2019 medicinal cannabis conference...therapeutic goods order no. 93 (standard for medicinal...
TRANSCRIPT
Slide 1 © PharmOut 2019
2019 Medicinal Cannabis Conference
Analytical Cannabis Testing – TGO 93 explainedRob Curran – Senior Consultant, PharmOutMarch 2019
Slide 2 © PharmOut 2019
Analytical TestingWhat and why do we test?
Typically, all raw/starting materials used in the manufacture of medicines are tested.
Any excipients used in the final dosage form of a product are tested.
All finished products
Testing ensures:Product safetyProduct efficacyRegulatory compliance
Slide 3 © PharmOut 2019
What is TGO 93?
Therapeutic Goods Order No. 93 (Standard for Medicinal Cannabis)
It is a standard that specifies the minimum quality requirements for medicinal cannabis products.
It is an offence under the Therapeutic Goods Act 1989, to import, export, or supply therapeutic goods that do not conform to an applicable standard
Slide 4 © PharmOut 2019
What does TGO 93 apply to?
Any medicinal cannabis product imported into, exported from, or supplied in Australia
Any cannabis plant used in the manufacture of medicinal cannabis products
Any other ingredients used in the manufacture of medicinal cannabis products, such as excipients
Steps and procedures carried out in the manufacture of medicinal cannabis products
Slide 5 © PharmOut 2019
What’s required?
Aflatoxins
Foreign Matter
Heavy Metals
Ochratoxin A
Pesticides
Total Ash
Identification
Potency
Slide 6 © PharmOut 2019
Identification
Macroscopic examination Description of colour, size, smell palmate arrangement of the leaflets the pinnate appearance of the leaflets the serrated edges of the leaflet fluted stems and/or stalks
Slide 7 © PharmOut 2019
Microscopic examination Presence of microscopic hair like projections called trichomes. Non-glandular and glandular trichomes present Magnification factor of 40 required
Slide 8 © PharmOut 2019
Chromatographic procedures Thin Layer Chromotography (TLC)or High Performance Liquid Chromatography (HPLC)
Slide 9 © PharmOut 2019
Potency
All active ingredients must be quantified and accurately reported
Herbal form: 80 – 120% of label claim
Tablet/capsule form: 90 – 110% of label claim
Other dosage form: 90 – 110% of label claim
High Performance Liquid Chromatography (HPLC) with UV detector
Slide 10 © PharmOut 2019
Mycotoxin Testing
Mycotoxins are toxic chemical products produced by fungi such as Aspergillusthat readily colonise crops.
They are capable of causing disease and death in humans and animals.
Aflatoxins as per Ph. Eur. 2.8.18Aflatoxins B1 ≤ 2µg/kg,Total Aflatoxin B1, B2, G1, G2 ≤ 4µg/kg
Ochratoxin A as per Ph. Eur. 2.8.22Ochratoxin A ≤ 20µg/kg
HPLC/UPLC/LC-MS
Slide 11 © PharmOut 2019
Foreign Matter
Examine for foreign matter by unaided eye or using a lens (6 X)
Not more than 2% w/w
Sampling as per Ph. Eur. 2.8.20 Herbal Drugs: sampling and sample preparation
Slide 12 © PharmOut 2019
Heavy Metals
Ph. Eur. 2.4.27Options for analysis: Atomic Absorption Spectrometry (AAS) Inductively Coupled Plasma – Atomic Emission Spectrometry (ICP-OES) Inductively Coupled Plasma – Mass Spectrometry (ICP-MS)
Limits:≤ 3.0 ppm arsenic≤ 0.5 ppm cadmium≤ 5.0 ppm lead≤ 0.5 ppm mercury
Slide 13 © PharmOut 2019
Pesticides Must comply with limits indicated in Ph. Eur. 2.8.13
Full solution requires both GC-MS/MS and LC-MS/MS
Acephate Alachlor Aldrin and dieldrin Azinphos-ethyl Azinphos-methyl Bromophos-ethyl Bromophos-methyl Brompropylate Chlordane ChlorfenvinphosChlorpyriphos-ethyl Chlorpyriphos-methyl Chlorthal-dimethyl Cyfluthrin Λ-Cyhalothrin Cypermethrin DDT Deltamethrin Diazinon Dichlofluanid Dichlorvos Dicofol Dimethoate Omethoate EndosulfanDithiocarbamates Endrin Ethion Etrimphos FenchlorophosFenitrothion Fenpropathrin Fensulfothion Fenthion FenvalerateFlucytrinate Τ-Fluvalinate Fonophos Heptachlor LindanHexaclorobenzene Hexachlorocyclohexane Malathion & Malaoxon Mecarbam MethacriphosMethamidophos Methidathion Methozychlor Mirex MonocrotophosParathion-ethyl Paraoxon-ethyl Parathion-methyl Paraoxon-methyl Pendimethalin Pentachloranisol Permethrin Phosalone Phosmet ProcymidonePiperonyl butoxide Pirimiphos-ethyl Pirimiphos-methyl Profenophos ProthiophosPyrethrum Quinalphos Quintozine S-421 Tecnazene Tetradifon Vinclozolin
Slide 14 © PharmOut 2019
“The competent authority may grant total or partial exemption from the test when the complete history (nature and quantity of the pesticides used, date of each treatment during cultivation and after the harvest) of the treatment
of the batch is known and be checked precisely according to good agricultural and collection practice (GACP)”
Slide 15 © PharmOut 2019
Total Ash
Ph. Eur. 2.4.16 Limit: ≤ 20.0% w/w
Laboratory oven Balance Muffle furnace - 600°C
Slide 16 © PharmOut 2019
Is that it???Ph. Eur. 2619 – Pharmaceutical Preparations
Herbal Drugs (Ph. Eur. 1433) Herbal Drug Preparations (Ph. Eur. 1434) Herbal Drug Extracts (Ph. Eur. 765) Substances for Pharmaceutical Use (Ph. Eur. 2034) Essential Oils (Ph. Eur. 2098) Herbal Drugs for Homoeopathic Preparations (Ph. Eur. 2029) Functionality-related Characteristics of Excipients (Ph. Eur. 5.15)
Microbiological quality of non-sterile pharmaceutical preparations and substances for pharmaceutical use (Ph. Eur. 5.1.4)
Microbiological quality of herbal medicinal products for oral use and extracts used in their preparation (Ph. Eur. 5.1.8)
Slide 17 © PharmOut 2019
Surely that’s it???Herbal drugs (Ph. Eur. 1433)
Loss on drying Water Ash insoluble in HCl
Extractable matter Swelling index Bitterness value
Radioactive contamination Microbial contamination
Microbiological quality of herbal medicinal products for oral use and extracts used in their preparation (Ph. Eur. 5.1.8)
Microbial enumeration tests (Ph. Eur. 2.6.12) Test for specific micro-organisms (Ph. Eur. 2.6.13) Microbiological examination of herbal medicinal products for oral use (Ph. Eur.
2.6.31)
Slide 18 © PharmOut 2019
Method Validation
Why? To confirm that the analytical
procedure employed for a specific test is suitable for intended use
The methods support the identity, quality, purity and potency of the drug substance and drug product
ICH Harmonised Tripartite Guideline – Validation of Analytical Procedures: Text and Methodology Q2 (R1)
Slide 19 © PharmOut 2019
Method Validation
Parameters: Specificity Accuracy Precision (repeatability) Precision (intermediate) Detection Limit Quantitation Limit Linearity Range Robustness
Revalidation required if:
Analytical procedure changes
Drug substance changes (eg. Synthetic route)
Drug product changes (eg. Composition)
Slide 20 © PharmOut 2019
Other TGOs Required
TGO 100: Microbiological standards for medicines Total Aerobic Microbial Count (TAMC)
Total Yeast and Mould Count (TYMC)
Bile tolerant gram-negative bacteria
Salmonella
Escherichia coli
Staphylococcus aureus
Slide 21 © PharmOut 2019
Other TGOs Required
TGO 78 / TGO 101: Standards for tablets, capsules and pills
TGO 69: General requirements for labels for medicines
TGO 91: Standards for labels of prescription and related medicines
TGO 95: Child-resistant packaging requirements for medicines
Slide 22 © PharmOut 2019
Thank You
Rob Curran
Senior Consultant, PharmOut
www.pharmout.net