TGA GMP cannabis facility considerations

Transcription

1 TGA GMP cannabis facility considerations Trevor Schoerie - Managing Director August 2018 Slide 1 PharmOut 2018

2 Typical Engineering Project Presented by Trevor Schoerie 8 August, 2018 XXYYZZ_XXX

3 Architectural and Engineering Slide 3 PharmOut 2018

4 Six Project Steps Slide 4 PharmOut 2018

5 STEP 01 FEASIBILITY Project charter Business idea and requirements Pre-design hazard analysis Order of magnitude estimate Project brief 5% 3 MONTHS Slide 5 PharmOut 2018

6 STEP 02 Conceptual Development Project definition Quality by design User requirements specifications Conceptual development / Option analysis Project delivery strategy Preliminary hazard analysis Conceptual estimate (±30%) 5% 1 MONTH Slide 6 PharmOut 2018

7 STEP 03 Preliminary Design Project delivery plan Testing strategy Functional design Preliminary design documentation Design qualification Preliminary hazard analysis Basis of design 10% 2 MONTHS Slide 7 PharmOut 2018

8 STEP 04 Detailed Design Design management Detailed design documentation Process Architectural Mechanical Electrical Automation Design qualification Safe design Value engineering Pre-tender cost estimate 15% 2 MONTHS Slide 8 PharmOut 2018

9 STEP 05a Implementation Procurement Assistance and Management Supplier pre-qualification Procurement packages Tender evaluation FAT / SAT ODC Cultivation / Production / Manufacture Licence State Licence and related SOPs OCD Import licence 10% 3 MONTHS Slide 9 PharmOut 2018

10 STEP 05b Implementation Construction Assistance and Management Construction documentation Contractor submittals Construction assistance 15% 12 MONTHS Slide 10 PharmOut 2018

11 STEP 05b Implementation Testing and Licence Commissioning IQ/OQ/PQ Process Validation Training State Licence and related SOPs PQS and Qualification for TGA licence 40% 3 MONTHS Slide 11 PharmOut 2018

12 STEP 06 Close-Out Documentation handover Contractual close out Post project review Slide 12 PharmOut 2018

13 GMP considerations Presented by Trevor Schoerie 8 August, 2018 XXYYZZ_XXX

14 52 PIC/S member authorities (1 January 2018) Iceland Norway EUROPEAN UNION Member States Agencies (29) Ukraine South Korea Canada Turkey Japan Switzerland Israel Liechtenstein Hong Kong Taiwan USA Iran Malaysia Thailand Mexico Singapore Indonesia New Zealand Argentina Australia 4 Partners EDQM EMA UNICEF WHO South Africa Slide 14 PharmOut 2018 Newest members 1 Jan 2018

15 Software Six GMP Requirements 1.PQS How will you run your facility 2. Validation Documentary evidence the process / test method works Slide 15 PharmOut 2018

16 Good Documentation Practice GDP Missing entry Incorrect entry Unit not specified No explanation why N/A Empty space. Cross out + initials and date Doc is still in draft. Use the approved test sheet Initials but no date. Ditto marks not allowed What us the company policy on rounding? Date and initials but original text not readable Slide 16 PharmOut 2018

17 Designing DI into systems (ALCOA) Paper-based Initials & Signature registers Control of blank forms, pen policy/white out Documents available in right place at right time, +/- time limits Verified true copy, scans Reflective of the observation data checking Attributable Legible/ Permanent Contempora neous Original Accurate Active directory, e-sig, audit trails, metadata Data annotation tools, audit trail System clock, sync., transaction window Metadata, data about the data that permits reconstruction Data capture, manual data entry Electronic Slide 17 PharmOut 2018

18 Product types -Edibles Slide 18 PharmOut 2018

19 US FDA Sativex (EU/AU) - MS Epidiolex (FDA) - Dravet syndrome (epilepsy) Marinol (US FDA EU) Nausea Slide 19 PharmOut 2018

20 Construction considerations Presented by Trevor Schoerie 8 August, 2018 XXYYZZ_XXX

21 Hardware - Where do we start? Feasibility / Concept design 1. User brief product mix, initial & eventual volumes and jurisdictions 2. Working backwards focussing on the process 3. Consider WCM / Lean drives design 4. Consider Economic Batch Quantities (EBQ) 5. Shadow equipment in processing areas, 6. Then wrap the room around the process 7. Consider the entire flow 8. Even is you have BIM, consider marking out (tape) the floor 9. Close your eyes, visualise each activity Slide 21 PharmOut 2018

22 Actions and decision register is keep up to date to ensure speed of delivery Slide 22 PharmOut 2018

23 Greenhouse vs indoors vs broadacre? How do you choose your growing method? Climatic factors will determine best options Canada vs Australia Sub-arctic vs temperate Slide 23 PharmOut 2018

24 TGA code PIC/S version 13 should = must 3.9. Where starting and primary packaging materials, intermediate or bulk products are exposed to the environment, interior surfaces (walls, floors and ceilings) should be smooth, free from cracks and open joints, and should not shed particulate matter and should permit easy and effective cleaning and, if necessary, disinfection Pipework, light fittings, ventilation points and other services should be designed and sited to avoid the creation of recesses which are difficult to clean. As far as possible, for maintenance purposes, they should be accessible from outside the manufacturing areas. Slide 24 PharmOut 2018

25 Example of Indoor Grow Slide 25 PharmOut 2018

26 Heating Ventilation And Cooling (HVAC) Temperature Humidity Ventilation Carbon Dioxide Lighting Turn down Extreme weather event Airflow / mixing FMEA? In room vs external DX vs centralised Slide 26 PharmOut 2018

27 The main source of contamination is? Did you know 50% of house dust is skin? Slide 27 PharmOut 2018

28 Systems Configuration Single Plant Central AHU Particles Moisture Cooling ZC = Zone control Air volume & reheat Z C Z C Z C Z C Z C Z C Slide 28 PharmOut 2018

29 Prevention of cross-contamination Consider Air locks and air extraction/ventilation and air filtration Risk assess Insects Batch to batch Pressure change when changing grades Dedicated clothing Within reason safety takes precedence over GMP Standard for most MC facilities will be ISO8 (at rest) ISO Slide 29 PharmOut 2018

30 Pressure cascade for LIQUIDS o zero pressure + - increase of (min.) 10 Pa ++ - additional increase of (min.) 10 Pa Corridor o Door to open against the direction of the air flow. (closing with the air flow) Airlock + Operational Zone ++ Supporting Zone Direction of air flow Slide 30 PharmOut 2018

31 Pressure cascade for POWDERS o zero pressure + - increase of (min.) 10 Pa ++ - additional increase of (min.) 10 Pa Corridor ++ Door to open against the direction of the air flow. (closing with the air flow) Airlock + Operational Zone o Supporting Zone Direction of air flow Slide 31 PharmOut 2018

32 Pressure cascade for BUBBLE o zero pressure + - increase of (min.) 10 Pa ++ - additional increase of (min.) 10 Pa Corridor + Door to open against the direction of the air flow. (closing with the air flow) Airlock ++ Operational Zone + Supporting Zone Direction of air flow Slide 32 PharmOut 2018

33 Pressure cascade for SINK o zero pressure + - increase of (min.) 10 Pa ++ - additional increase of (min.) 10 Pa Corridor ++ Door to open against the direction of the air flow. (closing with the air flow) Airlock + Operational Zone ++ Supporting Zone Direction of air flow Slide 33 PharmOut 2018

34 Differential Pressure Requirements GMPs require Cascading Air Flows using differential pressure from cleanest to least clean. Pressure difference between areas of different class: 0.05 wg = 12.5 Pascals PIC/S Annex 1: Pa (guidance value) Slide 34 PharmOut 2018

35 Preferred option for clean rooms Cost Shouldn t always be at the top of the list. Remember you should be considering >20 years life. Local sourcing Materials Labour to install Technical support Construction environment Clean/dirty Dry/wet Project lead times and decision making Have to make decisions early for pre-fabricated Have longer to cogitate for stick-built Modification and relocation requirements Is the systems compatible with development and evolution of the business operations? Repair In house Local resources Vendor dependent Slide 35 PharmOut 2018

36 Other attributes of the construction system Ceiling Suspended Bridging on walls Walk-on Low level return air ducts In wall construction Double wall required Plant on surface Services in walls In wall thickness In a service pod on wall In a service chase Slide 36 PharmOut 2018

37 Masonry construction Slide 37 PharmOut 2018

38 Masonry construction Masonry walls Concrete ceiling Hard plaster (gypsum) Door frames set into the wall structure Applied epoxy paint to walls Thin epoxy floor finish or vinyl Slide 38 PharmOut 2018

39 Gypsum or Calcium Silicate board and frame Metal frame Calcium silicate or Gypsum board attached Joints taped Finish applied this case a glass reinforced polyester resin. Slide 39 PharmOut 2018

40 Glass Reinforced Polyester (GRP) clean room system Slide 40 PharmOut 2018

41 Metal panel construction system Slide 41 PharmOut 2018

42 Metal panel construction system Floor Channels... Slide 42 PharmOut

43 Metal panel construction system.. Ceiling Channels... Slide 43 PharmOut 2018

44 Window details...glazing... Single Or double Slide 44 PharmOut 2018

45 Doors.Doors. Swing Slide Powered Roller Slide 45 PharmOut 2018

46 Door attributes Swing doors should close with air pressure. Often need to work with electromechanical interlock systems Doors should be self closing (soft close to avoid pressure shocks). Hygienic design. Avoid cavities and ledges. Powered doors Becoming more common Ensures optimum open/close rate Can help avoid hand contact Sliding doors Ensure cleanroom style Avoid floor tracks Ensure top track cleanable Slide 46 PharmOut 2018

47 Slide 47 PharmOut 2018 FLUSH with the Panel

48 Walk-on ceiling Slide 48 PharmOut 2018

49 Equipment Integration Slide 49 PharmOut 2018

50 Slide 50 PharmOut 2018

51 Thank you Trevor Schoerie Executive Consultant Slide 51 PharmOut 2018