Researchers at 3M Pharmaceuticals in St. Paul, MN questioned why metered dose inhalers (MDIs) were classified as hazardous materials for transportation.  The classification (UN1950, ORM-D) was based on the International Civil Aviation Organization/International Air Transport Association (ICAO/IATA) Special Provision A98 and stated that vapor pressures for compressed gasses greater than 720 kilopascals (kPa) at 55°C would be considered 'dangerous goods' for air and ground transport.  This classification required specification packaging as well as hazardous materials training for all sales reps and shippers.  Incurred costs included a hazard materials surcharge of >$50.00/pkg which contributed substantially to the customer cost of each pharmaceutical MDI.  Problems also existed in identifying carriers certified for transporting hazardous materials goods.

There had never been a reported transportation incident concerning MDIs, due in part to rigorous quality control programs. The industry standard had been such that all MDIs were subjected to a 55ºC water bath for 3 minutes before packaging, with any leaking units being discarded.

Thus, a decision was made to request a revision of the regulation, ICAO/IATA Special Provision A98. A multidisciplinary networking team was organized to broaden, and therefore strengthen and strategize the argument for revision. The team consisted of 3M Pharmaceuticals staff, agency contacts, and related industry professional organizations. The 3M team had four members: a Product Responsibility Liaison (PRL) with knowledge of the product and an understanding of the manufacturing process, a Transportation Regulatory Compliance Officer (TRCO) with an expert understanding of transportation regulations and maintaining a network of agency contacts, a Technical Expert (TE) knowledgeable in the details in formulations, raw materials, the manufacturing process and also competent to serve as an expert witness to field anticipated technical questions, and the General Counsel (GC) for legal direction.

The agency contacts in the network consisted of members of the Federal Drug Administration (FDA), Department of Transportation (DOT) and ICAO/IATA. The FDA representative substantiated the industry standard that resulted in MDI units failing quality control standards for leaks being discarded and not packaged. DOT and ICAO/IATA contacts helped to understand the reasoning why the vapor pressure limit of 720 kPa was chosen. They also agreed to participate in agency meetings where criteria for dangerous goods would be discussed and evaluated.

The two professional organization members of the network, Pharmaceutical Research and Manufacturers of America (PhRMA) and Council on Safe Transportation of Hazardous Articles (COSTHA) agreed with the intent to revise the regulation. They would submit letters to ICAO/IATA and DOT supporting the revision.

3M drafted a proposal for revision of the propellant vapor pressure classification from 970 kilopascals (kPa) in Special Provision A98 to 1500 kPa based upon specific justifications.  The propellant component of the MDI is necessary to effectively deliver drug to the lung, and selection of the propellant is based upon it's solubility with the drug, it's effect on the stability of the drug and availability in a pharmaceutical grade (purity).  Because of these three criteria, compressed gasses 11, 12, 114, 134a and 227 are the propellants of choice that are currently used in the pharmaceutical industry.  The suggested pressure of 1500 kPa was based on propellant 134a which had the highest vapor pressure (1466 kPa at 55ºC).

The draft was sent to the professional organization members of the network:  PhRMA and COSTHA.  The PhRMA members solicited support from those companies within the organization which formulated and manufactured MDIs. COSTHA scheduled a Pharmaceutical Healthcare Industry Roundtable which provided an opportunity for discussion and to request support from dangerous goods regulators

After receiving the proposal for revision of Special Provision A98 and months of corresponding with members of the network, ICAO/IATA revised Special provision A98: "Aerosols with a capacity not exceeding 50 ml and containing no constituents subject to these Regulations other than a Division 2.2 gas, are not subject to these Regulations unless their release could cause extreme annoyance or discomfort to crew members so as to prevent the correct performance of duties".

3M and PhRMA then requested the DOT to grant an exemption consistent with ICAO/IATA so that 49CFR would align with the United Nations and ICAO/IATA criteria for transport of aerosolized MDIs.

After the DOT concurrence with ICAO/IATA, the networking effort was considered a success. The vapor pressure limit was removed (instead of simply being raised) and MDIs could be transported by air and ground without being classified as 'dangerous goods'.

Defining the problem and utilizing the interdisciplinary expertise and power of the network, resulted in changing US and international transport regulations.

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Margaret A. Carlson, CHMM, CSP