固型製劑清潔確效方法之研究

近年來生技製藥在衛生主管機關，以提升國內製藥品質並與歐美先進國家製藥品質接軌之前提下，對製藥製程之清潔方法作業要求愈來愈嚴格，清潔確效已逐漸在製藥界佔有重要的地位。現行GMP條例也強調清潔作業是保證產品品質的關鍵性工作，自大宗原料藥的生產以迄最終劑型的生產製造作業，幾乎每一個製程均含有清潔作業。歐美國家及全球其他地區均有規範製藥業清潔作業的通則性指引，由此顯示清潔確效方法之重要性。本研究首先回顧相關國內外文獻及國內外標準規範，然後依南部地區某製藥廠之實例驗證，以「錠劑－微顆粒造粒/打錠/分包裝製程」為範疇，依據不同產品間共同接觸表面積，分別以1/1,000法、10 ppm法、目視標準法(Visually Clean Criterion)，試算容許殘留限量（Carryover Limit）。結果顯示最小殘留限量（Worst Carryover Limit）為0.82μg/cm2。清潔確效作業模式採1/1,000法為該藥廠在固型製劑清潔方法中是最嚴謹之方式，並依此採取該製劑適當之清潔類別、流程的研訂、取樣技術及分析方法，以期建立高品質之企業目標。

關鍵字

固型製劑；清潔確效作業；錠劑；微顆粒造粒；打錠製程

並列摘要

The cleaning validation has taken an important position in pharmaceutical industry in recent years. Current GMP regulations also stress the importance of cleaning validation and consider it the key step in product quality assurance. From the production of bulk active pharmaceutical ingredients to finished dosage forms, the cleaning procedure is needed in almost all the processing steps. United States, European and other developed countries have general regulation guideline in pharmaceutical cleaning validation which shows the importance of the cleaning validation method. This study first reviews the relative regulations described in the journal articles, and then take the “Tablets-micro granulation / tablating process” of a pharmaceutical company in southern Taiwan as an example to calculate the carryover limit of different products using 1/1,000, 10 ppm, and visually clean criterion methods. The result of this study indicates that the 1/1,000 method is the best cleaning validation method in respective dosage from with the worst carryover limit of 0.82μg/cm2. This respective cleaning procedure is developed to reach company’s goal of quality improvement. Key words: Solid Oral Dosage Forms; Cleaning Validation Process; Tablets, Granulation; Tablating Process.

並列關鍵字

Solid Oral Dosage Forms ； Cleaning Validation Process ； Tablets ； Granulation ； Tablating Process

參考文獻

2. 行政院衛生署（2001），清潔確效作業指導手冊，行政院衛生署。

10. International Organization for Standardization (1999). ISO 14644-1:1999, Cleanrooms and Associated Controlled Environments - Part 1: Classification of Air Cleanliness.

14. Pharmaceutical Inspection Co-operation Scheme (2009). Guide to Good Manufacturing Practice for Medicinal Product Part II, PE 009-9, Geneva.

1. 行政院衛生署（2011），國際醫藥品稽查協約組織（PIC/S）藥品優良製造規範指導手冊，行政院衛生署。