【正文】 ts 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。檢查、測試、決定39。大多數(shù)的cGMP要求質(zhì)量管理部門負(fù)責(zé)審查和批準(zhǔn)生產(chǎn)的程序，并且對它們的更改，大多數(shù)報(bào)告，程序和控制，認(rèn)為有必要確保過程和產(chǎn)品的質(zhì)量。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)證過程中產(chǎn)生的。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)國家是受監(jiān)管的。注意，兩個(gè)標(biāo)準(zhǔn)都必須滿足。事實(shí)上，這些原則適用于任何需要高質(zhì)量的化學(xué)品的生產(chǎn)。由于API是受管制物品，其質(zhì)量不僅取決于令人滿意的測試結(jié)果，也認(rèn)為工藝是由驗(yàn)證過程來保證的。一些還需要微生物分析，這取決于最終的劑型和所涉及的制造工藝上。其他屬性通常包括固體形式的顏色和或溶液，熔點(diǎn)，比旋度（如果有光學(xué)活性），晶體形態(tài)，等等。 for example, if it will be used as a powder blended with other excipients, careful consideration should be given to rate of dissolution and the eventual color of solution (for aesthetic reasons) when dissolved by the patient (or healthcare giver) prior to use. For this reason, final API specifications are always defined with the cooperation of the pharmaceutical development area. The quality assurance function approves final API quality standards, taking into consideration all requirements: process related, governmental, and customer.當(dāng)建立API的物理屬性時(shí)，要考慮的最重要的方面是其在制藥過程中的使用。出于這個(gè)原因，最終的API規(guī)范始終說明需與藥物開發(fā)領(lǐng)域的合作。在合規(guī)性方面，這意味著必須在試驗(yàn)中驗(yàn)證；也就是說，已經(jīng)證明程序的執(zhí)行可靠，而不是由干擾組分造成。C. Designing Quality into the Process 工藝中的質(zhì)量設(shè)計(jì)As described above, the pharmaceutical manufacturing process and end use of the drug product dosage form are the basis for establishing the limits of chemical purity and physical attributes. Having predefined these attributes, the synthetic chemist and chemical engineer have the task of designing quality into the process?；瘜W(xué)過程開發(fā)后，技術(shù)文件將解釋試劑，步驟，控制等的方式為什么和怎樣被選擇的將質(zhì)量設(shè)計(jì)于產(chǎn)品中。One should begin the approach to designing quality into the API, with the concept of designing a perfect system. Keep in mind that all the safety, environmental, and economic reasons for developing a perfect chemical synthesis are precisely consistent with the goal of designing quality into the process, and very well serve all regulatory process validation and control requirements. If one imagines a perfect process, there will be no toxic emissions about which to be concerned, no safety concerns or need for special safety controls, and the yield of each step will be 100% of the desired intermediate, stereo isomer, and end product. Such a process would be free of any impurities and would assay for 100% purity. The next challenge is to design the synthesis so that each step can be precisely controlled to always provide the same end result.用API質(zhì)量設(shè)計(jì)的方法來設(shè)計(jì)一個(gè)完美的系統(tǒng)。The design work requires a plete understanding of the chemical reactions in the synthetic process under development.Then a clever design can be developed to eliminate any undesirable side reactions. In some instances, this can be achieved by sophisticated use of functional group protecting agents, and in other instances by changing the sequence of functional group introduction onto the end product building block and sometimes by simple careful control over reaction parameters. Once the process has been perfectly designed, developed, and controlled, the last concern is over the control of quality and reliability of the raw materials, proper functioning of equipment, and errorfree operations by personnel. With the vision of a perfect system in mind, one can imagine how the API quality would be perfect and consistent.設(shè)計(jì)工作需要對開發(fā)中的合成方法的化學(xué)反應(yīng)有一個(gè)完整的理解。隨著設(shè)想的完善制度的實(shí)行，可以想見的API質(zhì)量將是完美的，一貫的。39?？刂浦R的證明39。合成途徑的動力學(xué)記錄在一個(gè)工藝手冊中。該知識闡述了從原料到最終API的化學(xué)途徑。這些控制在流程手冊中有描述，并在化工廠進(jìn)行規(guī)模化生產(chǎn)，并最終得到全面運(yùn)轉(zhuǎn)使用。它足以確保最終的API的質(zhì)量，該方法的發(fā)展提供了必要的信息，設(shè)計(jì)過程中的控制，以監(jiān)測每個(gè)步驟的進(jìn)展是需要的。Inprocess controls should always be ‘‘in the process,’’ that is, ‘‘online,’’ and not requiring a sample to be withdrawn and sent to a laboratory for testing and evaluation. Under some conditions, it may be necessary to take samples, but this should be avoided whenever practical.過程控制應(yīng)始終是過程中，而不是要求一個(gè)樣品被取出并送到實(shí)驗(yàn)室進(jìn)行測試和評估。建立適當(dāng)?shù)臏y試中，例如，紅外或紫外分析，可以通過以下的官能團(tuán)的消失，或分子上形成被生產(chǎn)預(yù)測的反應(yīng)的終點(diǎn)。一套標(biāo)準(zhǔn)是產(chǎn)品的規(guī)格，在第二部分討論。The section is written as if the regulations are in force throughout the world. This position is valid given the adoption of the ICH Q7A Guide.One final introductory ment before beginning a review of the ICH guidance: when describing the ‘‘cGMPs,’’ they are always prefaced by the adjective ‘‘current’’. Q7A acknowledges the equivalence of the terms ‘‘cGMPs’’ and ‘‘good manufacturing practices’’. The equivalence of the terms is deliberate. It requires that manufacturers continuously apply the current state of technology and practices when developing new drugs. In certain special cases, manufacturers will also be pelled to apply the new technology to older APIs and the processes, facilities, etc., whenever such application will play a significant role in assuring, or advancing, the end product quality. Furthermore, since the ‘‘current’’ is part of the guidance, manufacturers need to be aware of such advances and make the necessary changes to their systems and facilities to remain pliant. Hence, the guidance can be thought of as always being updated without return to the regulating bodies for approval.這部分內(nèi)容寫入法規(guī)在全世界通用。在某些特殊情況下，制造商也將被迫將新技術(shù)應(yīng)用到舊的API和流程，設(shè)施等，只要這種應(yīng)用將在保證或改進(jìn)最終產(chǎn)品的質(zhì)量方面發(fā)揮顯著的作用。 or ).However, it is not intended that this will represent a summary of the guidance. Instead, this text offers practical insight into the reasons and meanings of certain aspects of the requirements. Review and reference should that be necessary.The reason for selecting the ICH guide is due to its widespread adoption, its prehensive approach and its high quality as a reference document.本章的這一部分遵循的ICH指南的格式為2000年11月定稿的ICH（ “質(zhì)量”章節(jié)，“Q7A”；）。之所以選擇ICH指南是由于它的廣泛應(yīng)用，其綜合性方法和高品質(zhì)可作為參考文件。相反，本文從實(shí)用的觀點(diǎn)提供了法規(guī)要求的某些方面的含義和原因。因此，該指南可以認(rèn)為一直在更新，而不需要返回至監(jiān)管機(jī)構(gòu)審批。最后在開始ICH指南介紹前還有個(gè)定義：當(dāng)描述cGMP時(shí)，總是由形容詞“現(xiàn)行的”做前綴。大多數(shù)國家已經(jīng)批準(zhǔn)和實(shí)施的法規(guī)藥品，很少有與其中使用的API的具體規(guī)定。III. THE REGULATIONS FOR QUALITY質(zhì)量法規(guī)Introduction: The