Risk-based thinking: Why does risk impact how medicines are supplied?

The ethos that high-risk activities should elicit the most significant mitigation effort, and low-risk, lower effort has been a mainstay of the global regulatory approach to risk management of therapeutic products for many years. In 2006, ICH Q9 Quality Risk Management was published and included the statement:

The level of effort, formality and documentation of the Quality Risk Management process should be commensurate with the level of risk.

Risk-based thinking has become an increasingly embraced philosophy within the industry ever since. As an indicator of adoption, the word risk is mentioned in PE 009-16 PIC/S Good Manufacturing guidelines an eye-watering 637 times. For perspective, the original 1971 version mentioned risk 3 times …

But what does it actually mean? How is it implemented in the therapeutics industry? To the TGA it means:

Our ‘risk-based’ approach to regulating therapeutic goods is designed to ensure that regulation is only used where absolutely needed and, then, only to the extent needed to protect and advance public health. In practice, this means the level of regulation—and our regulation and compliance efforts—is commensurate with the risks posed by particular therapeutic goods.


The value of risk-based thinking is that it releases time, effort and money for those issues that need greater focus and expertise to reduce the risk to patients to an acceptable level.

Risk-based product management

One area in which a risk-based approach is utilised is the evaluation and monitoring of new and marketed therapeutic products. The TGA’s document “Product regulation according to risk: Overview of the way the Therapeutic Goods Administration (TGA) considers risks and benefits during the evaluation and post-market monitoring of products” describes how the regulator has categorised therapeutic products according to risk, with a view to the level of regulatory oversight such products should incur during the submission process and during ongoing monitoring.

In the context of product management:

  • risk means the chance that consumers of a therapeutic product might suffer an adverse event or reaction directly attributed to such,
  • a risk-based approach permits resources and focus to be better available for products which may pose greater risk to patient health, and require more rigorous assessment and assurance that the benefit outweighs the risk,
  • the identified risk level dictates the route by which products might be available to the consumer as a means of mitigating the risk.

As an example, medicinal products are categorised into a “schedule” which prescribes how consumers might access to these medicines:

Herbs and multivitaminsSupermarket, off-the-shelf
Travel sickness tablets
e.g. hyoscine hydrobromide
Pharmacy medicine
Codeine-based cough syrup,
e.g. dihydrocodeine tartrate
Over-the-counter (pharmacist only)
Blood pressure medication,
e.g. lisinopril 
Prescription only

A word of caution: Do not assume that a risk assessment, and subsequent control measures, assures that there is no risk to the patient. It is the TGA’s responsibility to assess the evidence of risk against the evidence of benefit for each product; this is a balancing act in which they try to ensure that the latter outweighs the former. So, even if the evidence of adverse outcomes is significant, products may still be approved where NOT administering the product poses the greater risk to the patient e.g. chemotherapy for cancer.


Risk management and therapeutic product types

MedicinesRegistered medicines
• Higher risk medicines that require full evaluation of quality control, safety and clinical use data to determine the risks vs benefits
• A TGA delegate will assess and determine whether a medicine may be registered on the Australian Register of Therapeutic Goods (ARTG)

Listed medicines
• These lower risk products are not individually evaluated
• The applicant must certify the quality and efficacy of their product before it is listed on the ARTG
Biologicals• Products containing human cells or tissues pose additional risks (such as infectious disease transmission) and are more difficult to withdraw from use
• Whilst the products are more complex, the approach remains the same with 4 categories reflecting 4 risk levels
Unapproved products• Access to unapproved products may be sought through a number of pathways (e.g. Special Access Scheme for cannabis)
• In these cases, the risk-benefit assessment is the responsibility of the patient’s healthcare provider

Post-market monitoring

Evaluation of therapeutic products does not cease once approval for release to market is granted. Regulatory authorities employ a number of tools to continually monitor the performance of marketed products, and ensure safety and efficacy is as expected (i.e. that the benefits continue to outweigh the risks).

  • Risk management plan
  • Adverse event/reaction reporting
  • Annual reports
  • Pharmacovigilance audits
  • Literature review

The approach to managing any issues that are identified during monitoring is also driven by risk-based thinking, allowing screening, prioritisation and time-appropriate action. Such actions might include:

  • Conditions on supply
  • Variation to product documents
  • Suspension or cancellation from the ARTG
  • Civil or criminal sanctions

PharmOut are available to help you with all your risk management activities. In addition to eLearning courses in Annex 20 Quality Risk Management and ISO 14971 Risk Management for Medical Devices available via www.onlinegmptraining.com, we would be happy to provide face-to-face training, in the classroom or online. And, of course, our consultants are always available to support you directly in your risk management activities.