌和热源检测除外，中国对于原料的留量没有提及） The retention time is as follows: (1) For an active ingredient in a drug product other than those described in paragraphs (a) (2) and (3) of this section, the reserve sample shall be retained for 1 year after the expiration date of the last lot of the drug product containing the active ingredient.（应留样至使用该原料的最后批次成品的有效期后一年，这个和我们国家的至少留样至产品放行后二年不一致）（注*这里的原料是除了放射性药品和没有有效期的OTC药品的原料） (2) For an active ingredient in a radioactive drug product, except for nonradioactive reagent kits, the reserve sample shall be retained for:（对放射性药品的使用的原料） (i) Three months after the expiration date of the last lot of the drug product containing the active ingredient if the expiration dating period of the drug product is 30 days or less; or （对于放射性药品的有效期小于或等于30天，原料的留样时限应该在最后一批使用该原料的放射性药品有效期后3个月，这个和我们国家GMP 放射性药品附录中提到的30天不一致，并且我们国家的没有考虑分(i)、(ii)这两种情况） (ii) Six months after the expiration date of the last lot of the drug product containing the active ingredient if the expiration dating period of the drug product is more than 30 days. [size=13.3333px]（对于放射性药品的有效期大于30天，原料的留样时限应该在最后一批使用该原料的放射性药品[size=13.3333px]有效期后6个月） (3) For an active ingredient in an OTC drug product that is exempt from bearing an expiration date under 211.137, the reserve sample shall be（可以） retained for 3 years after distribution of the last lot of the drug product containing the active ingredient.（针对与在211.137条款下允许没有有效期的OTC药品使用的原料） （成品留样可以至使用该原料的最后一批药品放行后的3年） (b) （成品留样）An appropriately identified reserve sample that is representative of each lot or batch of drug product shall be retained and stored under conditions consistent with product labeling（应和标签规定的环境一致）. The reserve sample shall be stored in the same immediate container-closure system（这里说的是直接接触的container-closure,是否对于想片剂，就只是铝塑泡罩呢??而不需要外面的盒子呢？？？那么这样说来对于API原料药，如果是使用的PE袋密封和fibre drum的包装形式的，留样就只需要PE袋密封，当然若对light比较敏感的话，需要避光的) in which the drug product is marketed or in one that has essentially the same characteristics. The reserve sample consists of at least twice（至少两倍） the quantity necessary to perform all the required tests, except those for sterility and pyrogens.（在美国也是说到除了无菌和热源检测） Except for those for drug products described in paragraph (b)(2) of this section, reserve samples from representative sample lots or batches selected by acceptable statistical procedures shall be examined visually at least once a year（前提是除了放射性药品并且是不嗯呢该影响留样的完整性，每年需要至少目视一次，美国人想得挺周到的） for evidence of deterioration unless visual examination would affect the integrity of the reserve sample. Any evidence of reserve sample deterioration shall be investigated in accordance with 211.192. The results of the examination shall be recorded and maintained with other stability data on the drug product（检测结果需要和稳定系数据结合在一起或者文件归在一起）. Reserve samples of compressed medical gases need not be retained(压缩的医药气体不需要留样）. The retention time is as follows: (1) For a drug product other than those described in paragraphs (b) (2) and (3) of this section, the reserve sample shall be retained for 1 year after the expiration date of the drug product.（针对与在211.137条款下允许没有有效期的OTC药品，成品留样至药品有效期后1年） (2) For a radioactive drug product, except for nonradioactive reagent kits, the reserve sample shall be retained for: (i) Three months after the expiration date of the drug product if the expiration dating period of the drug product is 30 days or less; or [size=13.3333px]（对于放射性药品的有效期小于或等于30天，成品的留样至放射性药品[size=13.3333px]有效期后3个月） (ii) Six months after the expiration date of the drug product if the expiration dating period of the drug product is more than 30 days. [size=13.3333px]（对于放射性药品的有效期大于30天，成品的留样至放射性药品[size=13.3333px]有效期后6个月） (3) For an OTC drug product that is exempt for bearing an expiration date under 211.137, the reserve sample must be （必须）retained for 3 years after the lot or batch of drug product is distributed. [size=13.3333px]针对与在211.137条款下允许没有有效期的OTC药品，成品必须留样至药品放行后的3年） [48 FR 13025, Mar. 29, 1983, as amended at 60 FR 4091, Jan. 20, 1995] 这样看来FDA在制定留样时间，如果有有效期的都是以有效期做参考的，没有有效期的都是以distribution time point作为节点的，！其实也存在原料或者成品过期，但是依然留样的问题，就想hongwei2000老师说的，留样和是否在有效期是没有关系的，但是如果超出有效期了，追溯评价调查已经过期的原料和有效期又有什么意义呢？？？ PART 211—CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS 不知道为什么FDA没有要求对辅料，包装材料的留样????@uiofer @hongwei2000

叶非

beiwei5du 发表于 2016-6-8 12:15
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留样的目的是为了一旦发现问题后，可以使用留样来进行调查。对于制剂来说，留样本来就包括了包装材料，所以没有必要再单独留了。对于辅料，坦率的说，留的意义也不是太大，因为辅料本身也是做为制剂的一部分，如果调查的时候，调查产品本身就足够了。至于说为什么没有对辅料和包装材料的规定，两种法规体系，欧盟的法规更细致，而FDA的原则更多些。也许人家认为只要基于科学性的规定，都是可以接受的吧！