驗(yàn)證后，現(xiàn)場(chǎng)需要清潔嗎？近日，F(xiàn)DA在發(fā)給Alembic Pharmaceuticals Limited的483缺陷報(bào)告中提及驗(yàn)證后未對(duì)現(xiàn)場(chǎng)進(jìn)行清潔的缺陷：
Your firm failed to test for residue of (b)(4) (b)(4) to determine if further cleaning is deemed necessary after conducting (b)(4) smoke studies were completed used (b)(4) (b)(4) and (b)(4)
貴公司未對(duì)XXXX的殘留進(jìn)行檢測(cè)，以確定在進(jìn)行煙霧試驗(yàn)后是否需要進(jìn)一步清潔。
According to document titled, “Rational for Cleaning activity after Smoke study in Line (b)(4) states “the vendor declared that the smoke does not generate any residue. So, extensive area cleaning was not performed. However, routine cleaning of equipment & area has been performed (b)(4) (b)(4) as per SOP: Cleaning and Disinfection of Aseptic and Clean area’ No. SD/PD/SOP053. So no risk/impact is involved in the area.” The vendor’s statement was not scientifically verified by your firm.根據(jù)貴公司提供的題為《xx生產(chǎn)線煙霧試驗(yàn)后的清潔活動(dòng)的論證》的文件，其中提到 “供應(yīng)商聲明該煙霧不會(huì)產(chǎn)生任何殘留，因此未開(kāi)展大面積區(qū)域清潔。但已按照SD/PD/SOP053《無(wú)菌及潔凈區(qū)域清潔與消毒規(guī)程》對(duì)設(shè)備及區(qū)域進(jìn)行了常規(guī)清潔，因此該區(qū)域沒(méi)有風(fēng)險(xiǎn)/影響。” 貴公司未對(duì)供應(yīng)商的該聲明進(jìn)行科學(xué)確認(rèn)。
在FDA對(duì)Essential Pharmacy Compounding LLC和Custom RX, LLC的檢查中，也提及氣流流型測(cè)試后未執(zhí)行適當(dāng)?shù)那鍧嵉娜毕荩?/span>
Custom RX, LLC：
煙霧測(cè)試（用于驗(yàn)證層流罩氣流）后，沒(méi)有文件記錄表明對(duì)生產(chǎn)區(qū)域進(jìn)行了清潔以去除煙霧殘留物。反而在測(cè)試后，公司立即在同一層流罩內(nèi)生產(chǎn)了多種無(wú)菌藥品。
Essential Pharmacy Compounding LLC：
在煙霧研究（驗(yàn)證氣流流型）后啟動(dòng)無(wú)菌生產(chǎn)前，未對(duì)設(shè)備、物品進(jìn)行清潔。特別是，沒(méi)有文件記錄證明用于清除煙霧殘留物的清潔步驟，也沒(méi)有驗(yàn)證措施確保ISO 5級(jí)層流罩內(nèi)的殘留物已被清除。
在新版PDA TR 22《培養(yǎng)基模擬灌裝指南》中也提及培養(yǎng)基模擬灌裝驗(yàn)證后清潔相關(guān)要求：
To prevent contamination risk product-contact parts must be cleaned by a validated cleaning procedure to remove any growth-media residues. Cleaning may require removing gaskets and valves after an APS to avoid media contamination of commercial product.為防止污染風(fēng)險(xiǎn)，接觸產(chǎn)品的部件必須通過(guò)經(jīng)驗(yàn)證的清潔程序清除所有培養(yǎng)基殘留物。清潔時(shí)可能需要在APS后拆卸墊圈和閥門，以避免培養(yǎng)基污染商業(yè)產(chǎn)品。
Defined procedures should be in place, and cleaning validation should account for the effective removal of residual media from direct and indirect product-contacting equipment surfaces. Procedures on how to handle spillage during filling should be in place to avoid media entering difficult to clean areas. Where it is not possible to clean surfaces that may have been contacted by media, such as for gaskets and seals, these should be replaced.應(yīng)建立程序，清潔驗(yàn)證需確保直接/間接接觸產(chǎn)品設(shè)備表面的培養(yǎng)基殘留物被有效清除。需制定灌裝過(guò)程溢出處理規(guī)程，避免培養(yǎng)基滲入難以清潔區(qū)域。對(duì)于無(wú)法清潔的可能接觸培養(yǎng)基的表面（如墊圈密封件），應(yīng)予以更換。
Material utilized as a placebo or surrogate should be packaged and handled as closely as possible to the material being simulated, and the justification for its appropriateness as a substitute for the simulation should be documented. Any differences in the packaging and handling of the placebo should be assessed for potential impact to the process and the need for additional cleaning and/or dedicated cleaning validation.用作安慰劑或替代物的材料應(yīng)盡可能接近被模擬的材料進(jìn)行包裝和處理，并應(yīng)記錄其作為模擬替代物的合理性。應(yīng)評(píng)估安慰劑包裝和處理中的任何差異對(duì)工藝的潛在影響以及額外清潔和/或?qū)ｉT清潔驗(yàn)證的需要。
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