SUPPORT AND UTILITIES VALIDATION

Dr. D.Y. Patil College Of Pharmacy, Akurdi.

Presented By,Asmita Rajendra Magare

M. Pharm 1st year (QAT)

Guided By,Mrs.Sonali Mhaprle

2

Introduction

•All utilities that could impact on product quality should be qualified and appropriately monitored and action should be taken when limits are exceeded.

•There are different type of utilities in the pharmaceutical product manufacturing

3

VALIDATIONTo prove the performance of processes or

systems under all conditions expected to be encountered during future operations.

Validation involves proving-

1. Engineering design2.Operating procedures and acceptable ranges for control parameters3. Maintenance procedures to accomplish it

4

utilities

Water system

Pure steam system

HAVCsystem

Compr-essed

air

5

High-quality water is essential for the manufacturing of pharmaceuticals. Water is the most commonly used raw material in pharmaceutical manufacturing.

Water is directly or indirectly used in the pharmaceutical manufacturing such as a major component in injectable products and in cleaning of manufacturing equipment.

Water is thus an important raw material in GMP and in validating the manufacturing process.

Pharmaceutical water system

6

SYSTEM QUALIFICATION

7

Validation of water system should consist of at list three phases as follows,

• Phase 1 (investigational phase)• Phase 2(verification step)• Phase 3 (verifying long term control)

QUALIFICATION PHASES

8

• A test period of 2-4 weeks – monitor the system

• System to operate continuously without failure or performance deviation.

• Chemical and microbiological testing should include in accordance with a defined plan.

Phase 1 (investigational

phase)

• A further test period of 2-4 weeks – further intensive monitoring of the system

• Utilization of all the SOPs after the satisfactory completion of phase 1.

• Water can be used for manufacturing purposes during this phase.

Phase 2 (verification step)

• Over 1 year after the satisfactory completion of phase 2.

• Water can be used for manufacturing purposes during this phase.

• sampling frequencies and tests should be reduced based on established procedures proven during phases 1 and 2.

Phase 3 (verifying long term control)

9

It is prepared by Verification of design documentation, including-

Description of installation and functions Specification of the requirements

Instructions for performance control Operating procedures Maintenance instructions Maintenance records Training of personnel (program and records) Environmental records Inspection of plant

Finally certification (Sign.) by Engineer, User (Production) and QA Heads.

COMPLETE DOCUMENTATION

10

Types of steam system in pharmaceutical industries:

1.House steam-

contains steam generator and distribution system made of iron or steel.

Constructed with rusting material.

This system is usually treated with various substances like amines, hydrazine or other boiler additives to arrest corrosion.

2. Clean steam-

It established when steam is used for directly treating the product or product contact surfaces.

Constructed with non-rusting material. E,g. stainless steel.

This system use either purified or distilled water as feed water.

Steam System

11

Steam system validation include the

following steps:

Make a process diagram and identify major

process steps

Define major equipment in the process

Carry out IQ, OQ, PQ.

12

waterWater

pretreatment

Distillation

equipment

Holding tank

Steam generator

Distribution system

Process outline of clean steam

13

INSTALLATION QUALIFICATION

1. For clean steam generator

Connect the generator to the reqired utilities and verify on to their correctness

Tighten flanges or other fittings, clean generator chemically and passivate generator after installation. Label the utilities feeding the generator

Carry out pressure testing and record the results.

Check and calibrate all critical processes instruments.

14

2. Distribution system

material of construction is as per the specification

Compare the design drawing

All branches

of the system

should be labeled

Clean the distribution

system

Carry out the pressure

test

15

OPERATIONAL QUALIFICATION

1.Clean steam generator

Acc. To SOP, start up and run the clean steam generator

Check that all instruments and alarms are working correctly. Record their status.

Check that the generated steam meet the specifications and can be produced in quantities required.

16

2. Distribution system

Test all the use points of the system for adequate supply of steam under maximum load or other production condition.

Quality of steam should be tested at all the use points.

Use point should also be tested to find out that excess condensate is not present under operating conditions.

17PERFORMANCE QUALIFICATION

Several tests under

defined load

conditions

It required testing

specified in the

protocol

PERFORMANCE QUALIFICATION

18

Compressed Air system 2 types of compressed air system are used

in the pharmaceutical industry.

1. Conventional oil lubricated compressors for operating instruments and machinery where no contact with product or the environment, where product is being mfg. is involved.

2. An oil free compressed air system used in clean room areas.

It contains mainly compressor, dryer, storage tank and distribution system.

19

INSTALLATION QUALIFICATION

1. Oil free compressor

Check specification on purchase order and actual delivery specification

Verify that no oil or other lubricant is used in the compressor

Check that all required utility requirements have been met and connected properly

Check whether pre-start up procedures were performed

Check whether all critical instruments have been calibrated

Document above all

20

2. Compressed air storage tank

Compressed air

storage tank

Confirm that the

material of construction is as per specificatio

n

Check the capacity of

the tank against

purchase specificatio

n Carry out a pressure hold test .

Examine the

cleaning procedure

adopted for the tank .

Check all pressure rates for

tank against the purchase

specification

21

3. Distribution system

Confirm the material of construction and design parameter specified by the company

Compare the drawing of the system with “as-built” drawing to show whether any modification have been made and note the modifications.

Pressure test the system to confirm its integrity and record the result

Examine the cleaning procedures after installation

22

OPERATIONAL QUALIFICATION

Check all the use points for the tests mentioned below and record the results.

Identity Nonviable particle count Microbial count

Check several worst-case locations for purity.

Test all instrument and alarms for their operational status and record.

Test the compressor output for hydrocarbons.

23

PERFORMANCE QUALIFICATION

It consist of completing the documentation from various steps mentioned above and repeating operational testing as specified in the validation protocol.

In case of the system PQ can be considered as validation.

24

Heating Ventilation and Air Conditioning

system(HVAC)

HVAC systems can have an impact on product qualityIt can provide comfortable conditions for operatorsThe impact on premises and prevention of contamination and cross-contamination to be considered at the design stageTemperature, relative humidity control where appropriateSupplement to basic GMP

Test procedure and key aspects

Maximum time interval

Objective Test Parameter

Particle count test Readings and positions

6 months or 12 months depending on Class

Verifies cleanliness

Particle count

Measure pressure difference

12 months Absence of cross-contamination

Air pressure difference

Measure supply and return air, calculate air change rate

12 months Verify air change rates

Airflow volume

Velocity measurement

12 months Verify unidirectional airflow and or containment condition

Airflow velocity

25

SCHEDULE OF TESTS TO DEMONSTRATE CONTINUING COMPLIANCE

Air flow measurement

Filter Integrity Testing

Pressure Differentials

Particulate count measurement

Recovery test

Temperature and Relative Humidity

Air Flow Pattern

Microbial Count26

VALIDATION PARAMETERS

27

NON-VIABLE PARTICLE COUNTS

Equipment Optical Particle Counter . Air sample is drawn into the instrument & passed through

light scattering device. The signal that this generates is electronically processed to display particle counts at different size ranges.

Acceptance criteria:

The particle concentration under the dynamic

condition should not more than 100 particle of 0.5µm and larger per cubic meter (for class 100 area)

28

PRESSURE DIFFERENTIALS

- Correct degree of overpressure can be maintained relative to the adjacent areas of lower classification to ensure that air moves from clean areas to less clean areas.

- It is calculated by making use of the manometer attached at the walls of the adjacent area.

- The pressure difference is generally kept between 5 and 20 mmHg pressure.

29

AIRFLOW VELOCITY

Equipment :- Anemometer

Reading should be taken 10cm from the surface of filter. Record velocity reading from all the four corners and the

Centre of the filter surface. Repeat twice at each location For Grade A laminar flow workstations, the air flow

rates shall be 0.3 meter per second + 20% (for vertical flows) and 0.45 + 20% (for Horizontal flows)

Solution : Alteration of fan speed or HEPA filter replacement

30

HEPA filter integrity test (DOP test) Purpose : To confirm that no damage to filter, seals and no leakage of

particles.

Equipment : 1. Aerosol generator 2. Photometer

Acceptance criteria:An unacceptable leak is defined as a penetration of 0.03% or more of particle, 0.3µm and larger than the reference calibration curve for 99.97% efficient filter

31

Recovery test

The recovery of temperature and humidity is checked. For this, the humidity and temperature are checked at the off position of the HVAC system.

Then the humidity is increased to 75% and temperature to 400°C and again the temperature and humidity are measured after switching on the HVACsystem, and the time required to stabilize the temperature and humidity is noted.

32

MICROBIOLOGICAL TESTS

Solid growth media (e.g. settle and contact plates) Soybean Casein Digest Agar medium can be used for both Bacteria & Fungi tested.

The recommended size of solid media is 90 mm in diameter (for settle plates)

55 mm for contact plates.

33

Air flow or smoke patternFor the evaluation of this parameter, a titanium tetrachloride stick is taken and burnt and the burning stick is placed in front of the AHU. The distribution of smoke is observed.

It should be uniform.

Particle countA particle counter is used to conduct the test. Particle count is taken before the operation as well as during the working condition.

The particle count should be within the range as per the standards of Grade A, B, C, and D area.

34

Validation in pharmaceutical industry” edited by P.P.sharma ;first edition 2007 ; 193-220.

References

Pharmaceutical validation Dr.Sohan S. Chitlange First Edition April 2014,Page no :5.1-5.40.

Demand of pharmaceutical facility functionality: Validation and qualification of HVAC system Anamika Singh, Sapna Malviya, Anil Kharia, Asian Journal of Pharmaceutics - April-June 2014 Page no: 125-129.

35

Validation Of HVAC Systems In Pharmaceutical& Biotechnology Facilities Part 1 Brian Scott, Jeff Hargroves, and Jerry Bauers,Page No:32-37.

Guidelines On Validation – Appendix 6 3 Validation On Qualification Of Systems, Utilities 4 And Equipment5 (June 2016) Page No:1-24.

Potdar MA. Pharmaceutical Quality Assurance, Nirali Prakashan, Pune, Edition II, 2012. Page No: 154-162.

36

Thank you