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Presented by,
Y.Maheshwara prasad
M pharmacy (Pharmaceutics) 1st semester
Care college of pharmacy,warangal
Contents:
• Introduction to process controls involved in the
manufacturing of pharmaceutical dosage forms
• Statistical process control
• Control charts
• Control charts for attributes
• Control charts for variables
• Control chart patterns
• Applications in pharmacuticals
3-2
Process controls involved in the manufacturing process of
pharmaceutical dosage forms
95%
99.74%
-3σ -2σ -1σ µ =0 1σ 2σ 3σ
3-12
Process Control Chart
Out of control
Upper
control
limit
Process
average
Lower
control
limit
1 2 3 4 5 6 7 8 9 10
Sample number
3-13
A Process Is in Control If …
3-14
Types of Control Charts:
• Control charts are one of the most commonly
used tools in statistical process control.
• They can be used to measure any characteristic
of a product, such as the weight of a cereal box,
the number of chocolates in a box, or the volume
of bottled water.
• The different characteristics that can be
measured by control charts can be divided into
two groups: variables and attributes.
A control chart for variables:
• A control chart for variables is used to monitor
characteristics that can be measured and have a
continuum of values, such as height, weight, or
volume.
• EG: Syrup solution bottling operation is an
example of a variable measure, since the
amount of syrup solution in the bottles is
measured and can take on a number of different
values.
• Other examples are the weight of a bag of
paracetamol powder, the temperature of a Hot
air oven, or the diameter of plastic tubing.
A control chart for attributes:
• A control chart for attributes, on the other hand, is used
to monitor characteristics that have discrete values and
can be counted. Often they can be evaluated with a
simple yes or no decision.
• Examples include color, taste, or smell.
• The monitoring of attributes usually takes less time than
that of variables because a variable needs to be
measured.
• An attribute requires only a single decision, such as yes
or no, good or bad, acceptable or unacceptable
• e.g., the apple is good or rotten, the meat is good or
stale, or counting the number of defects e.g., the number
of broken cookies in the box, the number of dents in the
car, the number of barnacles on the bottom of a boat.
A control chart for variables:
• Two of the most commonly used control
charts for variables monitor both the
central tendency of the data (the mean)
and the variability of the data (either the
standard deviation or the range).
• Mean (x-Bar) Charts
• Range (R) Charts
Mean (x-Bar) Charts:
• A mean control chart is often referred to
as an x-bar chart. It is used to monitor
changes in the mean of a process.
• This chart serves mainly in validation.
• Changes in the process can be detected
by these charts.
• Accuracy may also be monitored to some
extent.
Construction of x-bar Chart:
= x1 + x2 + ...
x
xn
=
Where, x = average of sample means.
n
z =standard normal variable (2 for
95.44% confidence, 3 for
99.74%confidence).
=
n = sample size.
σ x = σ /√n, σ =population (process) SD.
3-20
x-bar Chart Example:
Standard Deviation Known (cont.)
3-21
x-bar Chart Example:
Standard Deviation Known (cont.)
3-22
x-bar Chart Example:
Standard Deviation Unknown
=A R
UCL = x + LCL =
= x - A22R
2
2
3-23
Control
Limits
3-24
x-bar Chart Example:
Standard Deviation Unknown
OBSERVATIONS (RING DIAMETER, CM)
SAMPLE k 1 2 3 4 5 x R
1 5.02 5.01 4.94 4.99 4.96 4.98 0.08
2 5.01 5.03 5.07 4.95 4.96 5.00 0.12
3 4.99 5.00 4.93 4.92 4.99 4.97 0.08
4 5.03 4.91 5.01 4.98 4.89 4.96 0.14
5 4.95 4.92 5.03 5.05 5.01 4.99 0.13
6 4.97 5.06 5.06 4.96 5.03 5.01 0.10
7 5.05 5.01 5.10 4.96 4.99 5.02 0.14
8 5.09 5.10 5.00 4.99 5.08 5.05 0.11
9 5.14 5.10 4.99 5.08 5.09 5.08 0.15
10 5.01 4.98 5.08 5.07 4.99 5.03 0.10
50.09 1.15
3-25
x-bar Chart Example:
Standard Deviation Unknown
(cont.)
∑R 1.15
R= = =
0.115k 10
= ∑x 50.09
x= = = 5.01 cm
k 10
=
UCL = x + A2R = 5.01 + (0.58)(0.115) = 5.08
=
LCL = x - A2R = 5.01 - (0.58)(0.115) = 4.94
Retrieve Factor Value A2
3-26
5.10 –
5.08 –
UCL = 5.08
5.06 –
5.04 –
5.02 – x= = 5.01
Mean
5.00 –
x- bar 4.98 –
Chart 4.96 –
LCL = 4.94
Example 4.94 –
(cont.) 4.92 –
| | | | | | | | | |
1 2 3 4 5 6 7 8 9 10
Sample number
3-27
Range (R) chart:
• Range (R) chart a control chart that monitors
changes in the dispersion or variability of
process. Whereas x-bar charts measure shift in
the central tendency of the process.
• The method for developing and using R-charts is
the same as that for x-bar charts.
• The center line of the control chart is the
average range, and the upper and lower control
limits are computed as follows:
R- Chart
∑R
R=
k
where
R = range of each sample
k = number of samples
3-29
R-Chart Example
OBSERVATIONS (RING DIAMETER, CM)
SAMPLE k 1 2 3 4 5 x R
1 5.02 5.01 4.94 4.99 4.96 4.98 0.08
2 5.01 5.03 5.07 4.95 4.96 5.00 0.12
3 4.99 5.00 4.93 4.92 4.99 4.97 0.08
4 5.03 4.91 5.01 4.98 4.89 4.96 0.14
5 4.95 4.92 5.03 5.05 5.01 4.99 0.13
6 4.97 5.06 5.06 4.96 5.03 5.01 0.10
7 5.05 5.01 5.10 4.96 4.99 5.02 0.14
8 5.09 5.10 5.00 4.99 5.08 5.05 0.11
9 5.14 5.10 4.99 5.08 5.09 5.08 0.15
10 5.01 4.98 5.08 5.07 4.99 5.03 0.10
50.09 1.15
3-30
R-Chart Example (cont.)
3-31
R-Chart Example (cont.)
0.28 –
0.24 – UCL = 0.243
0.20 –
Range
0.16 – R = 0.115
0.12 –
0.08 –
0.04 – LCL = 0
| | | | | | | | | |
0–
1 2 3 4 5 6 7 8 9 10
Sample number
3-32
Control Charts for Attributes
p-chart
uses portion defective in a sample
c-chart
uses number of defective items in
a sample
3-33
P-charts:
• P-charts are used to measure the proportion of
items in a sample that are defective. Examples
are the proportion of broken vials in a batch .
• P-charts are appropriate when both the number
of defectives measured and the size of the total
sample can be counted.
• The center line is computed as the average
proportion defective in the population, . This is
obtained by taking a number of samples of
observations at random and computing the
average value of p across all samples.
p-Chart
UCL = p + zσ p
LCL = p - zσ p
z = number of standard
deviations from process average
p = sample proportion
defective; an estimate of process average
σ p = standard deviation of sample
proportion
p(1 - p)
σ =
p
n
3-35
Construction of p-Chart
NUMBER OF PROPORTION
SAMPLE DEFECTIVES DEFECTIVE
1 6 .06
2 0 .00
3 4 .04
: : :
: : :
20 18 .18
200
3-36
Construction of p-Chart (cont.)
total defectives
p= = 200 / 20(100) = 0.10
total sample observations
3-37
0.20
0.16
0.14
Proportion defective
0.12
p = 0.10
0.10
0.08
0.06
0.04
2 4 6 8 10 12 14 16 18 20
Sample number
3-38
C-charts:
• C-charts are used to monitor the number of
defects per unit.
• Examples are the number of recalled products in
an industry in a month, and the number of
bacteria in a milliliter of water.
• Note that the types of units of measurement we
are considering are a period of time, or a volume
of liquid.
• The average number of defects, is the center
line of the control chart. The upper and lower
control limits are computed as follows:
c-Chart
UCL = c + zσ c
σ = c
LCL = c - zσ c
c
where
c = number of defects per sample
3-40
c-Chart (cont.)
Number of defects in 15 sample rooms
NUMBER
SAMPLE OF
DEFECTS
190
1 12 c= = 12.67
15
2 8
UCL = c + zσ c
3 16
= 12.67 + 3 12.67
: : = 23.35
: : LCL = c - zσ c
15 15 = 12.67 - 3 12.67
190 = 1.99
3-41
24
UCL = 23.35
21
18
Number of defects
c-
c = 12.67
15
Chart 12
(cont.) 9
3 LCL = 1.99
2 4 6 8 10 12 14 16
Sample number
3-42
Contol chart for capsule weight
data
Application to pharmaceuticals
• Drug potency
• Tablet or capsule inprocess characteristics
• Powder chcharacteristics like mean particle size
• Microbial count
• Drug content application (nasal spray )
• Fill weight and fill volume
• Liquid charecteristics like viscosity and refractive index
• Consumer complaints and industrial safety
measurements
Conclusion
• statistical process control improve the quality
of the processes
• Statistical process control provides a
statistical approach for evaluating process
• When statistical process controls
implemented benefits can be derived through
a reduced cost of manufacture, improved
quality ,reduced trouble shooting crises
References:
• Quality assuarance and quality management in
pharmaceutical industry by Anjaneyelu.
• Encyclopedia of pharmaceutical technology
volume -6 by James Warrick
• Theory and practice of industrial pharmacy
by Leon Lachlan
.