1. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Giorgio Mari
Elena Sturchio
Dipartimento Insediamenti Produttivi ed Interazione con
l’Ambiente
National Institute for Health and Safety at Work
“Containment Technology for Safe
Handling of Highly Potent or Unknown
Materials and Micro-Organisms”
3. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Nuclear
Pharmaceuticals production: “Highly Active” powder handling
Pharmaceuticals Research and Development: handling of
unknown substances and micro-organisms
Hospital pharmacies: for cyto-toxics preparation
Bio-terrorism, non-conventional attack (army, police, fire brigades)
for INDUSTRIAL HYGIENE purposes (general)
Use of isolators
(protection of operators)
5. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Sterile products
Pharmaceuticals production: Lyophilization; parenteral preparation;
…
Pharmaceuticals: sterility tests
Product sensitivity to oxygen, moisture, etc….
(different concept of isolators. Not part of this report)
Use of isolators
(protection of products)
6. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Permanent material barrier:
- Sheet metal
- Glass
- Gloves
- Doors (and gasket)
- Couples, connections and links
“Passive” containment Concept
8. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
“Active” Containment – a fan keeps pressure below the environment:
The negative pressure assists in case of:
- Possible gaskets leaks
- Glove breakage (vel. In > 0,4 m/s)
- Accidental door (or connection) opening
Dual filter System (both air inlet and outlet)
In case of fan stop, the “passive” containment is however assured
“Negative Pressure” Concept
10. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
CIP - Cleaning in Place
- Spray balls, spray gun
- CIP distribution in the factory
- CIP “dedicated” systems
- Liquor disposal
- Cleanability of external surfaces of containers
- Everything must be “water proof”: scale; mill; …
- Electronic instruments are to be protected
- No printer or paper
Cleaning Systems
12. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
The following data should be searched (or estimated) before
handling “Highly Active” or potentially toxic substances or
micro-organisms:
- Solubility (water; solvents; oils; etc…)
- Temperature and solubility condition
- Additives for solubility
- Active powder “Inactivation” (chemical)
- Micro-organism “disinfection” (biological)
- Cleaning procedure
Items to be discussed before use
13. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
- EVERYTHING must be inside the chamber at the
beginning (until the chamber is clean)
- OPERATIONS with the active powder or micro-organism
- EVERYTHING must be cleaned before opening the
chamber
“One Chamber” Isolators
14. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
- Everything is inside at the beginning
“One Chamber” Isolators
15. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
- e.g.: weighing; dispensing; powder dissolution
- Everything becomes potentially contaminated
“One Chamber” Isolators
Operations
16. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
- COMPLETE cleaning MUST be done before the door is opened
“One Chamber” Isolators Operations
17. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
What happens if I forgot to insert something?
- I MUST clean EVERYTHING before opening the door
again
What happens if I need to extract something?
- I MUST clean EVERYTHING before opening the door
again
- Cleaning the object which has to be extracted is NOT
enough
“One Chamber” Isolators
19. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Large ingress/egress flexibility is allowed
presence of a pre-chamber (or washing chamber)
- Materials can be inserted during operations
- Objects can be washed, extracted and reused
- The main chamber cleaning is done only at the end of
the campaign
Dual Chamber Isolator
21. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
- Individual negative pressure in the 2 chambers (2 fans)
- The main chamber has a pressure “more negative” compared to
the pre-chamber. This prevents a massive contamination of the
pre-chamber
- Materials cleaning in the pre-chamber is allowed (presence of
gloves, glass, CIP)
- Pre-chamber as small as possible (easier to be cleaned)
- No operations, no tools, no instruments in the pre-chamber
Dual Chamber Isolator
23. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Rapid Transport Port (RTP)
INDUSTRIAL APPLICATIONS
24. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Rapid Transport Port (RTP)
ISO 11933 - 3
1. approach1. approach 2. connection
isolator
glove
container
25. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Rapid Transport Port (RTP)
3. door opening3. door opening 4. sample transfer
26. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
Rapid Transport Port (RTP)
exterior surfaces are mainteined uncontaminated
CLEAN
CLEAN
5. door closing5. door closing 6. disconnection
30. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
MATERIAL FLOW for Suspicious Samples
(according to NATO practice)
RECEIVING
SAMPLES
MOBILE LABORATORY
RTP
CONTAINER
RTP
DOOR
WASTES
TO BE
DISPOSED
ISOLATOR
CHAMBER FOR
SAMPLES
PREPARATION
AUTOCLAVE
WITH TWO
DOORS
HOOD
Immunological,
DNA,
bioluminescence
methods
31. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
MATERIAL FLOW for Suspicious Samples
RECEIVING
SAMPLES
MOBILE LABORATORY
RTP
CONTAINER
RTP
DOOR
WASTES
TO BE
DISPOSED
ISOLATOR
CHAMBER FOR
SAMPLES
PREPARATION
ISOLATOR
CHAMBER FOR
ANALISYS
AUTOCLAVE
WITH TWO
DOORS
HOOD
32. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
ISOLATOR CHAMBERS APPLICATIONS
MOBILE LABORATORY
RTPDOOR
SAMPLES
PREPARATION:
solutions
preparations;
aliquotes; dilution;
vials filling; filtration
(for M1M)
ISOLATOR CHAMBER FOR ANALISYS
M1M analyzer
Immunoassay based on
electrochemiluminescence
Anthracis Spores - Botulinum neurotoxins A,
B, E, F - Listeria - E. Coli 0157 – Salmonella
– Campylobacter – Ricina – Staphylococcus
enterotoxins A/B
33. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
ISOLATOR CHAMBERS APPLICATIONS
MOBILE LABORATORY
RTPDOOR
SAMPLES
PREPARATION:
DNA extraction External
vials
washing
34. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
HOOD APPLICATIONS
MOBILE LABORATORY
Real-Time Polymerase Chain
Reaction
B. Anthracis - Brucella spp -
F. Tularensis - Y. Pestis - C.
Botulinum - Variola (smallpox)
– Listeria - E. Coli 0157 –
Salmonella – Campylobacter -
Criptosporidium
35. ISTITUTO SUPERIORE PER LA PREVENZIONE E LA
• ISO 10648-1, Containment enclosures, part. 1 Design principles
• ISO 10648-2, Containment enclosures, part. 2 Classification according to
leak tightness and associated checking methods
• ISO 14644- 7 Cleanrooms and associated controlled environment
• ISO 11933 – Components for containment enclosure – Parts 1 ÷ 5
• AS 4273-1999, Design, installation and use of pharmaceutical isolators
• HSE/MCA Handling cytotoxic drugs in isolators in NHS pharmacies
• PDA Technical Report n. 34, design and validation of isolator systems for
the manufacturing and testing of health care products
• AGS-G001-1998 (second edition) (186 pages). American Glovebox Society
• ISPE Assessing the particulate containment performance of pharmaceutical
equipment
TECHNICAL STANDARDS
