LEO Pharma A/S Environment

1. LEO Pharma A/SEnvironment Topics Introduction (pharmaceutical production in general / LEO plant at Ballerup) Environmental department Environmental regulation: Environmental approval / waste water permit Environmental management system Example of process Emission control air emissions waste water soil and ground water waste

2. Pharmaceutical productionflow, input and output Research & development Feedstock • Hazardous waste • Atmospheric emissions: • organic solvents • CO2, NOx, SO2 • Waste water: • organic solvents Solvents Excipients Water: Cleaning/cooling Energy: ventilation, pumps etc. Chemicals production. Manufacture of medically active compounds. Chemical synthesis/biological production Active substances • Hazardous waste • Atmospheric emissions • organic solvents • CO2, NOx, SO2 • Waste water: org. solvents Filling agents Solvents Excipients Energy Water Packaging Pharmaceutical Production, Finishing and packing of Pharmaceutical products • Pharmaceutical products Distribution Sales & Marketing

3. LEO Pharma A/SBallerup

4. Environmental organization Department of environmental affairs • Refers directly to the technical manager4 full time employees • 1 Environmental manager • 2 Environmental coordinators • 1 Working environment consultant Production • 12 environmental coordinators from different departments of the production • Safety organization according to Danish legislation • App. 40 supervisors and 40 safety representatives are organized in safety groups • One safety committee

5. Environmental regulation • An environmental approval is given by the regional authorities in Denmark (IPPC approval). • Sets out terms of compliance for production regarding air emissions, noise, pollution of soil and groundwater etc. • A permit for emission of waste water is given by the local authority (Ballerup Municipality) in Denmark • Sets out requirements for the presence and concentration of various substances in the waste water, internal inspection etc. • Other legal requirements • Solid waste (local authority - waste regulative from Ballerup Municipality)

6. LEO Pharma A/SEnvironmental Management System (EMS) • Based on ISO 14001 - Not certified • LEO system: • 13 Environmental Guidelines • Procedures and instructions primarily implemented by adding to existing QA documents • Employee participation in the EMS is based on the local environmental coordinators (currently 12) • 4 annual meetings between the environmental coordinators and the environmental department • Environmental coordinators responsible for: • Integrating environmental issues in departmental SOP’s and instructions • Environmental communication to and from the department (e.g. answer everyday questions from colleagues) • Registering consumption of raw materials • Identifying and reporting new or changed environmental impacts • Annual environmental targets are defined for LEO Pharma A/S

7. EMS13 Environmental Guidelines • Identification, assessment and prioritization of environmental impacts • Environmental objectives, targets and projects • legal and other requirements • Communication • Control of documents • Identification of the need for instructions (operational control) • Competence and training • Emergency preparedness and response • Internal control • Nonconformity, corrective action and preventive action • Control of records • Internal audit • Management review • (Procurement)

8. Environmental targets 2006 • Continue the work regarding cleaning the air from Chemical Special Production and Chemical Process Development. • Perform a pilot project regarding limitation of the odor emission from heating of the corn steep in the Fucidin®-area. • Evaluate the influence of LEO Pharma on the primary groundwater on the basis of. performed tests and results. • Write a SOP regarding action in case of spills of liquid chemicals to waster or surface water – focusing on critical volumes. • Send an inventory to the environmental authorities regarding the status of LEO Pharma in relation to the new statuary order on risk (storage of dangerous substances), 18. November 2005. • Write a WI (work instruction) on environmental and working environmental assessment of new cleaning materials. • Write an Environmental Guideline on procurement • Perform a risk assessment of the Fucidin®-area. • Make an environmental statement for the year 2005 and hold a number of meetings with relevant authorities regarding the statement • Continue working with environmental assessment of an active substance according to the relevant guideline of environmental assessment of pharmaceuticals (FDA and/or EMEA) • Continue the development of the EMS and the information regarding environment on Bulleting Board.

9. (12 synthesis steps) Example:Production of Vitamin D analog

10. Air emissions • VOC (Volatile organic compounds) from production • (Carbon filters, scrubbers) • NOX, SO2 and CO2 from energy production • Dust: All sources with a possibility of dust emission have dust filters • various types incl. HEPA filters (“absolute filter” ~ 99,97 % reduction of dust) • Odour: No significant odour emission • except from heating corn steep - current project

11. B1 Waste water sampling (cesspools) Where waste water pipes join and leave the site B5 B3 B4

12. Waste water - regulationExample: Cesspool no. 4 • Sampling: 1 monthly flow proportional 24 hours sample • Flow is measured • Sample is analyzed for: Limit value: • Inhibition of nitrification <50 % (20 %) • NH3 /NH4 • COD COD/BOD < 3,0 • BOD • pH 6,5 – 9,0 • Sulfate < 500 mg/l average 12 months (max. 650 mg/l pr sample) • Chlorine < 1000 mg/l average 12 months (max. 1300 mg/l pr sample) • Suspended sludge < 500 mg/l average 12 months (max. 650 mg/l pr sample) • Organic solvents • DMF

13. Soil contamination and remediation - Ballerup • The site was used as farmland until LEO began production in 1946 • Discovered contaminated areas due to handling and storage of chemicals in the old days • Contaminations are often discovered in relation to building activities • Typically: Solvents and oil • Policy: • Remove and clean contaminated soil • Take new samples to prove contamination is removed • If remediation is not necessary or possible - a risk assessment is performed • In special cases the pollution is monitored by periodically taking samples of down stream ground water

14. Mapped area, level 2, 13,233 m2 Mapped area, level 1, 6,892 m2 Location of newer buildings (Z12 is a tankstorage) Location of ground water borings (all except from B6 to primary magasin) Soil contaminations: Mapping by Copenhagen County

15. Ground- and drain water monitoring V G4 G B21 S E C/D Ground water flow direction Z9 B22 Z7 Z0 GBJ B5 Drain water monitoring Ground water monitoring

16. General strategy: As much reuse and recycling as possible Al waste is preseparated at the source in each department The waste is then transported to a central waste site where it is stored in large waste containers A haulage contractor collects the waste when the containers are filled. Waste fractions Paper Cardboard Soft plastic (hard plastic) Glass (no color) Glass (with color) Pyrex glass (from laboratories) Aluminum (from cans and tubes without plastic caps) Metal (mostly iron) Stainless steel Blister packages PVC Alcohols from production Regenerated acetone from production Pallet (wood) Pallet (plastic) Small combustable waste Large combustable waste Electronic Waste Chemical Waste (from laboratories) Clinical Risk Waste Waste handling

17. Environmental award 2000