material sampling and dispensing
needs to be done in accordance with approved written procedures
in order to detect contamination by environmental microbes says
in other industries, in pharma quality has to be built into the
product by following the well-laid down SOPs (standard operating
procedure). End product testing only will indicate whether the product
complies with the specifications. Quality of pharmaceutical
products, if not manufactured in appropriate environment may pass
the checks immediately after manufacturing, but may fail over a
period of time (which is within the shelf life of the product).
Also it is very much dependent on the ability and training of staff
engaged in all processing, engineering, housekeeping and ancillary
tasks associated with it.
of the samples need to be tested and analysed for microbial content
against the specified limits. So, one has to ensure that during
sampling environmental microbes do not contaminate the samples drawn.
Hence now-a-days sampling is carried out in sampling booth or mobile
tent equipped with LAF unit, where air is filtered through a Hepa
should be done in accordance with approved written procedures that
The method of sampling
The equipment to be used
Instruction for any subdivision of the sample
The type and the condition of the sample container to be used
The identification of containers sampled
Any special precautions to be observed, especially with regard
to sampling of sterile or noxious materials
The storage conditions
Instructions for the cleaning and storage of sampling equipment
samples should be representative of the batch of materials or products
from which they are taken, other samples may also be taken to monitor
the stressed part of a process (e.g. beginning or end of the process).
containers should bear a label indicating the contents with the
batch number, the date of sampling and the containers from which
samples have been drawn. On fixing this label it will be ideal to
deface the suppliers approved label.
materials required for formulations come in packs of various sizes
like Aerosil 5kg bag, Hpmc 25kg, Titanium dioxide 25kg, Shellac
50kg etc., and actives like Paracetemol in 25kg bag. Accuracy of
weighing is very critical, as any of the weighing errors will affect
the composition of final product. Requirement of these ingredients
varies from micrograms to kilograms based on the batch size.
on the batch size each ingredient pack needs to be opened, necessary
quantity transferred into a clean container (preferably SS316 or
double polybag) and leftover material in the container to be closed
and returned to approved storage area.
utmost care should be taken as most of the powders are white in
colour and look alike, if by mistake labels of two ingredients fall
down, identifying the correct material will be next to impossible
and chances of committing major mistakes like mix-up are very very
the operation of dispensing should always be carried out in the
presence of qualified chemists from production and quality assurance,
for ensuring tracking and dispensing of required material in required
quantities as per the BMR (batch manufacturing record). Always one
needs to remember in dispensing is, a small mistake of wrong material
or wrong quantity can take out the patients life.
the raw materials and actives, excepients needs to be opened and
transferred in the same quality of environment as manufacturing.
Like class conditions, temperature and humidity. Further operating
staff needs to be protected from exposure to any of the drug powders
in general and potent drugs in particular (which may cause serious
health hazards to the working personnel). So specially designed
dispensing booths are employed.
only top point exhaust connected to central exhaust system used
to be provided so that any powder rising while opening of container
or transferring of the material would be exhausted out, but in the
process when surrounding air is moving up it takes flying drug particles
move over the operators breathing zone, thus exposing the
operator to the active ingredients which will seriously affect the
his or health. This is more serious in case of highly potent drugs
like tranquilizers, antibiotics and biotechnology products etc.
the quality of the air is not controlled and is a point of concern
for contamination, degradation in case of temperature/humidity sensitive
products like aspirin, potassium clavulnate, dispersible formulations
etc., So to overcome these problems dispensing booths are employed.
Fig. No.1 shows typical dispensing booth of recent version. This
is a down flow or reverse flow type with air being blown from top
moving down and sucked from bottom level and passed through coarse
filter followed by 5 microns of 95 percent and finally through HEPA
(high efficiency particulate arrestor) filters to give class 1000
conditions (which is almost sterile air) and part of air is exhausted
through additional HEPA filter on the front side as shown in the
figure to ensure exhausted air free of drug particles.
booths made of different materials:
Laminated MDF (medium density fiber board)
MS painted structure
Acrylic sheets with powder coated steel framework
Latest version is made out of stainless steel 304 sheet
filters ensure a laminar flow in dispensing zone, which is ideal
for avoiding the spreading of drug particles. To ensure the laminar
flow the filter conditions and blower speed play a critical role.
As the filter gets blocked the airflow reduces affecting the air
velocity. Now-a-days differential pressure gauges across each filter
bank are provided to indicate the condition of the filters. If they
are blocked/choked then first and second stage cleanable filters
to be cleaned and fixed back. These differential gauges also monitor
further filter integrity. Hence logging and checking of these differential
pressure gauge readings is must before every dispensing. Operating
personnel need to ensure that readings of these gauges are within
specified limits before dispensing.
versions of dispensing booths are equipped with:
Speed control mechanisms
Differential pressure switches
Microprocessor based controller, digital display unit
Audible alarms in case of filters choking or any other malfunction
stores and dispensing operations barcode/matrix code are employed
to keep track of the movement of each and every container. Here
the container is scanned at the first entry/inwarding point and
moved by the AGVs (automatic guided vehicles) to the allocated
shelf by entering the shelf number in the computer, further once
it is approved, it is moved on to the approved storage area by AGV.
approved material storage area to dispensing again container labels
are scanned for appropriate container as per the work order (given
by the QA based on the production requisition which is in turn based
on the production schedule). Once weighing/dispensing operations
are over dispensed labels and complete record of the issued and
dispensed materials is generated by the computer. Further, as the
material is issued the stock records get updated accordingly. These
dispensed labels are fixed on to the dispensed material bags thus
avoiding any chance of mix-ups during the entire stores operation.
this system, very few people can manage the entire stores operations.
Again barcode scanners at the entry of dispensed material staging
in production area ensure only the programmed and designated container
enters into the particular manufacturing area. Here a word of caution
to be noted. A computer controlled operations sound and look good
but they need to be rigorousl checked for proven track record, the
entire software should be thoroughly validated and should have provision
for periodic validation. Otherwise, instead of aiding the manufacturing
operations, it will become a major hindrance. Proven track record
of software is essential and should be major criteria for selection