VALIDATION OF TABLET COMPRESSION MACHINE

Presented by.. Mr. Sagar H. Navale M.Pharm (Sem-II) Guided by.. Prof. (Mrs.) D. N. Sanghai Dept. of Pharmacognosy

Dept. of Quality Assurance Techniques Stess Sinhgad Institute Of Pharmacy,Narhe,Pune-41 2011-12 1 of 47

CONTENTS:

Definition of validation. Why to validate? Overview of equipment validation. Tablet compression machine and its components. Typical variables of compression process. Components of equipment validation.

Guidelines for validation of tablet compression machine.

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INTRODUCTION TO VALIDATION

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VALIDATION

According to USFDA Validation, is defined as A documented programme , which provides a high degree of assurance that a specific process or equipment will consistently produce, a product

meeting its pre-determined specifications and quality attributes.

Validation is the process which gives the written proof that our equipment complies with all the specifications of the cGMP.
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WHY TO VALIDATE?

Equipment validation is Vital for Safety Fewer interruptions of work Lower repair costs Elimination of premature replacement Less standby equipment Identification of high maintenance cost Reduction of variation in results Greater confidence in the reliability of results
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EQUIPMENT VALIDATION

As mentioned earlier, each piece of must be validated in order to legally operate within the facility.

The goal is to produce consistent results with minimal variation without compromising the integrity of the product and the persons operating the equipment.

A plan of validation should be drafted and executed by Q.A personnel & engineers in order to satisfy guidelines. The validation plan generally consists of DQ, IQ,PQ and OQ sections.
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EQUIPMENT VALIDATION

Any major equipment changes after the initial validation will

result in the need for subsequent revalidation.

In the end, equipment validation will create specification ranges and tolerances that will be applied to the normal operation of equipment.

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TABLET COMPRESSION MACHINE:

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TABLET COMPRESSION MACHINE:

Tablet compression machine is designed with the following components: Hopper (s) for holding and feeding granulations to be compressed. Dies that define size and shape of the tablet. Punches for compressing the granulation within the dies. Cam tracks for guiding the movements of the punches. A feeding mechanism for moving granulation from hopper into the dies. Weight adjustment knob. Pressure adjustment knob.
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a)

b)

c)

d)

e)

f)

g)

TABLET COMPRESSION MACHINE:

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DIFFERENT COMPONENTS OF VALIDATION

1 8 2

4 6 5

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GUIDELINES FOR COMPRESSION MACHINE VALIDATION:

Validation of the equipment is performed in four steps:

DESIGN QUALIFICATION (DQ).

INSTALLATION QUALIFICATION (IQ).

OPERATIONAL QUALIFICATION (OQ).

PERFORMANCE QUALIFICATION (PQ).

These four protocols are used to define tests that will demonstrate that the process consistently and repeatedly produces the desired product.

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DESIGN QUALIFICATION:

Preparation of User Requirement Specification

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URS FOR TABLET COMPRESSION MACHINE

Model: LAB PRESS It must be multi tooling No of stations must be Turret rpm must be min/max Maximum Operating Pressure Maximum Tablet Diameter Maximum depth of the fill Output tablet per hour Electric motor MOC: Turret Hopper Discharge chute Dust collection nozzle Feed frame Main body Outside doors and covers

D, B & BB 12. 10 30. 6.5 ton. 23mm. 20mm. 2,400 to 7,200. 2Hp,3 phase. SG IRON 400/12 SS 316 SS 304 SS304 gun metal SS304 cladded SS3o4
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URS FOR TABLET COMPRESSION MACHINE

In addition to above specification. D, B, BB, tooling set must be present. Dies loading and unloading equipment must be present. Punches loading and unloading equipment must be present. Tablet hardness tester, vernier calliper, micrometer, screw gauge, scale must be

present.

Emergency shut off must be present. Manual must be present.

Drawing must be present.

List of lubricants to be used DQ protocol
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INSTALLATION QUALIFICATION

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INSTALLATION QUALIFICATION

This is the first step in validation.

This protocol insures that the system/equipment and its components are installed correctly and to the original manufacturers specifications.

Calibration of major equipment, accessory equipment, and/or

utilities should be performed in this step as well.
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INSTALLATION QUALIFICATION
a. b.

Verify approved purchase order. Verify invoice.

c.
d. e. f.

Check manufacturer and the supplier.

Verify Model no. and serial. no. Check for any physical damage. Confirm location and installation requirement per recommendation of the manufacturer Verify that the utilities required are available. Ensure that all the relevant documents i.e. user manual, maintenance manual, list of change parts, electrical drawing, mechanical drawing are received.
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g. h.

IQ of the following:

1.

IQ for turret. IQ for punches.

2.

3.

IQ for dies. IQ for hopper.

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4.

IQ FOR PUNCHES
URS SPECIFICATION

PARAMETER
UPPER PUNCH Length Diameter MANUAL DRAWINGS LIST OF SPARE PARTS

OBSERVATION

COMPLIANCE

D= B= BB= YES YES DIFFERENT PUNCHES (D,B,BB)

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IQ FOR DIES:
PARAMETER URS SPECIFICATION OBSERVATION COMPLIANCE

NO. OF DIES

4 sets of each of D, B, BB.

D= B= BB= D= B= BB= Thickness adjusting knob
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DIAMETER

HEIGHT

INPUT/ OUTPUT

IQ FOR HOPPER:
PARAMETER URS SPECIFICATION OBSERVATION COMPLIANCE

Height Inlet diameter Outlet diameter MANUAL YES

INPUT/ OUTPUT CONTROLS

YES

TEST EQUIPMENT

Scale, vernier calliper

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PARAMETER

URS SPECIFICATION Power on/off, pressure adjusting knob, thickness adjusting knob. Temp=25+/-2C. RH=55+/-5%

OBSERVATION

COMPLIANCE

INPUT/ OUTPUT CONTROLS

ENVIRONMENTAL CONDITION UTILITIES

Yes

TEST INSTRUMENT

Tablet hardness tester

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REPORT OF IQ

Deficiency and corrective action report Final report Summery The equipment was procured as per the required specification. Installation was carried out as per manufacturers recommendations and users applicability. Supporting utilities are connected.

The machine was installed at the location. Supporting utilities are connected and are functioning properly. Standard operating procedure shall be identified and listed. History card is prepared for the equipment.

Approval IQ protocol
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OPERATION QUALIFICATION (OQ)

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OPERATION QUALIFICATION (OQ)

This step proceeds after the IQ has been performed. In the OQ, tests are performed on the critical parameters of the system/process. These are usually the independent and/or manipulated variables associated with the system/equipment.

All tests data and measurements must be documented in order to set a baseline for the system/equipment.

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OPERATION QUALIFICATION (OQ)

Operational qualification is performed to verify the operational attributes of the equipment which are critical to serve the intended purpose of the equipment. It is dynamic process.

OQ involves the following:

1) 2) 3) 4) 5)

System description Key functionality test SOP verification Training Acceptance criteria.
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A. SYSTEM DESCRIPTION

As mention earlier LAB PRESS compression machine works in a

systematic manner as per the specification that has been laid down

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B. KEY FUNCTIONALITY TEST:

Key functionality test is performed to check that the control panel and other manual operations of the equipment i.e. tablet compression machine are working properly.

The test data sheet of the key functionality test is as follows:

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KEY FUNCTIONALITY TEST DATA SHEET

PARAMETERS OBSERVATION COMPLIANCE

MAIN SWITCH ON/OFF MAIN MOTOR ON

MACHINE STARTS/STOP GREEN LIGHT GLOWS ON PANEL MACHINE STOPS AND YELLOW LIGHT GLOWS

EMERGENCY OFF

RESET BUTTON

MACHINE IS RESET

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KEY FUNCTIONALITY TEST DATA SHEET

PARAMETERS OBSERVATION COMPLIANCE WEIGHT ADJUSTMENT WT IS INCREASED OR KNOB DECREASED THICKNESS ADJUSTING KNOB SPEED OF PRESS PRE-COMPRESSION COMPRESSION FORCE FEED FRAME (OPEN/FORCED) FEEDER SPEED THICKNESS IS INCREASED OR DECREASED INCREASED MANUALLY RISE IN COMPRESSION FORCE OPEN

CONTROLLED MANUALLY
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C. SOP VERIFICATION:

A draft SOP is to be prepared using suppliers guide prior to the

qualification testing.

Then equipment is to be operated as per the draft SOP and any deviations in SOP are recorded and changes are made and the SOP is confirmed.

This confirmation of the SOP is recorded in the SOP verification part of protocol.
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D. TRAINING:

Before starting with the actual qualification the personnel should be trained by the engineers from the suppliers on the operational features of the equipment.

This training shall be recorded.

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E. CALIBRATION:

For tablet compression machine following parameters are to be calibrated:

1.

Revolution speed of the tabletting table. Counter pressure at pre compression station. Counter pressure at the main compression station.

2.

3.

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REPORT OF OQ

Summary

The operation of the equipment 12 Stn. Multi tooling Lab Press Machine was carried out
as per standard operating procedure.

The equipment parameters that have a significant impact on the equipment ability to operate and achieve the process are satisfactory and confirm to the acceptance criteria.

Approval

OQ Protocol

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PERFORMANCE QUALIFICATION:

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PERFORMANCE QUALIFICATION:
It is also dynamic process and is performed with load. In PQ actual performance of the equipment is checked by running pilot batch on the machine. The product (tablets) so obtain is evaluated for following parameters:

Appearance Weight variation Hardness/friability Thickness Moisture content Disintegration/dissolution Assay/dose uniformity
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WEIGHT VARIATION:
In weight variation uniformity of the die filling can be checked. Perform on 20 tablets Determine mean and percent deviation. No more than two tablets have a variation as large as that shown below; no tablet is twice the variation.

The acceptance criteria for weight variation test is as follows: Weight (in mg) 130 mg or less More than 130mg but less than 324mg 324mg or more % Deviation allowed 10% 7.5% 5%
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THICKNESS: First 20, last 20, middle 20 (throughout the run)

Determine mean and percent deviation. The Standard Deviation should be less than or equal to 5% Deviations allowed: +/- 5% of specified thickness. HARDNESS: First 20, last 20, middle 20 (throughout the run)

Determine mean and percent deviation for baseline. Must meet each tablet specifications. Deviation allowed: +/- 5% of specified hardness.
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FRIABILITY: Test Perform on 20 tablets

Friability should not be more than 1%

calculated using following formula

% Friability = wt of tablet after test wt of tablet before test

x 100

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DISINTEGRATION TIME: For uncoated tablets it should not be more than 15 mins.

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REPORT OF PQ

SUMMARY The performance of the equipment 12 stn. Multi Tooling Lab Press Machine, was carried out as per standard operating procedure.

The equipment performs within the assigned limits when operated as per approved standard operating procedure.

Performance parameters that have a significant impact on the equipment ability to operate and achieve the process are satisfactory and confirm to the acceptance criteria.

Approval. PQ Protocol

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F. REQUALIFICATION CRITERIA

The equipment shall be requalified if;

Location of the equipment is changed. There is change of spare/parts, major maintenance or breakdown that have a direct effect on the performance of the equipment

When there is major modification in the equipment. At normal revalidation schedule.

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REFERENCES
1)

Hapse, S. Sawant, R. (2011) fundamentals of Quality Assurance Techniques. first edition, Text book career publication. Pp 65-73

2)

Agalloco, P. J. Carleton, J. F. (2006) Validation of pharmaceutical processes second

edition, Marcel Dekker, Inc. pp 131-150 Haider, S. I. (2007) Pharmaceutical Master Validation Plan first edition published by Informa Healthcare. pp 71-79, 118 Nash,R.A.Wachter,A.H. (1993). Pharmaceutical Process Validation. An International Third edition, vol.129, CBS Publishers and Distributers pp.443-462 Potdar, M.A. (2009) Pharmaceutical Quality Assurance Nirali Prakashan, pp.8.13-

3)

4)

5)

8.20
6)

Sharma,P. P. (2007) Validation in pharmaceutical industry.,first edition, Vandana publications Pvt ltd., pp . 83
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REFERENCES
7) Guidance for Industry Process Validation: General Principles and Practices, U.S. Department of Health and Human Services, Food and Drug Administration, January 2011 Current Good

Manufacturing Practices (CGMP) Revision 1

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.ht m 8) Donald M. R. Validation of Pharmaceutical Process Equipment www.freewebs.com/wasimeexpress4/vector.pdf
9)

Validation protocol for 12 stn. Multi tooling lab press machine Cip Machineries Pvt. Ltd. www.cipmach.com/www.roll-compactor.com

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