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. INTRODUCTION

2. PROCESS FLOW AND VARIABLES

3. CAPSULE FILLING

MECHANISM

4. QUALIFICIATIONS

5. REFERENCES

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.

1.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 swallow.

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

INTRODUCTION

Sr No. Capsule Size

Volume (ml)

Lactose(mg)

Aspirin(mg)

1. 000 1.37 1340 1000

2. 00 0.95 929 600

3. 0 0.68 665 500

4. 1 0.50 489 300

5. 2 0.37 362 250

6. 3 0.30 293 200

7. 4 0.20 195 125

8. 5 0.13 127 60

Various Sizes of Capsules:

INTRODUCTION

Various Sizes of Capsules:

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

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

INTRODUCTION

2. PROCESS FLOW AND VARIABLES

PROCESS FLOW CONTROL VARIABLES MEASURED RESPONSED

ADDITION OF:1. RAW MATERIALS,2. API AND3. EXCIPIENTS

MIXING AND MIXER

ADDITION OF LUBRICANTS AND DISINTEGRANTS

BLENDING AND BLENDER

CAPSULATING

1. LOAD SIZE2. RPM3. MIXING TIME

1. LOAD SIZE2. RPM3. BLENDING TIME

1. CAPSULATION SPEED2. POWER FEED RATE

MIX UNIFORMITY

1. WEIGHT VARIATION2. DISINTEGRATION TIME AND3. LOCKING

1. BLEND UNIFORMITY2. FLOW CHARACTERISTICS

FILLING OF VARIOUS ENTITIES

TABLET FILL

PELLET FILL

PELLET MIX FILL

LIQUID FILL

3. TYPES OF CAPSULE FILLING

MECHANISM

1. Tamping-In and Stroking

2. Continuous Tamping

3. Auger Filling

4. Compression Filling

5. Vacuum Fill

v v V

STROKING IN AND TAMPING MACHINE

CAPSULE BODY DOSING DISCPOWDER OR GRANULATE

TAMPING AND VOLUME FILL

AGITATOR

AUGER FEED MECHANISM

DOSAGE HOPPER

PICK-UP RING FOR CAPSULE BODIES

AUGER MECHANISM OF FILLING

DOSING PISTON

LIQUID FILL

CAPSULE BODY

OUTLET VALVE

LIQUID/ SEMISOLID

FILLING METHOD

v v v v vv

BASE PLATE

DOSING DISC

TAMPING STATION

1ST 2ND 3RD

4TH

TRANSFER STATION

DETECTOR TAMPING PUNCH

CAPSULE BODY

CONTINOUS TAMPING FILLING

v v v v vv

DOSAGE PUNCH

DOSAGE TUBE

DOSAGE BLOCK

CAPSULE BODY

BUSHING

DOSAGE HOPPER

COMPRESSION FILLING

DOSAGE PUNCH

DOSAGE TUBE

DOSAGE BLOCK

CAPSULE BODY

BUSHING

DOSAGE HOPPER

VACUUM

DOSAGE TROUGH

DOSAGE TUBE

FORMATION OF PLUG

VACCUM FILLING METHOD

PLASTIC PISTON WITH FILTER

GELATIN TANK

SPREATER BOX

COOLING DRUM

PRODUCT MATERIAL TANK

INJECTION WEDGE

RIBBON

CONVEYER BELT

PRODUCT PUMP

DIE ROLL

SOFT GELATIN CAPSULE FILLING

GELATIN TANK

SPREATER BOX

COOLING DRUM

PRODUCT MATERIAL TANK

INJECTION WEDGE

RIBBON

CONVEYER BELT

PRODUCT PUMP

DIE ROLL

FOR HARD GELATIN CAPSULE:

CONTROL PARAMAETERS

SR NO. VARIABLE RESPONSE

1. MACHINE SPEEDDOSE UNIFORMITY

2. BED HEIGHTWEIGHT VARIATION

3. COMPACTION PRESSUREAPPEARANCE/ LENGTH

4. DOSING PRESSURECONTENT UNIFORMITY

5. CLOSING VOLUME

A. DISSOLUTIONB. MICROBIAL COUNTC. MOISTURE CONTENT (BRITTLENESS)

FOR SOFT GELATIN CAPSULE:

CONTROL PARAMAETERS

SR NO. VARIABLE RESPONSE

1. SPEED OF DIE ROTATION

ELEGANCE/ COLOR

2. TEMPERATURE OF GELATIN CAPSULE FILL WEIGHT

3. RIBBON THICKNESSCAPSULE SHELL WEIGHT

4.TEMPERATURE AND

HUMIDITY OF PROCESSING AREA

A. CAPSULE WALL THICKNESSB. ASSAY AND CONTENT UNIFORMITYC. DISSOLUTION D. MOISTURE CONTENT E. LEAK TEST

Basic document that is root for all validation and 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

4. USER REQUIREMENTS

SPECIFICATIONS (URS)

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.

1. Operation: Production Speed ______ Capsules/ min2. 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

OPERATIONAL REQUIREMENTS

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 Operator or Communication Link- input7. 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 Sounds Protective Guard Operation : When Protective Guards are removed Machine Stops7. Control Function Test : Main and

Vacuum Motor Rotation

Direction

Emergency STOP :

ALARM OR WARNINGS:

SR NO. ALARMS OR WARNINGS IMMEDIATE OPERATOR/ ALERT

1. EMERGENCY STOP X

2. PROTECTIVE GUARDS NOT IN PLACE X

3. NO CAPSULES X

4. LOW PRODUCT LEVEL X

5. CONTROL POWER FAULT X

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 rate2. 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: _____________ It is anticipated the equipment will be cleaned on a _______

basis

The Installation Qualification(IQ) shall confirm detail from:

1. The Equipment Specifications2. Equipment Purchase Order3. cGMP Guidelines and Requirements

It has to be Ensured that the Equipment has been installed as specified by the vendor

INSTALLATION QUALIFICATION

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


Equipment name, make & model no. shall be recorded In-house identification no. shall be recorded e.g. INH ID No.: 4052 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


Equipment name, make & model no. shall be recorded In-house identification no. shall be recorded Location for installation shall be checked e.g. Location: Room 147 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


Equipment name, make & model no. shall be recorded In-house identification no. shall be recorded Location for installation shall be checked Utilities required shall be listed down 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 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


Equipment name, make & model no. shall be recorded 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 e.g. Machine Parts of Filling, Control Cabinet Software etc Where stirring devices or augers are used to ensure homogeneity and improve flow then specification of these parts must be checked


Equipment name, make & model no. shall be recorded 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 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

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 specifications2. 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 verified4. Oil leaks that could contaminate the process are observed

OPERATIONAL QUALIFICATION

SET-I CAPSULE FILL

CHECK

SET-II CAPSULE FILL

CHECK

SET-III CAPSULE FILL

CHECK

OPERATION CHECK FOR CAPSULE FILLING

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 equipment- calibrated The Equipment when operated shall not - produce abnormal sound - show any discrepancy in its smooth operation.

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.

PERFORMANCE QUALIFICATION

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

5. Production speed i.e. capsule per minute should be evaluated

Q-1 Discuss Criteria for Validation of Tablet Machine and Capsule Filling Machine - 5 marks May 2012Q-2 Describe Unit Operation along with their Process Variables for Hard Gelatin Capsules

QUESTIONS ASKED IN GTU????

6.REFERENCES

1. Nash RA. And Wachter AH. “Pharmaceutical process

validation”; 3rd edition ; Basel (NY): Marcel Dekker

Inc , 1993, Pg No. 83-1102. 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, 1204. PP Sharma, “Validation in

Pharmaceutical Industry”, First Edition, Vandana

Publication, 2008, Pg No. 83-99

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”, Special Indian Edition, 2009, Pg No. 374-412

QUALITY NEEDS TO BE BUILT INTO THE PRODUCT

GARVIN’S 8 DIMENSIONS OF QUALITY:

1. PERFORMANCE2. SECONDARY FEATURES3. DURABILITY4. AESTHETICS5. PERCEIVED QUALITY6. SERVICES7. CONFORMANCE8. RELIABILITY

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Capsule Filling MC Validation

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