與化學(xué)合成原料藥相比，發(fā)酵化學(xué)原料藥的生產(chǎn)存在技術(shù)上的特殊性。相比傳統(tǒng)的化學(xué)合成工藝，發(fā)酵工藝的優(yōu)點(diǎn)包括可利用微生物或其他生物組織特異的代謝途徑提高反應(yīng)的選擇性并實(shí)現(xiàn)更高通量的生產(chǎn)；對很多含復(fù)雜結(jié)構(gòu)單元的化學(xué)藥來說發(fā)酵仍是獲得足量原料藥的唯一途徑；由于工藝條件相對溫和、所用物料對環(huán)境相對友好等特點(diǎn)可提供更高的經(jīng)濟(jì)性和可持續(xù)性。結(jié)合國內(nèi)外相關(guān)法規(guī)或指導(dǎo)原則及審評經(jīng)驗(yàn)，從菌種管理（菌種來源、菌種鑒定、菌種庫的建立和內(nèi)控標(biāo)準(zhǔn)、菌種穩(wěn)定性）、物料管理（培養(yǎng)基設(shè)計(jì)、內(nèi)控標(biāo)準(zhǔn)）、發(fā)酵工藝（生產(chǎn)條件、工藝參數(shù)）、提取純化工藝（產(chǎn)品富集、雜質(zhì)去除）等方面，簡要介紹與發(fā)酵化學(xué)原料藥生產(chǎn)工藝部分注冊申報(bào)相關(guān)的基本要求，旨在提高發(fā)酵化學(xué)原料藥生產(chǎn)工藝研發(fā)與注冊申報(bào)的系統(tǒng)性和規(guī)范性。

Compared with chemically synthesized active pharmaceutical ingredients (APIs), there are technical peculiarities in the production of fermentation chemical APIs. Advantages of fermentation processes over traditional chemical synthesis include the ability to utilize specific metabolic pathways of microorganisms or other biological tissues to improve reaction selectivity and achieve higher throughput; fermentation is still the only way to obtain sufficient quantities of APIs for many chemicals that contain complex structural units; and the process is relatively benign and environmentally friendly, providing greater economy and sustainability. According to the relevant regulations or guidelines and drug-review practice, the basic requirements related to the manufacture part of the application of the fermentation chemical APIs is demonstrated briefly, with respect to the strain management (source, identification, cell bank establishment and specification, stability), material management (microbiological media design and specification), fermentation process (manufacture conditions, process parameters), extraction and purification process (product enrichment, impurity removal) and other aspects in order to improve the R&D and registration of fermentation chemical APIs to a more systematic and standardized level.