research based, people driven 1 LEO Pharma A/S Environment 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

research based, people driven 2 Pharmaceutical production flow, input and output Chemicals production. Manufacture of medically active compounds. Chemical synthesis/biological production Solvents Excipients Water: Cleaning/cooling Energy: ventilation, pumps etc. Hazardous waste Atmospheric emissions: organic solvents CO 2, NO x, SO 2 Waste water: organic solvents Research & development Pharmaceutical Production, Finishing and packing of Pharmaceutical products Filling agents Solvents Excipients Energy Water Packaging Hazardous waste Atmospheric emissions organic solvents CO 2, NO x, SO 2 Waste water: org. solvents Feedstock Active substances Pharmaceutical products Distribution Sales & Marketing

research based, people driven 3 LEO Pharma A/S Ballerup

research based, people driven 4 Environmental organization Department of environmental affairs Refers directly to the technical manager 4 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

research based, people driven 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)

research based, people driven 6 LEO Pharma A/S Environmental Management System (EMS) Based on ISO 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

research based, people driven 7 EMS 13 Environmental Guidelines 1.Identification, assessment and prioritization of environmental impacts 2.Environmental objectives, targets and projects 3.legal and other requirements 4.Communication 5.Control of documents 6.Identification of the need for instructions (operational control) 7.Competence and training 8.Emergency preparedness and response 9.Internal control 10. Nonconformity, corrective action and preventive action 11.Control of records 12.Internal audit 13.Management review 14.(Procurement)

research based, people driven 8 Environmental targets Continue the work regarding cleaning the air from Chemical Special Production and Chemical Process Development. 2.Perform a pilot project regarding limitation of the odor emission from heating of the corn steep in the Fucidin®-area. 3.Evaluate the influence of LEO Pharma on the primary groundwater on the basis of. performed tests and results. 4.Write a SOP regarding action in case of spills of liquid chemicals to waster or surface water – focusing on critical volumes. 5.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 Write a WI (work instruction) on environmental and working environmental assessment of new cleaning materials. 7.Write an Environmental Guideline on procurement 8.Perform a risk assessment of the Fucidin®-area. 9.Make an environmental statement for the year 2005 and hold a number of meetings with relevant authorities regarding the statement 10.Continue working with environmental assessment of an active substance according to the relevant guideline of environmental assessment of pharmaceuticals (FDA and/or EMEA) 11.Continue the development of the EMS and the information regarding environment on Bulleting Board.

research based, people driven 9 Example: Production of Vitamin D analog (12 synthesis steps)

research based, people driven 10 Air emissions VOC (Volatile organic compounds) from production –(Carbon filters, scrubbers) NO X, SO 2 and CO 2 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

research based, people driven 11 Waste water sampling (cesspools) Where waste water pipes join and leave the site B4 B3 B1 B5

research based, people driven 12 Waste water - regulation Example: Cesspool no. 4 1.Sampling: 1 monthly flow proportional 24 hours sample 2.Flow is measured 3.Sample is analyzed for:Limit value: –Inhibition of nitrification<50 % (20 %) –NH3 /NH4 –CODCOD/BOD < 3,0 –BOD –pH6,5 – 9,0 –Sulfate< 500 mg/l average 12 months (max. 650 mg/l pr sample) –Chlorine< 1000 mg/l average 12 months (max mg/l pr sample) –Suspended sludge< 500 mg/l average 12 months (max. 650 mg/l pr sample) −Organic solvents −DMF

research based, people driven 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

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

research based, people driven 15 Ground- and drain water monitoring Drain water monitoringGround water monitoring GBJ Z0 Z7 B5 B22 Z9 C/D E B21 G G4 V S Ground water flow direction

research based, people driven 16 Waste handling 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

research based, people driven 17 Environmental award 2000