Non-viable particle count in classified
To establish the written procedure for monitoring of non-viable particle count in the classified Area S mall Volume Parenteral section.
DEFINITIONS
Clean Area: An area in which defined environmental control of particulate & microbial contamination, is constructed & used in such a way as to reduce the introduction, generation,& retention of contaminants within the area.
Particle Counter: A particle counter is an instrument that detects & counts physical particles. The nature of particle counting is based upon either light scattering, light obscuration, or direct imaging. A high-intensity light source is used to illuminate the particles as they pass through the detection chamber. Recorded video analyzed by computer software to measure the particle attributes.
A classified/Controlled Area is an enclosed environment or room with flawless control over particulate contamination. More especially the area has a controlled contamination level, which is specified regarding the number of particles for every cubic meter, for a specific particle size.
ABBREVIATION
SVP: Small Volume Parenteral
IPA: Isopropyl Alcohol
USP : United State Pharmacopeia
FDA: Food & Drug Administration
HEPA: High-Efficiency Particulate Air
NVPC: Non-viable particle counter
ISO: International Organization of Standardization.
RESPONSIBILITY
Originating department shall be responsible:
Preparation of the SOPs.
To follow the procedure & content of SOP.
Execution & updation of required documents as per SOP.
The head of Originating department/designee shall be responsible for:
- To provide the training of SOP to the concerned person.
- Implementation & compliance of procedure mentioned in SOP.
The Quality Assurance department shall be responsible for:
- To verify that all content of SOP is relevant to the concerned equipment & process.
- To verify that all the instructions are followed properly as per the given SOP.
- To verify that relevant records/log books are maintained as per the defined system.
Head – Quality Assurance/ Designee shall be accountable for:
- To approve new or revised SOP.
- To ensure the implementation of the defined system.
The plant Head shall be accountable for:
- To approve new or revised SOP.
- To ensure the implementation of the defined system.
PROCEDURE:
SAFETY/PRECAUTION/EHS
- Never change the location while the particle counter is in operation.
- Keep the particle counter in a dry place & clean place.
- The chemist/operator should follow all instructions of clean room behavior during the operation of the particle counter in mfg. room & filling room.
- Cleaning shall be avoided during the monitoring of particle count.
MONITORING OF NON-VIABLE PARTICLE COUNT
Non-viable particles are to be monitored with NVPC (Non-viable particle counter) instrument as per SOP.
The purpose of non-viable particle monitoring in clean areas is to verify the environment meets the specification prior to operation or exposure of sterile products in the environment.
The limit of non-viable particle count in the area depends upon the classification of the area.
A number of sampling points, location selection, clean zone classification determination & quality of data will be generated as per ISO 14644-1 guidelines.
The minimum no. of sampling locations will be decided as per the following table of ISO 14644-1:2015 guidelines.
| Area of cleanroom(m2) less than or equal to | Minimum number of sample locations to be tested (NL) |
| 2 | 1 |
| 4 | 2 |
| 6 | 3 |
| 8 | 4 |
| 10 | 5 |
| 24 | 6 |
| 28 | 7 |
| 32 | 8 |
| 36 | 9 |
| 52 | 10 |
| 56 | 11 |
| 64 | 12 |
| 68 | 13 |
| 72 | 14 |
| 76 | 15 |
| 104 | 16 |
| 108 | 17 |
| 116 | 18 |
| 148 | 19 |
| 156 | 20 |
| 192 | 21 |
| 232 | 22 |
| 276 | 23 |
| 352 | 24 |
| 436 | 25 |
| 500 | 26 |
| 1000 | 27 |
| >1000 | Equation A |
The area detail of the manufacturing & filling room for NVPC is as follows.
| Sr. no. | Name of Location | ISO Class | Area of Location (m2) | Minimum no. of Sampling location |
| 1 | Manufacturing Room (I) | 7 | 14.883 | 06 |
| 2 | Manufacturing Room (II) | 7 | 18.225 | 06 |
| 3 | Filling Room | 7 | 25 | 07 |
Sampling location in the area preferred at corners, near the doors & near equipment or based on air flow pattern or as per our requirement.
Clean rooms & Zones are classified as per standard ISO 14644-1, WHO TRS-961 & Schedule M Guidelines as per the following table 1, 2 & 3.
TABLE 1 (as per ISO 14644-1)
| CLASS | MAX. PARTICLE Per m³ as per ISO 14644-1 | |
| 0.5 microns | 5.0 microns | |
| ISO-5 ISO-6 ISO-7 ISO-8 ISO-9 | 3520 35200 352000 3520000 35200000 | * 293 2930 29300 293000 |
| * To express an airborne concentration of 29 particles/m3 in the particle size range ≥ 5 µm in ISO Class 5 based on the use of LSAPC, the designation would be “ISO M (29; ≥ 5 µm); LSAPC” | ||
TABLE 2 (As per WHO TRS-961)
| Maximum permitted number of particles per m3 greater than or equal to the tabulated size | ||||
| At Rest | In Operation | |||
| GRADE | 0.5 µm | 5.0 µm | 0.5 µm | 5.0 µm |
| A B C
D | 3520 3520 352000 3520000 | 20 29 2900 29000 | 3520 352000 3520000 Not Defined | 20 2900 29000 Not Defined |
TABLE 3 (As per Schedule M)
| GRADE | Maximum permitted number of particles per m3 greater than or equal to the tabulated size | |||
| At Rest | In Operation | |||
| 0.5 µm | 5.0 µm | 0.5 µm | 5.0 µm | |
| A B C
D | 3520 3520 352000 3520000 | 20 29 2900 29000 | 3520 352000 3520000 Not Defined | 29 2900 29000 Not Defined |
NVPC in the manufacturing & filling area is to be measured with a non-viable particle counter (Make: Met-One) & flow rate of it is 100 LPM.
Transfer the instrument to the corresponding room through a dynamic pass box. Operate the instrument as per SOP).
For ISO class 7(mfg. room & filling room) the sampling time will be 1 minute to sample 2 liter of air & for ISO class 5 (FFS machine filling zone/SFS or under LAF zone) the sampling time will be 10 minutes to sample 1000 liters of air. Attach the print report of NVPC in BMR.
Frequency
For (SFS or LFR) ISO class 5 of filling machine: during startup of filling operation.
For (manufacturing room) ISO class 7: before & after every batch processing.
For (Filling room) ISO class 7: before starting and completion of every batch filling operation.
After the major breakdown in the filling room or FFS machine, as the machine starts again, NVPC will be monitored for the filling zone & filling room.
REFERENCE
WHO-TRS 961 guideline
FDA and schedule M
ISO-14644
