AUDITING/INSPECTION

of HVAC SYSTEM

Adopted from BPOM

Air Handling System
 AHS

An air supply system using metal ductwork,

pre-filters, hot water coil, chilled water coil,
centrifugal fan, and HEPA filters with a
pre-filtration.
 Principle

 Constant volume
 Air supply in diffrence of:
 temperature ,
 fresh air
 volume of circulation
 Critical Parameters
:
 Diffrence of the pressure in production
area
 Temperature
 Rh
 Particle & microorganism
 System Impact Assessment

Critical equipment &

Critical & non-critical component determination

Commissioning of system

Qualification Document
Design of HVAC System

Layouts ,e.g
the position of airlock, door

Room pressure differential cascades

&
Cross-contamination
Auditing/inspection of
HVAC
 Goals of Auditing
 Protect the safety & health of the user of
the medicinal product

 Promote compliance with national laws

governing medicinal products

 Promote product quality

 A Quality System
for GMP Inspectorate
Indonesian FDA
(BPOM)
 The Documentation
Pyramid
Level
1 Quality Policy
2
Quality Manual
3 System Procedures, Operating Procedures

in the form of:

SOPs, Work Instructions

Test Methods Evaluation Methods, etc Information

Documents

4 Forms & Records

Completed Forms, Completed Records, Logs, Calibration

Records, Training Records, Test Results, etc
 Technical Guide 1109
Risk based assessment for sanctions and
planning GMP auditing/inspection
Example of a risk matrix for human health risks
•Logically consistent
•Administratively Probability of Occurrence
Compatible
Severity Very Very
•Equitable
Scale Low Low Medium High High
•Fairly drawn so
that the interests Death M M H H H
of various
H
Hospitali
stakeholders are L M M H
balanced
-sation
•Compatible with Acute
L M M H H
cognitive constraints & Illness
biases
Worry L L L M M
L = low M = medium H = high
The Auditor/Inspector
I am going to inspect/audit
 Procedure for Auditing

 Organizing & planning

 Interacting with the company
 Collecting information &
investigating
 Report preparation & conclusions
Auditing/Inspection Plan
 Checklist – preferably for
training of new inspectors
 Aide-mémoire for inspection
 Develop inspection
programme
 Distribute inspection
programme
 Team

 Company
 Review of Documentation from
Regulatory Authority
 Company file
 Site Master File
 Manufacturing licence
 Registration dossiers Reports
 Adverse Drug Reaction Reports (ADRs)
 Previous inspections
 Records
 Complaints & recalls
 Regulatory test results (surveillance)
Example of . . . Being a Team-Player !!
 Plan - Timetable
 Opening meeting
 Orientation tour - optional to finalize what you
want to see, assess & to give time to company to
assemble data!
 Fact finding & assessment mix of facility &
documents, identify areas of work & schedule
 Review progress against audit plan
 Revise activity
 Final review/recommendations
 Exit review with management/closing meeting
 Report with time frame
 Q

Open questions starting with:

 What

 Why

 When

 How

 Where

 Who

e.g. Describe what you do…

How Thorough is the Inspection?

Expect not Expect to

to miss document
anything! everything
Auditing of HVAC System

SOP # 611 Quality System for GMP

Inspectorate Indonesian FDA
1. Document Reviewed
 SOPs
 Personnel
2. Data Reviewed
 System Drawing
 System Monitoring
 System Maintenance
 System Validation
Auditing of HVAC System
Key Design parameters
 Need for separate system
 Filter specification
 Recirculation or make-up air
 Temperature
 Humidity
 Air Changes
 Pressure differentials
 Design of ducting
 Alarm system
 Air flow direction -- LAF
Auditing of HVAC System
1. SOPs
 Complete index and complete set
 Availability to the operator
 Correctly organized
 Limits for temp & RH

2. PERSONNEL
 Training on GMPs, SOPs
 Knowledgeable about their job
 Qualified
 Auditing of HVAC System (4)
3. SYSTEM DRAWING
 Up-to-date drawing of HVAC
 Approved by QA & NRA
 Showing pressure differentials, air flow patterns

4. SYSTEM MONITORING
 Environmental monitoring (particle, microbes, T & RH)
 Pressure differential & frequency
 Conformity of pressure differentials
 Chemical residue testing
 Filters  replacement, maintenance program,
label/sticker stating date of last & next replacement
 Pressure gauges labeled with calibration sticker
 Daily check for filters  out of limit, replacement,
investigation for OOL, CA for OOL
 Alarm system function
 Auditing of HVAC System
3. SYSTEM MAINTENANCE
 Approved list of all filters
 Approved SOP for maintenance
 Records & evidence of preventive
maintenance  frequency, replacement

4. VALIDATION SYSTEM
 VMP
 Validation Protocols & reports
 DQ, IQ, OQ, & PQ
 Determining Facts

Everything should be documented

We have
some unusual
results right
on the
specification
limit
What happens when SOPs are not followed . . .
Several Critical GMP Deficiencies
 In-adequate air filtration
 No HVAC qualification
 No validation process
 Cleaning program not followed cleaning
procedures & evidence of dirty
premises/ equipment
 Inadequate pressure differencials
 Improper of raw materials testing
 No master batch documents available
Examples of Major GMP Deficiencies

 Damage (holes, cracks, peeling paint)

to walls/ceilings in manufacturing
areas where product exposed
 The temperature of critical
temperature controlled storage
areas not monitored & alarmed
 No raw material sampling area
 In-adequate initial & ongoing
training and/or no training records
 Examples of
Major GMP Deficiencies

 No cleaning records
 Equipment cleaning procedures
not validated
 Reduced QC testing of raw
materials without data to certify
suppliers
 Testing methods not validated
 Examples of
Major GMP Deficiencies
 Unapproved/undocumented changes to master
batch documents
 In-adequate internal audit program
 Recycling products without proper approval
 No system/procedures for handling
complaints or returned goods
 No ongoing stability program and/or stability
data for all products not available
 Regulatory Measures
For new plants
 No manufacturing licence/GMP certificate until
compliance

For licence/certificate holders

 Warnings
 Suspension/withdrawal of marketing authorization for
product(s)
 Suspension/withdrawal of manufacturing licence/GMP
certificate

Access to appeal  SOP # 1401

GMP Compliance Not by Force But…… in Spirits
 Conclusion
• Regulator’s perspective:
- “ If it is not documented, it did not happen . .
- “ Regulatory Authorities believe in God”.
All others must show the documentation ”

. Regulator’s experience:
- Compliance is poor, when Monitoring is inadequate.
- Compliance is better, when there is Regulatory
Pressure.
Inspection is a thankless job, but ………..
Somebody has to do it !!!
QUESTION ???????
1 Q  $ 100

2 Q  $ 500

No Q  Free

TERIMA KASIH