High Potent Drugs & Containment Technology

Transcription

1 High Potent Drugs & Containment Technology Technology Overview & Quality Risk-Based Design Selection Holger Fabritz Head of Quality & Validation Assurance

2 Part 1 Definition High Potent Drugs, OEL & hazardous classification Brief description of isolator and RABS technologies Isolator/RABS versus Clean room operation Technology & process examples Part 2 Risk Analysis Tool of design evaluation & QM Risk Analysis Standards, Workflow, Methods Project Management 2

3 Definition High Potent Drugs = Active Pharmaceutical Ingredients (HP-APIs)* 1. Highly selective pharmacologically active ingredients that binds to specific receptors or enzymes and/or could cause cancer, mutations, developmental effects or reproductive toxicity at low doses. 2. Pharmacologically active ingredient with biological activity at approx. 15 micrograms per kilogram of body weight or below in humans. Equivalent to a therapeutic dose at approx. 1 mg. 3. Active ingredient with an OEL at or below micrograms per m 3 air as an eight hour time weighted average. *Biological agents like a bacterium, virus, prion or fungus which may cause infection, allergy, toxicity or otherwise create a hazard to human health are not covered in this presentation 3

4 Definition Source: 4

5 Definition Hazardous Classification Max. hazardous potential Class 0 GASES Physical Condition 1 AEROSOL (liquid / air) 2 POWDER (micronized) 3 LYOPHILISAT 4 POWDER (API) 5 POWDER (API + Excipient) 6 LIQUIDS (API) 7 POWDER (humidified) 8 SUSPENSION Min. hazardous potential 9 SOLUTION (org. solvents) 10 SOLUTION (aqueous) 5

6 Typical HP-API substances Cytostatica (approx. 59%)* Hormones Antibiotics Narcotics Radio pharmaceuticals Products like e. g. Botulinum Toxin (Botox ) * Source: Shilpi Mehrotra, GBI Research chemica aggi / Chemistry Today - Vol.28 n 5 September / October

7 Commercial value of HP-API Global market value was at around $ 7.5 billion (2009)* representing approx. 10% of the overall API marketcytostatica (approx. 59%)* Estimated market growth rate till 2015 is 8.4% per year* Market split of annual sales within the world regions (2009)*: - North America: 46% (USA represents 94%) - Europe: 36% - Asia: 10% (fastest growing market) * Source: Shilpi Mehrotra, GBI Research chemica aggi / Chemistry Today - Vol.28 n 5 September / October

8 HP-API facility design Building Building utilities Equipment 8

9 Available cleanroom technologies Conventional cleanroom Open RABS Closed RABS (crabs) Isolator Open System No operator / environmental protection* Local containment Operator / environmental protection * Operator and environmental protection can be achieved by local measures 9

10 Conventional clean room Conventional cleanroom Open RABS Closed RABS (crabs) Isolator Open System No operator / environmental protection* Local containment Operator / environmental protection * Operator and environmental protection can be achieved by local measures 10

11 Open Restricted Air Barrier System (RABS) Conventional cleanroom Open RABS Closed RABS (crabs) Isolator Open System No operator / environmental protection* Local containment Operator / environmental protection * Operator and environmental protection can be achieved by local measures 11

12 Closed RABS Conventional cleanroom Open RABS Closed RABS (crabs) Isolator Open System No operator / environmental protection* Local containment Operator / environmental protection * Operator and environmental protection can be achieved by local measures 12

13 Isolator Conventional cleanroom Open RABS Closed RABS (crabs) Isolator Open System No operator / environmental protection* Local containment Operator / environmental protection * Operator and environmental protection can be achieved by local measures 13

14 Isolator & Process Equipment Example: Weighing & Compounding 14

15 Isolator & Process Equipment Example: Weighing & Compounding 15

16 Quality is not only a matter of technology. The circumstances at point of process need to be designed in detail. 16

17 Quality is not only a matter of technology. The circumstances at point of process need to be designed in detail. Example: Optimization of filling process VIDEO VIDEO 17

18 Why Risk Analyses? Systematic analysis of risks in order to identify adequate measures / tests Abstract analysis prior to the real performance (the opposite of trail and error ) Risk-based guidance to clear technical requirements Method to filter out the essential ( right ) requirements Systematic decision making 18

19 Damage without Risk Analyses Design requirements are not respected or forgotton Technical solutions are developed without clear requirements Tests (Qualification/Validation) are not complete Tests are performed although not necessary Conflicts may arise from not involving all competente persons Expensive solutions do not meet the major aims. Unforeseen conflicts 19

20 Fields of application Safety Environmental protection, health, safety at work (EHS) Security Operations with high hazard potential (Aviation and aerospace industry, medicine, radioactivity,.) Economy Quality Decision for investments (prospects and risks) Optimisation of costs (quality aims vs. costs) Readiness for delivery / time-management vs. costs Quality Management Design evaluation Change Management Quality control Inspection of incoming goods GMP Compliance: Equipment qualification, process validation, cleaning validation 20

21 International regulations concerning GMP Risk Analysis in the pharmaceutical & medical device industry EC Guide to Good Manufacturing Practice Annex 1 (Sterile Manufacturing), Annex 15 (Qualification and Validation), Annex 20 (Quality Risk Management) (2008) / ICH Q9 (2005) ISPE-GAMP5 ISPE Baseline Vol.1-Active Pharmaceutical Ingredients (2 nd Edition, 2007) ASTM E Standard ISO 14971(2007): Application of risk management to medical devices 21

22 GMP Risk Analysis Workflow Method & formal framework is traceable and agreed upon within the team The scope of Risk Analysis is be determined Project documentation on current status is available Interdisciplinary team of experts & process owners Unstressed workshop / meeting atmosphere 22

23 GMP Risk Analysis Workflow Risk Identification Risk Analysis Risk Evaluation Risk Reduction Risk Acceptance Risk Assessment Risk Control Source: ICHQ9 Quality Risk Management (since 2008 Annex 20 of the EC-GMP-Guide) Risk Assessment: Risks should be identified & not been solved Risk Control: measures and tests should be practicable 23

24 Risk Analysis Method FMEA / FMECA (Example) 24

25 Risk Analysis Method Determination of technical solutions / design by Risk Analysis (Example): 25

26 GMP Risk Analysis & Project Management Roles of project members Producer / Client Engineering / Service Supplier Equipment-Manufacturer 26

27 GMP Risk Analysis & Project Management Roles of project members Project Management Production Management Quality Assurance Purchasing Project Management Process Technology Infra Stucture Architecture Piping Construction CAD Installation Management GMP Compliance Equipment Manufacturer 1 Equipment Manufacturer 2 Equipment Manufacturer 3 27

28 28? Questions?