Regulation of Human Medicines

Find out more about the regulations for human medical products in key jurisdictions, international harmonisation, non-animal methods for regulatory use and recommendations for Australian regulators. This page is designed for those working in the medical industry as the primary audience. 

The purpose of this page is to give an overview of the regulatory landscape for human medicines in Australia and other countries with which Australia closely aligns its regulatory approach. It is not intended as legal advice and is intended solely to provide guidance materials to aid the human medicine industry to replace or reduce the use of animals in the regulatory setting. For specific regulatory questions, please contact the regulator in your country of operation.  Please note that this is a rapidly evolving field and this page compiles information relevant at the point of publication. 

Background key points: 

  • The Therapeutic Goods Administration (TGA) is the regulator in Australia.  
  • The TGA is part of the Health Products Regulation Group (HPRG), which comprises the TGA and the Office of Drug Control. 
  • Australia aligns primarily its regulatory approach with the European Union (EU), the International Committee on Harmonization (ICH), and the United States Food and Drug Administration (US FDA) through the adoption of its international guidelines.  
  • The TGA has mutual recognition agreements with Europe, the United Kingdom, Canada, New Zealand, and Singapore.
  • Australia has a cooperative agreement with the US FDA 
  • The TGA is an observer of the ICH. 
  • The TGA is legislated primarily through the Therapeutic Goods Act (1989), Therapeutic Goods Regulations (1990), and through Therapeutic Goods Orders, via the Therapeutic Goods Act 1989 (Chapter 3, Part 3-1, 10 Determination of Standards, (1)).
  • International scientific guidelines are adopted by the TGA

Legislation in Australia surrounding the use of animals in regulatory settings:

Whilst the TGA Act (1989) does not mandate animal testing, animal test data may be a condition of approval as implied by guidelines falling under this Act. Whilst most guidelines are subordinate to the Act, the M4 (safety) guidance sets a legislative requirement for mandatory requirements for an effective application.

This means applicants must “include such information as will allow the determination (preliminary assessment) of the application” and;

“Applications referred to in regulation 16C of the Regulations (including, Category 1 and Comparable Overseas Regulator (COR) report-based applications for new registrations, other than applications for an additional trade name) must comply with the following regulatory documents”

The M4 (safety) guideline states that “If alternatives to whole-animal experiments are employed, their scientific validity should be discussed.” This implies that whole animals should be used, and scientifically valid alternatives will be considered.

Guidelines that discuss scientific validity of alternative approaches that have been accepted by the TGA include:

PBPK guidelines

Guidelines

Guidelines (other than the M4) are not legislated but they are strongly encouraged to be followed

Guidelines may explicitly state that alternatives can be considered, for example:

ICH guideline S6 (R1) – preclinical safety evaluation of
biotechnology-derived pharmaceutica

In the above guideline, section 4.1 (Safety Pharmacology), it states that investigations may also include the use of isolated organs or other test systems not involving intact animals.”

Australia and the Australian Therapeutic Goods Administration have the following facilities and strategies which can decrease the use of animals and support the use of alternatives to animal use:

  1. The ability to adopt international guidelines.
    – International guidelines which the TGA have adopted can be found generally here though the search function: 
    – Guidelines which the TGA could adopt to reduce or replace the use of animals in alignment with the EMA review are here (please note some may already be adopted).  Additionally, some are recommended through the European Federation of Pharmaceutical Industries and Associations in their webinar.
  2. The publication of AusPars through the transparency agreement in the Therapeutic Goods Act (1989). An AusPar is an overview of the drug sponsors application which can provide insight into which non-animal models were used, or which animal tests were not justified.
  3. AusPar falls under the TGA Act (1989), Volume 2, Chapter 7, section 61, 5A section 61 “release of information”. The Secretary may release to the public therapeutic goods information relating to any decision or action taken under this Act or the regulations.”
  4. A regulatory science strategy published by the Health Products Regulation Group (HPRG): 
    a. The strategy focused on four key areas:
    i. Maintain and build skills in regulatory science
    ii. Improve domestic and international collaboration with other government agencies, scientific organisations and regulators
    iii. Increase responsiveness to emerging technologies
    iv. Improve communication and engagement with stakeholders about regulatory science.
  5. A non-animal models strategy published by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) making the following recommendations: 1) Establish a national consortium that coordinates and promotes Australia’s non-animal model capabilities, 2) Develop national data collection standards on the use of animals in scientific research, teaching, and testing, 3) Align TGA processes and industry guidance with new FDA procedures for accepting non-animal model data, 4) Develop a national biobanking and tissue collection network, 5) Integrate outputs from NCRIS platforms into a coordinated pipeline for non-animal models, 6) Facilitate IP (intellectual property) management and material access for research and industry collaborations, 7) Enhance commercial skillsets across the non-animal model sector, 8) Update biomedical R&D infrastructure to support non-animal model capabilities, 9) Conduct retrospective studies that compare animal and non-animal model predictivity, 10) Conduct systematic reviews of locally and internationally developed non-animal models

The Australian Government Department of Health and Aged Care also published a Scoping Report Towards alternatives to animal testing of industrial chemicals in Australia which has some crossover with medical products. 

 

Background Key Points 

The European Union and the European Medicines Agency have taken the following actions which can reduce the use of animals and support the use of alternatives to animal use: 

  1. Published an EU regulatory strategy to 2025.
  2. Conducted a review of all international guidelines so that EMA documents should not make reference to animal testing that is no longer considered appropriate.   
  3. Enacted a supportive legislation motion
  4. Enacted Directive 2010/63. Particularly: “(10) While it is desirable to replace the use of live animals in procedures by other methods not entailing the use of live animals, the use of live animals continues to be necessary to protect human and animal health and the environment. However, this Directive represents an important step towards achieving the final goal of full replacement of procedures on live animals for scientific and educational purposes as soon as it is scientifically possible to do so. To that end, it seeks to facilitate and promote the advancement of alternative approaches. It also seeks to ensure a high level of protection for animals that still need to be used in procedures. This Directive should be reviewed regularly in light of evolving science and animal-protection measures”  
  5. Established an Innovation Task Force in 2014  
  6. Established a Tracking System for Alternative methods towards Regulatory acceptance 
  7. Provision of guidelines for regulatory acceptance of 3Rs testing approaches: and concept paper in development 

Background Key Points 

The United States and the United States Food and Drug Administration have taken the following actions which can decrease the use of animals and support the use of alternatives to animal use:

Specific testing guidelines or agreements that are required in the regulatory setting:

  • The OECD Guidelines are the internationally agreed testing methods that are primarily used in regulatory safety testing and subsequent chemical notification and registration 
  • Under Mutual Acceptance of Data principle, OECD countries and full adherents have agreed that a safety test carried out in accordance with the OECD Test Guidelines and Principles of Good Laboratory Practice in one OECD country must be accepted by other OECD countries for assessment purposes.
  • OECD supports Integrated approaches to testing and assessment (IATA).
  • IATA combine multiple sources of information to conclude on the toxicity of chemicals, and this information is generated by new technologies and methods, such as in silico, in chemico and in vitro approaches, that reduce the need for animal testing, enabling toxicity testing that is faster, less expensive, and more relevant to human responses than traditional toxicity testing methods
  • IATAs are increasingly based on methods that measure or predict key events from Adverse outcome pathways (AOPs) relevant to the biological effect of interest
  • AOPs are “an analytical construct that describes a sequential chain of causally linked events at different levels of biological organisation that lead to an adverse health or ecotoxicological effect. AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on mechanistic reasoning.” 
  • The OECD  knowledge base and tools such as the AOP wikipedia which is a collaborative effort between the EU JRC and the US Environmental Protection Agency
  • The OECD has a series of educational webinars to promote knowledge sharing on emerging science to chemical safety testing 

World Health Organization (WHO) Guidelines for Biologicals

WHO Guidelines for Biologicals are available here. 

Read a NCRSs Review of animal use requirements in WHO biologics guidelines | NC3Rs

ISO Standards

ISO Standards for Medical Devices can be viewed here. 

The following are New Approach Methods, technologies, or guidance’s that can help reduce or replace animal use and have been considered at the regulatory level:

EMA

  1. Methods available on the TSAR – Tracking System for Alternative methods towards Regulatory acceptance
  2. Computational methods such as Quantitative Structure Activity Relationship, Grouping and read-across and Physiologically Based Pharmacokinetics (PBK). The Virtual second species is an example of the use of PBPK modelling that can reduce the use of animals in testing.
  3. PBPK guidance for industry has been developed by the EMA.

US FDA

The FDA has issued draft guidance to inform individuals and organizations interested in qualifying a Drug Development Tool (DDT) about the qualification process as outlined in the 21st Century Cures Act. For more information on FDA’s current thinking on the DDT qualification process please see here. Guidelines for the qualification process are here. 

Other methods/strategies that are commonly used which reduce animal studies:

The following resources have been produced by organisations which work to reduce animal testing in the regulatory setting:

Drugs or therapeutics approved or advanced to clinical trials without reliance on animal test data:

Further reading:

AI assisted medicine development 

A history of animal use in regulatory science what can we learn?

Medical Devices and regulatory testing

Replacing Animal Tests to Improve Safety for Humans
Kathy Archibald, Robert Coleman, Tamara Drake
Animal Experimentation: Working Towards a Paradigm Change, 2019, pp. 417-442 

Replacing Animal Tests to Improve Safety for Humans

Guidance Snapshot Pilot | FDA

UK Government confirms no legal requirement for animal testing in medical research – Animal Free Research UK and written response from UK Health Department.

Publications Co-authored by FDA on Alternative Methods | FDA

Legislation and Regulation – FRAME 

In addition to implementing the recommendations and key points of the CSIRO non-animal strategy and the MHRA regulatory strategy, Australia could:

  • Establish the equivalent of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICVAAM) or European Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) and relevant scientific advisory committees
  • Become an observer or member of the international cooperation on alternative test methods (ICATM)
  • Create the equivalent of the innovation task force (EU) or the Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program (US)
  • Enact supportive legislation where necessary
  • Adopt supportive guidelines both to reduce the number of animals used and to increase the uptake of alternative methods with guidances for credibility or validity of method
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