【正文】 C. The Facilities設(shè)施The facilities in which APIs are produced are also addressed in this chapter because a ponent of quality of an API is that it be produced in cGMPpliant facilities. Those ponents of the facility governed by cGMP are therefore part of this chapter. The essence of cGMP for facilities or, for that matter, any aspect of API manufacture is that the facility performs as designed to assure the quality of the product.生產(chǎn)API的設(shè)施在本章節(jié)也進(jìn)行討論，因?yàn)锳PI的質(zhì)量的組成部分是通過(guò)cGMP的標(biāo)準(zhǔn)設(shè)施來(lái)生產(chǎn)的。因此，由cGMP管轄的設(shè)施的組成部分是本章節(jié)的一部分。對(duì)于這個(gè)問(wèn)題，cGMP的設(shè)施或API制造的任何方面的的本質(zhì)是設(shè)施執(zhí)行的設(shè)計(jì)，以保證產(chǎn)品的質(zhì)量。Further, the performance characteristic must be documented, and management must demonstrate the facility continually performs as designed. Performance control monitoring, preventative maintenance, and carefully controlled and approved repairs or changes to facility ponents are all considered part of assuring quality of APIs.此外，性能特點(diǎn)必須記錄，管理必須證明該設(shè)施持續(xù)按設(shè)計(jì)執(zhí)行。性能控制監(jiān)控、預(yù)防性維護(hù)、精密控制和批準(zhǔn)的設(shè)備部件的維修或變更都被認(rèn)為是保證API質(zhì)量的一部分。D. The People人員The people who produce the API are considered a critical part of the system and, as such, bee part of the requirements for quality of APIs. To do their jobs effectively and to assure quality of the API, they must be properly trained and equipped. Qualified personnel must conduct the training。 the equipment must be of proper design and function. The supervisors of people manufacturing APIs must also be properly trained to do their jobs. Finally, there must be an adequate number of people to allow sufficient time to perform these responsibilities in a satisfactory manner.生產(chǎn)API的人員是該系統(tǒng)的一個(gè)重要組成部分，因此，成為API的質(zhì)量要求的一部分。為了有效地做好本職工作，以確保API的質(zhì)量，就必須進(jìn)行適當(dāng)?shù)呐嘤?xùn)和裝備。合格人員必須進(jìn)行培訓(xùn)。設(shè)備必須有適當(dāng)?shù)脑O(shè)計(jì)和功能。人造API的監(jiān)管人員也必須進(jìn)行適當(dāng)?shù)呐嘤?xùn)來(lái)做好本職工作。最后，必須有適當(dāng)?shù)娜藬?shù)，以便有充足的時(shí)間、以令人滿意的方式執(zhí)行這些職責(zé)。E. The Quality Management Department質(zhì)量管理部門(mén)As in most any other manufacturing enterprise, there is a quality control and or a quality assurance department. Today, these departments are usually bined into a QM department.因?yàn)樵诖蠖鄶?shù)的任何其他制造企業(yè)，有一個(gè)質(zhì)量控制部和/或質(zhì)量保證部。如今，這些部門(mén)通常被合并成一個(gè)質(zhì)量管理部門(mén)。The role of the QM department has also advanced from ‘‘checktestdecide’’ responsibility to being an equal partner with manufacturing and engineering to manage and improve the quality of the entire process and system.質(zhì)量管理部門(mén)的角色也從39。39。檢查、測(cè)試、決定39。的職責(zé)變?yōu)榕c制造和工程平等的參與者來(lái)提高全過(guò)程和系統(tǒng)的質(zhì)量。For APIs and drug products, the QM department, through its quality assurance arm, still has the responsibility vested in it by regulations to release all products for use and eventually to the market. As a ponent of the system to produce APIs, the activities and responsibilities of the QM department are also a ponent of product quality. Most cGMPs require that the QM department is responsible to review and approve production procedures, and any changes to them, most reports, procedures, and controls, deemed necessary to assure the quality of the process and product.對(duì)于原料藥和藥物產(chǎn)品，質(zhì)量管理部門(mén)，通過(guò)其質(zhì)量保證的手臂，還有賦予的責(zé)任，通過(guò)法規(guī)來(lái)釋放所有產(chǎn)品中使用，并最終推向市場(chǎng)。作為該系統(tǒng)的一個(gè)組成部分來(lái)生產(chǎn)原料藥，活動(dòng)和QM部門(mén)的職責(zé)是也產(chǎn)品質(zhì)量的一個(gè)組成部分。大多數(shù)的cGMP要求質(zhì)量管理部門(mén)負(fù)責(zé)審查和批準(zhǔn)生產(chǎn)的程序，并且對(duì)它們的更改，大多數(shù)報(bào)告，程序和控制，認(rèn)為有必要確保過(guò)程和產(chǎn)品的質(zhì)量。Finally, the QM department must have adequate laboratory facilities and properly trained and experienced people to effectively carry out their responsibilities.最后，質(zhì)量管理部門(mén)必須有足夠的實(shí)驗(yàn)室設(shè)施和適當(dāng)?shù)呐嘤?xùn)，經(jīng)驗(yàn)豐富的人來(lái)有效地履行其職責(zé)。F. The Regulatory Authorities 監(jiān)管機(jī)構(gòu)Health authorities in every country regulate drug products. In most countries, these regulations also include APIs. These cGMP regulations require that a drug must meet all predefined quality specifications and be produced from a documented validated process. Further, if the drug, or API, is not produced and controlled according to the established process, then the drug is considered adulterated, and therefore not fit for use or sale. The regulations address every aspect of drug product manufacture, and essentially require that the producer has documented evidence of proof of control over any aspect that might affect product quality. The regulators were deliberate in their use of the word ‘‘current’’ when the cGMPs were promulgated. This qualifier enables the agencies to continuously require that manufacturers maintain their facilities and processes at the state of the art, thereby always assuring the public that drug products are as safe and effective as possible.每一個(gè)國(guó)家由衛(wèi)生主管部門(mén)管制藥品。在大多數(shù)國(guó)家，這些法規(guī)還包括原料藥。這些的cGMP法規(guī)要求藥品必須符合所有預(yù)定的質(zhì)量標(biāo)準(zhǔn)，并從記錄驗(yàn)證過(guò)程中產(chǎn)生的。此外，沒(méi)有按已建立的方法制備并控制的藥物或API，則該藥物被認(rèn)為是摻假，因此不適合使用或出售。該法規(guī)涉及藥品生產(chǎn)每一個(gè)環(huán)節(jié)，而且基本上要求生產(chǎn)者記錄控制證明可能影響產(chǎn)品質(zhì)量的任何方面。監(jiān)管機(jī)構(gòu)頒布的法規(guī)即cGMP，不斷要求制造商維持其設(shè)備和工藝的狀態(tài)，從而保證始終如一的生產(chǎn)安全有效的藥品。G. The Regulations法規(guī)The production of APIs is regulated in most countries. The ICHharmonized tripartite guideline Q7A entitled as Good Manufacturing Practice Guide for APIs was remended for adoption at Step 4 of the ICH process on the 10th of November 2000. This document was adopted by the following agencies denoting its widespread acceptance:原料藥的生產(chǎn)在大多數(shù)國(guó)家是受監(jiān)管的。良好生產(chǎn)實(shí)踐指南API ICH三方協(xié)調(diào)指導(dǎo)Q7A（2000年11月10日）被建議使用。下列機(jī)構(gòu)表示普遍接受：_ European Union (EU) adopted by CPMP, November 2000, issued as CPMP/ICH/1935/00 歐盟采用CPMP，2000年11月，以CPMP/ICH/1935/00發(fā)行_ Japanese MHLW adopted November 2nd, 2001 MSB notification NO. 1200日本MHLW采用2001年11月2日的MSB通知，第1200期_ United States FDA published in the Federal Register, Vol. 66, No 186, September 25th, 2001, pages 49028–49029.美國(guó)FDA發(fā)表在聯(lián)邦注冊(cè)，第66卷第186期，2001年9月25日，2001年，第4902849029頁(yè)The production process and all tests and controls must be approved by the regulating government in which APIs will be used, and the facilities and systems in which they are produced must meet the manufacturing standards set down by the governing body. Thus, the quality of APIs is based on two ponents: meeting final quality specifications and being produced according to the regulated, approved process in a facility pliant with the appropriate manufacturing standards. It is important to note that both criteria must be met: final specifications and pliance to manufacturing standards. These two ponents will be dealt with separately in this chapter. It is also important to note that the app