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Comparable overseas bodies (COBs) for complementary medicines

Criteria and overview of the COB report-based process

4 December 2019

The TGA makes use of assessments from comparable overseas bodies (COBs), where possible, in evaluations for complementary medicines and listed OTC medicines (e.g. sunscreens).

In response to the Medicines and Medical Devices Review (MMDR) we have implemented:

  • transparent criteria for identifying comparable overseas bodies (COBs)
  • a process for using reports from nominated COBs.

We have also published our initial list of COBs.

Our goal is to reduce duplicating evaluations that have already been approved by a COB and to shorten evaluation timeframes while maintaining existing quality, safety and efficacy standards for medicines supplied in Australia.

The TGA can use evaluation reports from comparable overseas bodies (COBs) to evaluate:

  • registered complementary medicines
  • assessed listed medicines
  • substances for use as ingredients in listed medicines.

Comparable Overseas Bodies

4 December 2019

The COB report-based process is open to applications for:

  • registered complementary medicines
  • assessed listed medicines
  • evaluation of a substance for use as an ingredient in listed medicines

These medicines and substances must have received full marketing approval following a de novo application. Importantly, the application or marketing approval must not have been delayed, deferred, rejected, refused, cancelled or withdrawn at any time in any country (unless otherwise justified).

Pre-submission meetings

Due to differences in regulatory frameworks and evaluation process requirements, some applications may not be suited to the COB report-based process. We recommend that applicants request a pre-submission meeting with TGA to discuss their application before lodging.

For more information

4 December 2019

The COB criteria help us identify opportunities for enhanced international collaboration in the regulation of complementary medicines. They enable us to determine:

  • suitable COBs
  • COB evaluation reports using best-practice evaluation processes that best align with the TGA's regulatory framework to an acceptable level

Challenges in identifying COBs

Given the nature of complementary medicines and other low-risk medicinal products, few international bodies evaluate the quality, safety and efficacy of substances or medicines in a single report. Challenges that we face in identifying and using COB reports include, but are not limited to:

  • differences in evaluation processes: complementary and other low-risk medicinal substances or products may be regulated internationally as foods, medicines, cosmetics or dietary supplements
  • differences in inter-agency decisions: assessing these products or substances against different evaluation processes may lead to differences in inter-agency decisions about quality, safety and efficacy
  • difficulties accessing un-redacted or unpublished evaluation reports
  • use of a product or substance in the Australian context may differ from international use
  • language barriers.

Due to these challenges, the TGA makes the final regulatory decision on applications to ensure that safety, quality and/or efficacy are established in line with the Australian regulatory framework.

Note:

  • We will consider accepting reports from COBs that may not meet all the criteria where the applicant can provide adequate justification and/or additional data as required.
  • Where we have not yet determined the suitability of a particular COB, we will endeavour to provide advice in a timely manner as to the likely acceptance of that COB.
  • There are some circumstances where the TGA will not automatically accept a COB report.

The COB process has been divided into 2 stages:

Stage 1 criteria

Stage 1 describes the criteria used to establish sufficient similarity between TGA and the overseas body. This process enabled TGA to identify suitable bodies for the COB report-based process. These COBs were then included in the List of bodies or jurisdictions determined to be COBs for complementary and listed medicines. This is designed to support our use of existing, complete evaluation reports so that the TGA is not required to conduct an independent evaluation.

The COB is an internationally recognised body with an established track record of approving similar food, chemical or medicinal products/substances.

To meet this criterion, the COB:

  • Has a similar evaluation process to the TGA in terms of what must and must not be taken into account when making decisions.
  • Conducts:
    • independent de novo pre-market evaluations of the type of applications that are of interest to us (for example, evaluations of plant or herbal materials, vitamins and minerals)
    • similar pre-market safety, quality and efficacy evaluations of substances and/or medicines
    • similar post-market activities including pharmacovigilance programs.

The COB has a transparent system for decision-making.

Noting the uniqueness of the Australian complementary and listed medicines regulatory framework, this criterion does not limit the contexts or frameworks from which we will accept evaluation reports. Instead, it requires that the TGA be able to develop confidence in the transparency and robustness of the operating principles of the COB.

To meet this criterion, the COB would need to:

  • Have a transparent system for its evaluation processes.
  • Have a transparent system for legal accountability including:
    • confidentiality
    • intellectual property
    • impartiality
    • transparency
    • conflict of interest processes.
  • Have a clear decision-making framework.
  • Have clear risk-assessment methodologies that do not conflict with our operating principles.

The COB uses international guidelines and standards consistent with those adopted by the TGA.

Rather than mandating specific guidelines, this criterion captures the principle that we need to have confidence in the scientific processes used. To best make use of overseas evaluations, any differences in how these international standards are adopted needs to be well understood.

To meet this criterion, the COB would need to:

  • Have established scientific evaluation processes, such as processes in accordance with:
    • pharmacopoeial standards adopted by Australia:
      • European Pharmacopoeia
      • British Pharmacopoeia
      • United States Pharmacopeia - National Formulary
    • the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) or other international guidelines.

The TGA should have, or be able to establish, a relationship with the COB.

To meet this criterion, the COB would need to:

  • Be able to conduct their business and release reports in English.
  • Give Australian applicants the evaluation reports in English for inclusion in the Australian application (this can include reports that have been translated into English from another language by the COB, or a certified translation provided by the applicant). Obtaining a certified translation is not the responsibility of the TGA.
  • Be able to interact with the TGA in English, particularly where a sponsor submits certified English translations of evaluations.
  • Be able to clarify information and address issues of confidentiality or data protection with the TGA if required.

Stage 2 Criteria

Stage 2 criteria focus on the specifics of a particular application that proposes using COB evaluation report(s). Once we have identified a COB using the Stage 1 criteria, we will assess COB evaluation reports against the Stage 2 criteria to determine whether the COB reports can be used to support the application.

The TGA reserves the right to require the applicant to resubmit their application under a different application category if the COB report provided by the applicant does not meet the Stage 2 criteria.

The substance or medicine described in the COB report should be equivalent to that proposed in the application.

Any differences in characteristics such as formulation, manufacture, and indications must be clearly justified by the applicant. To meet this criterion:

  • The evaluation report should relate to the same medicine or substance as approved by or submitted to the COB, and have the same:
    • formulation
    • quality aspects
    • dosage form
    • dose
    • directions for use
    • route of administration.
  • The manufacturing process should be comparable to that evaluated by the COB. Under certain conditions, additional manufacturing sites can be included in the application to the TGA, where that manufacturing site has been validated and shown to be the same or better than the original manufacturer.
  • The proposed indication(s) for the medicine should be based on similar:
    • population demographics
    • disease profiles
    • expectations regarding public health outcomes between Australia and the COB.

There should be no new indications proposed beyond what the report considered.

For generic products, the proposed indication(s) should be the same as the indication(s) approved for the originator. For non-generic products, acceptable differences between the COB-approved and proposed indication(s) are limited to minor changes in the wording or minor differences in expression, as long as the text describes the same:

  • dosing range
  • patient population
  • health outcome expectation
  • intent and meaning.

Inter-agency comparison of efficacy is a complex process due to the different levels of indications/claims allowed and evidence required by each body.

The evidence requirements may be comparable in some situations; however, in other circumstances this will not be the case. In these circumstances, the TGA will make the final regulatory decision ensuring that efficacy is established in line with the Australian regulatory framework.

Evaluation reports should be prepared using guidelines and standards consistent with those used by the TGA.

To meet this criterion:

  • Evaluation reports should be consistent with the methodology used by the TGA, for example they should contain information consistent with the Common Technical Document (CTD) requirements.
  • Evaluation reports should contain all information necessary to support the relevant assessment parameters (safety, quality and/or efficacy).

Differences in methodology do not necessarily prevent the use of evaluation reports. However, applicants should address any differences by providing:

  • additional information to address any data gaps or other concerns
  • a justification explaining how the content of the COB report meets TGA's technical requirements.

The absence of this information may mean that the application cannot be accepted through the COB report-based process.

Evaluation reports should be un-redacted and complete.

To meet this criterion, the complete reports should include correspondence related to the application (for example, questions asked of, and deliberations by advisory bodies). The Australian applicant is responsible for providing the reports to us when lodging the application.

The TGA should be able to use reports from COBs and any supplementary information to publish general information about the safety, quality and/or efficacy of the medicine.

To meet this criterion, reports that are provided to us should not be subject to any restrictions on use or disclosure by the TGA beyond what would normally apply with any application.

For more information, see:

The report should be an independent evaluation made by a COB.

To meet this criterion:

  • The submitted report should be fully written by the COB (a de novo report).
  • The submitted report should present an independent evaluation of the data provided to the COB and not be an acceptance of another body's marketing approval.

Reports drafted as part of a self-affirmed/self-assessed report, such as the Generally Recognized as Safe (GRAS) self-affirmation, are not suitable as an independent de novo evaluation.

Where the COB makes decisions relating to market approval, the following 2 criteria are required:

  1. The medicine should have received full overseas marketing approval following the evaluation of the application by the COB.

To meet this criterion:

  • The medicine approved by the COB should be equivalent to the medicine proposed in the application (refer to Criterion 1).
  • The medicine should not be subject to any further restrictions or conditions that have not been identified in the report.
  • The medicine should not have resulted in a delayed, deferred, rejected, refused, cancelled or withdrawn application or marketing approval at any time, in any country, i.e. the medicine must have a current overseas marketing approval (unless otherwise justified).
  1. The substance should have received approval for use following the evaluation of the application by the COB.

To meet this criterion:

  • The substance approved by the COB should be equivalent to the substance proposed in the application (refer to Criterion 1).
  • The substance should not be subject to any further restrictions or conditions that have not been identified in the report.
  • The substance should not have resulted in a delayed, deferred, rejected, refused, cancelled or withdrawn application at any time, in any country, i.e. the substance must have a current overseas approval (unless otherwise justified).

List of COBs for registered complementary medicines, assessed listed medicines and substances for use in listed medicines

4 December 2019

The TGA will consider evaluation reports from the bodies specified in Table 1 for use in the COB report-based process. This list has been determined by the Secretary for the purposes of regulation 16GJ of the Therapeutic Goods Regulations 1990.

The list of COBs is still in the early stages of development and requires co-operation from multiple bodies. We will continue to build on the list of COBs as we gain a greater understanding of other bodies and the extent of differences between the overseas evaluation processes and the additional information required by the TGA, particularly with respect to substances or products evaluated internationally as foods/dietary supplements, cosmetic products/substances and non-prescription medicines.

If we receive evaluation reports from bodies that consistently meet the Criteria for COBs, the body will be included in the list of TGA-approved COBs. Applicants will then be able to submit evaluation reports from the COB as part of a COB report-based process instead of relying on the TGA to undertake an independent evaluation of their substance or medicine, provided the Stage 2 Criteria for accepting COB evaluation reports are met.

Some products regulated as complementary medicines in Australia are evaluated as prescription medicines overseas. These products are assessed against more stringent safety/quality/efficacy requirements than Australian listed complementary medicinal products. Therefore, the TGA will accept COB reports for complementary medicinal products that have been evaluated as prescription medicines by the COBs listed in Table 1 where the regulatory pathway has required a full data package/complete data dossier for assessment.

Body Country or jurisdiction How evaluation reports can be used
Safety Quality Efficacy Notes
Cosmetic Ingredient Review (CIR) United States tick icon red cross red cross Reports may be used to support safety of substances proposed for use as ingredients in listed medicines (IN1 or IN2) when the substance is intended to be used as an excipient ingredient in sunscreens or other topical products.
European Food Safety Authority (EFSA) European Union tick icon tick icon red cross Reports may be used to support safety and quality of substances proposed for use as ingredients in listed medicines (IN1, IN2 or IN3) when the substance is intended for oral use.
European Medicines Agency (EMA) European Union tick icon red cross red cross EU monographs may be used to support safety of substances proposed for use as ingredients in listed medicines (IN1 or IN2) when the substance is a herbal ingredient.
red cross tick icon red cross European Pharmacopoeia monographs may be used to support quality[1] of substances proposed for use as ingredients in listed medicines (IN1 or IN3) when the substance is a herbal ingredient.
tick icon tick icon tick icon Reports for medicines submitted under Article 8(3) of Directive 2001/83/EC (full or full-mixed application, complete dossier) and assessed via the centralised procedure[2] may be used to support safety, quality and efficacy of registered complementary medicines (RCM2, RCM3 or RCM4) and efficacy of assessed listed medicines (L(A)2).

Food and Drug Administration (FDA)

Center for Drug Evaluation and Research (CDER)

United States tick icon tick icon tick icon Reports that form part of a New Drug Application may be used to support the safety, quality and efficacy of registered complementary medicines (RCM2, RCM3 or RCM4); safety and quality of substances for use as ingredients in listed medicines (IN1, IN2 or IN3); and efficacy of assessed listed medicines (L(A)2).
tick icon tick icon red cross Monographs for OTC ingredients determined to be 'Generally Recognized as Safe and Effective (GRASE)' may be used to support the safety and quality[3] of substances proposed for use as ingredients in listed medicines (IN1, IN2 or IN3).
Food Standards Australia New Zealand (FSANZ) Australia tick icon red cross red cross Reports may be used to support the safety of substances proposed for use as ingredients in listed medicines (IN1, IN2) when the substance is intended for oral use.
Health Canada (HC) Canada tick icon red cross red cross Reports for Natural Health Products may be used to support safety of substances proposed for use as ingredients in listed medicines (IN1, IN2 or IN3).
red cross red cross tick icon Reports for Natural Health Products may be used to support efficacy[4] of assessed listed medicines [L(A)2].
tick icon red cross tick icon Reports for Natural Health Products may be used to support safety and efficacy[5] of registered complementary medicines (RCM2, RCM3 or RCM4).
tick icon tick icon red cross Monographs[6] from the Compendium of monographs may be used to support the safety and quality of substances proposed for use as ingredients in listed medicines (IN1, IN2 or IN3).
Health Sciences Authority (HSA) Singapore tick icon red cross red cross Reports for existing ingredients used in Chinese Proprietary medicines with a proposed new scope for use (e.g. dose, therapeutic use, route of administration) or with emerging safety concerns may be used to support safety of substances proposed for use as ingredients in listed medicines (IN1 or IN2).
Joint FAO/WHO Expert Committee on Food Additives (JECFA) Global tick icon red cross red cross The WHO Technical Report Series and WHO Food Additives series (FAS) may be used to support safety of substances proposed for use as ingredients in listed medicines (IN1or IN2) when the substance is intended for oral use.
red cross tick icon red cross The FAO JECFA Monographs[7] may be used to support quality of substances proposed for use as ingredients in listed medicines (IN1 or IN3) when the substance is intended for oral use.
National Industrial Chemicals Notification and Assessment Scheme (NICNAS) Australia tick icon red cross red cross Reports may be used to support safety of substances proposed for use as ingredients in listed medicines (IN1, IN2) when the substance is intended to be used as an excipient ingredient in sunscreens or other topical products.
Pharmaceutical and Medical Devices Agency (PMDA) Japan tick icon tick icon red cross Reports for Category 1 quasi drugs and Category 1 OTC products may be used to support the safety and quality of registered complementary medicines (RCM3).
Scientific Committee on Consumer Safety (SCCS) European Union tick icon red cross red cross Reports may be used to support safety of substances proposed for use as ingredients in listed medicines (IN1 or IN2) when the substance will be assessed as an excipient ingredient in sunscreens or other topical products.

Where there is a default standard for a substance, the quality of the substance is assessed against that standard. The default standards accepted by the TGA to support the quality of substances for use as ingredients in listed medicines (IN1 or IN2) are the:

  • British Pharmacopoeia (BP)
  • European Pharmacopoeia
  • United States Pharmacopoeia - National Formulary (USP-NFP).

Footnotes

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Version history

Version Description of change Author Effective date

V1.0

Original publication Complementary and Over the Counter Medicines Branch November 2019