1) The document discusses good practices for dispensing and sampling of raw materials in pharmaceutical manufacturing. It emphasizes carefully following standard operating procedures to prevent contamination. 2) Key steps in dispensing include cleaning the room, checking that the right chemical and amount are issued, weighing while being double checked, and immediately cleaning up any dust. 3) Tips to prevent contamination include sampling one material at a time in a segregated booth, cleaning all containers before storage, having appropriate air control systems, and avoiding simultaneous charging of raw materials for different batches.

2. Good Dispensing and
Sampling Practices
Saffron Pharmaceuticals (Pvt.) Ltd.
19 Km. Sheikhupura Road, Faisalabad-Pakistan.
• Presented by:
Dr. Yasir Mehmood
PhD Pharmaceutics,
MBA (Health
management)
• Head QA & VIRAC

3. Dispensing of Raw Materials
Dispensing the right materials to the right batches prior to
the manufacturing process is a key activity in life sciences and other process
industries. The process is critical when working with potent active pharmaceutical
ingredients (APIs) in
drug manufacturing.
“
“

4. Steps of dispensing out
starting material
After weighing there will be dust that must
be cleaned up immediately according to
paper work
4-Clean up
Take particular care and double check that
the right chemical, the right lot and right
amount are weighed
3-Weighing
Take particular care and double check that
the right chemical, the right lot and batch
no. has been issued by the weare house
against a paper
2- Setup
1-Room
clearance
Removal of all previous contaminations
and make the room clean for next batch

5. Contamination control
in Dispensing area
Dispensing of the material should be done carefully under the dispensing booth
to protect the material from contamination. Dispensing equipment must be
cleaned and free from contamination. The SOPs for the dispensing materials
needs to be carefully followed to prevent any cross contamination

6. Tips to prevent pharmaceutical contamination
2- Sampling in a segregated
cubicle/booth fitted with
suitable air control systems.
7- Simultaneous charging & loading of
raw materials for two different batches,
two different stages and two different
products should be avoided
1- Sample only one material
at a time
4- All containers packaged
must be effectively cleaned
before these are admitted to
the storage area
5- Evolve and follow suitable
equipment cleaning procedures.
Periodically validate them to confirm
the effectiveness
8- During the change over single
individual impurity is not more than 0.1%
(1000 PPM). Total impurity is not more
than 0.5% (5000 PPM).
1
3
4
5
7
8
2
6
3- Dispensing stations must be
equipped with suitable dust
extraction system
6- Air supply systems for the
production and dispensing areas must
be designed to avoid contamination
into the airflow (or) to the
manufacturing areas

7. cleaning and validation of dispensing area
2
1
6
5
4 3
Dispensing & sampling
room is to be cleaned at
the time of every
product change over &
after every sampling
Previous dispensed product
/sampled material container
and dispensing/sampling
equipment are removed from
the dispensing and sampling
area
Remove the powder from floor
and powder from the outer
surface of RLAF pre filter frame,
return riser filter and side panel
by using a vacuum cleaner.
Mop the entire surface of
pre-filter frames, return
riser filter and side panel &
Clean the Stainless Steel
Table and Balances
Dispensing/Sampling
Room floor shall be
cleaned as per schedule at
the beginning and
completion of work
Store person shall close the
polythene bags inside the waste
bin and send it to scrap yard &
Store person record the cleaning
activity in Dispensing Logbook

8. Equipment Wash and Preparation
Small items such as scoops, small c
ontainers and sample thiefs can be
cleaned in a specifically designed w
ashroom or within the weighing roo
m.
Larger equipment, such as pails,
drums and small IBCs (holding less
than 100 liters), are usually cycled thr
ough the manufacturing washroom
Large IBCs, particularly those above
1,000 liters, are normally cleaned with
Clean-In-Place systems, in
which spray balls are inserted through
the top opening
01
02
03
03
06

9. Health and safety
4
The sample storage
areas should have
adequate light and
ventilation
3
The sampler should have
safe access to and egress
from the place where the
sample is taken, and the
places where the samples
are taken for storage
1
Sampler should
wear appropriate
protective
clothing for the
task
2
If specific safety
precautions are
required, such as the
use of respiratory
equipment, the sampler
should be properly
trained in its use

10. Category II: <100 mcg/m3 -
>20 mcg/m3
This is the first category that
requires the use of special
equipment to create an additional
separation like laminar flow booth
between the operator and the
materials being handled
Category IV: <1 mcg/m3
Below the 1 mcg/m3 level, we have
reached the guaranteed limits of SBVs
and must look to isolation technology
to meet this containment requirement.
This includes the use of glove boxes
with rapid transfer ports (RTP).
Category I: >100 mcg/m3
At this level, following normal
cGMP is usually enough
protection for an operator
Category III: <20 mcg/m3 –
>1 mcg/m3
At this point, we have reached the
lower level of the capabilities of
laminar flow technology and another
level of control must be applied like
Split butterfly valves (SBV)
Specialized Suites – Potent Compounds

11. Warehouse Waste Move
ment
Non-hazardous solid waste (i.e., paper, cartons,
plastic, etc.) generated in the weighing area is
collected in plastic bins and transferred via a
dumpster to a waste compactor. All contaminated
solid waste should be disposed of in accordance with
hazardous material regulations

12. Gowning for dispensing
area/Secondary
gowning

14. De-Gowning for dispensing
area/Secondary
de-gowning

16. Good Weighing
Practices

17. Definition
Accuracy
Closeness of agreem
ent between a measu
red quantity value an
d a true quantity valu
e of a measured. VI
M .
Trueness
closeness of agreement
between the average of
an infinite number of r
eplicate measured quan
tity values and a referen
ce quantity value
Precision
Closeness of agreement
between indications or
measured quantity value
s obtained by replicate
measurements on the sa
me or similar objects un
der specified conditions.
VIM

18. 18
Imprecisely, accurately
(values are wide-spread)
Imprecisely, accurately
(values are wide-spread)
Precise, inaccurately (good
balance repeatability) Balance
accuracy and precision
Precise, accurately (good
balance repeatability)
Accuracy & Precision

19. 19
REPEATABILITY USP General Chapter <41>
Repeatability tolerance 0.10%
Expansion factor, K 2
Acceptance criteria 2 x SD/N ≤ 0.10%
Smallest possible sample weight/lowest
starting point
820 d (in optimal conditions)
Operating Range (2 x SD x 1000) to max capacity or
(2 x 0.41d x 1000) to max capacity (if SD < 0.41d)
ACCURACY USP General Chapter <41>
Tolerance Satisfactory if its weighing value is within 0.10% of the test weight value
Test weight Between 5% and 100% of the balance's capacity
Calibration uncertainty of the weight Must be ≤ 1/3 of 0.10%
Balances Requirement - USP

20. Basic principles should drive
the design of any
pharmaceutical
weighroom
 Unidirectional flow of
materials and personnel
 Segregation between hazardous
and non-hazardous materials
 Separation of storage and
manufacturing items and spaces

21. Calibration part of OQ
Tare function
Operation of ancillary
equipment
Manually triggered or automatic
adjustment by means of built-in
weights.
– Automatic adjustment
reduce the drift of the balance
Mechanical mobility of all
moveable parts
Control of stable indication
Operational
Qualification
OQ has to cover following, but not limited to;

22. Property Definitions Acceptance
Criteria
Examples
Sensitivity
Change in weighing value divided by the
change in load, usually measured between
zero and the capacity of the balance.
NMT 0.05% deviation
where 〈41〉 is
applicable. For other
uses, respective
tolerance requirement
divided by 2.
The test load at or
sufficiently close to
the capacity of the
balance
Repeat-
ability
Ability of a weighing instrument to display
identical measurement values for repeated
weighings of the same objects under the
same conditions.
Requirement from 〈41〉
where applicable. For
other uses, user
specified requirements
will apply
10 replicate weighing's
(test weight –few
percent of the nominal
capacity of the
balance).
Performance Test

23. Performance Test
Property Definition Acceptance
Criteria
Examples
Linearity
Ability of a balance to follow the linear
relationship between a load and the
NMT 0.05% deviation where
〈41〉 is
From 3 to 6 points over
the range of the
indicated weighing value. Nonlinearity applicable. For other balance.
usually is expressed as the largest uses, respective
magnitude of any linearity deviation tolerance
within the test interval. requirement divided
by 2.
Eccentricity
Deviation in the measurement value
caused by eccentric loading—in other
NMT 0.05% deviation where
〈41〉 is
Performed in the center
of gravity & 4
words, the asymmetrical placement of applicable. For other quadrants
the center of gravity of the load relative uses, respective Test load usually
to the load receiver. Eccentricity usually tolerance should be 30% of the
is expressed as the largest magnitude of requirement divided capacity of the
any of the deviations between an off-
center reading and the center reading
by 2. balance or higher
for a given test load.

24. The accuracy is satisfactory if its
weighing value, is within 0.10% of the
test weight value
A test weight is suitable if it has a mass
between 5% and 100% of the balance's
capacity
Maximum permissible error (mpe) or
uncertinity shall 1/3 of the applied test ie
0.03%. (ASTM E617)
Accuracy <41>:

25. Repeatability
(RP),
Eccentricity
(EC)
Linearity (L)
Sensitivity (SE),
According to USP General Chapter
<41> “Balances”, for substances to
be accurately weighed, the balance
used must be calibrated over the
operating range
The most important are ;
Balance Calibration

26. Perform 10 measurements with the same
reference weight
• Calculate the Standard Deviation [SD]
Repeatability is satisfactory if
– 2 x SD/Nominal reference weight used is ≤ 0.10 %
If the standard deviation obtained is less than 0.41d, (d-is the scale
interval),
replace this standard deviation with 0.41d.
–2x SD x 1000 If SD < 0.41d,
• In this case, repeatability is satisfactory if two times 0.41d, divided by
the nominal value of the weight used, does not exceed 0.10%.
– 2x SD (0.41d) x 1000 = 820d
Repeatability test <USP 41>

27. • Deviation in the measurement value caused by
eccentric loading— in other words, the asymmetrical
placement of the center of gravity of the load
• Performed in the center of gravity and the four
quadrants
• Test load usually should be 30% of the capacity of the
balance or higher.
Limit: NMT 0.05%
Deviation where (41) is applicable.
Eccentricity Test

28. It is a deviation of balance real curve from straightline joining
two points A:B – ideal weight.
Linearity test
• Linearity: To ensure that balance is accurate
at the desired level in the operating range
• Ability of a balance to follow the linear
relationship between a load and the indicated
weighing value.
• Limit: NMT 0.05% deviation where 〈41〉 is applicable. For other
uses, respective tolerance requirement divided by 2.

29. Use certified weights with an
appropriate weight class
2
Perform as performed for
repeatability test
3
Limit: NMT 0.05% deviation where
〈41〉 is applicable. For other uses,
respective tolerance requirement
divided by 2.
4
Change in weighing value divided by the
change in load, usually measured
between zero and the capacity of the
balance
1
Sensitivity Test

30. Install the balance on anti- vibration table &
Non-magnetic surface and grounded to
prevent static electricity
Room should be temperature and humidity
controlled
Vibration, air currents
Should be free of drafts and away from air
conditioner or fans or windows to avoid
strong air current or direct sunlight
Away from magnetic fields (magnetic stirrer),
electromagnetic radiation eg RF
generators/communication devices and electric
motors
Away from Corrosive materials are used
nearby.
01
02
03
04
05
06
07
LOCATION :
INSTALLATION
OF BALANCES

31. 01
02
04
03
Range of
operation
Intensity of
operation
Balance
stability in
time
Measurement
of weighting
process
LOREM IPSUM
Testing of Balance
parameters

32. 01
02
04
03
Receivers should be
nonmagnetic used at ambient
temperature
Weighing dishes should be
polymer or aluminum.
Antistatic and compatible
with the liquid sample.
All receivers must be clean,
dry, and inert.
Weighing uncertainty for
small samples, i.e., net
weights with a mass
determined around
repeatability
Precautions while weighting

33. Oscillations,
vibrations
Evaporation and
absorption phenomena
(hygroscopicity)
Breeze of air
Electrostatics
Temperature
drifts
Magnetism
nature of sample
Ambient area
and people
FACTORS AFFECTS THE WEIGHING
ACCURACY

34. Good sampling
practices

35. Preparation for sampling
Sampling operation and precautions
Storage and retention
Sampling process

36. Tools for sampling
01
02
03
04
05
A variety of pipettes
fitted with suction bulbs,
cups or beakers, dippers
and funnels are needed.
The use of glass
should be avoided.
Liquids of low
viscosity.
should be sampled
under aseptic
conditions
Sterile
pharmaceutical
suitable inert rod
Highly viscous
liquid
a sampling tube with a
shutter at the lower end used
to sample liquids in drums
or other large containers and
a slotted tube with a pointed
end used to sample
solids.
Non-uniform
materials
spatulas or scoops
Powdered and
granular solids

37. Weighing of Volatile samples
Weighing of low boiling liquid point
in a vessel with a gas-tight
enclosure of small diameter
01
Close immediately after transfer of
material
02
After the balance display stabilizes,
the analyst records the specimen
weight
03
02
03 01

38. Aseptic or Biohazardous Samples
Weighing the samples in the confines
area / bio-safety cabinet/isolator,
or similar containment device
When materials with OELs of less than 20
µg/m3 are handled, we require the use of
transfer bottles with split butterfly valves (SBV)
and glove boxes Care should be taken if airflow in
the hood may cause balance instability

39. Sterile Weighing
A B
C D
On completion, the sterile weighing
operator will manually bring the
work-in-progress to the MAL, where
it will be picked up by the material
handler
After the weighing operations are
complete, the room must be
sanitized. Cleaning carts and mop
handles should be dedicated to the
room
A material handler will deliver the
selected materials to a material
airlock (MAL) equipped with
ultraviolet light for the sterile weigh
room (ISO 7), where
the operator will pick them up.
The operator will transfer the
materials to the weighing area
under an ISO 7 LAF, where the
materials will be weighed and
double-bagged

40.  Antistatic weigh boats, antistatic guns, and antistatic screens
 Placing the container in a metal holder
 Balances with a built-in antistatic device is available (piezoelectric components or low amount of a
radioactive polonium) to generate a stream of ions that dissipate
How to prevent:
2
1
2
3
1
Slow drift of weighing
result
Large dispersion of
weighing results in a series
of measurements, and
No return to zero if a load
is taken off the weighing
pan
Dry, finely divided powders
may be charged with static
electricity
The static charge may
develop due to low relative
humidity, clothing worn
and gloves used
Samples with Electrostatics
Effect of electrostatic presence Possible source:

41. Magnetism as interfering factor
If magnetic load is measured,
electromagnetic field of a balance is
disturbed or weighed sample is influenced
by magnet installed in a balance
It will lead to incorrect mass reading of a
weighed sample.
High resolution balances are constructed
on basis of electromagnetic sets which
include a force-motor and magnet
01
02
03
04
How to avoid: Increasing a distance between a sample and balance mechanism. Use under-hook weighing with application
of special racks or hooks made of aluminum

42. Good storage Practices

43. Storage
areas
1 2 3 4
Precautions should be
taken to prevent
unauthorized persons
from entering storage
areas
Storage areas should be
of sufficient capacity to
allow the orderly storage
Storage areas should be
maintained within
acceptable temperature
limits & should be kept
clean and dry
Materials and products
should be stored off the floor
and suitably spaced to permit
ventilation, cleaning and
inspection
8 7 6 5
Narcotic products should be
stored in compliance with
international conventions,
and national laws and
regulations on narcotics
Materials and products
should be stored by
“first expired/first out”
(FEFO) principle
Materials and products
should be handled and
stored in such a manner
as to prevent
contamination, mix-ups
and cross-contamination
There should be a written
programme for pest control
and cleaning

44. Storage conditions
The storage conditions for materials and therapeutic goods s
should be in compliance with the labeling, which is based on
the results of stability testing.
Heating, ventilation and air conditioning systems (HVAC)
should be appropriately designed, installed, qualified and
maintained to ensure that the
required storage conditions are maintained
Where required, mapping studies for temperature and
relative humidity, as appropriate, should be done
01
02
03
04
04 The equipment used for monitoring should be
calibrated and be suitable for their intended use
Storage conditions for pharmaceutical products and materials should be in compliance with the
labelling, which is based on the results of stability testing

45. Labeling and
container
Receipt of incoming
materials and
pharmaceutical
products
Stock rotation and
Control
Documentation:
Written instructions
and records
Control of obsolete
and outdated materials
and pharmaceutical
product
01
04
03
02
05
Storage requirements

46. Equipments in storage area
Equipment, including
computerized
systems should be
suitable for their
intended use
If Computerized
systems are used those
should be capable of
achieving the desired
output and results.
Where electronic commerce (e-
commerce) is used, defined
procedures and adequate
systems should be in place to
ensure traceability and
confidence in the supply chain
and products concerned
Where GXP systems
are used, these
should meet the
requirements of
WHO guidelines on
computerized
systems
01 02 03 04

47. Quality Risk Management
in storage area
1 2 3 4
Simple
PowerPoint
Simple
PowerPoint
Simple
PowerPoint
Simple
PowerPoint
There should be
a system to
assess, control,
communicate
and review risks
identified at all
stages in the
supply chain
Appropriate
controls should
be developed and
implemented to
address any risks
identified
The evaluation
of the risk
should be based
on scientific
knowledge and
experience
The
effectiveness of
the controls
implemented
should be
evaluated at
periodic
intervals

48. Thank you