Proposed update to evidence guidelines for listed medicines

Closed 1 Apr 2022

Opened 3 Mar 2022

Results updated 21 Jun 2022


In March-April 2022, the TGA undertook a public consultation on draft revised Listed Medicines Evidence Guidelines (revised Guidelines), which are intended to replace the current Evidence guidelines – Guidelines on the evidence required to support indications for listed complementary medicines v 3.0, January 2019 (current Guidelines).

The revised Guidelines are intended to:

  • enhance the readability and utility of the guidelines
  • clarify the way the TGA interprets and analyses the different types of evidence, particularly in undertaking a listed medicine compliance review
  • clarify specific technical concepts that have been unclear in the current Guidelines.

The revised Guidelines do not change the regulatory requirements for listed medicines, involve any policy changes, nor change the existing requirements in law for sponsors to substantiate the evidence base for indications.

We reiterate that the revised Guidelines are not mandatory requirements but rather show sponsors what a TGA delegate considers in a compliance review and what will more likely result in a successful compliance review outcome. Providing transparent and clear guidance on the elements considered by a TGA delegate in a compliance review is good regulatory practice and aims to mitigate the risk of non-compliance.

Submissions to the consultation

29 submissions were received to the consultation:

  • Sponsors: 16
  • Industry groups: 2
  • Regulatory agents: 3
  • Health care professional groups: 4
  • Research/Academic institutions: 3
  • Individuals: 1

While several consumer organisations were contacted for input to the consultation, no submissions were received from these groups.

Submissions that consented to being published are available through the ‘view submitted responses’ link. 

The TGA thank all stakeholders for providing their feedback.

The submissions have provided constructive feedback which has been taken into consideration in the final Guidelines. For example, further clarification has been provided on: the purpose of the guidelines; the legislative basis for requiring efficacy for listed medicines; evidence sources for traditional medicines; efficacy expectations; and further explanation on what we consider is a critical appraisal.

Summary of submissions and TGA response

General comments on structure and content

In general, health care professional groups and research/academic institutions considered that the structure of the revised Guidelines was easy to follow and the content was relevant, provided helpful information and improved clarity on assessing relevance and quality of evidence sources. Conversely, a number of industry stakeholders stated that the information was overly complex and, although the revised Guidelines expressly did not involve any change in the evidence requirements or regulatory requirements, some industry stakeholders asserted that the revised Guidelines were inconsistent with the legislative requirements for low risk listed medicines. Several industry stakeholders requested that much of the content be moved to appendices.

All stakeholders appreciated the addition of tools such as tables and flowcharts. ‘Table 4: Minimum evidence requirements for scientific and traditional indications’ was well received and was considered a clear and useful summary. Several stakeholders requested more examples and clarifications be provided throughout the document.

An individual stated that there was no mention of the need to consider evidence relating to use by children, yet numerous listed medicines are targeted at young children. In addition, they stated that there is a need to consider interactions between multiple ingredients in a product, which cannot be adequately covered in safety reviews for permitted ingredients in listed medicines. The individual also stated that the revised Guidelines do not consider public health and safety and the inappropriate use of medicines.

A complementary medicine practitioner group commented that while the revised Guidelines may provide greater clarity on the TGA's interpretation of the evidence requirements, this implies that the TGA’s interpretation of their regulatory framework is correct and disregards industry’s interpretation and concerns.

TGA response

The purpose of the revised Guidelines is to clearly show what the TGA considers when determining whether or not the efficacy of a listed medicine appears to be acceptable. We believe that moving content to appendices would likely result in this information being missed by many readers.

The lack of clarity in the current Guidelines means that it has been difficult for some industry sponsors to adequately comply with legislative requirements. The approaches described (for example, how to assess and document evidence) are not mandatory requirements but rather show sponsors what a TGA delegate considers in a compliance review and what information would be required to support a potentially successful compliance review outcome.

The revised Guidelines include advice to sponsors on considering the relevance of population groups in the evidence source to the medicine’s target population. We have included more specific attention to children as a target population in the final Guidelines.

The scope of the revised Guidelines only includes the efficacy of listed medicines. The safety aspects of interactions between ingredients in a product, public health and safety and inappropriate use of medicines are thus outside the scope of this guidance document.

Demonstrating efficacy for listed medicines

A number of industry stakeholders objected to the use of the term ‘demonstrate efficacy’ for listed medicines, stating that sponsors are not required to show efficacy for their listed medicine, they are only required to ‘hold evidence’. Further, it was asserted that the TGA can only request information based on sponsor certifications and further, is only required to ensure that the efficacy is ‘not unacceptable’ which industry consider is a ‘lower bar’ than ‘demonstrating efficacy’.

A number of industry stakeholders and professional groups were concerned that the revised Guidelines implied that traditional medicines were now required to ‘demonstrate efficacy’ rather than establish a history of use as per the current Guidelines.

Many stakeholders rejected the definition of ‘efficacy’ in the revised Guidelines, stating it should be reviewed to relate to self-selected listed medicines, rather than referring to ‘the hands of a health professional’. A research group observed that the terms efficacy and effectiveness were used interchangeably.

TGA response

The requirement of sponsors to demonstrate efficacy for listed medicines is entirely consistent with the legislative framework. For example, Reg 16AA(2)(a) of the Therapeutic Goods Regulations 1990 permits the Secretary or their delegate to require information or documents about ‘the efficacy of the goods for the purposes for which the goods are to be used’. Paragraph 30(2)(a) of the Therapeutic Goods Act 1989 is applicable to both listed and registered medicines and enables the Secretary to cancel the registration or listing of the goods if it appears the efficacy of the goods is ‘unacceptable’.

It is not correct that the inclusion of the term ‘efficacy’ now implies that all indications for listed medicines (including traditional indications and nonspecific indications for nutritional supplementation) require clinical evidence i.e. clinical trials. There have been no changes to the regulatory requirements.

Our interpretation of ‘efficacious in expert hands’ is that it is efficacious when examined in clinical studies or, for traditional paradigms, in the expert hands of health practitioners (given the documentation of tradition of use for a therapeutic purpose is usually through the observations of health practitioners).

The consistent use of the term ‘efficacy’ when describing whether a medicine works as described by its indications (traditional or scientific) was intended to simplify these concepts in the revised Guidelines. We have improved the explanation of these concepts in the final Guidelines.

Perception that changes were made beyond clarification

A number of industry stakeholders complained that the revised Guidelines introduced new requirements and policy changes that were beyond the stated scope of ‘clarification’, including: systematic searches; documenting search methodology; non-systematic search strategy; justification for using a non-systematic search strategy; and in particular, including a critical appraisal as part of an evidence package.

Many industry stakeholders were concerned that these changes would cause significant regulatory burden as sponsors would be required to recreate existing evidence packages. While acknowledging that the revised Guidelines clearly state they are ‘guidelines’, these stakeholders expressed concern that it could be implied that these were mandatory requirements which will result in unsuccessful compliance review outcomes.

Industry stakeholders were generally positive about the following clarifications: all traditional indications being considered to be non-specific indications; using evidence categories A, B and C rather than using the terms ‘primary’ and ‘secondary’; general biomarker permitted indications being considered non-specific indications; a change to the wording for traditional ingredients to being considered as ‘sufficiently identical’ to ‘comparable’; and providing guidance on how evidence from diseased populations could be extrapolated to healthy populations.

TGA response

The revised Guidelines provide a clearer and more detailed explanation of existing policies and how they relate to a sponsor’s regulatory obligations. There are no changes to the regulatory requirements for listed medicines, including the long-standing requirement under the Therapeutic Goods Act 1989 for sponsors to hold evidence of efficacy of the listed medicine (section 26A) and that a listed medicine may be cancelled by the TGA if its efficacy appears to be unacceptable (section 30).

Explanations of how to: conduct systematic searches; document search methodology; conduct a non-systematic search strategy; justify using a non-systematic search strategy; and provide a critical appraisal as part of an evidence package were provided in the revised Guidelines. None of these are mandatory requirements, but rather they show sponsors what a TGA delegate considers in a compliance review and if followed, what will likely result in a successful compliance review outcome.

Providing clear guidance on the elements considered by the TGA in a compliance review is good regulatory practice as it provides transparency and aims to mitigate the risk of non-compliance.

The revised Guidelines have not changed existing requirements reflected in the current Guidelines or how the TGA conducts compliance reviews.

Literature search, assessment of evidence

While some industry stakeholders considered the guidance on literature searches helpful, others considered the guidance excessive. Some industry stakeholders requested further clarity on: search requirements for non-specific and traditional indications; a list of guidelines for clinical trials; and how many databases are required to be searched.

A research group stated that requiring a systematic review for scientific evidence would be overwhelming for an individual sponsor. Further, there was inadequate guidance on traditional evidence sources, and it was suggested that more information for identifying traditional literature should be included e.g. ethnobotany, ethnomedicine, ethnopharmacology and medical anthropology. In addition, the following resources should be referenced: PRISMA guidelines; SPIDER model (Sample, Phenomenon of Interest, Design, Evaluation, Research type); Cochrane Handbook for Systematic Reviews; CONSORT extensions; non-English databases such as CNKI, LILACs and Relayte; Google scholar; NHMRC GRADE guidance; the GRADE-CERQual (‘Confidence in the Evidence from Reviews of Qualitative research’); and Joanna Briggs Institute checklists.

A research group observed that different terms were used to describe the quality of the evidence throughout the revised Guidelines, with some sections refer to ‘certainty’, while other sections refer to ‘high quality’ or ‘weak’ evidence. The group advised ‘certainty’ was the more appropriate term to use.

TGA response

The revised Guidelines aim to provide advice on how to collate evidence that is objective, unbiased and provides a balanced view of the evidence landscape. These are not mandatory requirements, given it is the sponsor’s responsibility to determine how to demonstrate that the efficacy of their medicine is acceptable.

The current Guidelines state “the requirements for literature-based submissions for listed medicines and registered complementary medicines is the same as for prescription medicines”. The revised Guidelines recognise that it may be difficult to conduct systematic searches for traditional and non-specific indications and therefore provides guidance on how to conduct non-systematic literature searches.

The revised Guidelines outline that systematic searches are not always required for traditional indications and non-specific indications. However, it is the sponsor’s responsibility to have thought about what type of search is best for their unique scenario. The guidance invites the sponsor to consider what research question they are trying to answer and determine whether a systematic or non-systematic search is appropriate for their medicine’s particular indications.

The removal of guidance specifying the number of databases to be searched was to provide sponsors flexibility to determine how many is appropriate for their circumstance.

In consideration of industry feedback, the TGA has provided greater clarification on the number of databases to be searched, included additional guidance for traditional medicines and refined wording on expectations.

Traditional medicines /evidence

A number of stakeholders objected to the reference to the 2011 document 'Guidance on Equivalence of Herbal extracts in Complementary Medicine', stating that this document requires review.

Industry stakeholders welcomed clarification that all traditional indications are classified as ‘non-specific’. Further, regarding active ingredients in traditional medicines, the use of the term ‘comparable’ rather than ‘identical’ was positively received.

A number of industry stakeholders disagreed with the statement that traditional use claims cannot support a mechanism of action or underlying physiological process e.g., anti-inflammatory. Further, there was concern with the level of emphasis placed on herbal extract comparability to method of preparation. It was asserted that preparations in the context of traditional evidence should be described based on effectiveness, not efficacy.

A healthcare professional stakeholder expressed concern that the revised Guidelines continue to permit a product’s indications to be based on a mix of evidence of traditional use and scientific evidence.  The stakeholder considers that permitting evidence of traditional use is fraught with risk and evidence of traditional use should be discarded in favour of, solely, scientific evidence.

TGA response

The current Guidelines include references to the document 'Guidance on Equivalence of Herbal extracts in Complementary Medicine', this is not a new addition. However, we acknowledge that the referenced document was published in 2011 and we will consider if the document requires review in the future.

The regulatory requirements for traditional complementary medicines have not changed. Modification of a preparation method can significantly affect the safety profile and efficacy of the preparation.  Sponsors can provide justifications in their evidence package to demonstrate how the method of preparation they have chosen is comparable to that used traditionally. This highlights the importance of providing a critical analysis in the evidence package and the flexibility this provides sponsors.

In relation to mixing evidence for traditional use and scientific indications, this is permitted under the listed medicine framework. The sponsor certifies that the medicine is safe for the purpose for which it is to be used and that they hold evidence supporting the indications.

Gaps/discrepancies Critical appraisal/ Justification

A healthcare professional considered that listed medicines require critical analysis in the interest of public safety and reliability. However, most industry stakeholders considered a critical appraisal of the evidence (proposed to support the efficacy of the product) was a new requirement.

An industry stakeholder added that the connection between indications and evidence are obvious to those with expertise in complementary medicines.

A research stakeholder stated that as weaknesses can be identified in even the best studies, reference to ‘reasonable supportive evidence’ is more appropriate.

TGA response

The TGA delegate must make decisions based on the legislation and regulations following assessment of relevant evidence and data, not that of expert opinion. It is reasonable to expect sponsors to provide evidence that clearly explains why their listed medicine will work as described by its indications.

The current Guidelines commonly state that justifications may be required yet provide no guidance on what this means. This has been a frequent criticism from industry stakeholders and the reason why we have provided clearer guidance in the revised Guidelines.

There is no requirement for an upfront critical analysis of every ingredient and indication. The revised Guidelines outline what is recommended to be included in an evidence package to increase the likelihood of a successful efficacy review, if a particular product is subject to such a review.

Provision of a critical analysis avoids extensive ‘back and forth’ communication with sponsors which can be a significant burden for them.

In responding to a compliance review, sponsors are encouraged to provide the TGA an explanation of how the different elements of the evidence sources (they have chosen to include in their evidence package) come together to support the efficacy of their medicine.

It is reasonable to assume that a sponsor has analysed the information available to support the efficacy of their medicine before the company makes investments in product development and marketing and, given the legal requirements to hold evidence, list the product in the ARTG. It is also reasonable to assume that consumers expect the efficacy evidence to have been critically analysed prior to the product being available on the market.

Evidence sources/ hierarchy

Some industry stakeholders considered the proposed hierarchy provides clarity, while others stated the categories should be focused on substantiating low risk/low level health claims, rather than a hierarchy of evidence quality.

A number of industry stakeholder responses considered international regulator publications from agencies such as Euopean Medicines Agency and Health Canada should be classified as higher than Category C evidence.

Some health care professionals commended the TGA for updating the terminology regarding the hierarchy of evidence sources based on risk of bias. However, one academic group considered that the hierarchy of evidence categories does not take into consideration NHMRC 'body of evidence considerations' and it appears that case control studies are discouraged and fails to differentiate between systematic reviews of RCTs versus lower levels of evidence.

One stakeholder stated that allowing evidence for multiple ingredients is a sub-standard practice. A well-conducted randomised controlled study of the actual proposed product should be required. The descending order of evidential value should also be made clear.

TGA response

The revised Guidelines recognise that, although a hierarchy of evidence types can be described based on the risk of bias, whether the evidence source is of high quality depends on multiple factors. The categories of evidence have been provided as a guide to assist sponsors with sourcing evidence for their medicine.

As international monographs vary in their quality, currency and international recognition, they have been generally categorised as Category C.

Clinical/ non-clinical studies for scientific indications

Some industry stakeholders submitted that the revised Guidelines imply that the TGA only accept indications supported by direct or extrapolated clinical trial evidence rather than based on scientific consensus. They suggested that some indications/claims are scientifically valid but are not feasible to be clinically trialled. It was proposed that non-specific indications which describe the action / role / structure-function of the substance should be able to be supported by reliable scientific information or scientific consensus, irrespective if that is from clinical/ non-clinical evidence. 

A healthcare practitioner group stated that the preference for original clinical trials for scientific claims over international monographs and regulatory authority reviews is inappropriate, given listed medicines are directed to a healthy population. It is difficult to conduct randomised double blind clinical trials on healthy individuals for a condition they do not have. It was proposed that non-clinical studies alone should be considered sufficient to support a scientific indication if there is a biologically plausible, or well demonstrated link, to the biomarker in animal or test tube studies.

Therefore, while it was consistent with the current Guidelines, several industry stakeholders disagreed that non-clinical studies on their own are not sufficient evidence to demonstrate efficacy.

A healthcare practitioner group stated that the TGA, like other government regulatory authorities, should provide permitted claims based on monographs.

TGA response

The revised Guidelines outline when clinical trials are expected to support the efficacy of a medicine and when international monographs or publicised international regulatory authority articles would be sufficient. They do not state that only randomised double blind clinical trials are required to demonstrate efficacy, however, we have strengthened the working in the final Guidelines to make this clear.

As acknowledged in the submissions, to rely on non-clinical or in-vitro studies on its own to be sufficient to demonstrate efficacy would be a policy change, which is beyond the scope of this revision.

Specific/non-specific indications

The new decision tool to assist with classification of specific and nonspecific indications received mixed reviews. While some considered the tool helpful, others considered it too subjective and that it will result in inconsistent outputs. A number of industry stakeholders consider the tool classifies indications as ‘specific’ that were previously thought to be ‘nonspecific’, for example: ‘Antioxidant/Reduce free radicals’; ‘Maintain/support’ indications; symptom indications not linked to a condition; ‘Relieve urinary frequency’; ‘Reduce occurrence of abdominal bloating’; and indications that refer to ‘the symptoms of’ a named condition. In addition, a number of stakeholders disagree that the inclusion of a population qualifier could make an indication specific.

Some industry stakeholders commented that some indications are not captured by the tool and are difficult to categorise. Guidance should be provided to account for these and in addition, sponsors should be able to provide a justification if they disagree with a classification.

Some stakeholders consider that the definitions of specific and non-specific indications have changed, and ‘decrease’ being added to health benefit changes this definition. One stakeholder commented that the guidelines state that, depending on the mechanism of action, the words ‘aids/assist' mean either 'supports/helps' or ‘increase/decrease’ which is confusing and leaves a lot of room for misinterpretation.

TGA response

No indications have been altered from non-specific to specific. It is stated in the revised Guidelines that “while the tool is intended to increase the consistency of classification, we acknowledge that there may be some indications that are difficult to categorise for individual medicines … We reiterate that when the TGA conducts a compliance review of a listed medicine, the medicine is considered on its individual merits. If you consider there is ambiguity in classifying your medicine’s indication, you may wish to include a justification or rationale in your evidence package for classifying an indication as non-specific or specific to show the TGA how you came to your conclusion”.

In the current guidelines, the definition of ‘health enhancement’ is “specific beneficial effects of nutrients and other substances on the physiological and psychological state of the body above and beyond normal growth, development and functions of the bod”’. Therefore, where an indication implies or describes a therapeutic use beyond general symptom relief and that, increases or decreases a physiological process then in accordance with the current guidelines, the indication would be specific – as the therapeutic effect would be above and beyond normal functions of the body. While further explanation and examples have been provided in the revised Guidelines, there is no change in policy from the current Guidelines.

Nutritional supplementation

Several industry stakeholders considered the revised guidance for supplementation indications were a change from the current Guidelines, including that a higher level of evidence appears to be required for supplementation indications referring to a specific population group. These stakeholders also consider that listed medicines should be able to make claims in line with allowable claims for foods.

Industry stakeholders noted that the allowance of 10% RDI for claiming content of vitamin/mineral had been removed and requested it be reinstated to allow nutrient content claims. It also needs to be made implicit that indications/claims can be made for less than 25% RDI if a sponsor holds evidence.

A number of industry stakeholders expressed concern that there were increased requirements for demonstrating a nutrient is absorbable. One stakeholder commented that the current Guidelines stated that the nutrient should be absorbable on principle, while in the revised Guidelines there is an expectation for ‘proof’ (bioavailability studies) which is a change. The disintegration requirements of tablets combined with the approved nutrient has been considered sufficient in the past.

A number of stakeholders consider that the TGA’s clarification is not consistent with how industry have interpreted the current Guidelines. The indication ‘Helps prevent dietary (state vitamin/mineral/nutrient) deficiency’ has been widely used by industry as a supplementation indication requiring only 25% RDI and should be included in the section ‘special evidence requirements’. Sponsors consider that all supplementation claims are non-specific indications and appropriately supported by ≥25% rule. In particular, ‘health maintenance supplementation’ has always been supported by 25% RDI. Further, there are indications that relate to the functional nutrient roles and providing 25% RDI still contributes to these health outcomes.

Industry stakeholders considered that clinical evidence should not be required for supplementation indications - monographs, referenced based scientific or biochemistry textbooks are sufficient. Non-specific supplementation claims are supported if the nutrient has an established role and any departure from this is a new requirement. In addition, evidence/dosage requirements in the revised Guidelines are not consistent with international regulators. Further, requiring dose for non-specific supplementation indications is not practical.

An academic group noted that RDI, AI and NRV are defined but the source of these needs to be referenced. 

One academic group stated that the proposed supplement claims are potentially misleading e.g., ‘Maintains calcium within normal range’ is allowed by simply having 25% RDI calcium, without any consideration of co-factors like vitamin D.

A healthcare professional group stated that it should be mandatory to include "Helps" in all supplement claims.

TGA response

Supplementation claims have been the main area where differences in interpretation have led to inconsistent compliance by industry. The revised Guidelines now include definitions for what is meant by a supplementation claim as opposed to an indication.

Neither the current nor revised Guidelines require clinical trials for supplementation claims. Other evidence sources such as reference-based scientific and biochemistry textbooks are considered sufficient for demonstrating efficacy.

25% RDI can only be used, on its own, to support supplementation claims. It has never been the case that a supplement containing 25% of the RDI is, on its own, is sufficient to demonstrate the efficacy for all non-specific indications used in a supplement, as there is no scientific basis for assuming that this particular dose would be effective for all therapeutic benefits described by all non-specific indications. For example, sponsors cannot assume that just by providing 25% RDI of calcium that the product will ‘maintain hair health’.

Consideration of the therapeutically relevant and active dose is required for each active ingredient. If a sponsor believes that 25% RDI (or less) is appropriate for their circumstance (irrespective of whether the indication is non-specific or specific), based on their critical evidence analysis, the rationale can be explained in the evidence package – this is captured in section 5.1.3 of the revised Guidelines.

In relation to the reference to ‘10% RDI’, this was removed in the revised Guidelines as it was never sufficient on its own, to support a supplementation claim or an indication. However, given that it is considered enough to support the claimed presence of a vitamin or mineral it has been included in the final Guidelines.

The statement ‘the nutrient is in a form able to be absorbed by the body’ is identical to the statement included in the current Guidelines and there are no statements in the revised Guidelines to the effect that bioavailability studies are required.

Biomarker indications/ healthy population

A research stakeholder stated that the current requirement for listed medicines to only target ‘healthy individuals with biomarker levels that lie within the normal healthy range’ is not possible to prove in a clinical trial. They proposed that this should be reworded to ‘listed medicines should only target otherwise healthy individuals who may have biomarker levels that lie moderately outside the normal range'. The stakeholder notes that this principle is already applied within the current Guidelines to ‘overweight, but otherwise healthy individuals’.

TGA response

We have provided some guidance in the revised Guidelines on how sponsors may be able to justify extrapolating evidence conducted in non-healthy individuals to support the indications made for their listed medicine.

Weight loss

Further clarification was requested around the “use of terminology that implies weight loss" and whether these are taken to always imply weight loss or if the interpretation is dependent on contextual factors. Some industry stakeholders considered that the required parameters are very strict and is unclear what weight management claims are specific vs non-specific.

Academics and consumer stakeholders criticised that the guidance on temporary weight loss indications has no evidence basis and no references cited. In addition, the required label statement for this indication does not sufficiently guard against inappropriate use of the medicine.

TGA response

Clarification has been included in the final Guidelines regarding whether the terms in Table 6 of the revised Guidelines will always be taken to imply weight loss or will be viewed in context of the product’s presentation.

We also note the comments provided on temporary weight loss indications.

Case studies

While most stakeholders were appreciative of examples being included in the revised Guidelines, many  provided criticism of individual case studies, for example: industry considered the compliance conclusions in Case study 2 are incorrect as the indication ‘anti-inflammatory’ is supported by the other ingredients; an academic stakeholder considered the Beans Policosanol example flawed because lowering cholesterol may potentially only be demonstrated in individuals with slightly elevated cholesterol; and one submitter stated that all case studies were flawed and should be withdrawn.

An industry stakeholder stated that the case studies do not provide an accurate reflection of how the TGA has been evaluating products during post market reviews. More detailed case studies that better reflect the issues are needed.

TGA response

Stakeholder feedback reiterates the difficulty the TGA experienced in providing hypothetical case studies with named ingredients. That is why the conclusions in the case studies are all related to whether the evidence source was considered relevant to the hypothetical medicine rather than whether efficacy has been demonstrated. We have emphasised in the final Guidelines that the case studies are hypothetical examples only and that they are not implying that there is, or is not, evidence for the ingredients included in the examples.

We also note the large number of suggestions for further examples and will consider the possibility of providing further examples in other formats on the TGA website.

Example B12 evidence package

The B12 evidence package was heavily criticised across the range of stakeholders.

Industry stakeholders considered the justification and evidence excessive and inconsistent with the guidance provided on vitamin supplementation in the revised Guidelines. A research group considered there were many discrepancies in the evidence that were not resolved through justification but left for the critical appraisal to address. An individual stakeholder commented that the information does not establish that generally healthy individuals need supplementation with Vitamin B12 or that such individuals are at any risk of a vitamin B12 dietary deficiency that requires prevention.

TGA response

The Vitamin B12 example evidence package was provided only as an example. There are no statements in the updated Guidelines that ‘require’ sponsors to provide evidence in a specific format. Sponsors can choose to continue using the evidence checklists referred to in the current guidelines.

To avoid confusion, we have deleted the Vitamin B12 example from the updated Guidelines.

Published responses

View submitted responses where consent has been given to publish the response.


The Therapeutic Goods Administration (TGA) is seeking feedback on the updated ‘Listed medicines evidence guidelines – How to demonstrate efficacy for listed medicines’ (the Guidelines), which is intended to replace the existing ‘Evidence guidelines – Guidelines on the evidence required to support indications for listed complementary medicines v 3.0, January 2019’.

Listed medicines do not undergo pre-market assessment but are subject to post-market compliance reviews that determine whether these medicines comply with the relevant regulatory requirements for listing. This includes holding the appropriate evidence to substantiate the indication(s) being made for the medicine and being able to demonstrate to the TGA that the efficacy of the medicine is acceptable. The Guidelines set out the factors that the TGA considers when assessing the efficacy of a listed medicine. It therefore provides a roadmap to help sponsors put together an appropriate evidence package. In addition, it increases transparency and consumer confidence about the efficacy of self-selected medicines on the market.

The purpose of this update is to enhance the readability and utility of the Guidelines; clarify the way the TGA interprets and analyses the different types of evidence; and clarify specific technical concepts that have been problematic or unclear in the existing Guidelines. The update of the Guidelines is not intended to change the regulatory requirements for listed medicines and will not change the existing requirements to substantiate indications. Nevertheless, it is inevitable that some clarifications may appear to be a change to some readers, given that the previous lack of clarity would have resulted in different interpretations.

The purpose of this consultation is to provide an opportunity for relevant stakeholders and interested parties to provide feedback on the content, presentation, and usability of the updated Guidelines.

Why your views matter

The TGA is requesting feedback to help refine the proposed update to the Guidelines.

To assist sponsors with this consultation, the TGA will be providing two webinars during the consultation period to outline the proposed changes to the Guidelines and give an opportunity for interested parties to give early feedback on the update. Information on the webinars will be published on the TGA website.


  • Health professionals
  • General public
  • Complementary medicines


  • Non-prescription medicines