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藥用酒精

#1
GTP 發表於 2019 / 06 / 12
專家您好 請問無菌操作中用來擦拭消毒的藥用酒精是直接購入的,不需再另外配置 這種藥用酒精是否還需要先經過濾膜過濾處理 謝謝您
管理員回覆

PIC/S GMP Annex 1的第62 條文「消毒劑與清潔劑應監測其微生物的污染;稀釋液應保存在預先洗淨的容器中,且除非經過滅菌,應只在界定的期間內儲存。使用於A 級及 B 級區的消毒劑與清潔劑,使用前應是無菌的。」
因此在A或B級區的無菌操作為使用的酒精其無菌性應該確認。

From TPDA
2019/6/21
Abby 發表於 2019 / 06 / 26
清潔確效殘留限量中,其中一項為任何產品出現在隨後產品之最大每日劑量的量,不得大於該產品正常治療每日最小劑量的零點一百分比,目前公司生產胜肽合成動物疫苗劑量為100 ug/ml, 初次先注射一劑,之後8周後注射第二劑投藥結束,依現況恐無法計算此限量規定? 我司目前以WFI規格500ppb為殘留限量,請問是否可行?再請給予指導感謝
管理員回覆

可行。但請先確認
1.產品含有可被氧化的碳
2.主成分總碳量的計算結果(根據0.1%治療劑量標準)應低於WFI的規格 500ppb
3.考量其他含碳成分可能影響試驗結果
4. WFI本身TOC的含量與差異性
5.定量法或限量法:定量法需考量定量範圍(線性),業界通常都使用限量法
 
如果你們使用專用設備,經過合理評估,或可使用目視清潔為清潔確效的標準。
 
目前清潔確效仍使用PIC/S PI 006-3 所建議的三個規格:0.1%治療劑量,10 ppm,目視清潔。但此三規格被挑戰只是通用的規格並未針對個別產
品的毒性風險進行科學評估。如果是新藥且打算進入歐美市場,建議請根據 EMA : Guideline on setting health based
exposure limits for use in risk identification in the manufacture of
different medicinal products in shared facilities  來設定標準,包括非專一性的方法(TOC)。
 
茲附上FDA 與PDA有關TOC作為清潔確效標準的資料供參考:
 
請參考FDA 網站Questions and Answers on Current Good Manufacturing Practices—
Equipment的Q3 網址:
<https://www.fda.gov/drugs/guidances-drugs/questions-and-answers-current-goo
d-manufacturing-practices-equipment#TOC>
https://www.fda.gov/drugs/guidances-drugs/questions-and-answers-current-good
-manufacturing-practices-equipment#TOC
 
 
摘錄如下
 
 3.  Can Total Organic Carbon (TOC) be an acceptable method for detecting
residues of contaminants in evaluating cleaning effectiveness?
 
Yes. Since the publication of the inspection guide on cleaning validation in 1993, a number of studies have been published to demonstrate the adequacy of TOC in measuring contaminant residues.
 
TOC or TC can be an acceptable method for monitoring residues routinely and
for cleaning validation. In order for TOC to be functionally suitable, it should first be established that a substantial amount of the contaminating material(s) is organic and contains carbon that can be oxidized under TOC test conditions. This is an important exercise because some organic compounds cannot be reliably detected using TOC.
 
TOC use may be justified for direct surface sample testing as well as indirect (rinse water) sample testing. In either case, because TOC does not identify or distinguish among different compounds containing oxidizable carbon, any detected carbon is to be attributed to the target compound(s) for comparing with the established limit. Thus, a firm should limit background carbon (i.e., carbon from sources other than the contaminant being removed) as much as possible. The established limit, or the amount of residue detected for comparison to the specification, should correct for the target material’s composition of carbon. As for any cleaning method, recovery studies are necessary (21 CFR 211.160(b)). If TOC samples are being held for long periods of time before analysis, a firm should verify the impact of sample holding time on accuracy and limit of quantitation.
 
 
另外,請參考 PDA技術報告 TR 49 Points to Consider for Biotechnology Cleaning Validation
 
4.1.1 Establishing Limits for Actives in Formulation and Final Fill
…Some companies choose to set limits based on more stringent criteria, such as the WFI TOC specification of 500 ppb TOC. Such an approach is acceptable, but should only be used if it can be demonstrated that the WFI TOC specification is more stringent than the TOC result, as determined by a carryover calculation.
 
4.1.2 Establishing Limits for Actives in Bulk Manufacture …As noted above, the residues of the active are generally measured“indirectly” by measuring a property like TOC (for purposes of this report, TOC will be used as an example of such analytical methods, although assays like Total Protein could also be used). Typical quantitation limits for TOC for cleaning validation purposes are on the order of 100-500 ppb carbon, which is equivalent to about 200-1,000 ppb protein for proteins containing about 50% carbon. Therefore TOC cannot be used as an analytical method if limits are based on a carryover calculation using the surface area of the entire equipment train.
 
6.5.2 Compendia Methods
Compendia methods do not require separate analytical method validation, provided those methods are used within the parameters in the compendia. For example, a compendia method for endotoxin is generally appropriate for measuring endotoxin in final rinse water samples. When using TOC in rinse water samples (a compendia method), additional work should be done to support the applicability of that method to test samples that could have TOC values above 500 ppb, or where a linear range is to be established. Just performing system suitability as specified in the various pharmacopeias may not be adequate to demonstrate that the analytical procedure could accurately analyze samples at 1 ppm or 5 ppm. For that reason, analytical method validation as for any other method should be considered. An additional reason for formal method validation for TOC in rinse water samples is that the compendia methods are essentially set up as a pass/fail test, not as a quantitative assay.

FROM TPDA
2019/07/15

 

 

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