1. Modelling exposure to pharmaceutical agentsJ W Cherrie1 , A T Gillies2 , A Sleeuwenhoek1 ,M van Tongeren1 , P McDonnell3 , M Coggins3 , S R Bailey4 1. Institute of Occupational Medicine, UK. 2. Gillies Associates Ltd, UK. 3. National University of Ireland, Galway, Ireland. 4. GlaxoSmithKline, UK.

2. Summary

Background

The model used for this study

Adaptions for the pharmaceutical industry

Results from avalidation exercise

Discussion of future uses

3. Background

Powders are widely handled in the pharmaceutical industry

Occupational inhalation exposure to these dusts may be harmful

• Some substances have exposure limits < 1g/m 3

Within and between worker variability, and between plant variability make it difficult to reliably measure exposure with reasonable sampling effort

Modelling exposure is one way to leverage scarce resources

4. The model

Originally developed for use in epidemiological research

Use being extended into regulatory risk assessment

• Advanced REACH Tool (ART)

Simple source-receptor model that relies on the assessor to select appropriate model parameters

Validated in a number of previous situations, including mineral fibres, respirable dusts, PAH, benzene, solvents

5. Typical validation data 6. The model

intrinsic propertiesof the contaminant ( i ),

• the dustiness of a solid and the proportion of API in the mixture

the way the material ishandled (h) ,

• • e.g. careful scooping of a powder

the efficiency oflocal controls(1- lv ).

These parameters are multiplied together

7. The model

passive or fugitive emission ( p )

the fractional time the source was active ( t a )

the efficiency of respiratory protection (1- ppe )

C= ( i .h .(1 -lv) .t a+ p) . (1 - ppe)

8. The model

Near and far-field

Dispersion term dependant on the room ventilation and size

C NF = ( ( i .h .(1 - lv)) NF.t a,NF+ p,NF ) .(1 - ppe ) . d gv,NF

C FF = ( ( i .h .(1 - lv )) FF.t a,FF+ p,FF ) . (1 - ppe ) .d gv,FF

9. Adaptions for the pharma industry

Specific guidance for the industry

10. Validation

Three assessors (JWC, AS and PMcD)

27 scenarios with widely differing circumstances

Assessors get written description of the scenario and then estimate the inhalation exposure level

Blinded to the measurements

11. Results 12. Discussion

Model appears useful for pharmaceutical powder handling

Gives agreement with measurements comparable to other circumstances

Need better information on dustiness of powders

This approach could be very useful for managing potential risks in the pharmaceutical industry