Capsule Filling MC Validation

CAPSULE FILLING
MACHINE VALIDATION
Filled By:
SACHIN.T.PREMI,
M.Pharm, Sem- III,
PQA
Babaria Institute of Pharmacy,
Varnama 391240, NH- 08, Vadodara
BRIEF VIEW OF
CONTENTS
1.
INTRODUCTIO
N
2. PROCESS FLOW
AND VARIABLES
3. CAPSULE
FILLING
MECHANISM
4. QUALIFICIATIONS
5. REFERENCES
1.INTRODUCTION
CAPSULE:
They
are generally gelatin shells filled with

the ingredients that make up an individual
dose.
Dry powders, semi-solids, and liquids that do
not dissolve gelatin may be encapsulated.
Capsules account for about 20% of all
prescriptions dispensed.
INTRODUCTION
Advantages:
I. They may be used to mask the unpleasant tastes,
aromas, or appearance of a drug.
II. They allow powders to be dispensed in an
uncompressed form, thus allowing for quicker
dissolution and absorption of the drug following oral
dosing (as compared with tablets).
III. They offer the pharmacist versatility to prepare any
dose desired for a variety of administration routes
(e.g. oral, inhalation, rectal, or to be diluted for
vaginal, rectal, oral or topical use) and thus aid to
alter release rate.
IV.They may be easier than tablets for some people to
INTRODUCTION
Disadvantages:
I. They are easily tampered with (although
techniques exist for preventing this).
II. They are subject to the effects of relative
humidity and to microbial contamination.
III. They may be difficult for some people to
swallow.
IV. More expensive (commercially)
INTRODUCTION
Properties:
Hard Gelatin Capsules consists of a Base or a Body and a
Shorter Cap.
For human use, eight sizes of capsules are available. The
capacity of each size varies according to the
combination of
drugs and their apparent densities.
Capsules are available as clear gelatin capsules or in a
variety of colors.
The pharmacist can use the different colored capsules to
distinguish two capsule formulations for the same
patient, or
to encapsulate unattractive ingredients.
INTRODUCTION
Various Sizes of Capsules:
Sr No.
Capsule
Size
Volume
(ml)
Lactose
(mg)
Aspirin
(mg)
1.
000
1.37
1340
1000
2.
00
0.95
929
600
3.
0.68
665
500
4.
0.50
489
300
5.
0.37
362
250
6.
0.30
293
200
7.
0.20
195
125
8.
0.13
127
60
INTRODUCTION
Various Sizes of Capsules:
INTRODUCTION
EQUIPMENT VALIDATION IMPORTANCE:
1. Safety
2. Fewer Interruptions of Work
3. Elimination of Premature Replacements
4. cGMP Requirement
5. Reduction of Variation in Results
6. Greater Confidence in the Reliability of
Results
INTRODUCTION
1. Safety
4. cGMP Requirement
Results
INTRODUCTION
1. Safety
4. cGMP Requirement
Results
INTRODUCTION
1. Safety
4. cGMP Requirement
Results
INTRODUCTION
1. Safety
4. cGMP Requirement
Results
INTRODUCTION
1. Safety
4. cGMP Requirement
Results
INTRODUCTION
WHO SHOULD DO EQUIPMENT VALIDATION:
VENDOR OR USER???
1. DQ is always done by the User
2. IQ for small and low cost instrument is done by the
User
3. IQ for large, complex and high cost instrument is
done by the Vendor
4. OQ can be done either by the User or Vendor
5. PQ should always be done by the User
2. PROCESS FLOW AND

VARIABLES
PROCESS
FLOW
ADDITION OF:
1. RAW
MATERIALS,
2. API AND
3. EXCIPIENTS
MIXING AND
MIXER
ADDITION OF
LUBRICANTS
AND
DISINTEGRANTS
BLENDING AND
BLENDER
CAPSULATING
CONTROL
VARIABLES
1. LOAD SIZE
2. RPM
3. MIXING TIME
1. LOAD SIZE
2. RPM
3. BLENDING
TIME
1. CAPSULATION
SPEED
MEASURED
RESPONSED
MIX UNIFORMITY
1. BLEND UNIFORMITY
2. FLOW
CHARACTERISTICS
1. WEIGHT VARIATION
2. DISINTEGRATION
TIME AND
FILLING OF VARIOUS
ENTITIES
LIQUID
FILL
PELLET
FILL
TABLET
FILL
PELLET
MIX FILL
3. TYPES OF
CAPSULE FILLING
MECHANISM
1. Tamping-In and Stroking
2. Continuous Tamping
3. Auger Filling
4. Compression Filling
5. Vacuum Fill
TAMPING AND VOLUME FILL

STROKING IN AND TAMPING MACHINE
v v
CAPSULE
BODY
DOSING
DISC
POWDER
OR
GRANUL
v v
AUGER MECHANISM OF
FILLING
AGITATO
R
DOSAGE
HOPPER
AUGER
FEED
MECHANI
SM
PICK-UP
RING FOR
CAPSULE
BODIES
LIQUID
FILL
LIQUID/
SEMISOLID
FILLING
METHOD
DOSING
PISTON
OUTLET
VALVE
CAPSULE
BODY
CONTINOUS TAMPING FILLING

TAMPING
STATION
TRANSF
ER
STATION
4TH
3RD
2ND
1ST
TAMPIN
G
PUNCH
DETECT
OR
v
v
DOSIN
DISC
CAPSULE
BASE
v
v
v
v
COMPRESSION FILLING
DOSAGE
BLOCK
DOSAGE
TUBE
DOSAGE
HOPPER
DOSAGE
PUNCH
CAPSULE
BODY
BUSHING
DOSAGE
BLOCK
DOSAGE
TUBE
DOSAGE
HOPPER
DOSAGE
PUNCH
CAPSULE
BODY
BUSHING
VACCUM FILLING METHOD
VACUUM
DOSAGE
TUBE
FORMATION OF
DOSAGE
TROUGH
PLASTIC
PISTON
WITH
FILTER
SOFT GELATIN CAPSULE

FILLING
GELATI
N TANK
SPREA
TER
BOX
COOLI
NG
DRUM
INJECTI
ON
WEDGE
RIBBO
N
PRODU
CT
MATERI
AL
TANK
PRODU
CT
PUMP
DIE
ROLL
CONVEY
ER BELT
GELATI
N TANK
SPREA
TER
BOX
COOLI
NG
DRUM
INJECTI
ON
WEDGE
RIBBO
N
PRODU
CT
MATERI
AL
TANK
PRODU
CT
PUMP
DIE
ROLL
CONVEY
ER BELT
GELATI
N TANK
SPREA
TER
BOX
COOLI
NG
DRUM
INJECTI
ON
WEDGE
RIBBO
N
PRODU
CT
MATERI
AL
TANK
PRODU
CT
PUMP
DIE
ROLL
CONVEY
ER BELT
CONTROL
PARAMAETERS
FOR HARD GELATIN CAPSULE:

SR
NO.
VARIABLE
1.
MACHINE SPEED
2.
BED HEIGHT
3.
COMPACTION PRESSURE
4.
DOSING PRESSURE
5.
CLOSING VOLUME
RESPONSE
DOSE
UNIFORMITY
WEIGHT
VARIATION
APPEARANCE/
LENGTH
CONTENT
UNIFORMITY
A. DISSOLUTION
B. MICROBIAL
COUNT
CONTROL
PARAMAETERS
FOR SOFT GELATIN CAPSULE:

SR
NO.
VARIABLE
1.
SPEED OF DIE
ROTATION
2.
TEMPERATURE OF
GELATIN
3.
RIBBON THICKNESS
4.
TEMPERATURE AND
HUMIDITY OF
RESPONSE
ELEGANCE/ COLOR
CAPSULE FILL WEIGHT
CAPSULE SHELL
WEIGHT
A. CAPSULE WALL
THICKNESS
B. ASSAY AND
CONTENT
UNIFORMITY
4. USER
REQUIREMENTS
Basic document
that is root for all (URS)
validation and
SPECIFICATIONS
qualification activities
The goal of working out user requirement
specifications is to document the needs of the
manufacturing department
A well prepared URS is the key to project success
Project without detailed URS have a tendency to
demand lots of change later on thus increase cost
and start up time
For evaluation of URS, the coordinated approach

among production, QA, engineering units of the
pharmaceutical company is required
Some companies even use the services of external
resources to create a URS
The key aspects of any URS is to generate a
document detailing all the GMP requirements the
technical system has to fulfill.
A detail URS will result in a better and more
competitive offer for the technical system.
Without comprehensive URS, a pharmaceutical
company cannot get a clear understanding of
supplier and may be led to a wrong decision.
OPERATIONAL
REQUIREMENTS
1. Operation:
Production Speed ______ Capsules/ min
2. Capsule will be filled to the target weight
______%
3. The Machine Shall not experience more than
______ % downtime at the production speed,
during 8 hour production run
4. Product contact part: Shall be constructed
from material acceptable to the product
Certificates for Material, Weld and Finish
shall be defined.
Products Contact Part shall be Defined
5.
Power Failure and Recovery:

On Power Failure the System shall fall in
SAFE STATE
6. On Power Restoration, the System shall not
restart
without
Emergency
Operator
or Communication Link- input
STOP
:
7.
Buttons shall be supplied within the reach
of the Operator at
the Normal Operator Station
Protective Hood Operation : Machine
must STOP if Hood
remains
open
Acoustic Signal Operation : When Error
Occurs the Buzzer
ALARM OR WARNINGS:
SR
NO.
ALARMS OR
WARNINGS
IMMEDIAT OPERATOR/
E
ALERT
1.
EMERGENCY STOP
2.
PROTECTIVE GUARDS
NOT IN PLACE
3.
NO CAPSULES
4.
LOW PRODUCT LEVEL
5.
CONTROL POWER
FAULT
DATA AND SECUIRTY:

Controls provided with a data collection
system intended for use in the manufacture of
pharmaceutical products shall comply with 21
CFR, Part 11 of the FDA cGMP regulations.
DATA COLLECTION:
Data required for collection
1. Machine rate
2. Alarms and warnings.
3. System status (e.g. off, on, standby
states, etc.)
Other (specify)
ENVIRONMENT:
1.PHYSICAL CONDITION
The CAPSULE FILLER needs to be installed in
an environment in with Temperature range
between ______ to ______ F or C and Relative
Humidity between _____ to _____ %
Vibration Levels and Electromagnetic
Interference Levels:
(a) Negligible
(b) Others(specify)
2.CLEANING CONDITION
The Equipment will be Cleaned Utilizing
following Compounds/ Detergents/ Cleaning
Agents:
INSTALLATION
QUALIFICATION
The Installation Qualification(IQ) shall confirm
detail from:
1. The Equipment Specifications
2. Equipment Purchase Order
3. cGMP Guidelines and Requirements
It has to be Ensured that the Equipment has
been
installed as specified by the vendor
PURCHASE DETAILS:
Check the Following and should be as per
Purchase Order:
Purchase Order Number and Its Date

The Accessories and Its Spare Parts
Delivery Period
Supplier, Manufacturer Name and Address
NOTE: Any Deviation if Observed needs to be

reported to the
Manufacturer or Supplier
DETAILS OF THE EQUIPMENT:

Equipment name, make & model no. shall be
recorded
e.g. (i) Name:
CapsulCN Capsule Filler
(ii) Model No.: 2GM
In-house identification no. shall be recorded
Location for installation shall be checked
Utilities required shall be listed down
A detailed specification must be written which
highlight
those parts of machine that are in product contact
Where stirring devices or augers are used to
ensure
homogeneity and improve flow then specification
of
these parts must be checked

recorded
e.g. INH ID No.: 4052
highlight
Where stirring devices or augers are used to ensure
of

recorded
e.g. Location: Room 147
highlight
of

Equipment name, make & model no. shall be recorded

e.g. Electrical Utilities must meet all electrical codes
Volts: 480 10%
Amps: Motor= 6.5, Vacuum= 1.7
Compressed Air: > 87 psig
Power Supply Source, Breaker Box, Wire
Number etc
highlight
homogeneity and improve flow then specification of

recorded
highlight
e.g. Machine Parts of Filling, Control Cabinet
Software etc
of

recorded
highlight
Where stirring devices or augers are used to
ensure
of
e.g. Lubricants Where Used: Gear and Motor
Reducers
ACCEPTANCE CRITERIA FOR IQ:

Fulfill the selection criteria & its purpose of
Application
The equipment shall be as per purchase order
Accessories received shall be as per purchase
order
Should meet pre-selected design parameters
Manufacturer/supplier shall provide complete
equipment manual
Material of construction shall be as per
purchase order
OPERATIONAL
QUALIFICATION
Before initiating OQ ensure SOPs for Operating and
Cleaning of Capsule Filling Machine are available
PROCEDURE:
1. Check all the dynamic attributes of the capsule filler

conform to the required specifications
2.
Initiate the actual operation of the equipment to
ensure
that machine is operate within the desired rate of
output.
3. The operation of indicators, controls and alarms is
verified
4. Oil leaks that could contaminate the process are
observed
OPERATION CHECK FOR CAPSULE

FILLING
SET-I
CAPSULE
FILL
CHECK
SET-II
CAPSULE
FILL
CHECK
SET-III
CAPSULE
FILL
CHECK
ACCEPTANCE CRITERIA FOR OQ:

All operating inputs provided on the equipment
when tested
shall-successfully comply
-Meet Tolerance Limit
The Equipment should successfully perform when
operated
as per SOP
Critical alarm/indicators provided on the
equipmentcalibrated
The Equipment when operated shall not
- produce abnormal sound
- show any discrepancy in its smooth operation.
PERFORMANCE
QUALIFICATION
PQ activities demonstrates and documents that the
equipment is able to perform its intended functions
within
the variable process limits for a specific product
Acceptance criteria are developed according to the
regulatory requirements and production parameters
To ensure that the quality and purity of the product is
maintained
The PQ's require replicate testing; triplicate testing as
the
generally accepted minimum.
The PQ will also test the extremes of the operation, or
the
peak load conditions, but it does not include testing to
failure.
PROCEDURE:
1. The accuracy and precision of placebo
powder fill will be evaluated for each
capsule size that will be used in normal
production
2.
Record the number of damaged capsules
3. Capsules from throughout the lot/different

batches should be tested for weight
uniformity
4. Capsules from throughout the lot/different
batches should be tested for blend content
uniformity
QUESTIONS ASKED IN
GTU????
Q-1 Discuss Criteria for Validation
of Tablet
Machine and Capsule Filling
Machine
- 5 marks
May 2012
Q-2 Describe Unit Operation along
with their
Process Variables for Hard
Gelatin Capsules
6.REFERENCES
1. Nash RA. And Wachter AH.
Pharmaceutical process
validation; 3rd edition ; Basel (NY):
Marcel Dekker
Inc , 1993, Pg No. 83-110
2. Mehta RM. Dispensing Pharmacy,
3rd Edition;
Vallabh Prakashan, 2008, Pg No. 108-145
3. Syed Imtiaz Haider, Pharmaceutical
Master
Validation Plan, St. Luicepress, Pg No.
114, 119, 120
4. International conference on
harmonization of
technical requirements for registration
of pharmaceuticals for human use, ICH
harmonised tripartite guideline.
Good manufacturing practice
guide for active pharmaceutical
ingredients Q7, current step 4
version.2000
5. Graham C. Cole, : The Design and
Operation of a Facility for Filling
Hard Gelatin Capsules, Middle
Green, Bringham- ARTICLE
6. Leon Lachman, The Theory and
Practice of Industrial Pharmacy,
QUALITY NEEDS TO BE BUILT INTO THE

PRODUCT
GARVINS 8 DIMENSIONS OF QUALITY:

1.PERFORMANCE
2.SECONDARY FEATURES
3.DURABILITY
4.AESTHETICS
5.PERCEIVED QUALITY
6.SERVICES
7.CONFORMANCE
8.RELIABILITY
TH
AN
K
Y
O
U

Capsule Filling MC Validation

Transféré par

Informations du document

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Capsule Filling MC Validation

Transféré par

Droits d'auteur :

Formats disponibles

CAPSULE FILLING

are generally gelatin shells filled with

2. PROCESS FLOW AND

TAMPING AND VOLUME FILL

CONTINOUS TAMPING FILLING

VACCUM FILLING METHOD

SOFT GELATIN CAPSULE

FOR HARD GELATIN CAPSULE:

FOR SOFT GELATIN CAPSULE:

For evaluation of URS, the coordinated approach

Power Failure and Recovery:

LOW PRODUCT LEVEL

DATA AND SECUIRTY:

Purchase Order Number and Its Date

NOTE: Any Deviation if Observed needs to be

DETAILS OF THE EQUIPMENT:

DETAILS OF THE EQUIPMENT:

DETAILS OF THE EQUIPMENT:

DETAILS OF THE EQUIPMENT:

In-house identification no. shall be recorded

DETAILS OF THE EQUIPMENT:

DETAILS OF THE EQUIPMENT:

ACCEPTANCE CRITERIA FOR IQ:

1. Check all the dynamic attributes of the capsule filler

OPERATION CHECK FOR CAPSULE

ACCEPTANCE CRITERIA FOR OQ:

Record the number of damaged capsules

3. Capsules from throughout the lot/different

QUALITY NEEDS TO BE BUILT INTO THE

GARVINS 8 DIMENSIONS OF QUALITY:

Vous aimerez peut-être aussi