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受检机构/公司：Patheon Biologics LLC（Thermo赛默飞的CDMO业务，大分子）
城市：St. Louis, MO 63134
类型：API (Biotech) Manufacturer （生物药原液生产）
FEI号：3003418999
Observation 1
Laboratory control records are not
protected to ensure they include complete data derived from all tests conducted
to ensure compliance with established specifications and standards, including
examinations and assays.
实验室控制记录没有得到保护，以确保它们包含所有测试得出的完整数据，以确保符合既定的规格和标准，包括检测和分析。
Specifically,具体来说，
A. The data acquisition software and
workstations, including the systems used for endotoxin, biological assay, and
biochemistry testing, have not been suitably maintained to ensure that the data
generated for routine release and stability testing of bulk drug substances are
free of manual manipulation or deletion.
数据采集软件和工作站，包括用于内毒素、生物学活性和生物化学测试的系统，没有得到适当的维护，以确保生成的用于原料药物常规放行和稳定性测试的数据不受手动操作或删除的影响。
西门的吐槽：计算机化系统的数据完整性，最主要是两点，前端权限和后端检查，一个是用技术确保权限最小化，确保数据受控，一个是用全面的检查方式，让数据管理的失效可探测度加高。这里有意思的点是，没有查到明显的数据删除情况，只是部分防删除功能漏开，落到了第一，也就是检查员认为最严重的发现项。
For example, during the walkthrough of the
analytical laboratories on 23Feb2023, we observed analytical instruments used
for release and in-process testing, including the (b)(4) (for (b)(4) testing)
and (b)(4) (for (b)(4) activity), in which the testing data lacks protection
from deletion within the computer system by an analyst.
例如，在2023年2月23日对分析实验室的现场检查中，我们观察到用于放行和中控测试的分析仪器，包括(b)(4)（用于(b)(4)测试）和(b)(4)（用于(b)(4)活动），其中测试数据缺乏防删除保护（分析师在计算机系统中可以删除数据）。
These instruments are used to support the
in-process, release, and stability testing of bulk drug substances, including
(b)(4).
这些仪器用于支持原料药物的中控、放行和稳定性测试，包括(b)(4)。
A preliminary investigation conducted
during the inspection into the ability to delete data files generated from
these instruments identified three instruments, including the (b)(4), and
(b)(4) (used for (b)(4) determination) in which there is a lack of control from
deletion of raw data since approximately July 2021.
在检查期间进行的初步调查，调查了从这些仪器生成的数据文件的删除能力，确定了三台仪器，包括(b)(4)和(b)(4)（用于(b)(4)测定），自大约2021年7月以来，缺乏对原始数据删除的控制。
B. There is no procedure that describes the
appropriate use of (b)(4) for acquired data within the (b)(4) chromatography
system nor do (b)(4) events require explanation.
没有程序描述在(b)(4)色谱系统中获取数据的适当使用，也没有(b)(4)事件需要解释。
For example, during the review of the
stability data supporting (b)(4) Lot (b)(4) interval at the long-term storage
condition, all chromatograms, including assay control and test samples,
contained (b)(4) integrated peaks with reason “integration”.
例如，在审查支持长期储存条件下(b)(4)批次(b)(4)间隔的稳定性数据时，所有色谱图，包括测定控制和测试样品，都包含(b)(4)积分峰，原因是“积分”。
西门的吐槽：任何特异的行为，只要是非固有，那就不能简单的”写错“，或者简写，这不利于追溯，应该是一段文字，能显示缘由。
The analytical method states, “(b)(4)”.
分析方法指出，“(b)(4)”。
The method does not include how to properly
apply these (b)(4) integration events to process the analytical data and no
procedure was provided on how to report (b)(4) integration within the result
sets.
该方法没有包括如何正确应用这些(b)(4)积分事件来处理分析数据，也没有提供如何在结果集中报告(b)(4)积分的程序。
In addition, during the review of
chromatographic results obtained within (b)(4) from 01Jan2023 to 02Mar2023,
including results supporting the release and stability testing of (b)(4)
approximately 4700 of (b)(4) individual injections made had been (b)(4)
integrated.
此外，在审查2023年1月1日至2023年3月2日期间在(b)(4)内获得的色谱结果时，包括支持(b)(4)放行和稳定性测试的结果，大约4700次(b)(4)单针进样已被(b)(4)积分。
西门的吐槽：单针进样，很敏感，最好该被禁止，但是如果需要被使用，至少应该能有全面审核的方式方法，这里色魔家大概率用的是变色龙，像empower做法比较多，可以锁定通道（锁定通道，防止为这些通道生成更多结果），也可以使用数据审核中的"单针进样run single injection"选项，来确认是否有孤儿数据（预进样或者刻意遗漏等）
C. Acquired raw data and audit trails from
the (b)(4) Vi-Cell instruments, which are used during cell banking activities
(including the production of the (b)(4) working cell bank) and drug substance
manufacturing (including (b)(4)), are not reviewed at the for completeness,
accuracy to the reported results, and for unreported data.
从(b)(4) Vi-Cell仪器获取的原始数据和审计追踪，这些仪器用于细胞库活动（包括生产(b)(4)工作细胞库）和原液生产（包括(b)(4)），没有被审查以确保完整性、报告结果的准确性和未报告的数据。
The results from the Vi-Cell are used as an
in-process check during the manufacturing of drug substances, including during
the (b)(4) step for the manufacturing of (b)(4) Lot (b)(4), to determine cell
viability, which is identified in your manufacturing record as a key process
attribute (KPA).
Vi-Cell的结果在原液生产中用作中控，包括在制造(b)(4)批次(b)(4)的(b)(4)步骤中，以确定细胞活力，这在您的生产记录中被识别为关键工艺属性（KPA）。
西门的吐槽：一般生物药上游的工艺中，CQA比较少，很多公司基于资源，可能对于CQA和CPP必查，但是KPA 或者 KPP不是能不查，所有数据都要复核，一般可以接受的是可以降档。vicell一般是确认细胞活率，只影响产率，不影响产品质量，所以划到KPA，也没毛病，确实没那么重要。
