Therapeutic Goods (Standard for Tablets, Capsules and Pills) (TGO 101) Order 2019 Post-market compliance monitoring of listed medicines Dr Adam Cook Director – Listing Compliance Section Complementary & OTC Medicines Branch 13 May 2019
Part 2 -Tablets and capsules Division 1 - Requirements for tablets and capsules 8 General requirements (1) When there is an applicable monograph: (a) those requirements specified in that monograph, subject to the matters specified in Division 2; or (b) those requirements specified in Division 3 (the Australian specific requirements) together with the requirements relevant to the tablet or capsule that are specified in one of the following: (i) the general monographs in the EP; (ii) the general monographs in the BP; (iii) the general chapters of the USP-NF. (2) When there is no applicable monograph are: (a) the Australian specific requirements; and (b) the requirements relevant to the tablet or capsule that are specified in one of the following: (i) the general monographs in the EP; (ii) the general monographs in the BP; (iii) the general chapters of the USP-NF. 1 TGO 101 – Listed medicines compliance
What are some of the monographs that may be relevant to listed medicines? This includes*: - BP (EP) general monographs for capsules and tablets - BP (EP) individual monographs (for formulated preparations) - BP (EP) monographs for medicinal and pharmaceutical substances - BP (EP) Herbal Drugs, Herbal Drug Preparations and Herbal Medicinal Products - USP-NF <2> Oral Drug Products - Product Quality Tests - USP-NF <2021> to <2750> Dietary Supplements chapters - USP-NF individual monographs - USP-NF Dietary Supplements monographs * Not exhaustive 2 TGO 101 – Listed medicines compliance
Australian specific requirements (Division 3) • Same as TGO 78 – Assay of each active ingredient; limits specified in Schedule 1 and Schedule 2 – Tablets or capsules containing 100 mcg or more folic acid – Dissolution – Disintegration – Fineness of dispersion for dispersible tablets – Uniformity of dosage units and uniformity of weight • New in TGO 101 – Elemental impurities and residual solvents 3 TGO 101 – Listed medicines compliance
Post-market assessment of compliance • TGO 101: tool to control risks that impact safety and efficacy: – Improper dissolution leading to incorrect dosage being delivered; – Solvent residues and elemental impurities leading to toxicity or allergic reactions; – Non-uniform dosage units leading to incorrect dosage being delivered; etc • The design of the medicine (including initial stability data), together with its overall risk control strategy and validation (including ongoing stability data) can be used to demonstrate compliance with TGO 101 • Control of risks in the finished good must be demonstrated, but this may be via – testing of the finished good or testing of raw materials, or – By some other means so long as control of the risk in the finished good can be demonstrated . 4 TGO 101 – Listed medicines compliance
Post-market assessment of compliance • Example: elemental impurities – If testing is conducted at the raw material stage only § Evidence must be held to demonstrate that introduction of elemental impurities into the finished goods subsequent to raw material qualification will not occur to ensure compliance with Permitted Daily Exposures (PDEs). § Introduction during manufacturing? Testing of solvents; Validation of filtering or purification steps 5 TGO 101 – Listed medicines compliance
Post-market assessment of compliance • It is not expected that all of the tests set out in the TGO 101 must be performed on all medicines, or on all batches of a medicine. • It is up to the sponsor to demonstrate how the risks have been controlled and therefore, compliance with TGO 101. • Applicable monographs must be followed in full • Sponsors cannot select tests and limits from different default standards to create a unique testing protocol (i.e. no ‘cherry picking’) 6 TGO 101 – Listed medicines compliance
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