Australian regulation of prescription medical products

The necessity for registration

The Therapeutic Goods Act 1989 (the Act) requires that medical products imported into, supplied in, or exported from Australia must be included in the Australian Register of Therapeutic Goods (ARTG). In order for a prescription medicine to be included in the ARTG, a sponsoring company is required to submit an application to the TGA. A submission to register a prescription medicine consists of:

• data that support the quality, safety and efficacy of the product for its intended use,
• completed forms, and
• the payment of fees.

Data to support applications

A description of the data required is included in the Australian Regulatory Guidelines for Prescription Medicines (ARGPM). Some guidelines issued by the EMA and adopted by Australia give guidance about the data to be included to support applications.

The TGA works with international counterparts in order to reduce the worldwide regulatory burden and increase the global uniformity of data requirements. Thus, wherever possible, the TGA's requirements are the same as those of other major regulatory agencies.

Data packages should be in the Common Technical Document (CTD) format.

Data evaluation

The data submitted with an application is divided into three types.

• Quality data
  • The composition of the drug substance and the drug product
  • Batch consistency
  • Stability data
  • Sterility data (if applicable)
  • The impurity content
• These data are evaluated by chemists, biochemists, microbiologists, toxicologists and others working for the TGA.
• Nonclinical data
  • Pharmacology data
  • Toxicology data
• These data are evaluated by toxicologists.
• Clinical data
  • Mostly results of clinical trials
• These data are usually evaluated by a medical doctor.

The data set submitted is evaluated by technical staff with the relevant expertise and several, separate evaluation reports may be produced. Each evaluation area has the opportunity to ask the sponsors questions about the data submitted. The ability to require the sponsor to provide information is provided by section 31 of the Therapeutic Goods Act 1989. Once each evaluation area has assessed the sponsor's response, final evaluation reports are prepared and reviewed internally before they are authorised and sent to the sponsor; the sponsor then has the opportunity to make comments.

Advisory committees

There are two committees that provide advice to the TGA about matters related to the registration of medicines:

• The Advisory Committee on Prescription Medicines (ACPM)
• The ACPM Pharmaceutical subcommittee (PSC)

The decision to register the medical product

The decision to register a medicine on the ARTG is made by a delegate, that is, someone who has been delegated the power to make this decision by the Secretary of the Department. The delegate for most application types is a Medical Officer. However, for generic medicines, the delegate is often a scientist, because the data is principally scientific. When making the decision, the delegate takes into account all of the advice given by the evaluators and the advisory committees, along with comments provided by the sponsors.

Appeal processes

If the sponsoring company does not agree with the decision made by the TGA, the Act provides a comprehensive system for review of administrative decisions. The appeal mechanisms are described in more detail in the Australian Regulatory Guidelines for Prescription Medicines (ARGPM). Briefly, the formal appeal process usually involves:

• An appeal under Section 60 of the Act.

This can be followed by:

• An appeal to the Administrative Appeals tribunal (AAT).

Publication of regulatory decisions: AusPARs

The transparency of the decision process increased at the end of 2009 when the first AusPAR (Australian Public Assessment Report) was published. An AusPAR provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve an application. For applications that are approved, the AusPAR will generally be published no more than a month after the product has been registered on the ARTG. For an application that has been rejected, the AusPAR cannot be published until a 90 day appeal period is complete.

Regulation after registration

Applications to change conditions of registration

Once a product has been registered, the sponsor can make further applications to change the conditions of registration. Some examples of the types of change that might be applied for:

• A change in manufacturer
• An increase in shelf life
• A change in patient population (e.g. allowing children to use the medicine)
• Changing the intended use (usually adding an extra medical condition that can be treated)

Monitoring the safety of registered products

The TGA has a multi-faceted program for monitoring approved products that are on the market.

• A Risk Management Plan has been required since April 2009 for certain application types. This plan identifies how safety concerns will be identified and mitigated post-registration.Monitoring the safety of registered products.
• Regular post-market reports are required from sponsors.
• Sponsors are required to inform the TGA of any international concerns related to safety or efficacy.
• The TGA publishes a Medicines Safety Update in each edition of the Australian Prescriber.
• The TGA has a problem reporting system for reporting:
  • Medicine deficiency or defect
  • Adverse reaction to a medicine
• Random and targeted sampling of approved products is undertaken by the TGA Laboratories.
• Once a problem has been identified possible regulatory actions vary from continued monitoring to withdrawing the product from the market. Actions the TGA can take include:
  • informing health care professionals and consumers about the risks of using the product
  • re-assessing the benefit-risk profile
  • requiring product labelling changes
  • requiring design or manufacturing change
  • requesting post-marketing studies
  • restricting access
  • recalling products
  • removal of the product from the ARTG.

Access to medicines that are unregistered

There are some legal exemptions to the requirement for a prescription medicine to be registered on the ARTG. These are implemented through:

• The Special Access Scheme (SAS)
• The clinical trials systems (CTA and CTN)