Sanitation, Fumigation

and Its Validation

Presented by FQ
for ISPE Indonesia Affiliate
 Content
• Terminology & Definition
• Classification of Disinfectant
• Selection of Disinfectant
• Selection of Fumigation Methods
• Cold Process Disinfection
• Evaluation & Validation
 Definition & Terminology
• Sanitation
a process that reduces microorganisms on an inanimate object to a level below that of
infectious hazard

• Fumigation
Process to deliver or to disperse a fume /gas into a room

• Disinfection
The destruction of pathogenic and other kinds of microorganisms but (only vegetative
forms not neccessary all bacterial spores). Disinfectant (Surface)

• Sterilization
Validated process used to render a product free of all forms of viable microorganisms
 Sterilant

• Decontamination (Biodecont)
Disinfection or sterilization of infected articles to make them suitable for use
 Antiseptics
chemicals that kill microorganisms on living skin or mucous
membranes.
• Germicide
an agent that destroys microorganisms, especially pathogenic
organisms.
Other terms with the suffix -cide (e.g., virucide, fungicide,
bactericide, sporicide, tuberculocide) destroy the
microorganism identified by the prefix
 Terminology

Manufacturer
USP -HPV or VHP (Vaporized
Hydrogen Peroxide)
VPHP (Vapor Phase
Hydrogen Peroxide)  Minncare DFS

BPOM Others
Fogging,
Fumigasi Biodecon(tamination),
Room Disinfection
 Classification of Disinfectant

Low Level Disinfectants Intermediate Level Disinfectants

- Phenolic Disinfectants - Alcohol
- Quaternary - Hypochlorites
Ammonium - Iodine and Iodophor
Compounds

High Level Disinfectants

- Aldehyde group : Formaldehyde,
Glutaraldehyde, Ortophtalaldehyde
- Hydrogen Peroxide
- Peroxy Acetic Acid (PAA)
 Low level disinfection
• Low level disinfectants kill most
vegetative bacteria and some fungi as
well as enveloped (lipid) viruses (e.g.,
hepatitis B, C, and HIV).
• Low level disinfectants do not kill
mycobacteria or bacterial spores.

Intermediate level disinfection

Intermediate level disinfectants
kill vegetative bacteria, most
viruses and most fungi but not
bacterial spores
 High level disinfection
• High level disinfection destroy
vegetative bacteria, mycobacteria,
fungi and enveloped (lipid) and non
enveloped (non lipid) viruses, but not
necessarily bacterial spores.
• High level disinfectant chemicals (also
called chemical sterilants) must be
capable of sterilization when contact
time is extended.
Classification of Antimicrobial Products
 Selection of Disinfectant
for Pharmaceutical Application

• Efficacy : - Low/ Intermediate/ High Level

- Sporicidal
- Claim as sterilant

• Safety : - to Human/Operator
- to Environment

Make Sure : - Pharmaceutical Grade Disinfectant

- EPA Approved Disinfectant !

• Consider :
 Availability, easy to obtain  Reputation of The Supplier
 Supporting Documents or Certificates from regulatory body, Manufacturer,
Independent Lab or Institution, etc
 Price/ Cost per cycle instead of Packing Price

Second Supplement USP-NF <1072> Disinfectants and Antiseptics

Current Problems of using Disinfectant:

• Effectiveness
• Toxicity of the Chemicals Used
• Adaptation of the Microrganism
• Long Contact Time
• Very Long Time for Venting
• Neutralization Needed
• Corrosion
• Residuals
• Lack of Documentation/ Certificate
 DISINFECTANT EFFICACY (D-value)
Exposure Formaldehyde NaOCl H2 O2
HP+PAA*
Time (2%) (0.001%) (0.2%)
(1%)
0 minutes 2.3 x 106 2.3 x 106 2.1 x 106 2.0 x 106
15 minutes 1.1 x 106 2.3 x 106 2.2 x 106 2.3 x 106
30 minutes 3.0 x 101 2.1 x 106 1.1 x 106 2.3 x 106
60 minutes <10 2.0 x 106 4.0 x 104 2.0 x 106
2 hours <10 1.5 x 105 1.0 x 104 2.0 x 106
4 hours <10 1.2 x 105 1.0 x 103 1.5 x 106
6 hours <10 1.0 x 103 <10 1.0 x 106
12 hours <10 <10 <10 1.0 x 103
24 hours <10 <10 <10 <10
D-Value 6 minutes 113 minutes 69 minutes 250 minutes
6D-Value 36 minutes 678 minutes 414 minutes 1500 minutes
* Minncare Cold Sterilant
 DISINFECTANT EFFICACY
Exposure Time HP+PAA * H2 O2 H2 O2
(1%) (5%) (10%)

0 minutes 2.3 x 106 2.1 x 106 2.0 x 106

15 minutes 1.1 x 106 2.0 x 106 2.0 x 106
30 minutes 3.0 x 101 2.0 x 106 2.0 x 105
60 minutes <10 1.0 x 105 <10
2 hours <10 <10 <10
4 hours <10 <10 <10
6 hours <10 <10 <10
12 hours <10 <10 <10
24 hours <10 <10 <10
D-Value 6 minutes 22 minutes 11 minutes
6D-Value 36 minutes 132 minutes 66 minutes
* Minncare Cold Sterilant
Activities of the Most Important Biocides
Bacteria Myco-
Biocides Gram -- Gram + bacteria
Spores Moulds Yeasts Virus

Alcohol (70%) ++ ++ + ++ ++
Alcohols ++ ++ 0 0 ++
Chlorine +++ +++ ++ ++ ++
Glutaraldehyde +++ +++ ++ + +++ ++ ++
Hydrogen Peroxide +++ +++ ++ ++ + + 0
Iodine +++ +++ ++ ++ ++ ++ ++
Peracetic Acid +++ +++ ++ ++ ++ ++ ++
Quatenary Ammonium +++ +* 0 0 + + +
* Not active on Pseudomonas

Chart based on internal testing and report by Guyader, 1996

 Mechanism of Action
PAA- H2O2
1. Disrupts Sulfhydrl (-SH) & Sulfur (S-S) bonds in Cell Wall
proteins and enzymes (Cell wall disruption) Disruption
Ruptured walls causes organism to die
2. Impede cellular activity by disrupting
chemosmotic function
3. Denature the properties of protein components
by altering the nucleic acid structure of
organisms
4. Damage vegetative cells by oxidation with
hydroxy radicals.
5. Produces organic radicals that act as reducing
agents for spores.
 “NO CHANCE”
For Micro-Organisms to Build
a Resistance
 Application of Disinfectant
• Surface Wiping wipes & mops
• Manual Spray (with Spray Bottles)
• Fumigation :
 Heating Process (Vaporization)
 Cold Process - Wet fogging
- Dry fogging
• Water System Disinfection

Disinfection is NOT a Cleaning Process

 Selection Of Fumigation Methods
Choose
• Validated Equipment ---- (not just IQ,OQ), PQ is a must !
• Easy/simple in Operation
• Time Consumption
• Safety
Make sure :
 Validation service is to includes Validation Report
 Is proven to the target room’s configuration/ layout

Consider:
 Operational Cost : Maintenace & Calibration Cost
 Handling: In case of trouble, sparepart availability
 Methods Of Fumigation

Vaporization of
Formaldehyde

Formaldehyde Tablet
Fogging (Wet Fogging)
  Uses 35% H2O2 Single Chemical ?
Electronic (PLC) System ?
Maximum Coverage only 250 M3
High Capital Investment est. € xx
Calibration ?

Bioquell BQZ
 Cold Process Disinfection
(New Innovative Technology)

 Uses Diluted of Minncare Cold Sterilant appr.10% 

approx. 2,2% HP & 0,45% PAA (final conc.)

 Only Compress Air needed (No Electricity)

 Ideal For 35 m3 - 1000 m3 of Room Volume

 Dosage : 1.5 ml Minncare per 1 m3 room volume

 Very Simple Calibration

 Relatively Low Capital Investment, US$ X

Minncare Dry Fog™ System
 The Phenomenon of Dry Fog

Small droplets bounce and

do not burst upon Large droplets burst and
collision. make things wet.
Clean Room Disinfection example - 950 m³

6 log reduction in spore

B. Stearothermophylus
ATCC 7953

Surface control: 0 germ

Air control: 0 germ

Room 950 M³

100
90

% RH
80 RH1 (%)

70 RH2 (%)
RH3 (%)
60
50
0 20 40 60 80 100 120
Time (min)
 Example 2
Fumigation By Minncare DFS
Minncare Dry Fog – Software Support – Reports – Cycle Data
Dry Fog – Software Support – Reports –
Relative Humidity Tracking
Dry Fog – Software Support – Reports – Data
Controls
Clean Room Disinfection using Minncare Dry Fog™
 Evaluation
• Diffusion Testing Additional Testing
– Relative Humidity
• Multiple Room Locations
• Microbiological Testing
– Biological Indicators
• Multiple Organisms
• Multiple Room Locations
– Worst Case Locations
Acceptance Criteria
 Efficacy:
None of exposed BI Growth
 Coverage :
Reach the furthest and the most difficult location
 Residual limit :
Passed, meet OSHA Standard
 Safety :
 operator
 environment (incl. machines etc.)
 Validation

Effectivieness:
BI  No Growth

Residue
 H2O2 
Less 1 ppm
 Acetic Acid
Less 10 ppm

Biological Indicator in stainless

steel disc for Vapor Hydrogen
Peroxide, contains Geobacilus
stearothermophilus, log 6
USP-NF (1035) BI for sterilization
H2O2 Vapor Detector Tube, 0.1 to 3 ppm
Acetic Acid Detection Tube, 5-80 ppm
OSHA, Regulations (Standards - 29 CFR) TABLE Z-1
Limits for Air Contaminants. - 1910.1000 TABLE Z-1
QUESTIONS?
 References
 Guidance for industry, Sterile Drug Products Produced by Aseptic Processing – Current Good
Manufacturing Practice, US Departement f Health and Human Services Food and Drugs Administration,
CDER,CBER,ORA, September 2004

 A Guide to Selection and Use of Disinfectants, BCCDC Laboratory Services, 2003

 Disinfection, Sterilization and Preservation, Seymour S. Block, Lippincott, Willian & Wilkins

 BPOM-RI, PETUNJUK OPERASIONAL PENERAPAN PEDOMAN CARA PEMBUATAN OBAT YANG BAIK ANEKS
1 PEMBUATAN PRODUK STERIL EDISI 2013, POPP-Aneks 1-Ped-04/CPOB/2013

 USP-NF <1035> Biological Indicator for sterilization

 Second Supplement, USP-NF <1072> Disinfectants and Antiseptics