-
Guidance in defining critical process
parameters
关键参数的定义指南
The
criticality
of
a
process
parameter
is
an
assessment
of
the
probability
that
it
can
be
consistently
and
reproducibly
controlled
within
the
proven
acceptable
range
(PAR)
during
routine manufacturing.
工艺参数的
关键性是指在生产中对可接受范围的持续重复控制的可能性的评估，
This probability depends on
可能性主要取决于：
t
he robustness of the
process parameter (the width of the PAR)
工艺参数的稳定性（可接受范围的宽度）
?
t
he
ability to technically control the parameter
(technical limitations)
参数控制的技术能力（技术限制）
?
t
he
uncertainty
of
the
measurement
of
the
parameter
(reflected
by
the
standard
deviation σ)
参数测量的不确定性（用标准偏差来反映）
?
The
robustness of a process parameter is reflected by
the width of the proven acceptable range.
The wider the range within which a
parameter could
be varied during
process
qualification
without impacting product quality, the
more robust it is.
可接受的参数范围反映工艺参数的稳定性。<
/p>
在参数确认中不影响产品质量的可改变的参
数的范围越宽，工艺越
稳定。
The
ability
to
technically
control
a
parameter
is
a
function
of
a
combination
of
process
properties
and
equipment
capabilities.
For
example,
a
highly
exothermic
reaction
might
be
well
controlled
in
a
small
stainless
steel
vessel,
but
could
prove
impossible
to
control
in
a
larger glass-lined vessel.
参数的技术控制能力是工艺特性和设备能力的综合功能。例如，一个高放热的反应可能在
一个
小的不锈钢反应釜内能够很好的被控制，
但是在一个大的塘
玻璃反应釜内证明是不可能控制的。
The
uncertainty of
a measurement
(
σ
) is
the
combined uncertainty of the calibration
of the
probe, the variance of the probe
itself, and the variance of the signal
transmission from the
probe to the
distributed control system (DCS). If the
measurement is normally distributed, 3.4
out of a million data points will be
outside a range of +/- 4.5 standard deviations.
This is the
basis of the ‘six sigma’
theory. The difference of 1.5 between 4.5 and 6 is
an empirical value
chosen based on the
observation that the mean of real processes tends
to drift by this value
over time.
Based on the ‘6
σ
’
-
concept we define a
parameter as ‘critical’ when the proven
acceptable range is narrower than
±
six standard deviations.
测量的不确定性是探头或检测器的校验，监测器本身的变化和从探头到
< br>DCS
的信号传
输的变化的不确定因素的综合。如果测量
结果是正态分布的，
3.4PPM
（百万分之一）将
在
+/-4.5
标准偏差的范围之外。这是六西格
玛理论的基础。
4.5
和
6
之间
1.5
的差异是一
个
经验值基于观察实际工艺趋势相对时间数值的漂移。
基于六西格玛概念当一个参数的
可接受的范围比
+/-
六个标准偏差窄时，
我们定义这个参数为关键参数。
figure 1: critical parameter
set
point
figure 2: non-
critical
parameter
set
point
5
5°
6
0°
5
5°
6
0°
4
0°
4
5°
5
0°
6
5°
7
0°
4
0°
4
5°
5
0°
6
5°
7
0°
6
σ
6
σ
6
σ
6
σ
proven acceptable range
lower/upper
edge of failure
proven acceptable
range
lower/upper edge of
failure
Whereas
a
proven
acceptable
range
depends
only
on
the
process,
the
variance
of
a
control
system
is
equipment-specific.
The
variance
of
a
control
system
for
the
same
process
parameter
might
be
different
in
another
operational
environment,
which
could
result
in
a
different criticality
assessment (e.g. a critical process parameter in
one plant may be judged to
be non-
critical in another plant which has a control
system with a lower variance).
如果一个可接受的参数范围仅仅依赖于工艺，控制系统的变异是设备属性。对同样的工
< br>艺参数的控制系统的变异可能在另一个操作环境下不同，
这个可能导致一个不同的
关键
性评估
（比如在一个工厂的一个关键参数在另一个有较低变
异的控制系统的工厂就可能
被判定为不关键）
The following table can be used for
guidance to assess the criticality of a process
parameter
以下列表在指南中用于评定一个工艺参数的关键性
type
of
parameter
工艺参数的类型
process
assumption
minimum PAR for
non-critical
Comment
parameter (±
6
σ
)
for
σ
备注
判定不关键的最小可接受范围
For
the
typical
measurement
range
of
Temperature
温度
0.6%
+/-4%
(of measurement range)
(
检测范围的
)
-20 to 180°
C: +/-
8°
C
对于典型的测量范围
-20~
180°
C
，范
围为
< br>+/-8°
C
Amount
(quantity) by
weight
0.8%
重量
+/-5%
(of set point)
（设定点的）
+/-12%
(of set point)
（设定点的）
+/-0.6pH-
units
+/- 1.0 pH-units
1)
The
limits
of
the
balance
have
to
be
taken into account. See:
称的限度应该带进数量
Important:
a
certain
minimal
flow
has
to be
exceeded
重要提示：
必须超过确定的最小流量
The
pH
is
typically
more
difficult
to
control than to measure.
pH
是典型的控制难于检测
Pressure
is
typically
more
difficult
to
Amount (quantity)
by volume
体积数量
2%
pH
0.1
pH-unit
Pressure (vacuum)
压力（真空）
0.8%
+/- 20%
2)
control than to measure.
压力是典型的控制难于检测