1

Instrument validation

PRESENTED BY Prashik s shimpiM.Pharm I SEM

DEPARTMENT OF QUALITY ASSURANCER.C. PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION &

RESEARCH,SHIRPUR.

2

contentsIntroductionDefinationInstrument validation processPrinciple of AutoclaveValidation of AutoclaveConclusionReferences

3

Introduction Instrument is one of the basic components of the pharma

processing and hence, a critical validation issue also .if we want a pharmaceutical process to be validated then the instrument used play a very major role in the whole process.

A validation programme involves various components in pharmaceutical organisation related to process, equipment and product.

It is a regulatory requirement for pharmaceutical companies to perform Instrument Validation on all new instruments.

Instrument Validation requires detailed knowledge of the instrumentation system being validated and is therefore usually performed by the company supplying the instrument

4

Defination of Validation “A documented programme, which provides a

high degree of assurance that a specific process will consistently produce, a product meeting its pre-determined specifications and quality attributes’’.

5

Instrument validation processUser Requirement Specification. (URS)Preparation of Design Qualification and is its

certification. (DQ)Installation Qualification. (IQ)Operational Qualification. (OQ)Performance Qualification. (PQ)Revalidation

6

User Requirement specificationsSize of the equipment.Speed of the equipment. Effectiveness of equipment.Ease of operation,cleaning and maintenance.Low dust and sound generation.Auto control systems.Materials of construction.Overall good construction and workmanship

etc.

7

Preparation of Design Qualification and is its certification.(DQ)Standard equipment then the preparation of D.Q does not verry importatnt 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 design qualification document become verry important and essential.

At this stage to identify the stages during fabrication of the equipment ,where visual, instrumental,or even physicochemical testing may be performed.

Generally ,the Factory Acceptence Test is performed at the manufacturer’s premises before despatch of the equipment to the purchaser.

8

Installation Qualification (IQ)Installation Qualification may be defined as

“Documented verification that all key aspects of the installation adhere to manufacturer’s recommendation, appropriate codes and approved design quallification’’.

The simple meaning of this statement is that the equipment in question can be installed when it is qualified for installation i.e. when it passes the I.Q. Test.

9

Operational Qualification (OQ)Operational Qualification may be defined as

“Documented verification that the system or subsystem performs as intended throught all specified operating range.”The equipment should be operated only when it passes the Operational Qualification Test.

10

Performance Qualification (PQ)Performance Qualification is considered by

many as synonymous with O.Q some experts consider O.Q. as verification of performance of the system or sub system without load and P.Q. is the same with load.

Purpose- To define testing requirements in a product/process/performance/qualification/validation protocol.

11

Principle of AutoclavingA basic principle of chemistry is that when the

pressure of a gas increases, the temperature of the gas increase proportionally.

At 15 psi pressure 121oC temperature can be obtained.

Moist heat coagulates cell proteins of the microorganisms and thus kills all the living entities including spores in 15 to 20 minutes.

It is sufficient to kill all the vegetative forms and spores of the organisms.

12

Validation of AutoclaveBASIC VALIDATION APPROACH

13

INSTALLATION QUALIFICATION• Installation tests should include checking: 1. That the electrical supply is suitable for the autoclave.

2. That the temperature and humidity are sufficiently well controlled.

3. That there is no interference to or from other equipment.

4. The accuracy of indicators has been certified to national standards.

5. The temperature and pressure of the chamber during a sterilization cycle are within specifications.

14

INSTALLATION QUALIFICATION6. The leakage into the chamber during a vacuum cycle

does not exceed the specified maximum.

7. That there is no leakage of steam, water or effluent at any point during the sterilization cycle.

8. That both water quality and steam quality comply with the sterilizer specification

15

INSTALLATION QUALIFICATION9. Mechanical equipment specification (Chamber, valves, traps, stainers, filters, regulators, vacuum pump,

heat exchanger, condenser, etc.)

10.Control & instrumentation specifications (programmable logic controller, operator interface, printer/recorder,

control valves, transducers, pressure & temperature transmitters, resistance temperature devices, switches, level sensors, interlocks, photocells.)

11. Site specifications/utilities (power, grounding, surge protector, uninterruptible power supply,

breakers, water, clean steam, plant steam, drain, isolation valves)

16

INSTALLATION QUALIFICATION12.Approval documentation ( pressure vessel, electrical bill

of materials, vendor specification sheets, purchase orders, preventive maintenance programme, piping installation verification, operating & maintenance manuals.)

13.Control system documentation (system configuration/block diagram, flow sheets, display

layouts, general process limits, data monitoring, software inventory, electronic application code listing, system security.)

17

The OQ process is intended to demonstrate that the components of the autoclave operate properly & that the autoclave is deemed ready for performance or load testing.

An OQ may include the following checks:Operational tests(operator/supervisory/maintenance modes, doors,

abort & emergency stop, programmable parameter, menu navigation, power-up & shut down, procedure select/start control switch & interlock tests.

Leak/air removal/steam penetration/vacuum hold testJacket mappingSaturated steam checkEmpty chamber tests

OPERATIONAL QUALIFICATION

18

Empty chamber heat distribution studiesIntent of this study to demonstrate the temperature

uniformity and stability of the sterilizing medium throughout sterilizer.

Temperature uniformity may be influenced by type, size, design & installation of sterilizer.

In production size sterilizer, 15-20 thermocouples are used & distributed geometrically throughout sterilizer.

Thermocouple should be placed in the exhaust drain which is adjacent to the sensor that control vessel temperature.

Temperature deviation should not greater than +2.5 degree celsius of the mean chamber temperature.

19

Thermocouple locations

20

PERFORMANCE QUALIFICATIONLoaded chamber steam penetration tests: intent of this study is to determine the coolest point

within a specified load. Load cool points are dependent on the type of objects

that compose the loads i.e. liquid filled containers, process equipment.etc.

The penetration thermocouples are positioned within liquid filled containers at the cool point.

21

Loaded chamber microbiological challenge studies Microbial challenge test :Keep ampoules containing spores suspension of Bacillus

Stearothermophilus & clostridium sporogenes 106 population at various location of the autoclave along with probes and maintain the sterilisation temp. at 15 psi and 121oC during the heat penetration studies,once on the maximum load.

Acceptance criteria: Autoclaved ampoules containing Bacillus stearothermophilus spores suspension ampoules should not show any colour change after five days of incubation.

1 22

Revalidation Change of formula,equipment,procedures or

quality of raw materials.Major changes to process parameters.Change & replacement of equipment.Changes to facilities and installation which

influences the process.Document Required Sop and records of

prospective,concurrent,retrospective&revalidation.

23

Conclusion:To ensure that qualification and validation

are performed correctly, the test should only be carried out by suitably qualified & experienced personnel & organization.

To achieve the high standards of purity & quality product

24

References1. Pharmaceutical Quality Assurance,by M.A. Potdar, Nirali

Prakashan, Pune.page no 8.1, 8.13 & 8.14.2. Indian Pharmacopoeia 1996 vol II, Govt. of India

Ministry of Health & family welfare.Appendix-12 Monograph- A-139,A-140.

3. The theory & practice of industrial pharmacy, by Leon Lachnan . Herbert A. Lieberman, Joseph L. Kanig. 3rd edition,page no.625.

4. Pharmaceutical process validation,by Robert A. Nash, Alfred H.Wachter.3rd edition,volume-129,

Page no.98,148-150.100 & 101.

25

Web Referenceshttp://pharmainfo.net/http://www.askaboutvalidation.com http://pharmaceuticalvalidation.blogspot.

in/

www.pharmaweb.net

26

Thank you