isolators icoh presentation

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”


Isolator


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)


ISOLATORS: Industrial Applications


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)


Permanent material barrier:

- Sheet metal

- Glass

- Gloves

- Doors (and gasket)

- Couples, connections and links

“Passive” containment Concept


Isolator

SHEET METAL

DOOR

GLASS

GLOVES

COUPLE


“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


Negative Pressure Isolator


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


Cleaning Systems


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


- 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


- Everything is inside at the beginning



- e.g.: weighing; dispensing; powder dissolution

- Everything becomes potentially contaminated

“One Chamber” Isolators Operations


- COMPLETE cleaning MUST be done before the door is opened

“One Chamber” Isolators Operations


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



tubular film for disposal


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


- 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



RTP 350 mm la Calhène connection


Rapid Transport Port (RTP)INDUSTRIAL APPLICATIONS


Rapid Transport Port (RTP)ISO 11933 - 3

1. approach1. approach 2. connection

isolator

glove

container


Rapid Transport Port (RTP)

3. door opening3. door opening 4. sample transfer


Rapid Transport Port (RTP)exterior surfaces are mainteined uncontaminated

CLE

AN

CLE

AN

5. door closing5. door closing 6. disconnection


SECURITY FORCES APPLICATION


ISOLATOR ACCESSORIES


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


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


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


ISOLATOR CHAMBERS APPLICATIONS

MOBILE LABORATORY

RTP

DO

OR

SAMPLES PREPARATION: DNA extraction External

vials washing


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


• 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

isolators icoh presentation

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