MONITORING OF NON-VIABLE PARTICLE COUNT IN CLASSIFIED AREA OF SVP SECTION
MONITORING OF NON-VIABLE PARTICLE COUNT IN CLASSIFIED AREA OF SVP SECTION
PURPOSE
To establish the written procedure for monitoring of non-viable particle count in classified Area SVP section.
SCOPE
This SOP shall be applicable for monitoring of non-viable particle count in classified area of SVP section
REFERENCE(S) & ATTACHMENT(S)
REFERENCE(S)
- WHO-TRS 961 guideline
- FDA and schedule M
- ISO-14644
CROSS REFERENCE DOCUMENTS
- Document(s) and Data Control Procedure
- Training Program for Employees
- Preparation, review, approval, issuance & retrieval of standard operating procedure (sops)
- Operation & cleaning of non-viable particle counter
DEFINITION & ABBREVIATION(S)
DEFINITIONS
Clean Area: An area in which defined environmental control of particulate & microbial contamination, constructed & used in such a way to reduce the introduction, generation,& retention of contaminants within the area.
Particle Counter: A particle counter is instrument that detect & count 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 it pass through the detection chamber. Recorded video analyzed by computer software to measure the particle attributes.
Classified/Controlled Area is an enclosed environment or room with a flawless control over particulate contamination. More especially the area have a controlled contamination level, which is specified regarding the number of particles for every cubic meter, for a specific particle size.
ABBREVIATIONS
cGMP : Current Good Manufacturing Practice
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 perform the operation/cleaning/activity as per the respective SOP.
To impart the training of the SOP to concerned personal.
To get SOP approval from all signatories.
To follow the described here in.
To maintain the record.
Initiation of change control to modify/revise the SOP.
To co-ordinate with engineering/external agencies to perform maintenance or calibration.
Head of Originating department/designee shall be responsible for:
Ensure that sub-ordinate, operators are trained before performing any task or operation.
To check the SOP for proper contents/technical parameter as per the equipment.
To get the SOP approval from Quality Assurance or designee.
To provide the training of SOP to the concerned personnel before effective date of the SOP.
To ensure implementation of the SOP on effective date.
To maintain the controlled copies of the SOPs at required location.
To ensure the compliance of SOP.
Quality Assurance department shall be responsible for:
To verify that all content of SOP are relevant to the concern equipment & process.
To maintain the approved master copy of the SOP of all department for document control.
To issue the required number of controlled copies to the departments and document the same.
To verify that all the instructions are followed properly as per the given SOP.
To ensure implementation of SOP.
To verify that records/log books are maintained as per defined system.
To verify instrument is calibrated before operation.
Head – Quality Assurance/ Designee shall be responsible for:
To approve new or revised SOP.
Review of draft SOP for technical, function, regulatory and cGMP compliance.
Final approval of the SOP by signing off as approved by.
To ensure the implementation of the defined system.
To verify that equipment/process & concern person are following cGMP aspects.
Plant Head shall be responsible 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 dry place & clean place.
Chemist/operator should follow all instructions of clean room behavior during operation of particle counter in mfg. room & filling room.
Cleaning shall be avoided during monitoring of particle count.
MONITORING OF NON-VIABLE PARTICLE COUNT
Non-viable particle to be monitored with NVPC (Non-viable particle counter) instrument as per SOP
The purpose of non-viable particle monitoring in clean area to verify the environment meets the specification prior to operation or exposure of sterile products in environment.
The limit of non-viable particle count in area depends upon the classification of area.
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 location will be decide as per 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 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 area preferred at corners, near the doors & near equipment or based on air flow pattern or as per our requirement.
Clean room & Zones are classified as per standard ISO 14644-1 and WHO TRS-961, Schedule M Guidelines as per following table 1 & 2.
TABLE 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
| 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 |
VPC in manufacturing & filling area to be measured with non-viable particle counter (Make: Met-One and Model No.: 3445.) & flow rate of it is 100 LPM.
Transfer the instrument to the corresponding room through dynamic pass box.
Operate the instrument as per (SOP no
For ISO class 7(mfg. room & filling room) the sampling time will be 1 minutes 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 of every batch processing.
For (Filling room) ISO class 7: before start and completion of every batch filling operation.
After major breakdown in filling room or FFS machine, as machine start again, NVPC will be monitor for filling zone & filling room.
REVISION HISTORY
New SOP introduce in system.