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Listed medicine compliance reviews

28 November 2018

Listed medicines are included on the Australian Register of Therapeutic Goods (ARTG) without undergoing a full pre-market evaluation by us. This relies on the medicine satisfying certain criteria for low risk medicines and certification by the sponsor that their medicine meets all of the requirements of section 26A of the Therapeutic Goods Act 1989.

To ensure listed medicines on the ARTG comply with relevant regulatory requirements, we conduct post-market compliance monitoring, which includes us selecting some medicines for a compliance audit (review). If we find that a medicine is non-compliant, we take action according to the risk posed by the medicine to ensure the medicine is either brought into compliance or removed from the ARTG.

Refer to Overview of listed complementary medicines for information on the regulatory framework for listed medicines.

How we select medicines for a compliance review

There are approximately 12,000 medicines listed on the ARTG at any one time and over 1000 are newly listed each year. Given the low risk nature of listed medicines, we select only some of those on the ARTG for review each year. Listed medicines may be subject to any number of compliance reviews while they remain on the ARTG.

Targeted reviews

We may select listed medicines with suspected or potential deficiencies in meeting regulatory requirements for targeted review according to a risk-based approach. We give priority to deficiencies that:

  • may result in an immediate or potential health risk to consumers
  • could significantly mislead the Australian public, particularly where there is a health impact
  • involve a new or emerging issue of concern
  • are likely to become widespread if we do not intervene
  • are the subject of public or media scrutiny and concern
  • are of national or international significance
  • could lead to a loss of stakeholder confidence in the TGA or in therapeutic goods

Priority may also be given to medicines that:

  • are a 'relisting' of a medicine that was recently cancelled from the ARTG (by either the sponsor or the TGA)
  • belong to a sponsor with a history, based on past compliance reviews, of their medicines being non-compliant
  • a particular type of product (e.g. medicines with particular ingredients or indications) for which there are concerns of non-compliance.

We use information from a variety of sources to select medicines for targeted review that include, but are not limited to:

  • reports from the public, media, healthcare professionals or other external sources
  • information from other regulators
  • screening the ARTG for recently listed medicines
  • information from previous compliance reviews, such as medicine characteristics, the nature of the compliance deficiencies identified and the identities of the sponsors
  • complaints or referrals, if appropriate.

Random reviews

We also randomly select a proportion of listed medicines for review using a computer algorithm. Random reviews serve several purposes:

  • Identifying compliance issues that may be the focus of future targeted reviews
  • Profiling medicines and sponsors that are not compliant
  • Encouraging sponsors to ensure the ongoing compliance of their medicines

The compliance review process

How to access a pdf document

The review process comprises several stages, which are outlined in the Compliance Review Process poster (pdf,172kb).

Compliance review process for listed medicines

We conduct compliance reviews of listed medicines that are on the market to check whether they meet regulatory requirements. The typical steps in the review process are:

Review stage Actions
Initiation
  1. We send a Request for Information notice to the sponsor requesting selected information about the medicine.
  2. The sponsor supplies the requested information to us by the due date. If the sponsor does not provide an adequate response, we may cancel the medicine under section 30 of the Act.
Review
  1. We assess the information provided against relevant legislation; this assessment may be broad or focused on a limited set of selected legislated requirements.
  2. If we do not find any compliance deficiencies based on the information provided at that time, the TGA will go to the Decision Stage, assign an 'A' Compliance Review Rating and conclude the review. No further action is taken.
  3. If we identify medicine compliance deficiencies, we send a Proposal to Cancel notice to the sponsor notifying them of the deficiencies and the corresponding Compliance Review Rating.
Response
  1. The sponsor considers the deficiencies identified in our Proposal to Cancel notice and may make a submission to us with evidence or justification that the compliance deficiencies we identified are invalid. The sponsor may also respond to any questions we have about the deficiencies identified. They may also include actions they have already taken in the interim to remedy the compliance deficiencies.
  2. We consider the sponsor's submission. If no submission is provided, there is no additional information to consider and the medicine remains non-compliant.
Decision
  1. We make a final decision about the deficiencies and the corresponding Compliance Review Rating of the medicine as at the time of the review. We notify the sponsor of our final decision, including the Compliance Review Rating and regulatory action, in our final letter to them.
  2. Under certain circumstances, we may provide additional time for the sponsor to rectify the deficiencies identified to bring their medicine into compliance and allow it to remain on the ARTG.
  3. If, after consideration of the sponsor's submission, we are not satisfied that the deficiencies were adequately addressed, or the sponsor did not make a submission, the medicine is considered to be non-compliant and we cancel the medicine from the ARTG.
  4. The sponsor can request for our decision to be reconsidered under section 60 of the Act if they do not agree with it. This must be done within 90 days of the decision being made.
Publication
  1. We currently publish details of medicines that are cancelled from the ARTG on the TGA website. From November 2019 we will publish the outcome of each individual compliance review on the TGA website, including the Compliance Review Rating of the medicine at the time of the review and any actions taken by the Sponsor.
  2. The outcomes of compliance reviews are also included in the TGA Annual Performance Statistics Report.

For more resources and further information go to: Australian regulatory guidelines for complementary medicines (ARGCM) or email: Complementary.Medicines@health.gov.au.

The key messages to sponsors about the process are:

  • When we initiate a review of a medicine, the sponsor will receive a notice from us by email. In most cases, where there is no imminent safety concern about the medicine, we request that the sponsor provides relevant information about their medicine for us to assess, and provide them with specific details about the review, including the due date for their response. If the sponsor does not respond to our request for information or provides false or misleading information, we may take further regulatory action, which can include cancellation of the medicine from the ARTG.
  • We review the information provided by the sponsor to determine whether there are any breaches of the relevant regulatory requirements (termed 'deficiencies'), including those in the Therapeutic Goods Act 1989, the Therapeutic Goods Regulations 1990, Therapeutic Goods Orders, conditions of listing and other applicable legislative documents. We may also view websites or other advertising material to consider whether advertising for the medicine complies with the Therapeutic Goods Advertising Code.
  • In determining whether regulatory requirements have been breached and what, if any, regulatory action to take, we notify sponsors of the deficiencies we have identified - as well as the corresponding Compliance Review Rating that conveys regulatory compliance of the medicine at the time of the review - and afford them procedural fairness and a right of response. Where circumstances allow, we provide sponsors with the opportunity to rectify compliance deficiencies we have identified to bring their product into compliance and allow it to remain on the ARTG.
  • After taking into account the sponsor's response, if one was provided, we then notify sponsors of the final decision including the Compliance Review Rating assigned to their medicine at the Decision phase of the compliance review.
  • We then will publish the details of medicines that are cancelled from the ARTG on the TGA website.

Information we may request in a compliance review

We do not necessarily review the compliance of a medicine with all listing requirements. According to our risk-based approach, we may assess compliance with either a broad range or a narrow set of specific listing requirements ('broad' or 'limited' scope, respectively). We determine the scope either randomly or based on information we possess about the medicine or sponsor.

Depending on the scope of the review, we usually request one or more of the following from the sponsor under the provisions of section 31(2) of the Act:

  • labels for the medicine as it is supplied in Australia
  • finished product specifications
  • a certificate of analysis for the last released batch
  • manufacturing formula including a list of all ingredients and their quantities
  • the evidence held by the sponsor that supports the indications and claims made in relation to the medicine
  • if applicable, information relating to Transmissible Spongiform Encephalopathy.

We may also request information such as:

  • raw material specifications and certificates of analysis
  • methodology and results of a specific test
  • copies of permits and/or licenses allowing the importation of the medicine if it contains substances that are prohibited imports for the purposes of the Customs Act 1901
  • promotional and advertising material.

Possible findings during a compliance review

There are three possible findings by us during a compliance review.

We do not identify any compliance deficiencies for the selected listing requirements

We close the review and notify the sponsor. The medicine remains on the ARTG.

As our reviews often cover only selected listing requirements, sponsors must actively ensure ongoing compliance with all relevant requirements of the regulatory framework at all times.

We do identify compliance deficiencies

Where a deficiency is identified, we take appropriate regulatory action - refer to Regulatory action for a non-compliant medicine.

We are unable to determine the compliance status

We may be unable to determine the compliance status of a medicine if:

  • The medicine was cancelled by the sponsor before assessment commenced, or
  • The medicine was cancelled by us due to non-payment of fees by the sponsor, or
  • The medicine has not been manufactured

The sponsor can request that their medicine be cancelled from the ARTG at any stage of the compliance review. However, if this medicine is subsequently relisted, a targeted review may be undertaken according to our prioritisation strategy.

When we are unable to determine the compliance status of a medicine due to one of the above scenarios, we close the review without further action.

How we rate compliance

Compliance Review Ratings

As part of a compliance review, we determine a Compliance Review Rating for the medicine at the time of the review that indicates the concern for consumers due to the totality of the deficiencies we have identified. This rating will be conveyed to the sponsor as part of the notification of the compliance review findings. The definitions and criteria for the Compliance Review Ratings are shown in the table below.

There will be some circumstances where we cannot assign a Compliance Review Rating for a medicine, such as when the sponsor cancels the medicine from the ARTG upon the initiation of a review or during the review process. In such a case, the medicine is assigned a 'Not Determined' rating.

Compliance Review Rating Definition Default Criteria
A No deficiencies identified. No concerns held about the safety, efficacy or quality of the medicine based on the information reviewed. No deficiencies were identified.
B Medicine has deficiencies that are not expected to adversely affect the rights or safety of consumers. 1 or more Minor deficiencies.
C One or more indications or efficacy claims are unsupported, misleading, compromised or not permitted on a listed medicine, but consumer safety is not expected to be adversely affected.
  • 1 or more Significant deficiencies (may also have Minor deficiencies) or
  • 1 or more Minor deficiencies that cause the good to meet the rating definition.*
D Potential adverse impacts—likely to be minor in nature—on consumer safety, or potential risk to public health.
  • 1 or more Major deficiencies (may also have Minor and/or Significant deficiencies) or
  • 1 or more Minor and/or Significant deficiencies that cause the good to meet the rating definition*
F Expected adverse impacts—possibly serious—on consumer safety, risk to public health, and/or regulatory requirements were deliberately contravened due to fraud, misrepresentation or falsification of data. 1 or more Critical deficiencies (may also have Minor, Significant or Major deficiencies)*
Not determined The medicine was not reviewed as it was cancelled from the ARTG by the sponsor upon receiving a Request for Information or had not been manufactured.

* determined at the discretion of the Delegate in exceptional circumstances when the cumulative effect of many Minor deficiencies is considered to raise an efficacy or safety concern, or the effect of many Significant deficiencies is considered to raise a safety concern.

How are Compliance Review Ratings determined?

The definitions for the Compliance Review Ratings determine when a particular rating applies to a medicine that we have reviewed. Where the totality of the deficiencies identified by us during a review cause a particular definition to be met, the corresponding rating will be assigned.

How to access a pdf document

To support a systematic and predictable approach to determining the Compliance Review Rating of a medicine, we have categorised most breaches of regulatory requirements (or 'deficiencies') that we observe during compliance reviews into Deficiency Ratings. The Deficiency Ratings correspond to escalating concern about the risk to consumers due to the deficiencies. Refer to the Deficiency Rating Poster (pdf,141kb)

Deficiency ratings for listed medicines

This fact sheet relates to the Compliance Rating Scheme that we implemented in November 2018 as part of a suite of enhancements to our existing compliance monitoring program for listed medicines.

For more information on the Scheme, please see our webpage on listed medicine compliance reviews.

What are Deficiency Ratings and what are they for?

Where a regulatory requirement for a listed medicine has not been met, it is called a deficiency. We have categorised the most common deficiencies into four categories to show how each has a different level of concern or risk associated with it. We use the number and category of deficiencies that we identify during a compliance review to determine the Compliance Review Rating for a medicine.

The Deficiency Ratings

There are four different deficiency ratings: Minor, Significant, Major and Critical. The most commonly-observed deficiencies corresponding to each are:

Minor

All deficiencies that are not rated as Significant-Critical and are consistent with the definition of a Compliance Review Rating of 'B', such as:

  • Minor inconsistency with the medicine name on the label.
  • Ingredient names on label are incorrect according to the Australian Approved Name requirements.
  • The name of the dosage form is incorrect or missing from the label.
  • The quantity of the goods is not included on the label.
  • Incorrect or missing batch number/expiry date/storage conditions/supplier details/AUST L number.
  • Label legibility requirements are not met.
  • Advertising breaches that do not mislead as to the proper contents, identification or use of the goods, such as unacceptable endorsements or misleading/untruthful non‑therapeutic claims.

Significant

  • Sponsor does not hold evidence that supports the medicine indications or claims.
  • Formulation of the goods is different to the formulation on the ARTG.
  • Dosage form of the goods is different to that on the ARTG.
  • Indications or claims are different to those on the ARTG.
  • Quality control standards not met for dissolution rate, uniformity of weight, disintegration, preservative content assays, ingredient quantification, conduct of relevant tests and limits.
  • Advertising that is likely to impact the consumer's ability to appropriately use the goods in line with their intended purpose.
  • Deficiencies that meet the definition for a compliance rating 'C'.

Major

  • Contains an ingredient in an amount that exceeds the permissible limit for listed medicines according to the Therapeutic Goods (Permissible Ingredients) Determination.
  • Contains an ingredient or substance (impurity or contaminant) that is included in a schedule of the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).
  • Microbial quality control standards have not been met.
  • A manufacturer of the good is not entered on the ARTG listing.
  • Required GMP licences or clearances are not held by the manufacturer.
  • Manufacturing deficiencies likely to compromise safety such as microbial testing having not been validated or microbial test method not in accordance with default standards.
  • Mandatory label warning statements are incorrect or missing.
  • The medicine refers to a prohibited or unapproved restricted indication or claim.
  • Advertising that potentially impacts the consumer's ability to safely use the goods.
  • Requirements for child resistant packaging have not been met.
  • Deficiencies that meet the definition for a compliance rating 'D'.

Critical

  • Contains an ingredient that is not included on the Therapeutic Goods (Permissible Ingredients) Determination.
  • Contains a prohibited substance e.g. aristolochic acid.
  • Advertising non-compliance that is likely to lead to harm or risks public health.
  • Has a Major Deficiency of a nature or extent that represents an imminent safety concern for consumers.
  • An instance of fraud, misrepresentation or falsification of data, or intentional or reckless contravention of listing requirements.
  • Any other deficiencies that meet the definition for a compliance rating of 'F'.

The assigned Compliance Review Rating will in most cases correspond to the highest Deficiency Rating observed during a compliance review. However, we may use our discretion, based on a case-by-case expert scientific assessment, to assign a different Compliance Review Rating at the conclusion of the compliance review in accordance with the definitions.

Regulatory action for non-compliant medicines

If we find that a listed medicine does not comply with a regulatory requirement there are a number of regulatory actions we can pursue, including, but not limited to:

We issue a Proposal to Cancel Notice under subsection 30(3) of the Act

If this occurs, we:

  • Advise the sponsor of the deficiencies that we have identified
  • Notify the sponsor of the corresponding Compliance Review Rating for their medicine
  • Provide the sponsor a reasonable opportunity to refute our findings or address the deficiencies with evidence or justification.

One of the following outcomes may occur:

  • The sponsor satisfactorily addresses all non-compliance issues and the medicine remains on the ARTG
  • The sponsor requests that the TGA cancel the medicine from the ARTG
  • The TGA may cancel the medicine (under subsection 30(2) of the Act) if the sponsor does not satisfactorily address all non-compliance issues.

The medicine is cancelled from the ARTG

Under subsections 30(1), 30(1A) or 30(1C) of the Act, we may cancel the medicine without issuing a Proposal to Cancel Notice, where:

  • there is an imminent risk of death, serious illness or serious injury
  • the medicine is not 'eligible for listing', for example, it contains ingredients that are not permitted in listed medicines
  • the manufacturing of the product in Australia has not been performed by a person with a manufacturing licence
  • the medicine contains substances that are prohibited imports under the Customs Act 1901
  • the sponsor failed to provide the required information within 20 working days after requested to do so.

The medicine is recalled from the market place

A product recall is the removal of the medicine from supply on the Australian market. Recall of any distributed goods is required whenever public safety is at risk as a result of non-compliance. Further information on recalls is provided on our website: About recall actions.

If a medicine is cancelled from the ARTG

If a medicine is cancelled from the ARTG, it can no longer be imported, exported, manufactured or supplied for use in Australia. To do so is an offence under the Act. It can be either a criminal offence (s.19B) or a civil offence (s.19D). It is also an offence to advertise therapeutic goods that are not on the ARTG (s.42DL(1) and s.42DLB(1)).

Review of a TGA decision

Some decisions made by the TGA during a compliance review of a listed medicine can be reviewed. These include a decision to:

  • request information or documents (subsection 31(2) of the Act)
  • impose additional conditions of listing (section 28 of the Act)
  • suspend a product from the ARTG (section 29D of the Act)
  • cancel a product from the ARTG (section 30 of the Act)
  • recover (recall) a product (section 30(EA) of the Act).

Any person whose interests are affected by such a decision can ask for an internal review by a delegate of the Minister/Parliamentary Secretary - refer to Mechanism for review of decisions made under the Act.

Publication of compliance activities and review outcomes

The TGA has published the following information on compliance activities since 2012:

In the second half of 2019, we will commence publishing the outcomes of all listed medicine compliance reviews to make them publicly available on the TGA website. More information can be found on the Complementary medicines reforms page.

Contact

For further information contact the Complementary and OTC Medicines Branch.