PDA-确保微生物测试数据的完整性（三）
Microbiological Test Data – Assuring Data Integrity
微生物测试数据-确保数据的完整性
Edward Charles Tidswell and Tim Sandle
PDA Journal of Pharmaceutical Science and Technology 2017,
Access the most recent version at doi:10.5731/pdajpst.2017.0081
Microbiological Test Data – Assuring Data Integrity
微生物测试数据–确保数据的完整性（三）
上节回顾：
微生物测试数据-确保数据的完整性（一）
微生物测试数据-确保数据的完整性（二）
Microbial Enumeration and Bioburden Tests 微生物计数和生物负载试验
Assessment of microbial levels within samples per the compendial microbial enumeration test and on materials per non-compendial biobiorden tests is an important part of pharmaceutical process control.
根据《药典》微生物计数试验对样品中的微生物水平进行评估，根据《药典》生物负载试验对材料进行评估，是药物过程控制的重要组成部分。
With most pharmaceutical processes, samples are drawn from intermediate product at defined stages (with stages based on risk assessment, designed to inform about process risks and hold times).
在大多数制药过程中，样品是在规定的阶段从中间产品中抽取的(阶段基于风险评估，旨在告知过程风险和保存时间)。
Bioburden testing allows for the microbial levels to be tracked from upstream processing to downstream processing, with an expectation that the microbial levels decrease, or at least remain unchanged provided they are below an acceptable action level.
生物负载测试允许跟踪从上游加工到下游加工的微生物水平，期望微生物水平下降，或者至少在低于可接受的行动水平时保持不变。
For sterile products, there is an expectation that the sample prior to final filtration is not of a level that would pose a significant challenge to the sterilizing capabilities of the filter.
对于无菌产品，预期在最终过滤前的样品不会对过滤器的杀菌能力构成重大挑战。
Bioburden refers to the microbial content of a material (or on the surface) at a given point in
time.
生物负载是指某一物质(或其表面)在某一点上的微生物含量。
This could be prior to sterilization or in relation to a process hold time (Sandle, 2015).
这可能发生在灭菌之前，也可能与工艺保持时间有关(Sandle, 2015)。
As well as providing data essential to final product release and material release (microbial enumeration testing) bioburden enumeration (for example environmental monitoring and in- process testing) supports long-term trending for identifying:
除了提供最终产品放行和材料放行(微生物计数测试)所必需的数据外，生物负载计数(例如环境监测和过程中测试)还支持长期趋势的识别:
a) Samples that exceed an alert or action level 超过警戒或行动线的样本
b)Changes in the total or mean count 总数或平均数的变化
c)Changes in speciation profiles of recovered microorganisms 微生物形态特征的变化
Both microbial enumeration and bioburden testing is typically performed by a plate count method;
微生物计数和生物负载试验通常采用平板计数法进行;
either a pour plate agar method or, more preferably (due to the larger sample size), membrane filtration.
无论是倒平板琼脂法，或(由于样本量较大)更佳的膜过滤。
In all circumstances recovered discrete colonies are quantified as colony forming units (CFU).
在所有情况下，恢复的离散菌落被量化为菌落形成单元(CFU)。
These methods are inherently variable.
这些方法本身是可变的。
With the plate count methods, care needs to be taken in relation to selecting an appropriate
agar and with incubation time and temperature, in order to ensure optimal recovery (Sandle et al, 2013).
对于平板计数方法，在选择时需谨慎并配合琼脂的培养时间和温度，以保证最佳的回收率。
This can be assessed by microbial challenge recovery assessments.
这可以通过微生物挑战恢复评估来评估。
Collected samples should be assigned an expiry time (which will need qualifying) and storage of samples prior to testing would ordinarily be at 2-8 C in order to slowdown or suspend the rate of microbial growth.
采集的样本应指定一个有效时间(这需要经过资格认证)，为了减缓或暂停微生物的生长速度，测试前的样本存储通常为2-8摄氏度。
With the above factors, which introduce an element of variability there remain many variations with the plate counting methods used to assess bioburden.
由于上述因素引入了变异因素，用于评估生物群落的平板计数方法仍存在许多变异。
The first of these is with the limitations of the culture media.
首先是培养基的局限性。
No single culture medium or the conditions to which it is subjected to can detect all potential microorganisms in the sample that are culturable.
没有一种培养基或它所受的条件能够检测出样品中所有可培养的潜在微生物。
A bias can be built in towards, microorganisms associated with the human skin microbiota (if that population is desired) by selecting a general purpose medium (like soybean casein digest
medium) and incubating it at 30-35 C for 72 hours or longer.
通过选择通用培养基(如TSA)，可以对与人类皮肤微生物群相关的微生物(如果需要的话)在30-35℃下培养72小时或更长时间。
Here the microbiologist will need to consider the populations of concern.
在这里，微生物学家将需要考虑种群的关注。
It remains that in many cases test regimes are biased towards aerobic, mesophilic microorganisms.
在许多情况下，测试体系仍然偏向于好氧的中温微生物。
This is because such organisms are common to the environment;
这是因为这样的生物体在环境中很常见;
they will often be a problem should they contaminate the product since they are the most likely to grow;
如果它们污染了产品，往往会成为一个问题，因为它们最有可能生长;
and because most human pathogens fall within this grouping (Nyström, 2001).
因为大多数人类病原体都属于这一类(Nystrom, 2001)。
Secondly, as discussed above, the colony forming unit, the end result of the test, is most
appropriately regarded as an estimate of the number of viable bacteria or fungal cells in a sample.
其次，如上所述，菌落形成单位，即测试的最终结果，是被适合地认为是对样品中活菌或真菌细胞数量的估计。
The visual appearance of a colony requires significant microbial replication, furthermore it is unknown if the progenitor of the colony was a single microorganism or several microorganisms in close proximity.
菌落的目视外观需要大量的微生物复制，此外，还不知道菌落的祖先是单个微生物还是几个非常接近的微生物。
Hence, when counting colonies it is uncertain if the colony arose from one cell or 1,000 cells and importantly CFU is not a direct accurate measure of microbial numbers.
因此，当计数菌落时，不确定菌落是来自一个细胞还是1000个细胞，重要的是，CFU不能直接准确地测量微生物数量。
Thirdly, inaccuracies can also occur with the act of plate counting.
第三，平板计数动作也可能发生不准确。
Here a distinction needs to be drawn between the Limit of Detection for microbiological agar plates (assumed to be 1 CFU, but in reality untestable with conventional methods) and the Limit of Quantification (which is based on the countable range, which is partly a function of the size of the test plate).
在这里之间需要微生物的检测极限琼脂板(假定为1个CFU,但实际上不可测试与常规方法)和量化的限制(基于可数的范围,这在一定程度上是一个函数的测试板)的大小。
Due to the size of the agar plate there will be an optimal counting range, errors will occur
where microbial numbers are above an upper countable limit (due to confluence or overcrowding) or below a lower limit (due to statistical error in relation to accuracy of the count, particularly where dilutions have been performed) (Clarke, 1998).
由于琼脂板的大小会有一个最佳的计数范围，会发生误差微生物数量高于可计数上限(由于汇合或过度拥挤)或低于下限(由于与计数准确度有关的统计误差，特别是在已进行稀释的情况下)。
The USP guidance chapter (<1227> Validation of microbial recovery from pharmacopoeial articles) recommends 25 to 250 CFU for bacteria and yeast, such as Candida albicans; and 8 – 80 CFU for filamentous fungi.
USP指南章节(<1227>验证药典文章中微生物回收率)推荐25到250 CFU用于细菌和酵母，如白色念珠菌;和8 – 80 CFU用于丝状真菌。
These are in relation to 90-100 mm agar plates.
这些是关于90-100毫米琼脂板。
For 55 mm plates (as might be used with membrane filtration methods), countable ranges reduce to 20 to 80 CFU.
对于55毫米板(可能与膜过滤方法一起使用)，计数范围减少到20到80 CFU。
According to Sutton (2012), the upper range is due to a combination of colony size;
Sutton(2012)认为，上述范围是由于群体规模的组合;
colony behavior (including the effect of swarming or spreading);
群体行为(包括群集或扩散的影响);
the surface area of the agar plate;
琼脂板的表面积;
together with the general effects of confluence or over-crowding where large numbers of colonies are concerned.
以及大量蜂群聚集的汇流或过度拥挤的普遍影响。
Combined these factors lead to an assumption of error whereby at the ‘upper limit’ of the range the observed numbers of CFU will fall off relative to the expected numbers and the divergence becomes significant enough to render the observed count as too inaccurate to be of scientific value.
综合这些因素，可以得出一个误差假设，即在该范围的“上限”处，观测到的CFU数量相对于预期数量将会下降，而这种差异变得足够显著，以至于观测到的数量过于不准确，没有科学价值。
Similarly, with the lower range error arises since the pattern of CFU’s recovered become subject
to what Jarvis (1989) terms ‘total error’.
同样，由于CFU模式的恢复导致较低的范围误差出现成为贾维斯(1989)所说的“完全错误”课题，Total error associated with colony counts from spread plates, pour plates and membrane filtration total counts can be expressed as:
涂布法、浇注板和膜过滤菌落计数的总误差可表示为:
% Total error=± square root (A2+B2+C2)
Where: 式中
A=% sampling error取样误差
B=% distribution error分布误差
C=% dilution error 稀释误差
The issue is compounded by the three different sources of error, which may act singularly or in
combination.
这一问题因三种不同的错误来源而复杂化，这些错误来源可能是异常的，也可能是潜在的组合。
Examples of each error are: 每个错误的例子如下:
Sampling error:weighing and mixing. 取样误差:称重和混合。
Distribution error:counting errors and recording errors. 分布误差:计数误差和记录误差。
Dilution error:pipetting volumes and diluent volumes. 稀释误差:移液体积和稀释体积。
As a result of these errors, low counts follow Poisson distribution.
由于这些误差，低计数遵循泊松分布。
Fourth, a further source of error can arise with rounding up or down or through averaging.
第四，舍入、舍去或平均可能会产生进一步的误差。
Therefore, an estimation of microbial numbers by CFU will, in most cases, undercount the number of living cells present in a sample (Weenk, 1992).
因此，在大多数情况下，CFU对微生物数量的估计会低估样本中存在的活细胞数量(Weenk, 1992)。
Related counting inaccuracies and error can also occur with the act of colony counting.
在群体计数的过程中，也会出现相关的计数误差。
The counting of colonies manually is normally carried out using an artificial light source, such as a colony counter.
人工菌落计数通常使用人工光源，如菌落计数器进行。
A fifth area of concern is with spreading microorganisms, which are problematic for colony
counting.
第五个值得关注的领域是蔓延微生物，这对菌落来说是有问题的计数。
Colony counting error arises due to indistinguishable colony overlap (i.e., masking).
由于无法分辨的菌落重叠(即,屏蔽)。
For spreading colonies, there are usually of 3 distinct types:
对于蔓延菌落，通常有三种不同的类型:
1) A chain of colonies, not too distinctly separated, that appears to be caused by disintegration
of a bacterial clump.
一串没有明显分离的菌落，似乎是由解体引起的细菌群
2) One that develops in film of water between agar and bottom of dish
在琼脂和培养皿底部之间的水膜中形成的
3) One that forms in film of water at edge or on surface of agar
在琼脂的边缘或表面形成水膜的物质
Thus methods for enumeration of microorganisms (compendial microbial enumeration and
non-compendial bioburden tests) can only have the objective of providing the best indicator possible of the microbial bioburden but not the absolute bioburden.
因此微生物的计数方法(微生物计数和非药典生物负载试验）只能提供微生物生物负载可能的最佳指标，而不能提供绝对生物负载。
Variations are also assumed with the assays to which the pour plate methods are applied.
对采用倾注法的测定方法也假定了变化。
These methods are assessed using microbial challenges for which an acceptable recovery is expressed as 50-200%.
这些方法使用微生物挑战进行评估，其中可接受的回收率表示为50-200%。
Challenges are undertaken during method qualification to show that the method is suitable and that any antimicrobial substances have been neutralized or adequately diluted out.
在方法鉴定期间进行了挑战，以证明该方法是合适的，并且任何抗菌物质已被中和或充分稀释。
Even where this occurs, it is acknowledged that recoveries of microorganisms under the conditions of the test are variable.
即使在发生这种情况的地方，人们也承认微生物在试验条件下的回收率是可变的。
In-built within this range are the variabilities described above.
在此范围内内置的是上面描述的变量。
To add to this are the variations associated with sample handling, especially when it is subject to procedures like centrifugation, voretxing, and hand-mixing.
此外还有与样品处理有关的变化，特别是当样品需要离心、还原和手工混合等程序时。
Microbial recovery can also be affected by resuspension into a different liquid (as with an enrichment or a dilution step), especially when the liquid is of a different composition, osmolarity, pH or temperature to the original growth conditions.
微生物的恢复也会受到重新注入不同液体的影响(例如通过富集或稀释步骤)，特别是当液体的成分、渗透压、pH值或温度与原始生长条件不同时。
Specific to the recovery ranges, the upper range of the 50-200% is more likely to be a product
of pipetting or dilution error, as well as reflecting the biological complexities when microorganisms grow under one set of conditions and not under another.
具体到回收率范围，50-200%的上限更有可能是一个产品当微生物在一组条件下生长而不是在另一组条件下生长时，就会反映出生物学的复杂性。
The lower range is a reflection of occasional cell death or damage to challenged
microorganisms that might lead to suppressed recovery (this can increase in relation to any hold time).
较低的范围是反映偶尔细胞死亡或损伤的挑战可能导致抑制回收的微生物(这与任何保持时间有关)。
It is also important to keep in mind that no ingredient, even in a chemically defined culture medium, is absolutely pure, which can add a further variation.
同样重要的是要记住，即使在化学定义的培养基中，也没有任何成分是绝对纯净的，这可能会增加更多的变异。
Strategies For Assuring Microbiological Data Integrity 确保微生物数据完整性的策略
To error-proof the sterility and other microbiological tests is impossible;
无菌和其他微生物检验不可能准确;
it is fundamentally flawed, however potential data integrity issues associated with the test can be addressed.
它从根本上是有缺陷的，但是可以解决与测试相关的潜在数据完整性问题。
In terms of microbiological quality control tests, an appropriately qualified microbiologist performs a visual inspection or enumeration of a test result, uses good judgment to interpret or assess and accurately documents the conclusion.
在微生物质量控制试验方面，具有适当资质的微生物学家对试验结果进行目视检查或计数，运用良好的判断对结论进行解释或评价，并将结论准确地记录在案。
The discriminatory capacity of the test is therefore dependent upon visual observation and interpretation.
因此，测试的辨别能力取决于视觉观察和解释。
Both visual observation and inspection are areas in which the sources of data integrity – system error or an individual’s honest mistake can be addressed by many individually appropriate strategies.
视觉观察和检查都是数据完整性的来源——系统错误或个人的诚实错误，可以通过许多单独适当的策略来解决。
Designing out the compendial method.
设计超出药典方法。
Deming famously stated “Inspection with the aim of finding the bad ones and throwing them out is too late, ineffective and costly.
戴明有句名言:“以发现不良资产为目的的检查，然后把它们扔出去，太晚了，没有效果，而且代价高昂。”
Quality comes not from inspection but improvement of the process.” (Hayes, 2014).
质量不是来自检验，而是来自过程的改进。”(海斯,2014)。
The same thinking, that fundamentally recognizes testing as an inefficient means of assuring quality is articulated by regulatory agencies (FDA Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, U.S. Department of Health and Human Services, Silver Spring, MD, 2004).
监管机构也表达了同样的想法，即从根本上承认测试是一种低效的保证质量的手段。
In the case of the sterility test options for parametric release exist (Stevens-Riley 2015) totally removing the potential data integrity risk associated with this microbiology test.
在无菌试验的情况下，存在参数放行的选项(Stevens-Riley 2015)，完全消除了与该微生物试验相关的潜在数据完整性风险。
Data integrity is fundamentally a design issue that permits or offers an opportunity for a human to make an error.
数据完整性从根本上讲是一个设计问题，它允许或提供了人为犯错的机会。
Due to the inherent flaws of microbiological quality control tests and especially the sterility test, removing or obviating the need for the flawed test is the most effective means of removing sources of data integrity, supporting cGMPs and assuring the highest level of patient safety.
由于微生物质控试验特别是无菌试验本身存在缺陷，减少或消除对有缺陷试验的需要是消除数据完整性来源、支持cGMPs、确保患者最高安全水平的最有效手段。
Designing out the test can be achieved in several ways.
设计测试可以通过几种方式实现。
First and foremost a parametric program of sterile product release offers the greatest assurance of sterility through an appropriately designed and managed program.
首先，无菌产品放行的参数化程序通过适当设计和管理的程序提供无菌的最大保证。
Parametric release is described in standards USP <1222> and regulatory FDA guidance (FDA Guidance for Industry – Submission of Documentation in Applications for Parametric Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes, U.S. Department of Health and Human Services, Silver Spring, MD, 2010), it has also been covered in PDA Technical Report 30 (Parametric release of pharmaceutical and medical device products terminally sterilized by moist heat (revised 2012)).
参数放行在标准USP <1222>和FDA规范指南中有描述，PDA技术报告30也讨论了这个问题。
For an organization to adopt a parametric program of release in place of sterility testing it must be filed with and approved by a competent regulatory authority thereby meeting the established standards and guidance.
组织采用参数化放行程序代替无菌检查，必须经主管管理部门备案并批准，从而符合既定的标准和指南。
Parametric release is a far superior method of product release (Tirumalai and Porter 2005).
参数放行是一种优越得多的产品放行方法(Tirumalai和Porter 2005)。
Currently parametric programs of sterile product release apply to those items terminally sterilized and to specific short-lived radiopharmaceuticals per 21 CFR Part 211.165(a) and 21 CFR Part 212.
目前无菌产品放行的参数化程序适用于通过21 CFR第211.165(a)和21 CFR第212部分中无菌的项目和特定的短期放射性药物。
In the latter circumstance the other contributing elements of manufacturing design, management and control are entirely and collectively leveraged to provide an approved assurance of sterility via a non-terminal sterilization process.
在后一种情况下，制造设计、管理和控制的其他要素全部和集体地利用起来，通过非终端灭菌过程提供经批准的无菌保证。
Hitherto, other non-terminal sterilization process of manufacture producing sterile drug products may also feature in forthcoming standards and represent candidates for parametric release.
到目前为止，其他生产无菌药品的非终端灭菌过程也可能出现在即将发布的标准中，并代表参数化发布的候选过程。
Alternative to a parametric program of release is the adoption of modern test methods that are
equivalent per USP (<1223> Validation of alternative microbiological methods) to the compendial method and which remove the element of visual acuity and judgment-based interpretation.
参数化程序的另一种选择是采用现代的测试方法等效的按照USP(<1223>验证替代微生物方法)，的药典方法，其中删除了视力的因素和基于判断的解释。
There are several systems that are marketed and available which provide for this opportunity, furthermore several of these systems have been successfully implemented.
有几个已经上市和可用的系统提供了这种机会，而且其中几个系统已经成功地实现了。
Improve the test method. 改进测试方法。
Process improvement of the compendial test method is feasible to assist or aid the visualization of microbial growth;
对药典检测方法进行工艺改进，以辅助或辅助微生物生长的可视化是可行的;
turbidity in the case of the sterility test and colony forming units for agar plate-based methods.
在混浊的情况下进行无菌试验和菌落形成单位为琼脂平板的方法。
Machine, laser and optical technology can assist or entirely remove the need for a microbiologist to visually discriminate and assess microbial growth.
机器、激光和光学技术可以帮助或完全消除微生物学家在视觉上辨别和评估微生物生长的需要。
Assessment using technology resulting in digitized images provides the means not only to make a conclusion on the test but also to record, archive, reference and retrieve data fulfilling the complete elements of data integrity.
利用数字化图像技术进行评估，不仅可以对测试作出结论，而且可以记录、存档、参考和检索数据，实现数据完整性的完整要素。
Visual discrimination by a microbiologist can also be significantly improved, removing human error by the provision of lighting systems and light boxes (where ambient white light provides better visual acuity than yellow light) and simple enhancements to minimize erroneously and accidently failing to identify or accurately enumerate growth.
微生物学家的视觉辨别能力也可以显著提高，通过提供照明系统和灯箱(环境白光比黄光提供更好的视力)和简单的增强功能，可以最大限度地减少错误和意外地未能识别或准确列举生长情况，从而消除人为错误。
Throughout the test method life-cycle it is prudent to establish and maintain a design history file or equivalent that records the methods development including archiving of images and supporting information.
在整个测试方法生命周期中，明智的做法是建立和维护一个设计历史文件或等效文件，记录方法的开发，包括图像存档和支持信息。
Enhance personnel knowledge and know-how.
提高员工的知识和技能。
Irrespective of the sophistication of a quality system, or test method, pervading culture and individual knowledge and know-how provides the greatest means of assuring cGMPs.
无论质量体系或测试方法的复杂程度如何，渗透文化和个人知识和专门知识都是确保cGMPs的最佳手段。
Training, knowledge management and education are pivotal to provide the necessary experience and expertise in discriminating the visual signature of microbial growth within microbiology quality control tests; irrespective of whether it is within a sterility test canister or upon an agar plate.
培训、知识管理和教育对于在微生物质量控制测试中鉴别微生物生长的视觉特征方面提供必要的经验和专业知识至关重要;不管它是在无菌测试筒内还是在琼脂板上。
Equipping microbiologists with the fundamental knowledge and principles of the test and moreover the information (especially archived images) within a test method design history file is one of the most effective, expedient and efficient means of addressing data integrity issues.
为微生物学家提供测试的基本知识和原则，以及测试方法设计历史文件中的信息(特别是存档的图像)，是解决数据完整性问题的最有效、快捷和高效的方法之一。
It is not uncommon for certain product formulations to possess inherent physical or chemical characteristics (e.g. alumina adjuvants in vaccines) which may obscure a visual identification of growth or which could be mistakenly interpreted as growth.
某些产品配方具有固有的物理或化学特性(例如疫苗中的氧化铝佐剂)并不罕见，这些特性可能会模糊生长的视觉识别，或者可能被错误地解释为生长。
A program of interactive knowledge management and a library of images is exceptionally effective in preventing data integrity issues.
交互式知识管理程序和图像库在防止数据完整性问题方面非常有效。
Ongoing expert qualification.
持续的专家确认。
It is also necessary to accompany any expert training program with an initial and ongoing qualification program that not only establishes a microbiologist’s credential to make the assessment, regularly affirms that competency and ensure new information (as part of the test method life cycle and design history file) cogent to the test is provided to the microbiologist.
也需要伴随任何专家培训项目初始和持续的资格程序,不仅建立一个微生物学家的确认进行评估,定期确认能力和确保新信息(如测试方法生命周期的一部分,设计历史文件)令人信服的向微生物提供了测试。
Such training could include assessing the ability of the microbiologist to spot turbidity using standards of turbidity (such as solutions prepared along the McFarland scale) or broth cultures challenged with a range of microorganisms, designed to show different growth patterns in different media (Streptococcus bacteria grow very differently in tryptone soya broth compared with fluid thioglycollate medium, for example.
这种培训可以包括评估微生物学家利用浑浊度标准发现浑浊度的能力(如按照麦克法兰量表编制的解决方案)或者是受到一系列微生物挑战的肉汤培养基，设计用于在不同培养基中显示不同的生长模式(例如，链球菌在色氨酸大豆肉汤中与液体巯基乙酸盐培养基相比生长非常不同。
As eyesight inevitably declines with ageing, periodic reassessment is recommended.
随着年龄的增长，视力不可避免地会下降，因此建议定期重新评估视力。
A different example is with tests for color blindness, which are important for differentiating some microbial identification tests and the red-to-blue spectrum which applies to the Gram-stain.
另一个例子是色盲测试，它对区分一些微生物鉴定测试和适用于革兰氏染色的红蓝光谱非常重要。
As with any test, if there is any dubiety in the interpretation of the data, then this should automatically trigger a proceduralized escalation to a further form of evaluation; either by additional qualified microbiologists or other technology.
与任何测试一样，如果对数据的解释存在任何不确定性，那么这应该自动触发一个程序化的升级，从而形成进一步的评估形式;要么通过其他合格的微生物学家，要么通过其他技术。
Trending and analysis.
趋势研究和分析。
Thorough, routine, trending and evaluation of microbiological data, although primarily purposed as a monitor of manufacturing performance control, also permits the evaluation and identification of potential data integrity issues.
微生物数据的全面、常规、趋势和评估，虽然主要用于监测生产性能控制，但也允许评估和识别潜在的数据完整性问题。
Evaluation of microbiological data is a suitable diagnostic identifying any inconsistencies in microbiological data which might originate from a data integrity issue.
微生物数据的评估是一种合适的诊断方法，可以识别微生物数据中可能源自数据完整性问题的任何不一致性。
This is an especially powerful means of addressing potential data integrity risks when multiple microbiologists are routinely scheduled to perform tests, inspect the test and interpret results.
当多个微生物学家按常规计划执行测试、检查测试并解释结果时，这是处理潜在数据完整性风险的一种特别强大的方法。
Second person verification.
第二人确认。
Including a second person verification (an additional microbiologist of equal or better expertise and training to visually examine and interpret) doubles the number of personnel making the visual discrimination and conclusion.
包括第二个人验证(一个额外的微生物学家，具有同等或更好的专业知识，并受过视觉检查和解释的培训)，使做出视觉辨别和结论的人员数量翻了一番。
It can be argued that this provides an additional level of assurance of achieving the correct interpretation, however this in itself is a flawed argument because any assessment is fundamentally based upon the competency of the person making the assessment.
可以认为，这为实现正确的解释提供了额外的保证，但这本身是一个有缺陷的论点，因为任何评估基本上都是基于做出评估的人的能力。
If a training and knowledge management program is insufficient it may not matter how many microbiologist verify the test method data.
如果培训和知识管理程序不足，那么有多少微生物学家验证测试方法数据可能并不重要。
In other words this solution will only be effective if visual acuity and experience and knowledge of both are adequate.
换句话说，只有在视力、经验和知识都足够的情况下，这个解决方案才会有效。
This solution does not provide a means of addressing the maleficent intent of an individual or an organization; if there is a determination to manipulate data an individual will always find a means.
本解决方案不提供解决个人或组织不良意图的方法;如果有篡改数据的决心，个人总会找到办法。
Figure 2. Dimensionality of microbiological quality control test methods (adapted from Sawant, 2016). CQA: critical quality attribute, CPC: critical process control, IPC/Other: in- process control, QMS: quality management system.
图2。微生物质量控制检测方法维度(自Sawant, 2016)。CQA:关键质量属性，CPC:关键过程控制，IPC/Other:过程控制，QMS:质量管理体系。
（未完待续）
上节回顾：PDA-确保微生物测试数据的完整性（二）
下节预告：PDA-确保微生物测试数据的完整性（四）
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