A seminar

On

Validation Of Ampoule Filling & Sealing Machine

Department Of Quality Assurance

Maliba Pharmacy College

April 22, 2023 1

Introduction

• Validation may be defined as, “The documented act of demonstrating that

any procedure, process, and activity will consistently lead to the expected results which includes the qualification of systems and equipment”

April 22, 2023 2

Continued….

• The equipment validation process generally covers following steps..– User Requirement Specification (URS)– Preparation of Design Qualification (DQ)– Installation Qualification (IQ)– Operational Qualification (OQ)– Performance Qualification (PQ)

April 22, 2023 3

Stages of Qualification

4

• The previous figure depicts the most commonly used approach to the qualification process as used in the pharmaceutical industry

• It shows a pyramid, which is the best way in which to plan a qualification/validation project

• Investing more time in the first phases will save time and money in later and critical phases

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Who should do Equipment Validation?• The vendor or the user ?— User has the ultimate responsibility for the accuracy of the analysis results and also for equipment qualification— DQ should always be done by the user— While IQ for a small and low cost instrument is usually done by the user, IQ for large, complex and high cost instruments should be done by the vendor— OQ can be done by either the user or the vendor— PQ should always be done by the user because it is very application specific, and the vendor may not be familiar with these— PQ should be done on a daily basisApril 22, 2023 6

Validation of Ampoule Filling & Sealing Machine

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Validation Protocol

• The entire process of equipment validation is designed in the form of certain documented formats or protocols

• This helps in systematizing the study of equipment validation

• A validation protocol prepared by engineer or validation specialist

• The protocol sections contain required procedures and forms

April 22, 2023 10

Continued….

• The procedure describe “how” the system is to be validated, while the forms document these procedure and provide a written record of the performed qualification and validation processes

• Each protocol package is divided into three section:– Installation qualification (IQ)– Operational Qualification (OQ)– Performance Qualification (PQ)

April 22, 2023 11

User Requirement Specification

• The user of the equipment has certain requirement about the equipment which he wants to use

• Some of the general requirements may be stated in the form of certain parameters like…– Size of equipment– Speed of equipment– Availability of spares, change part, immediate service at

reasonable cost

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Continued….

– Low sound generation– Lesser breakdowns– Materials of construction– Auto control system

• This requirements are generally discussed with the suppliers and based on this discussion the selection of the equipment is done

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Continued….

For example,• In ampoule filling machine, a delivery tube

provided for repetitively forcing a measured volume of liquid through the orifice of delivery tube designed to enter the constricted opening of container

• The size of delivery tube depend on ..– the opening of container– the viscosity & density of liquid– speed of delivery desired

April 22, 2023 14

Preparation of D.Q. and its Certification

• If we are going to purchase an standard equipment then the preparation of D.Q. dose not become very important because we are accepting the manufacturer's design as it is

• However, if a particular equipment is to be fabricated as per our requirements then the detailed D.Q. document become very important and essential

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Continued….

• It is advisable to work out the detailed equipment specifications by sitting together with the equipment manufacturer

• It may also be advisable to perform Factory Acceptance Test (FAT) at the manufacturer’s premises before dispatch of the equipment to the purchaser

April 22, 2023 16

Installation Qualification

• “Installation qualification establishes that the instrument is received as designed and specified, that it is properly installed in the selected environment, and that this environment is suitable for the operation and use of the instrument”

April 22, 2023 17

Continued….

• The qualification involves,– Verification of approved purchase order– Verification of invoice– Check manufacturer and supplier– Verification of model number and serial number– Checking for any physical damage– Confirm location and installation requirements as per

recommendation of manufacturers– Verify that the utilities required are available– Installation shall be conducted as per instructions

provided in the manual

April 22, 2023 18

Continued….

• Ensure all relevant documentation is received like,− User manual− Maintenance manual− List of change parts− Electrical drawings

April 22, 2023 19

Operational Qualification• O.Q. is verification of performance of the system without

load• O.Q. section details the tests to be performed on the

equipment to document that it operates correctly• O.Q. involve,

– Verification of alarm control– Perform calibration requirements identified in the manual or

established by the validation team– Operate the equipment at low, medium, and high speed as per

operations manual to verify the operating control– Verify that all switches and push buttons are functioning

properly– Establish procedures (SOP) for operation, maintenance, and

calibration– Establish training program for relevant staff

April 22, 2023 20

Performance Qualification• P.Q. is verification of performance of system with

load• Filling studies will be run on all containers and fill

levels • The containers will be filled in triplicate runs • If a placebo is used, it should have similar physical

characteristics (viscosity, density, foaming) to the actual fill materials

• The study should be run at minimum, maximum and intermittent speeds (in terms of ampoules/minute)

• The filler must handle the containers without damage and without jams

• Accuracy and precision must meet specifications

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• P.Q. of ampoule filling and sealing machine involve,a) Wight variation testb) Filling volume accuracyc) Particle Contaminationd) Leaker teste) Oxygen content

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a)Weight variation test :– In the absence of specific criteria, weight variation

must conform to USP – In summary, all 10 units must be within 85.0 to

115.0% of target content, with a %RSD ≤ 6.0%, or not more than 1 of the 30 units outside of the 85.0 to 115.0% and no units outside of 75.0 to 125.0%, with a %RSD ≤ 7.8%

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Continued…..

b)Filling Volume Accuracy:The filling accuracy should be within ±% of the

adjusted and desired filling volume in accordance with the machine specification.

eg.– Attention limit: ±1%– Action limit: ±2%

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Continued….

c) Particle Contamination of Ampoules during Filling & Sealing Procedure:– Ampoules should be filled with water for injection

and afterward be inspected on the contamination with particles (particle classes: ≤10 μm and ≤25 μm).

– The inspection can be performed with a particle counter.

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Continued….

d)Leaker test:– Should capillary pore or tiny cracks be present,

micro-organisms or other contaminants may enter the ampoule, or the content may leak outside.

– Leaker usually detected by submerged ampoule in a deeply colored dye solution (usually 0.5 to 1.0% methylene blue).

– Limitation is that capillaries of about less than 15 um not detected by this method.

April 22, 2023 26

Continued….

e) Oxygen content,– If the filler produces a nitrogen purge, the

headspace gas should be analyzed for oxygen content

April 22, 2023 27

Requalification

• Requalification of systems and equipment should be done in accordance with a defined schedule

• The frequency of requalification may be determined on the basis of factors such as the analysis of results relating to calibration, verification and maintenance

• There should be requalification after changes • The extent of requalification after the change

should be justified based on a risk-assessment of the change

April 22, 2023 28

References...References...

1) R. A. Nash & A. H. Wachter, “Pharmaceutical process validation”; Third edition

2) Leon Lachman, H. A. Lieberman & J. L. Kanig, “The Theory and Practice of Industrial Pharmacy”; Third edition, Pg. No. - 667 to 674

3) Manohar A. Potdar, “Pharmaceutical Quality Assurance”, Pg. No.- 8.13, 8.14

4) Syed Imtiaz Haider, “Validation Standard Operating Procedure”, Pg. No. - 304 to 307

5) Syed Imtiaz Haider, “Pharmaceutical Master Validation Plan”, Pg. No. – 140

6) http://www.validationworld.com/

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