Slide 1 © PharmOut 2018

2019 Medicinal Cannabis Expo Johannesburg

Welcome

Esthi Bosch –Manufacturing PharmacistNovember 2019

Slide 2 © PharmOut 2018

About PharmOut

PharmOut is a leading international consultancy offering architectural, engineering, compliance, validation, regulatory, consulting services to the pharmaceutical, blood & tissue, pesticides and veterinary and medical device manufacturers, and more recently medicinal cannabis (3 years).

PharmOut holds ISO 9001:2015 certification from LRQA. Our Quality Management System is certified to the ISO 9001:2015 standard for the provision of architectural design and consultancy services.

SA Company and Local OfficesSince April 2019

Slide 3 © PharmOut 2018

Our Cannabis Specific Services

• Licensing, any country

• EU-PIC/S Compliance

• Regulatory submissions

• Quality Management Systems

• Cultivation Consulting

• GACP/GMP Cultivation Training

• Master & Strategic planning

• Architecture and design

• Engineering

• Equipment selection

• Qualification and Validation

• Temp., Light & RH Mapping

Slide 4 © PharmOut 2018

Two Pillars of ALL Pharmaceutical Products beforeyou can sell product

Marketing Authorisation

• Double blind ClinicalEvidence that it prevents, cures or alleviates symptoms.

Good Manufacturing Practice (GMP)

• Evidence of systems to ensure safe and reproducibleproduction

Product Registration and Manufacturing License

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Medicinal Cannabis

Software – Paperwork

Validation Lifecycle

- 3 stages of validation

Control Strategy

- Drives the “Design”

Pharmaceutical Quality System

- 200 documents

Hardware - Facility

Facility

- fabric, logical layout, mix up

Services

- power, water, laboratories

Equipment

- non reactive, cleanable

Slide 6 © PharmOut 2018

United Nations Single Drug Convention 1964

• Most countries are signatories to this convention

• Countries have since 1964 enacted laws to control drugs (beneficial and harmful drugs)

• Cannabis remains a banned substance, but it is changing

• Poisons scheduling

• Cannabis for non medicines are schedule 9 drugs, no useful medical use, but CBD and THC have clinical evidence

• USA THC from a botanical source is banned (USP).

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PIC/S Guide to GMP

Currently 54 authorities have adopted (28 from Europe)

•GMP Guidance’s used as regulatory requirements by EU and Asia-Pacific countries, including South Africa

•Is an informal “Cooperative Arrangement” between GMP regulatory authorities; i.e. it’s not a legal treaty.

PIC/S – Pharmaceutical Inspection Co-op Scheme

No obligation for member authorities to accept inspection reports of other members.

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Introduction to PIC/S GMP Guidelines

PIC/S PE 009 Guide to Good Manufacturing Practices is in 3 parts:

Guide to Good Manufacturing Practice for Medicinal Products Part I

Guide to Good Manufacturing Practice for Medicinal Products Part II (API manufacturing)

Guide to Good Manufacturing Practice for Medicinal Products Annexes

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54 PIC/S member authorities (1 January 2019)

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

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Pharmacopeia – 20

1. Pharmacopoea Slovaca

2. Indonesian Pharmacopoeia

3. Brazilian Pharmacopoeia

4. British Pharmacopoeia (BP)

5. British Pharmaceutical Codex

6. Pharmacopoeia of the People's Republic of China (Chinese Pharmacopoeia)

7. Czechoslovak Pharmacopoeia

8. German Pharmacopoeia (GP)

9. Pharmacopoeia of the United Mexican States (Mexican Pharmacopoeia)

10.Portuguese Pharmacopoeia

11.Indian Pharmacopoeia

12.Japanese Pharmacopoeia (JP)

13.Minimum Requirements for Antibiotic Products of Japan

14.Czech Pharmacopoeia

15.European Pharmacopoeia (EP)

16.French Pharmacopoeia

17.Swiss Pharmacopoeia

18.Hungarian Pharmacopoeia

19.International Pharmacopoeia

20.Royal Spanish Pharmacopoeia

21.United States Pharmacopeia (USP)

22.State Pharmacopoeia of the Union of Soviet Socialist Republics (Soviet Pharmacopoeia)

23.Yugoslav Pharmacopoeia

Slide 11 © PharmOut 2018

Six (EU – PIC/S) GMP requirements

Front End

Engineering

Study

(FEED)

Functional

and

Detailed

Design

Facility User

Requirement

Specification

(URS)

Tender Construction Installation CommisioningFacility

Handover

Validation

Master

Plan

(VMP)

Factory

Acceptance

Testing

(FAT)

Design

Qualification

(DQ)

Qualification

Protocol

Development

Pre-delivery

Inspection

(PDI)

Execute Installation

Qualification (IQ)

and Operational

Qualification (OQ)

Execute

Performance

Qualification

(PQ)

Facility/

Equipment

approved for

Manufacture

Supplier

Assessment

Process

Validation

Summary

Report

GMP /

Quality Risk

Assessment

Project

plannning/

scoping (includes org

structure)

System

Implem-

entation

Project Plan

and Schedule

Monitor

system for

effectiveness

System

development

and approval

Training and

assessment

Quality

Manual /

Policies

User

Requirement

Specification

Functional

Specification

(FS)

GMP Risk

Assessment

Design

Qualification

(DQ)

Factory

Acceptance

Testing (FAT)

Operational

Qualification

(OQ)

Performance

Qualification

(PQ)

Quality and

Project Plan

(QPP)

Pre-delivery

Inspection

(PDI)

Design

Specification

(DS)

Installation

Qualification

(IQ)

Qualification

Protocol

Development

Validation

Summary

Report (VSR)

ConstructionSupplier

Assessment

Site

Master

File

Rectify any

identified

deficiencies

GMP

license

application

Pre-GMP

licensing

audit

Lodge

application

with TGA

Requirement 1

GMP Facility Design, Construction and Validation

Obtain GMP

license

Requirement 3

GMP Quality System Development and Implementation

Requirement 2

Equipment / Lab Method / IT Validation

Requirement 5

TGA Good Manufacturing Practice (GMP) License

Requirement 6

Regulatory Product Registration

Common

Technical

Document

Product

Registration

TGA GMP Requirements for Pharmaceutical Drugs

Commercial

Manufacturing

Raw Material

Specifications

In-process

Specifications

Finished

Product

Specification

Requirement 4

Product Characterisation/Specification

Purchase

Purchase

Validation

Master

Plan

(VMP)

Most requirements are concurrent

Quality System Elements- Product Realisation + Raw Material procurement & assurance

+ Manufacture

+Testing

+ Batch Release

+Storage & Distribution

Supporting sub-systems- Document Control

- Vendor Assurance

- Training

- Validation

- Calibration

- Preventative Maintenance

- Deviation Management (CAPA)

- Change Control

- Self Inspection

A typical GMP compliant quality

system would include SOPs and

sub-systems as defined above.

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SAHPRA licensing process

• Need a solid business plan

• What is the pharmaceutical product you want to manufacture?

• The Facility must be built (similar to Greece)

• Security must be in place (expect to spend more than a R1m)

• Complete forms and submit

• Inspection

• Issue permit

• Reinspect

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Thank you

Esthi Bosch

Esthi.bosch@pharmout.net www.pharmout.net www.pharmout.co.za

I’m very happy to share my presentation.