1. LEONARD ALLEN
PROJECT ON CALIBRATION
PART A – THE IMPACT OF CALIBRATION ON OTHER PROCESS
RELATED MODULES THAT I AM STUDYING THIS SEMESTER
(SPRING 2012)
Calibration is an integral part of a quality management system, because it is a means of
determining whether measuring devices meet the required specifications by comparing their
accuracies against known standards.
In this section I outline where I have encountered the term “calibration” in each of the other
three modules that I am studying this semester, which are Introduction to Industrial
Biotechnology, Lean Manufacturing and Organic & Inorganic Chemistry.
My first laboratory practical in the Introduction to Industrial Biotechnology module involved
the calibration of instruments. I calibrated four devices and the results of these tests
determined if the devices met the required specifications.
The items calibrated in this practical were a densiometer, a pan balance, a hydrometer and a
pH meter. The results of the calibrations showed that the latter two met the required
calibration specifications. The densiometer was under reading by 0.002g/cm3
and the balance
which was calibrated for measuring the volume of water was over reading by 0.98 ml.
The fact that the pan balance in this instance was over reading is a common occurrence with
these instruments, because readings given when a balance is tared to zero are liable to
fluctuate. Such fluctuations are the result of vibrations caused by the movement of people or
other machinery that may be operating in its immediate vicinity. These factors are liable to
produce errors of a fraction of a gramme. Temperature is another source of such fluctuations.
I had a similar experience with such fluctuations when I was calibrating a pan balance for this
(Calibration Science) module because the balance in this case was also under reading by a
fraction of a gramme.
The fact that the densiometer did not produce an accurate reading would also have been the
result of environmental factors, similar to those experienced when calibrating pan balances.
In the Lean Manufacturing module, which is classroom-based, we were given a hand-out on
calibration entitled “Control of Inspection, Measuring and Test Equipment.” It gave a general
overview of calibration and outlined a control procedure from the perspective of the supplier
of a measuring device.
In this module it was also pointed out that an American gallon is different from a British/Irish
gallon, but all masses, liquid volumes, etc. in Europe are measured using the SI/metric
system.
At the outset of this module it was stated that calibration was an important element of a
quality management system. Calibration principles have to be documented, together with
records of calibrations. In this instance, we discussed pressure gauges and their calibration
procedures and principles.
In the Organic and Inorganic Chemistry module I calibrated a pH meter before beginning
laboratory practicals which involved acid-base titrations and analysis of buffer solutions. The

2. latter also examined conjugate acid-base reactions. At the beginning of these processes pH
meters were calibrated with pH 4 and pH 7 buffer solutions and met the required
specifications in both instances. This was the same process carried out when I calibrated pH
meters for both this (Calibration Science) and the Biotechnology module.
The materials used in the titration (Organic & Inorganic Chemistry practical) and their pH's
were as follows:
 Deionised water pH 5.53*
 Sodium Hydroxide pH 12.54
 Hydrochloric Acid pH 1.68
 Acetic Acid pH 2.59
The deionised water (marked with an asterisk) did not give a neutral pH of 7, because once it
was poured into a beaker it absorbed carbon dioxide from the atmosphere giving it a slightly
acidic pH. Sodium hydroxide and hydrochloric acid produced their respective strongly basic
and strongly acidic pH’s. The acetic acid surprisingly produced a strongly acidic pH of 2.59,
because its concentration was not known.
PART B – SCALES OUT OF CALIBRATION
Question 1 – What are the key risk(s) to be considered?
The key risks to be considered are:
 Are the ingredients being used in their correct quantities?
 Are these tablets in their correct dose format?
 Factors that cause the scales to go out of calibration
 Is this batch within or outside its control limits?
The initial risks to be considered are whether the tablets are in the correct dose format and if
the active pharmaceutical ingredients (API’s) and excipients have been used in the correct
quantities. These factors determine the efficacy of the tablets, which is their therapeutic effect
and the impact they may have on potential patients.
The balance is liable to go out of calibration due to environmental factors such as vibrations
and this causes the meter connected to the balance to under-read or over-read. This gives an
indication of whether the balance is exhibiting hysteresis. Hysteresis is a situation where the
balance consistently produces different output values (readings on the balance meter) for the
same input value (a weight of a particular mass placed on the scales).
Contaminants and/or incorrect quantities of ingredients used in the production of these tablets
determine whether this batch is outside its control limits. This is determined using control
charts, with the results of Six Sigma calculations. This data provides numerical values for the
control limits of a process. I would recommend Six Sigma for determining these criteria,
because it gives a prior indication of how deviations in a process can be prevented or
minimized. Six Sigma determines control limits at rates of three standard deviations above
and below the mean value of a process.
Question 2 – Is there any additional information required?
One piece of additional information required is whether a Hazard Analysis Critical Control
Points (HACCP) programme is in place. This determines evidence of potential hazards in the

3. production area and how they can be prevented. An example would be if a milling technique
was used because one of its drawbacks is the fact that metal particles from a mill can
contaminate a product and have grave consequences.
Root cause analysis and Corrective and Preventative Action (CAPA) are methods of
identifying the causes of such deviations. Results gained by using the former technique will
get to the root of the deviation and the latter is used to prevent a recurrence.
Details of quantities of ingredients used in the production of this batch and all equipment
used are also required, because the whole process has to be documented from start to finish.
Documentation is a mandatory GMP requirement.
Question 3 – Outline a calibration procedure for the balance, indicating what additional
information is needed about the balance.
Calibration Procedure
 Check the cleanliness of the area around the balance
 Check that the platform of the balance and that parts of the balance that are exposed
are clean and dry
 Check the level of the balance with the help of spirit level. If the balance is not level it
will have to be adjusted
 Switch on the main power supply of the balance
 Check the following parameters during the calibration: Accuracy, Linearity Precision
and Eccentricity Test.
The balance is calibrated for accuracy, which is a measure of how close the measured value
of a balance is to its true value. The measured value is the desired result of a measurement
while the true value is a result often given mistakenly. The accuracy of the balance is set by
the supplier and mathematically it is stated as:
Accuracy = MV +/-y.
In the above equation MV denotes measured value and y is the difference between the
measured value and the true value as set by the supplier.
For example if a balance has an accuracy of 5 grammes, it means that the mass of an object
being weighed lies within plus or minus 5 g of the balance reading. Thus a MV reading of
50g states that the true value of the quantity being measured is between 45g and 55g.
The precision of the balance is determined by its ability to produce the same reading for
repeated values of the same quantity being measured. A precise instrument does not guarantee
accuracy. The precision of a balance is susceptible to environmental factors such as
vibrations.
Acceptance criteria such as the recommended percentage standard deviation are set by the
supplier and if these tests produce satisfactory results, a calibration tag may be attached to the
balance.
The linearity of the balance is a measure of how close an output/input characteristic is to a
specified straight line. This is the ability of the balance to be equally sensitive throughout its
range. This is where the output reading of the balance is proportional to its corresponding
input.

4. The eccentricity test is carried out when a weight is placed in different positions on the
balance and the output of each is noted. If each reading falls within the acceptance
parameters, the balance is within calibration and a calibration tag may be attached.
Otherwise, the balance will have to be reset and this test repeated until the desired results are
produced.
Additional Information
Additional information required is obtained from the results of the accuracy, linearity,
precision and eccentricity tests and details of calibration schedules as set by the supplier. The
latter states how often the balance needs to be calibrated and the user needs to keep records of
these very important particulars.
Calibration records contain the following data:
 History of the balance
 Date of initial calibration
 Name of the person who carried out the initial and each subsequent calibration and
 Due date for next calibration
If measuring devices are not calibrated they must be placed in a quarantine area or labelled
with a “Calibration Void” decal (tag or sticker).
Question 4 - Under what circumstances would it be acceptable to release such a batch?
Outline justifications for this.
It would be acceptable to release such a batch if the tablets met the specifications and their
production process did not produce atypical results.
The tablets undergo three tests in the process room followed by five laboratory tests, which
determine whether they meet the required specifications.
In the production room, the tablets are tested for:
 weight
 hardness and
 metal contaminants.
The first test determines if they are of the correct weight and the latter two determine the
robustness of the tablets and whether metal contaminants in the form of ions are present. If
the tablets have passed these tests, they are sent to the laboratory to be tested under the
following headings:
 friability (rate of abrasion)
 stability
 disintegration
 dissolution and
 bioavailability
The initial test for friability determines the rate of abrasion of the tablets. Samples are
weighed and placed in a rotating drum at a speed of 30 rpm and weighed again after having
been spun. Friability is the difference between these masses. If the difference in masses
before and after this process is minimal, the tablets will be deemed to have passed this test.

5. The stability test is a means of determining the shelf life of the tablets and the latter three
determine characteristics of the tablets directly related to their impact on the patient.

6. Question 5 - Under what circumstances would it be unacceptable to release such a
batch? Outline justifications for this.
It would be unacceptable to release such a batch if traces of contaminants such as microbial
contaminants, human skin scales or metal ions were detected, because this would have
serious consequences.
If the balance deems the tablets to be potentially underweight, I would recommend that this
batch be weighed on a balance that is within calibration before deciding whether or not to
release them.
References
Calibration Procedure of a Balance (Question 3)
http://gmponblog.vinvarun.biz/2008/08/sop-calibration-of-balances.html

7. Question 5 - Under what circumstances would it be unacceptable to release such a
batch? Outline justifications for this.
It would be unacceptable to release such a batch if traces of contaminants such as microbial
contaminants, human skin scales or metal ions were detected, because this would have
serious consequences.
If the balance deems the tablets to be potentially underweight, I would recommend that this
batch be weighed on a balance that is within calibration before deciding whether or not to
release them.
References
Calibration Procedure of a Balance (Question 3)
http://gmponblog.vinvarun.biz/2008/08/sop-calibration-of-balances.html