TGA GMP cannabis facility – considerations · Active directory, e-sig, audit trails, metadata....

Slide 1 © PharmOut 2018

TGA GMP cannabis facility – considerations

Trevor Schoerie - Managing DirectorAugust 2018

Typical Engineering Project

Presented by Trevor Schoerie8 August, 2018

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Architectural and Engineering


Six Project Steps


STEP 01 – FEASIBILITY

• Project charter• Business idea and requirements• Pre-design hazard analysis• Order of magnitude estimate• Project brief

5%3 MONTHS


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


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


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


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


STEP 05b – Implementation

• Construction Assistance and Management• Construction documentation• Contractor submittals• Construction assistance

15%12 MONTHS


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


STEP 06 – Close-Out

• Documentation handover• Contractual close out• Post project review

GMP considerations


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52 PIC/S member authorities (1 January 2018)

4 Partners

EDQMEMA

UNICEFWHO

New Zealand

Iceland

Canada

USA

Argentina

South Africa

Australia

Malaysia

Taiwan

Switzerland

Norway

Indonesia

Ukraine

Singapore

Israel

Liechtenstein

EUROPEAN UNION Member States Agencies (29)

Japan

South Korea

Hong Kong

Thailand

Mexico

Iran

Turkey

Newest members 1 Jan 2018


Software “Six GMP Requirements”

1.PQSHow will you run your facility2. Validation –Documentary evidence the process / test method works


Good Documentation Practice GDP

Initials but no date.

Missing entry

Unit not specified

Date and initials but

original text not readable

Doc is still in draft. Use the approved test

sheet

Ditto marks not allowed

Incorrect entry

No explanation

why N/A

Empty space. Cross out + initials and

date

What us the company policy on rounding?


Designing DI into systems (ALCOA)

Attributable Legible/Permanent

Contemporaneous Original Accurate

Initials & Signature registers

Active directory, e-sig, audit trails, metadata

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

Data annotation tools, audit

trail

System clock, sync., transaction window

Metadata, data about the data that permits reconstruction

Data capture, manual data entry

Paper-based

Electronic


Product types -Edibles


US FDA

Sativex (EU/AU) - MS Epidiolex (FDA) - Dravetsyndrome (epilepsy)

Marinol (US FDA EU) Nausea

Construction considerations


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Hardware - Where do we start?

Feasibility / Concept design1. User brief product mix, initial & eventual volumes and jurisdictions2. Working backwards focussing on the process3. Consider WCM / Lean drives design4. Consider Economic Batch Quantities (EBQ)5. Shadow equipment in processing areas, 6. Then wrap the room around the process7. Consider the entire flow8. Even is you have BIM, consider marking out (tape) the floor9. Close your eyes, visualise each activity


Actions and decision register is keep up to date to ensure speed of delivery


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


TGA code – PIC/S version 13

§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.

§3.10 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.

should = must


Example of Indoor Growhttps://www.businessinsider.com.au/photos-canopy-growth-tweed-marijuana-grow-site-2017-3?r=US&IR=T


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


The main source of contamination is?

Did you know 50% of house dust is skin?


Central AHUParticlesMoistureCooling

ZC

ZC = Zone controlAir volume & reheat

ZC

ZC

ZC

ZC

ZC

Systems Configuration – Single Plant


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 14664


Pressure cascade for ‘LIQUIDS’

++

+

o

Direction of air flow

Airlock

Operational Zone

Corridor

Supporting Zone

Door to open against the direction of the air flow. (closing with the air flow)

o – zero pressure+ - increase of (min.) 10 Pa ++ - additional increase of (min.) 10 Pa


Pressure cascade for ‘POWDERS’

o

+

++


Airlock

Operational Zone

Corridor

Supporting Zone




Pressure cascade for ‘BUBBLE’

+

++

+


Airlock

Operational Zone

Corridor

Supporting Zone




Pressure cascade for ‘SINK’

++

+

++


Airlock

Operational Zone

Corridor

Supporting Zone




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: 10 – 15 Pa (guidance value)


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


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


Masonry construction


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


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.


Glass Reinforced Polyester (GRP) clean room system


Metal panel construction system


FloorChannels...


42


. . Ceiling Channels...



...Glazing...

…Single

Or

double

Window details


….Doors….SwingSlide

PoweredRoller

Doors


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


FLUSH with the Panel…


Walk-on ceiling


Equipment Integration



Thank you

Trevor Schoerie

[email protected]

Executive Consultant

www.pharmout.net

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