1.0 Purpose
1.1 To describe a procedure of In-Process Control in order to ensure product quality in forms (Tablet, Capsule, PFS and Liquid).
2.0 Scope
2.1 Applicable for IPC of all Tablets, Capsules, PFS and Liquid dosages form manufactured in NAME Pharmaceuticals Ltd.
3.0 Responsibility
3.1. Head
of Quality Assurance is responsible for compliance of the SOP.
3.2. QA
Officer is responsible for preparation and execution of the procedure.
3.3. QA
Officer / Production Officer is responsible to raise the NCR.
4.0 Abbreviations and Definitions
4.1 In Process Control (IPC) Checks performed during production in order to monitor and if necessary to adjust the
process to ensure that the product confirms to its specifications. The control of the environment or equipment may
also be regarded as a part of
In-Process Control.
4.2 Appearance: Its visual identity and overall “elegance” which is essential for consumer acceptance, for control of
lot to lot uniformity, tablet to tablet uniformity
and for monitoring trouble free manufacturing.
4.3 Shape: Outer form or outline
of a tablet that can influence the physical flaws.
4.4 Physical Flaw: Physical flaw is the imperfection of physical state of tablets which include capping and lamination,
picking and sticking, chipping, mottling, contamination
from foreign solid substance (e.g., hair, drops of oil and dirt) etc.
4.5 Disintegration Time (DT): The time by which each tablet is disintegrated into smaller particles or granules
is
the disintegration time.
5.0 Materials and Equipment
5.1 Precision Balance
5.2 Hardness Tester
5.3 Disintegration Tester
5.4 Friability Tester
5.5 Leak test Apparatus
6.0 Precaution / Health and Safety Considerations
6.1
After completion of in-process
checks tested / left over sample shall be destroyed.
7.0 Procedure
7.1 Production and QA personnel shall check
following before commencing In-process start
up checks:
7.1.1 Ensure that the Relative Humidity and
Temperature of the respective manufacturing areas are within limit.
7.1.2 Ensure Line Clearance of equipment,
instrument and area prior to start of activity.
7.1.3 Ensure that the Batch Manufacturing Record
(BMR) is available and completed up to the previous
stage.
7.1.4 Ensure all instruments / balance used for measuring purpose are cleaned, calibrated and have not exceed their
calibration due date.
7.1.5 Ensure that the status labels of equipment's
affixed and room’s status shall be updated prior to start of the activity.
7.1.6 Ensure that the all details are correct on status label of HDPE container / Drum and Blender etc. of respective
product at respective stage.
7.1.7 Prior to start of the tablet compression and capsule filling operation; ensure that the HDPE container /
Drum containing bulk material is affixed with
Approved label.
7.1.8 Verify that all start-up parameters has been checked by production department and Quality Assurance and
recorded in Batch Manufacturing Record of
respective product.
7.1.9 Ensure that all parameters are within the
acceptance limit as mentioned in manufacturing instructions.
7.2 In-process checks during Granulation :
7.2.1 At Granulation stage, Frequency of In process checks and in process sample size shall be specified in respective
Batch Manufacturing Record (BMR). For Example: If 5 gm sample required for LOD or Water content Checking then
withdrawn approx. Quantity of sample and use 5 gm sample for LOD or Water Content destroy the remaining
quantity of sample along with
tested sample after completion of in-process checks.
7.3 In-Process checks during Tablet
Compression Operation:
7.3.1 Ensure correct tooling / spares are set on
machine before loading of the product.
7.3.2 Production person shall follow Frequency of In process checks and in process sample size as specified in respective
Batch Manufacturing Record (BMR)
For Example: If required 30 Tablets for in-process checks then collect approx. sample of compressed tablets and
use 30 tablets for In-process; destroy the remaining quantity of sample along with tested sample after completion of
in-process checks.
7.3.3 In case of double rotary Tablet compression machine the sample size shall be collected from Right Hand Side
(RHS) & Left Hand Side (LHS) of compression
machine.
7.3.4 Ensure all in process checks are within acceptable limit as specified in Batch Manufacturing Record (BMR) of
respective product.
7.3.5 If all in process parameters are found within acceptable limit at Pre-Compression stage as specified in
Batch Manufacturing Record (BMR) allow for
the tablet compression operation.
7.3.6 If parameters are not being met the
predetermined specifications, inform to production personal to reset the parameters.
7.3.7 QA person shall be perform all in-process
checks at start up, middle and end of
batch and as specified in BMR.
7.3.8 During in-process checks at compression stage, Tablets shall be checked visually for any physical defects. If any
defects observed then stop the
machine immediately and inform to concern
supervisor and same shall be noted into BMR
7.4 In-Process checks during Tablet Coating
operation:
7.4.1 Production person shall follow Frequency of In process checks and in process sample size as specified in respective
Batch Manufacturing Record (BMR). Collect approx. Sample for in-process checks as per respective BMR for different
test and
record in-process checks in BMR.
For Example: If required 30 Tablets for in-process checks then collect approx. Sample of compressed tablets and
use 30 tablets for In-process and destroy the withdrawn quantity of sample along with tested sample after completion
of
in-process checks.
7.4.2 During in-process checks for coating stage, defected coated tablets/caplets as mention below shall be checked
visually for any physical defects. If any defects observed then machine shall be stop & shall be informed to concern
supervisor and same shall be noted into BMR
7.4.3 QA person
shall perform in-process checks as per instruction given in BMR
7.5 In-Process checks during Capsule filling operation:
7.5.1 Production person shall follow Frequency of In process checks and in process sample size as specified in respective
Batch Manufacturing Record (BMR). Collect approx. sample for in-process checks as per respective BMR for different
test and record in-process checks in BMR.
For Example: If required 30 Capsules for in-process checks then collect approx. sample of Filled Capsules and
use 30 capsules for In-process; destroy the remaining quantity of sample along with tested sample after completion of
in-process checks.
7.5.2 In process checks of different test shall
be performed as specified in respective Batch Manufacturing
Record (BMR).
7.5.3 If all parameters are found within acceptable limit at Pre-Encapsulation stage as specified in Batch Manufacturing
Record (BMR) allow
for the Encapsulation operation.
7.5.4 During in-process checks by QA person, If parameters are not being met the predetermined specification as
specified in BMR, inform to production personnel to reset the parameters.
7.5.5 QA person shall be perform all in-process
checks as specified in BMR, at start up , middle and end of batch.
7.5.6 For ongoing Encapsulation operation in
process sample size as mentioned in respective BMR shall be considered for different test.
7.5.7 During in-process checks at Encapsulation stage, capsule shall be checked visually for any physical defects. If any
defects observed then machine shall
be stop immediately and inform to
concern supervisor and same shall be noted into BMR
7.6 The following checks are carried out in IPQA Lab and result will record in Batch Manufacturing Record
(BMR) and IPC inspection Sheet
7.6.1 Tablet
7.6.1.1 Granulation
Stage: Loss on Drying (LOD)
7.6.1.2 Compression
Appearance
7.6.2 Capsule
7.6.2.1
·
Appearance
·
Average weight
·
Close length of filled capsule
·
Uniformity of weight & relative standard
deviation (RSD)
·
Disintegration time
·
Room condition (Humidity & Temperature)
Check the followings (as applicable
for the dosage form type) at the time of startup, middle and end.
·
Shape of the tablets, Surface Texture, Physical
Flaws, Consistency
·
Physical defects in case of Tablet and Capsule
i.e. capping, lamination, picking, sticking and cap lock
·
Visible particles/fibers
·
Embossing/Engraving/Break line on Tablet
·
Identification Marking of Tablet from each
punch at the time of start up.
·
Identification Marking of Capsule shell and
color of cap and body of capsule shell
7.7.1 Average weight: Take 2 composite samples, each of which consists of 10 Tablet at random from compression
Machine and check their average weight. In case of more than one counter take samples from each counter. Check the
average weight of Tablet at start, middle and end of compression. Composite Average Tablet weight must be within the
following range: If Table weight <300.0 mg, then average weight must be ±3.0 % and If Tablet weight >300.0 mg:
then average weight must be ±2.0%. Uniformity of Weight. For individual weight If observed average Tablet weight 80.0
mg, not more than two should be outside ±10.0% and none outside ±20.0% range of observed average Tablet weight. If
observed average Tablet weight is greater than 80.0 mg or less than 250.0 mg not more than two should be outside ±7.5%
and none outside ±15.0%range of observed average Tablet weight. If observed average Tablet weight 250.0 mg, not more
than two should be outside ±5.0% and
none outside ±10.0% range of observed average Tablet weight.
7.7.2 Capsule
Check the uniformity of capsule fill weight by weighing 20 Capsules individually. Weigh an Intact Capsule.
Open the Capsule without losing any part of the shell and remove the contents as completely as possible. Weigh the shell
_The mass of the contents is he difference between the weighing. Repeat the procedure with another 19 Capsules. Record the
data and determine average weight, Standard Deviation and % RSD Average fill weight must be within the fill Calculated
weight ±3% owing range: RSD not more than 4%. Keep record in the Capsule Inspection Sheet; calculate the range
specification for observed individual fill weight from the observed average fill weight. Individual Capsule fill weight
must be comply with the following specification. If observed average fill weight >300.0mg, not more than tow should be
outside ±7.5 % and none outside ±15.0% range of observed average fill weight. If observed average fill weight <300.0 mg,
not more than 10.0% and none outside ±20.0% range of observed average fill weight. Check the uniformity of Capsule
weight At the start, middle and of batch.
7.7.3 Take 6 tablet Check the Hardness and Thickness and diameter at the time of start, middle and end of compression.
Keep record in the Tablet Inspection Sheet
7.7.4 Perform Disintegration test at the start, middle and end of the compression for the Tablet and for Capsule
7.7.5 Visual Inspection of Coated Tablets, ‘Perform Visual Inspection of Coated Tablets” after complete the coating.
7.7.6 Perform the leak test at every one hour interval “Blister strips ever Bottles for power and liquid”
7.7.7 Depending upon the delivery/cutting channel of pick up single strip blister strip/Bottle from each Channel from
packaging line
7.7.8 If color enters into any pocket of the strip(s) blister ‘in to bottle(s)’ it is confirmed that the affected Sample is leak.
7.8 For
Liquid Manufacturing:
7.8.1 Check, purified water to be use in batch manufacturing shall be QC approved before starting the bulk material.
7.8.2 Line clearance of the bulk manufacturing area, equipment and process shall be given.
7.8.3 On receipt of “REQUEST FOR SAMPLING” from production, collect the bulk sample for IPQA and QC analysis.
7.8.4 Verification of the yield shall be done at the end of bulk manufacturing stage.
7.9 Bottle cleaning:
7.9.1 Line clearance of the bottle washing area, equipment and process shall be given.
7.9.2 Check the bottle for cleanliness.
7.10 Filling and Sealing Operation
7.10.1 Line clearance of the Filling and Sealing area, equipment and process shall be given.
7.10.2 On completion of initial setting of filling machine check the filled bottle for In process parameter.
7.10.3 Bottle shall be taken from each filling nozzle for In process checks.
7.10.4 If parameter of filled bottles is within specified limits of BMR, further operation of the filling machine shall be
allowed otherwise the setting shall be rectified accordingly.
7.10.5 IPQA Officer shall perform the In process checks at one hours frequency after the line clearance has been
given or whenever there is a break down or machine is stopped for then 1 hour.
7.10.6 Bottle taken for In process checks shall be treated as “Non recoverable”
7.10.7 Following In process checks shall be performed and recorded in “In-process check for oral liquid”
Ø Filled Volume
Ø Cleanliness of container
Ø Sealing quality
Ø Dented / scratch mark /stained / cracked bottle
7.10.8 If, during in process checks, it is found that any parameter of filled bottle is out of the specified limits, as per BMR, the machine shall be stopped.
7.10.9 The bottles filled between the last check (by production or QA whichever is latest) are current check shall be
segregated.
7.10.10 All
the bottles shall be checked for compliance (of In process parameter) to the
specification as per the BMR.
7.10.11 The bottles, which are out of specified limit, shall be labeled as “On Hold” and rest of the bottles shall be cleared
if all parameter are within specified
limits of BMR.
7.10.12 Head
of QA shall take the decision on “On Hold” bottles.
7.11
Labeling
and Packing Operation
7.11.1 Line clearance of the Labeling and packing
area, equipment and process shall be given.
7.11.2 Verified the coded label & packing material for details like Batch No. Mfr. Date, Expiry Date, MRP and
manufacturing Lic. No. etc. as per BMR.
7.11.3 Perform In process checks at a one hours frequency after the line clearance has been given.
7.11.4 Following In process checks shall be performed and recorded in “In-process checks for Liquid external- packing”:
i)
Cleanliness of container / Label
ii)
Text matter on label / Container
iii)
Coding details on label and container
iv)
Quality of gumming / missing of label / cross
labeling
v)
Number of containers in shipper and there
packing arrangement
vi)
Coding detail on shipper
vii)
BOPP taping quality
viii) Collect the packed finished sample, retention sample and stability samples or any other required
samples during packaging
operation
ix)
Verify the yield reconciliation after the
completion of packing.
8.0 Reference Document
8.1
Quality Manual- 6.2; British Pharmacopeia,
United States Pharmacopeia.
9.0 Annexure
9.1 Annexure-I : PACKING OPERATION INSPECTION SHEET
9.2 Annexure-II : IN-PROCESS CONTROL RECORD SHEET FOR LIQUID / PFS FILLING & SEALING
9.3 Annexure-III : LEAK TEST RECORD SHEET
9.4 Annexure-IV : IPC (IN-PROCESS CONTROL SHEET) FOR TABLET (Core)
9.5 Annexure-V : IN-PROCESS CHECK PFS AND LIQUID FILLING & SEALING
9.6 Annexure-VI : IPC (IN-PROCESS CONTROL SHEET) FOR CAPSULE
10.0 Revision History
|
Version No. |
Brief Reason for the Revision |
Effective Date |
Remarks |
|
01. |
New |
|
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|
|
|
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11.0 Training
11.1 Training is required for Managers and Officers
of all departments trained by Head of Quality Assurance.
