Medicinal Cannabis Access and GMP Maurice Makdessi Senior Inspector - PowerPoint PPT Presentation

Medicinal Cannabis Access and GMP Maurice Makdessi Senior Inspector Manufacturing Quality Branch Health Products Regulation Group Medical Devices and Product Quality Division, TGA 21 NOV 2019

Overview Medicinal Cannabis – Access – Regulations and Licensing (TGA/ODC) – GMP requirements and guidelines  Import/export  APIs and Finished products – Cases/Examples of License requirements 1

Medicinal cannabis Cannabis describes all plants of the Cannabis genus. Cannabis includes the seeds, extracts, resins, and the plant as well as any part of the plant The main two components reported to have medicinal properties: 2

Brief regulations/medicinal cannabis product access • The Australian Government Department of Health regulates medicinal cannabis products through: – The Office of Drug Control (ODC), which regulates controlled substances to prevent diversion and illicit use. ODC administers the Narcotic Drugs Act 1967. – The TGA, which regulates medicines by administering the Therapeutic Goods Act 1989 Note: The states and territories have local regulations regarding access to Medicinal Cannabis products to be adhered to when manufacturing and supplying in the relevant state/territory 3

Access to products • The TG Act provides a number of mechanisms to enable access to unapproved therapeutic goods “Approved Access Schemes’. For medicinal cannabis products: – Authorised Prescriber Scheme (AP) – Special Access Scheme (SAS) – Clinical trials (CTX- CTN) • Otherwise, Access via product registration pathway (ARTG) and Clearance for overseas manufacturers via sponsors 4

Access to products • Authorised Prescriber Scheme (AP): – Applies only to medical practitioners, 6 monthly reporting to TGA applies per product/ imported medicine per patient – Compounding Pharmacy /Hospital Pharmacy (Item 2, Item 3 Schedule 8) • Special Access Scheme (SAS): – SAS category A: notification for a patient defined as seriously ill – SAS category B: application pathway (Not A or C) – SAS category C: notification of use of specified therapeutic goods: established history • Clinical Trials: CTN/CTX 5

Multiple laws The Department of Health regulates Medicinal Cannabis Products through: • The TGA which administers the Therapeutic Goods Act 1989 – Quality (identity, purity, safety, efficacy) – Access to unapproved medicines including clinical trials – Access and controls implemented via the Poisons Standard (SUSMP) – There may be other laws to be considered/states and territories 6

Multiple Laws The Department of Health also regulates Medicinal Cannabis Products through: • The Office of Drug Control (ODC), which administers the Narcotic Drugs Act 1967 – Regulates controlled substances to prevent diversion/illicit use which includes quantities. – Regulates the Cultivation of medicinal cannabis – Regulates certain aspects of manufacture of medicinal cannabis – Regulates aspects of Import/Export 7 – There may be other laws to be considered/states and territories

Scheduling States and Territories play a vital role in implementing controls in their jurisdiction • Substances, the use or supply of which should be by or on the order of persons Schedule 4 permitted by State or Territory legislation to prescribe and should be available from a (Prescription Only pharmacist on prescription – e.g., cannabidiol containing < 2% other Medicine) cannabinoids • Substances which should be available for use but require restriction of manufacture, Schedule 8 supply, distribution, possession and use to reduce abuse, misuse and physical or (Controlled Drug) psychological dependence – e.g., nabilone, dronabinol, nabixomols, cannabis, THCs (these can be of natural origin or synthetic) • Substances which may be abused or misused, the manufacture, possession, sale or Schedule 9 use of which should be prohibited by law except when required for medical or (Prohibited scientific research, or for analytical, teaching or training purposes with approval of Substance) Commonwealth and/or State or Territory Health Authorities e.g., cannabis, THCs Cannabis that does not meet Schedule 4 or 8 are classified as Schedule 9 8

Differences between TGA and ODC licensing TGA and ODC licences serve different purposes TGA licence to manufacture ODC licence to manufacture Narcotic Drugs • GMP Manufacturing of APIs and Finished Goods: includes all licensed steps of • Cultivation licence/ experimental /research manufacturing and packaging licence • Manufacture of extracts/resins including • Marketing Authorisation/RFS purifying/concentrating/isolating • Clinical trials • Converting/transforming from one to another (ie.Cannabinoid to another) 9

Lic/Permit TG Act ND Act/ ODC States/Territories Process Patient need SAS/ AP Y Y Medical authorisation CTN/CTX ≥ Phase 2 Clinical Trials Y Y Importation Sponsor Clearance Y Y Finished Dosage Licence Required Y Y Manufacture API manufacture Licence Required Y Y Harvest N/A Y Y Cultivation N/A Y Y 10

Terminology can be different (TGA/ODC) • In the context of the Therapeutic Goods Act ‘production’ refers to the actual preparation of an active pharmaceutical ingredient or a finished medicinal product. As such, ‘production’ is considered a subset of ‘manufacture’. • In the context of the Narcotic Drugs Act ‘production’ refers exclusively to the harvesting of the specified plant parts, separating resin from plant by physical/water extraction, physical separation of the trichomes from the cannabis flowers or cannabis plant (eg. sieving, ice water separation etc..) • The plant or separated resin might then undergo a processing step (e.g. solvent extraction) which is termed ‘manufacture’. As such, ‘production’ is a separate step that is usually followed by ‘manufacture’. 11

Terminology can be similar (TGA/ODC) • Where the terminology is similar (e.g. manufacture) the definitions are quite different under the respective legislations. – A TGA GMP licence focuses on quality, whereas the narcotic manufacture licence specifies what drug may be produced and in what quantities. For this reason a manufacturer may require both licences. A licence issued under the Therapeutic Act does not remove the requirement for a licence under the Narcotic Drugs Act and vice versa. 12

Imported medicinal cannabis • Tightly controlled internationally /international drug conventions • Approval must be granted by both countries importing/exporting • In the case of importation for a particular patient CAT A. The doctor/dispensing pharmacist must have an import licence and apply for import permission. • In the case of CAT B patient, TGA approval required under the SAS CAT B (AP or • Other). Evidence to ODC for import permit. • Sponsors required to demonstrate compliance to SAS access (ie. AP, storage, QTY, records, patients). • Import to manufacture if manufacturer holds required import permit & ODC licence: cannabis material including extracts for use in manufacture. 13

Medicinal cannabis quality • TGO 93 Standard for Medicinal Cannabis: − Specifically for medicinal cannabis and incorporates the requirements of the various general monographs of the European Pharmacopoeia for herb drugs/extracts − Identification Physical/Chromatographic − Chemical constituents/Assay − Others: pesticide, aflatoxin, ochratoxin A, heavy metal, total ash, foreign matter − Decontamination by Ɣ / X ray allowed where product impact is assessed not to adversely affect product quality. Ethylene oxide use is not allowed 14

GMP requirements: Finished products manufacturers • Finished product is the dosage form in which the medicinal cannabis is intended to be administered to the patient, for example as an oil, tincture, extract, capsule, tablet etc. • Manufacturing medicinal cannabis finished product must comply with various product quality standards. − Manufacturing principles- PIC/S Guide to GMP PE009-13 unless exempt in Schedule 7 or 8 of the Therapeutic Goods Regulations 1990. − TGOs may apply to both locally manufactured/imported products e.g. microbiological TGO 100, tablet and capsule quality TGO 101, Medicinal Cannabis minimum quality testing TGO 93 (mainly for natural origin). − Guidance Documents: eg. Medicinal Cannabis, complementary medicines 15

GMP requirements/Guidance document • Complementary Medicines Guidance Documents: – Sampling and testing – Supplier assessment – On going stability testing – Validation – Product quality reviews 16

GMP/Guidelines • Sampling and testing/ Supplier assessment – The two guides allow for reduced sampling and testing (rotational) when certain requirements are met. Material type Pre- Post qualification qualification √ n +1 Apply √n +1 OR Excipients – starting materials reduced sampling plan if: Sample all Actives – starting material is from a site that – containers. materials manufactures only one product Scientifically justified – 17

GMP/Guidelines • Sampling and testing/ Supplier assessment – Rotational Testing: May be used for material from a qualified a supplier:  Perform critical tests on each delivery plus one non-critical test.  Rotate through all non-critical tests  Do not skip any non-critical tests without adequate justification. – Where supplier performance changes/deteriorates then rotational testing should be assessed (for the material in question or other) 18