16/11/2017 A Simple Process Validation Example | Iterations

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A Simple Process Validation Example

By Shrikant Kalegaonkar on August 14, 2011

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6 Votes

Consider the bread making process shown in the gure below. Someone developed it for making bread. The bread
made using this process has various characteristics that consumers nd desirable: look, feel, taste, etc. Each of these
characteristic can be measured and will have some target value (based on consumer research) such that if a loaf is
made with all its characteristics on target, there is a high probability that it will meet the consumers expectation and
the consumer will enjoy eating it. The question that process validation seeks to answer is will this process
consistently produce bread loaves of the specied quality.

(h ps://shrikale.les.wordpress.com/2011/08/clipboard02.jpg)

A fundamental assumption in manufacturing is that if the inputs to the process remain constant e.g. you use exactly
6 cups of bread our each time, and the process itself is constant e.g. the oven generates 350 F of heat every time,
then each output of the process will be the same as the previous with no discernable dierence. However, nothing is
constant: there is natural variability in the quantity of the our used; sometimes you might use as li le as 5.5 cups;
other times you might use as much as 6.5 cups. Even the oven periodically turns its heating mechanism on and o to

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provide a mean temperature of 350 F, but the actual temperature at any given instant is more likely than not to be
above or below the mean. So in the physical world each output of the process i.e. each loaf of bread will be dierent
from the previous.

The question then becomes is the loaf to loaf variability in the output, the result of the variability in the inputs and
the process, noticeable by the consumer? Each characteristic of the output not only has a target value but also a range
about the target that is considered acceptable. The bread may be okay if its crust is slightly more or less brown, but
rejected if it is signicantly dark (suggesting burnt) or light (suggesting underdone). What exactly are the limits of
acceptability for each characteristic? That is decided through consumer research. Assuming, for our purposes that
these limits are already specied, then if the measured value of a particular characteristic for a given loaf of bread
falls within its upper specication limit and lower specication limit, it is considered acceptable.

During process validation the process is kept constant i.e. step sequence, parameter se ings, etc. are xed, while its
inputs are varied between their extreme possible conditions. The thought is if the output of the process subjected to
such extreme conditions of its inputs is within acceptable limits, then the output of the process with normal
conditions of inputs will also be acceptable. The intent of this exercise is to demonstrate the robustness of the process
to the natural variations in its inputs.

(h ps://shrikale.les.wordpress.com/2011/08/clipboard03.jpg)

The design of experiments provides an ecient way to simultaneously vary every input between its extremes. For
the bread making process in this example, there are 6 inputs: amount of bread our, salt, vegetable oil, active dry
yeast, white sugar and water. If we assume that each of these inputs will vary from their specied quantity as shown
in the table below, then we can construct a two level six factor experiment for the process validation study.

Low (-) High (+)

A Bread our (cups) 5.75 6.25

B Salt (teaspoon) 1.25 1.75

C Vegetable oil (cups) 3/16 5/16

D Active dry yeast 1.25 1.75

(tablespoon)

E White sugar 5/9 7/9

F 100F warm water 1.75 2.25

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Such an experiment is referred to as a full factorial experiment i.e. one where every combination of high and low
values of every factor is made. Each combination will then be run through the process in randomized order. And each
resulting loaf of bread will have various quality characteristics measured e.g. look (I), feel (II), and taste (III). These
measured values will be plo ed on separate run charts with their respective specication limits drawn in. The
expectation is that the actual values will all fall within the spec limits. If that is the case, we can state with condence
that as long as the input variables remain within the upper and lower limits of their respective specications, the
quality characteristics of the resulting output will also be within their respective specication limits. And, thus we
can conclude that the process is validated for the set of inputs specications dened.

Note: A full factorial experiment is not necessary. I will have more to say about this in another post.

References

Guidance for Industry Process Validation: General Principles and Practices

(h p://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070336.pdf).
U.S. Department of Health and Human Services, Food and Drug Administration, CDER/CBER/CVM. 2011. Web.

Appendix Full factorial experiment design (order not randomized)

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Posted in: Quality, Statistics | Tagged: design of experiments, FDA, manufacturing, process validation, validation,
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5 responses

Murali May 15, 2013 at 6:40 PM | Reply

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Really good notication to understand the wordvalidation

Tomas March 25, 2014 at 7:05 AM | Reply

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Perfect article. Just wondering, were to nd an unswer to this one:

Note: A full factorial experiment is not necessary. I will have more to say about this in another post.

Shrikant Kalegaonkar March 25, 2014 at 9:39 AM | Reply

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Hi Tomas,

Thanks for your comment. Im glad you found the post useful.

I havent wri en the follow-up to the article yet. It sort of fell o my radar. However, I can provide a brief answer
for you.

As I understand things, for process validation, if you have identied the critical inputs to your process, then it is
necessary to conduct the full factorial experiment. This is because every extreme (or corner) of the inputs must
be investigated.

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Full factorial experiments are not necessary if you are designing a product or process. The be er way is to run a
sequence of partial factorial experiments. An excellent guide to industrial experimentation is Dr. Donald J
Wheelers book Understanding Industrial Experimentation
(h p://www.spcpress.com/book_understanding_indust_exp.php)

Best regards,
Shrikant Kalegaonkar

Tomas March 27, 2014 at 2:38 AM | Reply

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Hi Shrikant, thank You for the comments and suggestions. Also regarding software to help with process
validation and DOE ? Would you be able to suggest or recommend ?

Kind Regards,
Tomas

Shrikant Kalegaonkar March 27, 2014 at 8:04 AM | Reply

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Hi Tomas,

I have to tell you I am not a big fan of software for statistics. I personally use a spreadsheet program like MS
Excel or Libre Calc.

Having said that, Ive used Minitab and JMP. They are both powerful programs with comparable capabilities.
However, they are not cheap and I am not convinced they are worth the cost for something you can easily do
yourself in a spreadsheet program.

Best wishes on your choice,

Shrikant

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