14 May, 2008
Session 5a - Nanoparticles
09:45 a.m. - 10:50 a.m 

Adjusting OELs for Nano Pharmaceuticals

Presentation by: Martin Axon

Introduction and Aim:
The handling of active pharmaceutical ingredients (APIs) during the production of pharmaceutical products has historically been associated with health effects in the workforce.  This has especially been the case where the materials being handled are steroidal, cytotoxic, opioids, antibiotics, prostaglandins or other APIs which might be considered as “potent”. The industry has largely overcome these effects by setting appropriate occupational exposure limits (OELs) and controlling exposures down to these limits using advanced control and containment techniques. The setting of OELs is undertaken by qualified and experienced toxicologists based on data generated during toxicity testing and clinical trials. However where the particle size of the API is reduced from a micronised product to a nano-sized material, changes in pharmacological activity may result. The implication is that the nano-sized form of the API may require a lower OEL.

The aim of the presentation is to discuss the methodology for setting OELs, with a particular focus on nano-sized APIs and the effect that the reduced particle size has on therapeutic dose and bioavailability.

Method:
The safety factor approach to setting occupational exposure limits will be discussed. This involves identifying the critical endpoint or therapeutic effect from which the work should be protected. Then defining the no adverse effect level for that endpoint and calculating an OEL by applying appropriate safety and uncertainty factors. When considering nano-sized materials, bioavailability and  therapeutic dose may differ from those of the micro-particulate product. Available data for these factors must be taken into account when considering whether or not the OEL for the nano-sized product needs to be adjusted.

Conclusions:
When comparing micro-particulate with nano-sized APIs, the bioavailability may increase and the therapeutic dose may be lowered. These factors may compete to change the OEL proportionally to changes in the pharmacological properties of the API.

Martin Axon, MFOH, MIOSH, Principal Occupational Hygienist, European Operations. SafeBridge is a professional technical firm of health professionals and other scientific consultants providing EH&S services to pharmaceutical, fine chemical, and biotechnology industries.

About the British Occupational Hygiene Society

What is the aim of BOHS?

Every year in Britain alone, more than two million people experience symptoms of ill-health believed to have been caused or made worse by work and the latest figures published by the Health & Safety Executive show that an estimated 30 million working days are lost annually due to work-related ill-health (compared to nine million due to workplace injury). Established since 1953, BOHS’s aim is simple: to help to reduce work-related ill-health. We do this by promoting public and professional awareness, good practice and standards, and by researching and advancing education in the science of occupational health and hygiene.

For more information:
Tel.: David Riordan, +44 1332 250718

Email: david@bohs.org
URL: http://www.bohs.org/eventDetails.aspx?event=123

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