Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP - PowerPoint PPT Presentation

Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP Brief on regulations/Access to products Manufacturing and GMP requirements Maurice Makdessi Senior GMP Inspector Inspection Section, Manufacturing Quality Branch Medical Devices and Produce Quality Division, TGA RACI Supply and Use of Medicinal Cannabis Seminar 28 March 2017

Sections/content • Cannabis – Main components of interest • Brief Regulation/Access to Cannabis products • GMP requirements/Products/APIs • ‘Approved Access’ Products and GMP • References/useful sites for more information Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 1

Cannabis – main components 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: delta-9-tetrahydrocannabinol and cannabidiol 2 Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP

Brief regulations/access to products The Therapeutic Goods Act 1989 provides a number of mechanisms to enable access to unapproved therapeutic goods ‘Approved Access’. For medicinal cannabis products these include: • Authorised Prescriber Scheme (APS) • Special Access Scheme (SAS) - Category B ONLY • Clinical trials (CTX-CTN) Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 3

Summary Table : Regulations/access/licencing Process Therapeutic Goods Narcotic Drugs Act States and Act territories involved? Patient need Special access scheme Licence Medical Yes Authorised prescriber Permit authorisation CTN Clinical trials Licence CTX Yes Importation Permit Sponsor clearance Finished dosage Licence Licence required Yes form manufacture Permit Licence API Manufacture Licence required No Permit Licence No Harvest N/A Permit Cultivation N/A Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 4

GMP requirements/medicinal cannabis Domestically Manufactured Products/Materials • Manufactured products with intended access via the ‘approved access’ pathway, the currently adopted PIC/S Guide to GMP applies • For Clinical trial products, Annex 13 of the Code would be of particular importance • Domestically manufactured APIs are subject to current GMP and TGO93 Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 5

GMP requirements/medicinal cannabis • Exemptions for products manufactured in Australia – extemporaneous compounding (i.e. for identified patient):  Products compounded by pharmacist in public hospital not required to be under GMP if for supply for hospital from the premise and in same State or Territory  Products compounded by any other extemporaneous compounder required to be under GMP – Australian manufacturer with GMP (using imported starting materials) can supply CTN, CTX, SAS Cat A or B, authorised prescriber, under a contract with a public or private hospital (where product is not ‘substantially similar’ to one on the ARTG) Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 6

Medicinal cannabis API manufacture The API is the active ingredient that is the starting material for the manufacturing process of the finished product. For medicinal cannabis, the API could be: • An extracted and purified active component of the cannabis plant (for example a cannabinoid) • An extract of specified parts of the cannabis plant • Powdered specified parts of the cannabis plant Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 7

Medicinal cannabis API manufacture GMP requirements increasingly applies in the API manufacturing process as the process advances for example: • For extracted cannabinoids: GMP does not apply up to cutting and initial extraction but increasingly applies from the introduction of the API starting material into the process onwards • For herbal cannabis extracts: GMP does not apply up to cutting and initial extraction but increasingly applies from further extraction onwards Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 8

Medicinal cannabis API manufacture • For powdered cannabis plant parts: GMP does not apply up to cutting and commuting but increasingly applies from the moment of physical processing and packaging of the powder onwards Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 9

Medicinal cannabis API manufacture Application of Part II of the Code of GMP Type of manufacturing API extracted Collection of Cutting/initial Introduce the Isolate and Process plants extraction(s) purify and pack API starting (plant) material Herbal extracts Collection of Cutting/initial Further Process plants extraction(s) extract and pack (used as API) API powdered Collection of Cutting and Process commuting and pack herbs plants and/or cultivation and harvesting Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 10

‘Approved Access’ domestic product GMP • The finished medicinal cannabis 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. • The domestic manufacture of the finished medicinal cannabis product is required to be in compliance with Code of GMP, relevant Annexes, and relevant TGOs. i.e. TGO 77 (Microbiological STD),TGO78 (Capsules and Tablets STD), and TGO 93 (Medicinal Cannabis STD) Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 11

‘Approved Access’ domestic product GMP Where Clinical trials products are domestically manufactured Annex 13 of the PICS Guide applies. Annex 13 key points: • Quality Management system • Receiving/storage/usage/security (S8 requirements) • Personnel/training • Premises/Equipment • Manufacturing: Operation/Critical parameters • Packaging: operation/packaging materials/labelling/expiry/ blinding operation Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 12

‘Approved Access’ domestic product GMP • Quality control/verification effectiveness of blinding • Review/assessment/release of batches • Shipping/security codes/storage conditions • Complaints/recalls/returns/destructions • Documentation: specifications/methods/in-process • Approved labelling/clinical trials protocols/technical agreements/stability/storage records/manufacturing and packaging instructions and records Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 13

‘Approved Access’ domestic product GMP The application of quality risk management in the manufacture of medicinal cannabis could be utilised subject to the principles of Annex 13. The TGA had developed guidance documents for complementary medicines that contain information that may assist in manufacturing products to be made available via clinical trials or investigational product pathways. Particularly supplier qualification/sampling/testing/process validation. Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 14

‘Approved Access’ domestic product GMP • Supplier qualification: – Understanding the nature of the starting material (includes packaging) and acquisition of relevant information from starting material manufacturers – Approval of starting material specifications – Approval of starting material suppliers – Reduced sampling considerations – Reduced testing considerations – Periodic review Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 15

‘Approved Access’ domestic product GMP • Testing – Identification testing is critical. Active component testing is critical if component reported on label. Microbiological testing as required. Heavy metals tested on a rotational basis. C of A result acceptable for other criteria, including pesticides and residual solvents (where relevant). – If extracts are sourced from a manufacturer that is TGA licensed or has a TGA GMP clearance then extracts can be accepted on a C of A without further testing provided that supply chain and examination of packaging for integrity of seal are verified. Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 16

‘Approved Access’ domestic product GMP • Process Validation: Any risk based approach should be consistent with Annex 20 of current Code – Prior to validation, all requirements of equipment qualification and validation of test methods should have been appropriately completed – Concurrent or prospective validation would normally be expected for new dosage forms/processes – Product Grouping validation should be based on scientific justification which may be difficult to achieve for medicinal cannabis. Therefore each dosage form and batch size are required to be validated Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 17

‘Approved Access’ domestic product GMP • Sufficient samples should be taken for any Process Validation study to permit statistical analysis • In the case of extractions: sampling from the critical control points of the process to verify those controls (e.g. extraction completion, conversion completion, completion of separations/concentration etc.) • Dosage forms: sampling to ensure homogeneity in manufacturing, (e.g. blender/mixing tank, throughout compression, encapsulation and packaging Manufacture of Medicinal Cannabis Products under PIC/S Code of GMP 18