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Safety and efficacy information for a new registered complementary medicine
ARGCM Part D: Registered complementary medicines
Well documented ingredients/medicines
If an ingredient or medicine is well described and appropriately referenced in reputable texts or publications (for example: Martindale-The Complete Drug Reference) the TGA will consider these sources in the assessment of safety and efficacy where these are provided in the application. Indications, dosage and route of administration must be consistent with the reference provided. For guidance for applicants choosing to submit a literature-based submission, see Literature-based submissions for complementary medicines.
For other new medicines, that are not well described in literature, nonclinical and clinical data will be required to support the safety and efficacy of the medicine. Safety and efficacy data should be presented as 'nonclinical' and 'clinical' data modules (consistent with the CTD Modules 4 and 5).
Data that demonstrate the safety of the medicine include information on history and pattern of use, biological activity, toxicology, clinical data and reports of adverse reactions. The overall safety of the medicine is dependent upon its formulation, its intended therapeutic purpose, dosage, method or route of administration, duration of use, the target patient group (such as children or the elderly) and the potential for interaction with other medicine(s).
Safety may be established by detailed reference to the published literature and/or the submission of original study data. Where there is sufficient evidence based on human experience to support safety, the absence of extensive nonclinical investigations may be justifiable. Note that anecdotal or limited clinical reports of efficacy alone are not considered evidence of efficacy and safety.
Primary pharmacodynamics: in vitro and in vivo
Studies on primary pharmacodynamics should be provided and evaluated.
Secondary pharmacodynamics: in vitro and in vivo
Studies on secondary pharmacodynamics should be provided by organ system, where appropriate, and evaluated.
Safety pharmacology studies should be provided and evaluated. In some cases, secondary pharmacodynamic studies can contribute to the safety evaluation when they assess potential adverse effects in humans.
Pharmacodynamic drug interactions
Where they have been performed, pharmacodynamic drug interactions should be provided.
Analytical methods and validation reports
Provide the methods of analysis for biological samples, including the detection and quantification limits of analytical procedures.
Provide data on the extent and rate of absorption (in vivo and in vitro studies) and kinetic parameters, bioequivalence and/or bioavailability.
Where available, provide data tissue distribution studies, protein binding and distribution in blood cells and placental transfer studies.
Where available, provide data on:
- chemical structures and quantities of metabolites in biological samples
- possible metabolic pathways
- pre-systemic metabolism
- in vitro metabolism including P450 studies
- enzyme induction and inhibition.
Where available provide data on routes and extent of excretion and excretion in breast milk.
Pharmacokinetic drug interactions (nonclinical)
If they have been performed, provide nonclinical pharmacokinetic drug interaction studies (in vitro and in vivo).
Provide details of any contraindications or interactions with conventional and non-conventional medicines.
Other pharmacokinetic studies
If studies have been performed in nonclinical models of disease they should be provided and evaluated.
Single dose toxicity
The single dose data should be provided in order of species, by route and evaluated.
Repeat dose toxicity
Studies should be provided in order of species, by route and by duration and evaluated.
Genotoxicity: in vitro and in vivo
Where available, in vitro and in vivo mammalian and non-mammalian cell system genotoxicity studies should be provided and evaluated.
Carcinogenicity: long term studies and short or medium term studies
Where available, carcinogenicity studies should be provided and evaluated.
Reproductive, developmental toxicity
Where available, provide and evaluate studies on:
- fertility and early embryonic development
- embryo-foetal development
- prenatal and postnatal development
- studies in offspring.
If local tolerance studies have been performed, these should be provided and evaluated.
Other toxicity studies
Provide any other studies such as: antigenicity, immunotoxicity, mechanistic studies, dependence, metabolites and impurities.
Clinical data should preferably be presented as specified in Modules 2.5 Clinical Overview, 2.7 Clinical Summary and Module 5 Clinical Study Reports of the CTD format. The clinical overview provides a critical analysis of the clinical data in the dossier while the clinical summary is provides a detailed, factual summarisation of the clinical information.
Include information on the mechanism of action, if known. Include information to justify the proposed dose and dose interval and any information that may be relevant to formulation differences in the submitted studies and to possible interactions with other medicinal products.
Include data on the action of the medicine on the body including absorption, distribution, metabolism and elimination of the medicine.
Controlled and uncontrolled efficacy clinical trials
Provide and evaluate any published and unpublished efficacy clinical trials.
Australian Clinical Trials provides information for sponsors developing clinical trials for a medicine or a new complementary medicine substance.
Efficacy-related PI/CMI comments (where applicable)
Where the medicine has a PI or CMI document, provide any comments related to the efficacy clinical studies.
Controlled and uncontrolled safety clinical trials
Provide and evaluate any published and unpublished safety clinical trials.
Safety-related PI/CMI comments (where applicable)
Where the medicine has a PI or CMI document, provide any comments related to the safety clinical studies.
The application should include all relevant post-market data, including published and unpublished data. Any safety issues identified following marketing should be highlighted and any regulatory action relating to safety taken by an international regulatory agency should be detailed. The data should be presented as a tabulation of the adverse events that have been reported, including any serious adverse events and any potentially serious interactions with other medicines.
A Periodic Safety Update Report (PSUR) report is acceptable as post-marketing data.