Safe Handling of High Potent Solid Drugs

Transcription

1 Pharmaceutical Conference Poland Safe Handling of High Potent Solid Drugs Overview Themes Höfliger, Forum 2005

2 General What are high potent drugs? and Why do high potent drugs require special handling? The exposure of the product (API) over a certain time will be harmful for the operator The emission of the drug substance (API) to the operator is linked to the MAK value. To prevent negative influences to the human body the operator protection is mandatory. MAK: Maximum Allowed Concentration (largest amount of health damaging gases and fumes, volatile or floating materials that can be born with out health damage during 8 working hours. Example for MAK: Paracetamol: 10mg/m³ Foradil: 1µgr/m³ But high potent drugs are not toxic!! Overview Themes Höfliger, Forum 2005

3 Definition for the Exposure to the operator (Emission) Overview Themes Höfliger, Forum 2005

4 Example of OEB Overview Themes Höfliger, Forum 2005

5 General Available solutions for operator protection Operator gowning with protective garments Machine with containment Overview Themes Höfliger, Forum 2005

6 Limits of Containment A containment enclosure prevents the operator from being exposed to the API during regular production. but When is the operator able to open the machine containment? What about the exposure limits in the machine? - Limits for the air inside the production room? - Limits for the machine surface? => Methods e.g. WIP to reduce the exposure inside the machine are needed!! Overview Themes Höfliger, Forum 2005

7 Comparison Machine with Containment and with WIP Capsule Filling machine, c/h equipped with: 1x basic machine 1x dosing station 1x format part set 1x containment 1x line equipment (deduster, transfer units, checking system, vacuum cleaning and air handling system) Costs: 1,2 Mio Euro Above machine in WIP execution: Costs: 4,2 Mio Euro Overview Themes Höfliger, Forum 2005

8 WIP is the standard answer in the industry for cleaning! BUT: Is washing in place the best solution? How clean is WIP? What are the criteria's to make a judgment of what is clean? Is the WIP Machine that clean, to open the containment? Is the cleanness of the machine direct measured? How clean is the air inside the machine? How clean are the machine surfaces in the machine? What is the maximum allowed concentration of API? (OEL is an average concentration) Overview Themes Höfliger, Forum 2005

9 WIP is the current used method to reduce the exposure Current disadvantages of the WIP cleaning process!! No possibility to open the containment for manual trouble shooting Remaining bacteria in the piping due to washing solvent. Problems with crystallization of the API which leads to leakage of the seals Cost to recycle the waste water and cost for lost API while cleaning Due to the capillary force of the washing solution, the API remains in small gaps of the machine which are bolted together and are not sealed Adhesion force of the API is 10 times higher when exposed to water Water proofing measures and effectiveness will diminish over time Weight of handling parts are heavy due to the use of stainless steel Indirect measurement of waste water to determine the cleanness Machine surface is not completely clean and requires manual cleaning Total Cleaning time of the machine (washing and drying) Price of such a machine => Is WIP the future? Overview Themes Höfliger, Forum 2005

10 Alternative to WIP? DRY CLEANING Concept: Target: To reduce the number of particles in the air as well as at the machine surfaces before opening the containment to protect the operator and the GMP room from exposure to the API Allow the opening of the machine containment in the production without loss of time and API Limits for airborne particles: 1µg/cm³ Limit for machine surface: 1 µg/cm² Target costs: 40%less as the WIP Machine!! Overview Themes Höfliger, Forum 2005

11 Alternative to WIP? HH Strategy/ Content of the DRY CLEANING Concept: ModuC MS: 1. Determine the places of most powder spillage in the machine. 2. Reduce the powder loss in the machine. 3. Create an area for simple handling of parts and failures 4. Dry cleaning by compressed air and vacuum suction 5. Final cleaning with dry cleaning solvent. 6. New methods for the determination of the limits for airborne particle and machine surfaces. Overview Themes Höfliger, Forum 2005

12 Detailed machine, ModuC MS For more information about the DRY CLEANING Concept please contact us at our booth (Trade & Consult) Overview Themes Höfliger, Forum 2005

13 Detailed machine Free access to handling area for manual trouble shooting Overview Themes Höfliger, Forum 2005

14 Air handling for operator protection Compensation box for return air to ensure good underpressure control in the containment The air handling unit is supplied with return air and with air out of the cleanroom Air handling unit for temperature and humidity control Technical area Production room Overview Themes Höfliger, Forum 2005

15 Decontamination Concept as alternative for WIP Advantage of ModuC Dry Cleaning Concept : Operator protection during production and decontamination before manual final cleaning Containment in defined under pressure for protection of the operator against high potent or toxic emissions Avoiding the use of cleaning water to reduce waste and disposal cost Avoiding powder spillage in the production area due to housing of the powder trolley and addition cleaning of the lower segments Opening the machine for trouble shooting, access to all relevant parts without gloves and without loss of API Standard machine sealing is sufficient to prevent leakage Trolley machine can be used for more flexibility Time for decontamination process is only 30 minutes Overview Themes Höfliger, Forum 2005

16 What is Occupational Exposure Limit (OEL)? Overview Themes Höfliger, Forum 2005

17 Definition for the Exposure to the operator (Emission) How useful are these limits OEL and OEB? Does it tell me how good the machine protects the operator? What are the maximum allowed limits? Are there any difference in the limit during production or at the end of the production? When opening the machine, how clean is the air inside the machine room and what about the machine surfaces? Overview Themes Höfliger, Forum 2005