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Module 2: registered complementary medicines
ARGCM Part D: Registered complementary medicines
This guidance provides assistance with compiling Module 2 for an application to register a complementary medicine on the ARTG.
It relates to steps 4, 5, and 7 in the registration process for complementary medicines.
Ensuring consistency with the CTD format
Ensure you present an overall quality summary, and overviews of nonclinical and clinical safety and efficacy data, consistent with CTD Module 2.
To assist you, we have provided the general points mainly collated from the CTD guidance documents under the relevant subheadings.
For a complete description of all requirements, refer to the guidelines for Module 2: Common technical document summaries.
There is no single CTD guidance document that explains all of the content for Module 2.
The guidance for Modules 3, 4, and 5 each include a section on the information that must be provided in Module 2.
This guidance should be reviewed in combination with the registered complementary medicines data requirements matrix.
For RCM4 applications, only a Quality overall summary (included in Module 2) is required and overviews only are required for Module 4 (nonclinical) and module 5 (clinical).
For example an RCM 4 application for a medicine that includes a new therapeutic indication would require a nonclinical overview and a clinical overview including risk benefit analysis of the medicine to support the module 4 and 5 data.
Expert summaries and overviews
Include separate expert reports for:
For more information about what is required within each module see Common Technical document (CTD).
Quality summary (Module 2.3)
Provide a critical scientific summary explaining how you established the quality of the medicine.
When preparing your summary:
- You should normally not exceed 40 pages of text (excluding tables and figures).
- The structure of the summary should follow the scope and outline of the body of data in module 3 and should include an introduction.
- Include sufficient information from each section to provide an overview of module 3.
- Include discussion of key issues, integrating information for module 3 with supporting information from other modules of the dossier (e.g. qualification of impurities via toxicological studies), including cross references.
- Do not include information, data or justification that was not already included in module 3 or other parts of the dossier.
- Include proprietary name, non-proprietary name of the substance, company name, dosage from, strength, route of administration and proposed indications in the introduction.
- Emphasise key product parameters and justification where guidelines were not followed.
- Refer to quality overall summary – module 2 and 3 for detailed guidance.
Nonclinical overview (Module 2.4)
Provide an integrated and critical assessment of the pharmacological, pharmacokinetic and toxicological data for the medicine.
When preparing your nonclinical overview:
- You should normally not exceed 30 pages.
- Present the nonclinical overview in the following order: overview of nonclinical testing strategy, pharmacology, pharmacokinetics, toxicology, integrated overview and conclusions, list of literature references.
- Discuss and justify the nonclinical testing strategy.
- Interpret the nonclinical data, clinical relevance of the findings and cross-link with quality aspects and implications of the nonclinical findings for the safe use of the product.
- Consider the total amount of the active ingredient from both the medicine and other sources of the active ingredient such as food supply of the target population.
- Take into account the relevant scientific literature and properties of related products.
- Provide an appropriate justification that reviews the design of studies and any deviation from guidelines where you are using scientific literature instead of nonclinical studies.
- Discuss information of the quality of batches of drug substance used in referenced studies.
- Discuss inconsistencies in the data.
- Use consistent units throughout the overview.
- Detailed guidance on the sequence and content of the nonclinical overview is described in the guidance for nonclinical summaries of module 2 under section 2.4 nonclinical overview.
Clinical overview including risk benefit analysis of the medicine (Module 2.5)
Provide a critical scientific analysis of the clinical data.
When preparing your clinical overview:
- You should normally not exceed 30 pages.
- Present the clinical overview in the following order: product development rationale, overview of biopharmaceutics, overview of clinical pharmacology, overview of efficacy, overview of safety, benefits and risks conclusion, literature references.
- Include the proposed therapeutic indications, the target population, strength, dosage, duration and frequency of use, route of administration and pack size in the section on product development rationale.
- Describe the overall approach to establishing safety and efficacy of the medicine in its intended use.
- Take into consideration the history of use of the medicine and any traditional use of the medicine as subheadings of the product development rationale section.
- Present the conclusions and implications of the clinical data to create a succinct discussion and interpretation of both:
- the clinical findings
- any other relevant information (e.g. animal data or product quality issues that may have clinical implication).
- Present strengths and limitations of the development program and study results, including important limitations such as:
- absence of information in some patient populations
- use in combination with other products.
- Discuss each of the following:
- positive and negative outcomes
- adverse events (both serious and non-serious) noting any causal relationships.
- Analyse the benefits and risks of the medicine in its intended use, including interpretation of how efficacy and safety findings support the proposed dose and indication (in form of a critical scientific assessment).
- Provide a separate explanation on how the data supports each indication and claim.
- Address particular efficacy or safety issues encountered, and how they have been evaluated and resolved.
- Explore any unresolved issues and:
- explain why they should not be considered as barriers to approval
- describe plans to resolve them.
Further guidance on clinical overviews is provided under section 2.5 clinical overview of the ICH guideline on clinical efficacy.
History of use of the medicine
Provide information on the history of use of the medicine as a subsection in module 2.5.1 (product development rationale) of the clinical overview.
Provide a summary of human exposure data, dietary, traditional and commercial use in Australia and internationally.
Provide (and categorise) the estimated number of people exposed to the medicine since the start of supply by each of the following:
- dosage and route of administration
- treatment duration
- geographical location.
- Provide information on the history of use of the medicine as a subsection in module 2.5.1 (product development rationale) of the clinical overview.
- When applying evidence of traditional use, the traditionally used medicine described in this evidence and the proposed medicine must have the same:
- traditional preparation – ensuring consistent characteristics
- use (including dose, route of administration and duration of use).
Although long-term traditional use does not fully establish the safety and efficacy of a proposed medicine, we will consider the evidence as part of the safety evaluation.