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ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
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”
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Isolator
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
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)
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
ISOLATORS: Industrial Applications
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
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)
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Permanent material barrier:
- Sheet metal
- Glass
- Gloves
- Doors (and gasket)
- Couples, connections and links
“Passive” containment Concept
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Isolator
SHEET METAL
DOOR
GLASS
GLOVES
COUPLE
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
“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
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Negative Pressure Isolator
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
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
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Cleaning Systems
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
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
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
- 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
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
- Everything is inside at the beginning
“One Chamber” Isolators
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
- e.g.: weighing; dispensing; powder dissolution
- Everything becomes potentially contaminated
“One Chamber” Isolators Operations
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
- COMPLETE cleaning MUST be done before the door is opened
“One Chamber” Isolators Operations
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
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
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
tubular film for disposal
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
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
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Dual Chamber Isolator
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
- 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
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
RTP 350 mm la Calhène connection
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Rapid Transport Port (RTP)INDUSTRIAL APPLICATIONS
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Rapid Transport Port (RTP)ISO 11933 - 3
1. approach1. approach 2. connection
isolator
glove
container
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Rapid Transport Port (RTP)
3. door opening3. door opening 4. sample transfer
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
Rapid Transport Port (RTP)exterior surfaces are mainteined uncontaminated
CLE
AN
CLE
AN
5. door closing5. door closing 6. disconnection
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
SECURITY FORCES APPLICATION
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
SECURITY FORCES APPLICATION
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
ISOLATOR ACCESSORIES
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
MATERIAL FLOW for Suspicious Samples(according to NATO practice)
RECEIVING SAMPLES
MOBILE LABORATORYR
TP
CO
NTA
INE
R
RTP
D
OO
R
WASTES TO BE DISPOSED
ISOLATOR CHAMBER FOR SAMPLES PREPARATION
AUTOCLAVE
WITH TWO
DOORS
HOOD
Immunological, DNA,
bioluminescence methods
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
MATERIAL FLOW for Suspicious Samples
RECEIVING SAMPLES
MOBILE LABORATORYR
TP
CO
NTA
INE
R
RTP
D
OO
R
WASTES TO BE DISPOSED
ISOLATOR CHAMBER FOR SAMPLES PREPARATION
ISOLATOR CHAMBER FOR ANALISYS
AUTOCLAVE
WITH TWO
DOORS
HOOD
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
ISOLATOR CHAMBERS APPLICATIONS
MOBILE LABORATORY
RTP
DO
OR SAMPLES
PREPARATION:
solutions preparations;
aliquotes; dilution; vials filling; filtration
(for M1M)
ISOLATOR CHAMBER FOR ANALISYS
M1M analyzerImmunoassay based on
electrochemiluminescence
Anthracis Spores - Botulinum neurotoxins A, B, E, F - Listeria - E. Coli 0157 – Salmonella – Campylobacter – Ricina – Staphylococcus
enterotoxins A/B
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
ISOLATOR CHAMBERS APPLICATIONS
MOBILE LABORATORY
RTP
DO
OR
SAMPLES PREPARATION: DNA extraction External
vials washing
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
HOOD APPLICATIONS
MOBILE LABORATORYReal-Time Polymerase Chain Reaction
B. Anthracis - Brucella spp - F. Tularensis - Y. Pestis - C.
Botulinum - Variola (smallpox) – Listeria - E. Coli 0157 –
Salmonella – Campylobacter - Criptosporidium
ISTITUTO SUPERIORE PER LA PREVENZIONE E LA SICUREZZA DEL LAVORO
• 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
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