- Before going manufacturing of pharmaceutical
product verify the environment by monitoring method.
- Pharmaceutical Environmental monitoring of
controlled area is performed by two methods.
- Viable monitoring or Viable particle monitoring
- Non-Viable particle monitoring.
Viable Monitoring
or Viable Particle Monitoring:
·
Capable of working successfully.
· Living microorganism.
· Able to germinate.
- Capable of surviving or living successfully.
- A viable particle is a particle that contains one or more living microorganisms. These can affect the sterility of the pharmaceutical product and generally range from ~0.2µm to ~30µm in size.
- Viable particles includes bacteria, Fungi.
- Different types of monitoring method used for viable particle detecting, such like.
1. Passive Air Sampling
(settle plate method)
2. Active Air Sampling (Volumetric Air
Sampling)
3. Surface monitoring (swab sampling or Contact method)
4. Personnel monitoring (Contact method)
Viable
particles are not free floating they need a carrier to float from one area
to another area.
- Non-viable
particles main source for movement of the viable particles.
- Viable
particles (Bacteria and fungi) 0.5um to 5.0 um size. So this range of
particles are main source of product contamination.
- Less
than 0.5 um is critical of attachment of viable particle.
- Greater
than 5.0 um is large size of particle can not move easily and settle down.
Non-Viable Particles Monitoring :
·
Does
not contain living organism.
·
Non-feasible
(particle)
·
Unable
to survive independently.
·
Manufacturing
area, equipment, utilities and personnel are main source of particle
contamination in aseptic area.
·
Check
the particles of 0.5 um to 5.0 size
·
Electronic
particle counter is used for particle counting.
·
This instrument can’t differentiate between viable and non-viable particles.
·
Any
particle detected by the sensor of this instrument it will count this particles.
· For
example particles are generated through the movement in aseptic area so
movement of the personnel should be controlled and rhythmic in aseptic
area.Good manufacturing practices should be followed to control the particle
contamination in aseptic area.
·
As
per EU GMP 1 m³ air should be sampled per location for particle monitoring.
Particle contamination depends upon the activity in aseptic area. If there is
no activity in aseptic area then particle contamination would be low and if
activity is in progress in aseptic area then particle contamination would be
increased. That's why guidelines has defined different limits for at rest and
in operation conditions.
·
In
pharmaceuticals, online and continuous monitoring of particles are also
performed in which particle counter gives results in form of print out during
production hours. This is very important tool to have great control over the
aseptic area during production hours.
·
During
monitoring any deviation from the specified limits could results in
investigation. Below is the chart showing maximum number of permitted particles
in different classes of area as per EU GMP guideline.
·
So,
to control classified area we need to control both viable and non-viable
particles.
Maximum permitted number of particles
per m3 equal to or
greater than the tabulated size
Grade
|
At Rest
|
In
operation
|
||||
0.5 µm
|
5.0 µm
|
0.5 µm
|
5.0 µm
|
|||
A
|
3520
|
20
|
3520
|
20
|
||
B
|
3520
|
29
|
352000
|
2900
|
||
C
|
352000
|
2900
|
3520000
|
29000
|
||
D
|
3520000
|
29000
|
Not
defined
|
Not
defined
|
||
