【FDA警告信】320-18-48 印度 Goran Pharma

翻江鼠

警告信编号	320-18-48
检查公司	印度 Goran Pharma
检查时间	2017年11月13-15日
缺陷项
1.     Your firm failed to ensure the identity of components, including your activeingredients and excipients from various suppliers (21 CFR 211.84(d)(1) and(2)).你公司未能确保对来自不同供应商的组份包括你们的活性成分和辅料的识别（21 CFR 211.84(d)(1) and (2)。 You failed to test incoming components you use in manufacturing drug products to determine their conformance to identity, purity, strength, and other appropriate specifications. Your firm released components for use in drug product manufacturing based on certificates of analysis (COA) from your supplier without establishing the reliability of the suppliers’ analyses through appropriate validation. For example, your firm did not test each lot of glycerin used as a component of your drugs to determine whether diethylene glycol (DEG) or ethylene glycol (EG) was present. Because you did not test each glycerin lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of lots used in drug product manufacture. DEG contamination in pharmaceuticals has resulted in variousle thal poisoning incidents in humans worldwide. 你们未检测你们用于制剂生产的进厂组份以确定其符合鉴别、纯度、剂量及其它适当的质量标准。你们公司依据供应商的分析报告（COA）放行了组份用于制剂生产，而未通过适当的验证建立对供应商分析结果的可靠性。例如，你们公司并未检测用作你们药品的一种组份甘油（丙三醇）的所有批次批号，以确定其中是否含有二甘醇（二乙二醇DEG）还是甘醇（乙二醇（EG）。因为你们没有使得USP鉴别方法测试每批甘油发现这些危害性杂质，你们无法确保用于药品生产的所有批次的可接受度。DEG污染药品已导致了世界许多死亡事件。 Your response indicated thatyou will compare your laboratory results with the supplier’s COA to confirm there liability of testing for all lots, and you provided a revised standard operating procedure (SOP)Purchasing, Supplier Approval, Monitoring, andRisk Analysis (SOP No. GPPL/PUR/01). The revised SOP, provided with your response as Annexure 30, also discusses adding suppliers to an “approved vendor list.” 你们的回复说你们将比较你们化验室的结果与供应商的COA以确认所有批次检测的可靠性，你们还提供了一份修订后的标准操作规程（SOP）“采购、供应商批准、监测和风险分析”（SOP编号GPPL/PUR/01）。修订后的SOP是作为你们回复的附录30提交的，其中也讨论了增加供应商至一份“已批准供应商清单”。 Your response is inadequate because it is not clear whether you will indefinitely test each incoming component lot for all attributes to verify the accuracy of your suppliers’ COA, or you will instead qualify your suppliers’ test results through an initial round of testing as well as ongoing testing at appropriate intervals. Additionally, your response did not address whether your firm conducted retrospective DEG and EG testing for products distributed to the United States. 你们的回复是不充分的，因为没说清楚你们是否会检测每批进厂组份的所有属性以确认你们供应商COA的准确性，还是会通过初始一轮检测来确认你们供应商的检测结果然后以隔一定时间定期检测。另外，你们的回复并未说明你们公司对销往美国的药品进行回顾性DEG和EG检测。 2.     Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)). 贵公司未能建立充分的质量部门，使其具备权力和职责来批准或拒收所有组份、药品容器密闭器、中间体、包材、标签和成品（21 CFR 211.22(a)）。 Your quality unit releasedbatches without reviewing all production and control records. You shipped the(b)(4) batch (b)(4) prior to completion of microbiological testing. Your SOP IssueBatch No., Issue, Entry, Review and Control of BMR and Batch Release (SOPGPPL/QC/04) allows this practice. 你们质量部门未审核所有生产和检验记录即放行了多批产品。你们在微生物检测完成之前即发运了XX产品XX批号。你们的SOP“批号签发、BMR签发、录入、审核和控制以及批放行”（SOP GPPL/QC/04）允许你样如此操作。 Your response is inadequate because your revised SOP, supplied with your response as Annexure 31, statesthat in cases of “emergency” you will transfer the product to the shipping agent’s warehouse with a “not for sales” [sic] COA. This indicates that finished product may still be distributed prior to completion of testing andreview by your quality unit. Your SOP continues to state that if a failing result is obtained you will conduct a “recall/withdrawal” from the shipping agent. 你们的回复是不充分的，因为你们作为回复附件31所提供的修订后SOP中说如果“情况紧急”，你们会将产品转移至货代仓库，配以“不得销售”的COA。这表示成品仍在检测完成以及你们质量部门审核之前即被销售了。你们的SOP继续声称如果检测结果不合格，你们会从货代处“召回/撤回”产品。 3.     Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63). 贵公司在药品生产、加工、包装和存贮过程中未能使用经适当设计、具备足够尺寸、适当定位的设备以便于按其既定用途操作并进行清洁和维护（21 CFR 211.63）。 Your (b)(4) system was not appropriately designed. The system, which you indicated was “sterilized” (b)(4), contained (b)(4) piping with dead legs. This inappropriate system design fosters the development of biofilms. Moreover, due to the deficiencies noted in laboratory controls during the inspection, such as inappropriate storage of media, lack of growth promotion testing, and lack of positive controls, it is not certain you would be able to reliably detect bioburden or microbial limits failures. 你们的XX系统设计不恰当。该系统显示为“已灭菌”XX，其管道有死管。该不当设计会滋长生物膜。另外，由于在检查过程中在化验室看到的缺陷，例如，培养基存贮不当，缺少促生长试验，缺少阳性控制，因此无法确定你们能够可靠地检出生物负载和微生物限度失败情况。 In your response you stated you have procured an improved (b)(4) system. Your response is inadequate because it lacks detail on how you will validate the new (b)(4) system.You stated that you will “sterilize” the new (b)(4) system (b)(4) with (b)(4) for (b)(4), but you did not provide scientific rationale for the proposed frequency, (b)(4), or duration. Lastly, your response did not include a risk assessment for products within your control or that have been distributed to the United States that were manufactured using the previous (b)(4) system. 在你们的回复中，你们声称你们已经采购了更好的XX系统。你们的回复是不充分的，因为其中缺少你们将如何验证新的XX系统的详细信息。你们声称你们会对新的XX系统在XX“灭菌”XX时间，但你们并未为所拟频次、XX或时长提供科学合理性。最后，你们的回复并未包括对采用之前XX系统生产的仍在你们控制下产品和已销往美国产品的风险评估。 4.     Your firm failed to provide equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature when appropriate for the manufacture, processing, packing, or holding of a drug product (21 CFR211.46(b)). 贵公司未能提供设备用于充分控制空气压力、微生物、灰尘、湿度和温度使其适合于药品的生产、加工、包装和存贮（21 CFR 211.46(b)）。 You lacked an air handling system as well as control and monitoring of temperature and humidity in the manufacturing (e.g. filling, packaging) and warehouse areas. You confirmed thatyour drug products may be exposed to temperatures over 30°C (86°F) and that temperatures in your facility can reach 50°C (122°F) during hot weather months. 你们的生产（例如灌装和包装）和仓库区域缺乏空调系统以及温湿度控制和监测系统。你们确认你们的药品可能会暴露于高于30°C (86°F)温度之下，在最热的几个月你们场所的温度可能会高达50°C (122°F)。 It is unacceptable to manufacture drug products without an air handling system that has control over temperature, humidity, and air cleanliness. Your lack of air handling systems and control has the potential to adversely affect the quality of your raw materials, in-process materials, and finished products. 在没有空调系统控制温湿度和空气洁净度的情况下生产药品是不可接受的。你们缺乏空调系统可能会对你们的原料、中间体和成品质量产生不良影响。 Quality Unit Authority 质量部门权力 Significant findings in this letter indicate that your quality unit is not fully exercising its authority and/or responsibilities. Your firm must provide the quality unit with the appropriate authority, sufficient resources and staff to carry out its responsibilities and consistently ensure drug quality. 在此函中的严重缺陷表明你们的质量部门并未全面履行其权力和/或职责。你们公司必须为质量部门提供适当的权力、足够的资源和人员来履行其职责，持续确保药品质量。

本文摘自 OurGMP