Reformatting Product Information: Frequently asked questions

The TGA is changing the format of the PI document to ensure that the critical clinical information is more accessible within the document. TGA has developed the new format in consultation with health professionals and sponsors, who support its implementation. In addition, the new format has been developed to align with the formatting requirements of other international regulators, specifically the New Zealand medicines regulator Medsafe, and the European Medicines Agency.

The key changes are:

• the content of the PI is being re-ordered to bring critical clinical information together at the front of the document
• the headings and subheadings have been updated to align with headings used internationally.

Some new subheadings have been added to facilitate the harmonisation of format with that used in New Zealand and Europe. Many currently approved PIs already include content that relates to these headings, for example the effects of the medicine on a person's ability to drive and use machines. For these medicines, this information will now be located in a standardised place in the PI. For medicines that do not currently include such information, standard text has been provided in the Form for providing Product Information, and can be inserted as part of the reformatting process.

An annotated version of the form has been prepared to indicate where new content has been added, including optional and mandatory standard text.

A revised Form for providing Product Information was approved on 8 March 2018. The form was revised following recent amendments to the Therapeutic Goods Act 1989 (the Act). The new instrument of approval provides updated references to the appropriate subsections of the Act, updated transition arrangements and some other editorial changes. There have also been a number of changes to the form, which are:

• Clarification that only clinically relevant physical and chemical characteristics should be included in Section 2. Other physical and chemical characteristics should be included in Section 6.7.
• Clearly indicating which subheadings are mandatory in Sections 4.4, 5.1 and 5.3.
• Addition of a new mandatory subheading has been introduced in section 4.8 – 'Reporting suspected adverse effects'.
• Clarifying that only the subheadings that are relevant to the product need to be included in Section 5.2. For example, a product administered intravenously would not require the 'absorption' subheading.
• Providing an alternative optional standard text for section 6.6 which is more relevant to products used in healthcare settings.
• Other minor editorial changes have been made which do not affect the interpretation of the form.

These changes are also highlighted in the annotated version of the form provided at the end of these FAQs.

No. If you have already reformatted your PI you are not required to make further changes. However, it is recommended that you include the subheading 'Reporting suspected adverse effects' in section 4.8 at your next PI update.

Reformatting is considered as:

• updating or adding headings to align with the new PI format
• adding optional standard text and mandatory standard text, including additional sponsor contact information in section 8 as described in the Form for providing Product Information
• updating cross-references to include section number and updated heading, and updating table and figure numbers

Reformatting does not include other editorial changes such as re-ordering of information within a section, or rephrasing the approved content. These changes must be annotated on the PI, and requested with the appropriate application type (i.e. with a MEC application).

PIs can be submitted to the TGA in the new format now, for any application with a decision date after 1 January 2018. For Category 1 applications currently under evaluation, it is strongly recommended that the PI is reformatted as part of the current submission.

PIs accompanying Category 1 applications must be provided in the new format if they are submitted after 1 January 2018. In addition, Section 23 Category 3 applications and Section 23 Self-Assessable Requests must also be accompanied by a reformatted PI if submitted after 1 January 2018.

Reformatted PIs can also be submitted with any other application type related to that medicine, including minor variations, safety related requests, and applications to update medicine ingredient names. Reformatted PIs submitted with any other application type do not attract an additional fee.

Reformatted PIs can also be submitted as a stand-alone application. Fees are waived for stand-alone applications to reformat PIs if submitted between 1 January 2020 and 31 December 2020, if no other changes are made. See Submission FAQs for more information.

The new PI format will be implemented with a 3-year transition period. PIs that are updated through an application to the TGA during the transition period should be provided in the new format. Reformatted PIs may also be submitted with other application types that do not seek changes to the PI. There will be no additional fee to 'bundle' the reformatting of the PI with another application type. See 'Submission FAQs' for further information on how to submit reformatted PIs to the TGA.

Reformatted PIs can also be submitted as a stand-alone application. Applications should be submitted as a Minor Editorial Change (MEC) through the TBS portal, using the PMMV (Prescription Medicine Minor Variation) E-Form. See the relevant 'Process Guidance' for further information about how to submit a reformatted PI to the TGA as a stand-alone application. Applications where the only variation made to the product(s) is to reformat the PI (as described above) and no other editorial changes are made will be exempt from fees between 1 January 2020 and 31 December 2020. Applications where additional editorial changes are made at the same time as reformatting the PI will not be exempt from fees. See Submission FAQs for more information. Further information about fees is available on the TGA website.

No. Only products that are marketed are required to be reformatted during the transition period. If you decide to market the product, the PI will need to be reformatted prior to marketing. However, you may reformat the PI of non-marketed products during the transition period if you choose to.

As the content of the PI is not changing as part of the reformat, there is no requirement to update the table in the Australian Specific Annex (ASA) that compares the wording in the PI and the Summary of Product Characteristics (SmPC). When the ASA is next updated, you should consider whether any revision is warranted to the content of the table with respect to the headings and subheadings referred to in the PI.

No. It is acceptable for PIs in the old format to be phased out as sponsors exhaust stock of products that contain the PI in the old format. Following the PI being reformatted, new stock should have the new version of the PI included in the packaging.

The new PI format has been developed in consultation with Medsafe. The format of the PI aligns with the format requirements for the New Zealand Data Sheet. Sponsors should be able to use the Australian PI in the box of injectable products for Australia and New Zealand, if:

• the indications and dosing information align, and
• the content of the Australian PI also meets the requirements for use in New Zealand.

If additional content is required to meet NZ regulatory requirements, sponsors can seek to modify the Australian PI by submitting the appropriate application type to the TGA.

Yes. Any changes to PIs will require an application to the TGA, which may incur a fee. Applications for PI reformats can be bundled with another application, for example a Type F or J application, a safety-related request or a minor editorial change. These requests should be clearly indicated in the annotated version of the PI and the cover letter. Applications to reformat reformat a PI can be submitted as a stand-alone application. See Submission FAQs for more information. Further information about fees is available on the TGA website.

To ensure that no unauthorised changes have been made to the PI, sponsors will be required to acknowledge a legal declaration in the TGA eform. You must also include the declaration in your cover letter to facilitate timely processing of the reformatting application. If your application does not use the TGA eform, please ensure you have included the declaration in your cover letter. The legal declaration is as follows:

I declare that:

where Product Information (PI) is provided with this submission:

• no amendments other than the amendments that are identified in the annotated version of the PI in Module 1.3.1.2 will be made to the PI;
• apart from any amendments to the content of the PI identified in Module 1.3.1.2, all content of the current PI approved under section 25AA of the Therapeutic Goods Act 1989 has been retained;
• any changes to the PI that do not relate to the submission are limited to:
  • changes to the text that are required as mandatory standard text or specified as optional standard text in the form for Product Information that was approved on 8 March 2018; and
  • changes to headings and cross-references that are necessary in order to comply with the form for Product Information that was approved on 8 March 2018.

Note: Random audits of PIs that are reformatted to comply with the form for Product Information that was approved on 8 March 2018 will be undertaken to verify that no undeclared changes to content have been made.

If the PI is only being reformatted, without any content changes other than those considered part of reformatting (updating headings and/or subheadings, updating numbering and cross-references of tables and figures, and inclusion of standard text), then an annotated copy is not required. However, clean copies of both your currently approved PI and the reformatted PI should be submitted.

If the PI is being reformatted as part of an application to make content changes to the PI, then the PI should be reformatted prior to any updates to the content. Following the reformatting process, 'track changes' should be turned on to create an annotated version that clearly identifies the proposed updates to the PI. Any changes to the original content of the PI should be tracked. If you are adding new information under the new mandatory subheadings (e.g information from the ARTG for section 6.1 list of excipient or section 6.5 Nature and contents of container), please ensure you tracked those changes. For these applications the following documents should be submitted: clean copy (old format, no changes), clean copy (new format, no changes), annotated copy (new format, tracked/annotated changes) and clean copy (new format, with proposed changes).

Applications should be submitted using the online PMMV (Prescription medicine minor variation) e-form through the TBS portal. You will need to select the code 'PIME' for a minor editorial change (MEC) application. Please include the following text in the 'Comments Field' section and the cover letter of your dossier:

"This is a PI reformat only application for fee exemption."

As per standard billing processes, your company will still receive an invoice for the MEC application. We ask you to inform your billing department to withhold payment of this invoice as a subsequent credit note will be generated and provided to the sponsor which will nullify the invoice (i.e. the TGA will not be seeking payment of this invoice). If your organisation does proceed to pay an invoice and your application is eligible for a refund, this will be managed as per standard TGA process.

Your PI reformat only application will be subject to a filtering process to ensure all the PI changes proposed in your application comply with the Therapeutic Goods Regulations 1990, which enable the refunds and fee waivers to PI reformat only related applications. You will be notified if the fee waiver can be applied to your application. Once you have been notified, the application will proceed as per standard TGA processes.

You can still combine your PI reformat changes with your other minor variations applications. This type of application will not be subject to a filtering process, which can lead to possible delays.

Changes to the Therapeutic Goods Regulations 1990 came into effect in 1 January 2020, which enable refunds and waivers to be provided in relation to fees for PI reformat changes. The refunds and waivers will only apply in relation to requests expressly confined to PI reformat related changes. The refunds and waivers will not be extended to changes unrelated to PI reformat; these unrelated changes, will incur a fee and be progressed as per standard TGA processes.

Please see below for examples of unrelated PI reformat minor editorial changes that would therefore incur a fee:

• Changes to the corrections of the spelling in the PI, for example changing from frusemide to furosemide
• Addition of any new statements to the PI, unless the statements are mandatory or recommended standard statements. Example of mandatory or recommended statements include "No data available" or "In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging". For PI reformat standard texts, please see 'Form for providing Product Information'

• Any changes to currently approved texts, for example:

  "A reduction in hair growth, hair shaft diameter and hair pigmentation is are seen"

If additional changes to the PI have been identified during the filtering process, you will need to pay the invoice as the fee waiver cannot be applied.

You can submit your reformatted PI as part of an application (for example Category 1, Category 3, Safety-Related Request). For all applications, the cover letter should clearly state that "we request to reformat the PI as part of the application". In addition, for minor variations submitted using the e-form, please include the request to reformat the PI in the comments section of the e-form.

Updated electronic Common Technical Document (eCTD) specifications will be available for use from 1 January 2018, with the current specifications available until 30 June 2018.

Under the current specifications (version 3.0), Module 1.3.1.1 Product Information - clean should contain the clean copy in the new format, which includes the proposed changes. The other PI documents should be placed in Module 1.3.1.2 Product Information - annotated; this should include copies of the approved PI in the old format, the reformatted PI without changes, and the reformatted PI with tracked/ annotated changes.

Under the new specifications (version 3.1), Module 1.3.1.1 Product Information - clean should contain the clean copy in the new format, which includes the proposed changes. Module 1.3.1.3 Product Information - approved should contain the currently approved PI in the old format. Copies of the reformatted PI without changes, and the reformatted PI with tracked/ annotated changes should be provided in Module 1.3.1.2 Product Information - annotated.

More information on submitting a reformatted PI in eCTD format separately from an application will be provided when available.

Yes - your current title should be retained at the top of the PI. It is recommended that this title include the terms 'Australian Product Information', followed by the tradename and name of the active ingredient in brackets. It is considered best practice to also include the dose form when practical (for example 'tablets', 'solution for injection').

If your PI has a boxed warning its location should be the same in the reformatted PI. For example:

• if the boxed warning is currently located prior to the name of the medicine in the current PI, it should be located above Section 1 in the reformatted PI; or
• if it is currently located in the contraindications section, it should remain in the contraindications section (Section 4.3)

No. Adding or updating the text of headings and subheadings to align with the new form is considered to be part of the reformatting process. Similarly, updating references within the text to align to new headings and/or subheadings is not considered to constitute a 'content change'.

Yes. Following the reformatting process, you should ensure that the tables and figures in your PI are labelled in chronological order, and update the references to these tables and figures within the PI text. In addition, any cross-references to headings and subheadings should be updated to reflect changes to the wording of these heading and subheadings. The updating of these cross-references is not considered to be a content change. Cross-references to other sections of the PI should include the section number. It is considered to be best practice to include both the section number and section heading in the cross-references.

No. Inclusion of either the optional standard text or mandatory standard text in line with recommendations in the Form for providing Product Information is not considered to constitute a change in the content of the PI.

A PI template has been prepared by the TGA to assist sponsors in reformatting their PI, or preparing new PIs. There are two versions of the template - one for products included in the black triangle scheme, and one for other products. The templates contain the appropriate bookmarks for headings and subheadings. It is recommended that sponsors use the template to ensure appropriate headings and bookmarks are included in the PI. The templates can be found on the TGA website. The bookmarks should be retained during the pdf conversion. This can be done by selecting the appropriate preferences for the software you are using.

For example, in the 2010 version of Microsoft Word, this is done in the 'Acrobat' tab, by selecting 'preferences' then the 'bookmarks' tab and checking the 'convert word headings to bookmarks' box.

No, the fonts included in the PI template are indicative only.

No, only the first and second level headings should be numbered. Third level headings should not be numbered. The PI templates indicate which headings require numbering.

Only the Australian Approved Name(s) of the active ingredient(s) should be included in this section. Do not include trade names.

For reformatted PIs, the full excipient list included under 'Description' in the current PI can be retained in Section 2, and the optional standard text 'Refer to Section 2' should be included in Section 6.1.

For new PIs and those PIs being reformatted as part of an application to update the PI, excipients with 'known effect' should be listed in Section 2, and the full list of excipients included in Section 6.1. Excipients with 'known effect' are those included in Schedule 1 of TGO 91 or 92 (noting that the content of these schedules is the same). When listing excipients with known effects, please include the sub heading, 'Excipients with known effect', in section 2.

Information such as physiochemical properties (for example, colour of the Active Pharmaceutical Ingredient), solubility and pKa values should generally be moved to section 6.7 unless the information is of such clinical importance that it should be retained in this section.

For PIs being reformatted, it is acceptable to combine these sections with the following heading: '2 AND 3 QUALITATIVE AND QUANTITATIVE COMPOSITION AND PHARMACEUTICAL FORM'. It is recommended that this approach is only used if the current PI content contains the required information together in one statement. Wherever possible, it is considered best practice to separate these sections.

The dose form used to describe your product in Section 3 should be the same as that used in your application to register the product. The approved terminology for dose form can be found in the Code Tables (see Search for approved ingredients and accepted terminology in TGA Business Services).

No. However, if your current precautions include information on use in hepatic or renal impairment the content should be relocated to align with the order. Please also ensure you update the renal and hepatic subheadings to reflect the Form for providing Product Information.

Yes - these subheadings were required in the previous form, and remain mandatory in the new form. If your approved PI does not include these subheadings, the following options are available:

1. If there is no information available related to these subheadings then 'no data available' may be added.
2. If information is available in another section of the PI, a cross reference may be added (for example, 'See Section 4.2 Dose and method of administration')
3. If the PI contains an already approved statement regarding these headings, then the approved text may be replicated under these headings.

Any new text included under these headings should be indicated as a change in the annotated version of the PI.

If your current PI includes a statement on effects on ability to drive and use machinery, it should be relocated to Section 4.7. If there is a major effect of the medicine on the ability to drive and use machinery then this information should also be included as a precaution, with a cross-reference between sections 4.4 and 4.7. If you do not currently have a statement on these effects, you have two options:

1. the optional standard text 'The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration' can be added, or
2. you can apply to add the information as a Safety Related Request, or as part of a Category 1 application. Submission of the currently approved European Summary of Product Characteristics (SmPC) would be considered sufficient evidence to support the addition of the statement that is in the SmPC. For an SRR, it is appropriate to select the application type as one not requiring evaluation of data.

No, the content must still comply with the Australian requirements specified in the Form for providing Product Information.

Please note that there is a new requirement to include the mandatory statement on how to report adverse events in this section under the subheading 'Reporting suspected adverse effects'.

The entire content included under the current Clinical Trials heading should be relocated to Section 5.1, under the subheading 'Clinical Trials'. This should be located after the statements under the 'Mechanism of Action' subheading.

The subheadings of 'absorption', 'distribution', 'metabolism' and 'excretion' in section 5.2 are not mandatory. You should use these headings if they are relevant to the pharmacokinetics of your product.

If there are clinical statements under the carcinogenicity subheading currently included in the precautions section, then the entire carcinogenicity statement (clinical and nonclinical findings) should be included in Section 4.4 'Special warnings and precautions for use', with a subheading of 'Carcinogenicity'. In this situation, the carcinogenicity subheading should be retained in section 5.3, but the following text should state 'refer to Section 4.4 Special warnings and precautions for use'.

No. The information currently under the subheadings Genotoxicity and Carcinogenicity should be relocated to section 5.3.

For reformatted PIs, the full excipient list included under 'Description' in the current PI can be retained in Section 2, and the optional standard text 'Refer to Section 2' should be included in Section 6.1.

For new PIs and those PIs being reformatted as part of an application to update the PI, excipients with 'known effect' should be listed in Section 2, and the full list of excipients included in Section 6.1. Excipients with 'known effect' are those included in Schedule 1 of TGO 91 or 92 (noting that the content of these schedules is the same).

No. The optional standard text 'Incompatibilities were either not assessed or not identified as part of the registration of this medicine' can be used under this heading if no information is currently included in the approved PI.

It is recommended that sponsors include the optional standard text 'In Australia, information on the shelf life can be found on the public summary of the ARTG. The expiry date can be found on the packaging' under this heading. It is not recommended to include the actual approved shelf life (such as 12 months or 48 months) in the PI as this may change over time.

No. The information on storage conditions included in the current PI should be relocated under this subheading.

No. The optional standard text 'In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy' or 'In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements' can be used if your current PI does not include disposal information. Please choose the standard text most appropriate for the type of medicine, considering other factors such as the dosage form. For example, liquid cytotoxic medicines should not be disposed of at the local pharmacy.

It is recommended that you include contact details such as an email address, phone number and/or website address to section 8. This information assists users of the PI to communicate with sponsors, such as in the case of adverse event reporting.

This type of change is viewed as a revision to the approved PI. Therefore, the date in Section 9 should be the date the medicine was first entered into the ARTG, and the date of approval of the new tradename should go in Section 10.

The table should have two columns with the headings 'Section changed' and 'Summary of new information'. Only the number of the section that has been changed should be entered in the first column. A brief description of the change should be included in the second column. Safety related changes to the PI may be retained in the table even after a subsequent PI update. If your PI is for a New Chemical Entity, you do not need to include a table.

An example of how the table could be presented is shown below:

Yes. The content of the PI is not changed as part of the reformatting process. Therefore it is acceptable for the PI of generic and biosimilar medicines to be in the new format prior to the innovator reformatting.

Not unless safety-related changes were included in the innovator's PI at the time of reformatting. Inclusion of a safety-related change can now be identified from the information in the Summary table of changes, located in Section 10 of reformatted PIs.

Yes, applications to register a new medicine must be accompanied by a PI in the new format. To prepare a PI for a new generic or biosimilar medicine, the content of the innovator's PI should be provided under the headings of the new form. Where information is missing, the relevant optional standard text may be included.

The statement that '[Biosimilar product name] is a biosimilar medicine to [Reference medicine name]. The evidence for comparability supports the use of [Biosimilar product name] for the listed indication[s]' should be located in section 1, after the name of the active ingredient.

No. The Australian PI must conform to the format described in the Form for providing Product Information. While the headings and format of the PI generally align, there are some differences in the presentation of information. For example, the form describes the preferred presentation of adverse effects information.

For new PIs, the heading '10 Date of revision' should be included in the PI, and the statement 'not applicable' can be included under the heading. It is not necessary to include the summary table of changes for a new PI, but this table must be included following any revision to the PI.

PIs being prepared for new products should contain information under each heading and subheading. The suitability of the text under each heading will be considered as part of the registration process. In some sections, the optional standard text may be considered acceptable, such as the inclusion of:

• 'In Australia, information on the shelf life can be found on the public summary of the ARTG. The expiry date can be found on the packaging' in section 6.3 Shelf life, or
• 'In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy' in section 6.6 Special precautions for disposal.

Please note the new form contains the following mandatory standard text which must be included in your PI:

• 'Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://www.tga.gov.au/reporting-problems' in Section 4.8 Adverse effects (undesirable effects), and
• 'For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia)' in Section 4.9 Overdose.

1 NAME OF THE MEDICINE

• The Australian Approved Name (AAN) of the therapeutically active ingredient or, in the case of a fixed dose combination or composite pack containing multiple therapeutically active ingredients, the AAN of each therapeutically active ingredient.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

• A description of the formulation(s) including quantity, proportion or strength of each therapeutically active ingredient.
• A description of <clinically> relevant physical and chemical characteristics of each therapeutically active ingredient.
• List of excipients <with known effect, followed by the mandatory standard text 'For the full list of excipients, see Section 6.1 List of excipients.'>

Note 1: <For the purpose of this approved form, "quantitative composition" only relates to the quantity of the therapeutically active ingredient.>

Note 2: <Excipients with known effect are those listed in Schedule 1 to the Therapeutic Goods Order No. 91 - Standard for labels of prescription and related medicines and Schedule 1 to the Therapeutic Goods Order No. 92 - Standard for labels of non-prescription medicines.>

Note 3: Australian Approved Names should be used for the excipients.

Note 4: <For products registered prior to 1 January 2018, this section may be combined with section 3 under the heading '2 and 3 QUALITATIVE AND QUANTITATIVE COMPOSITION and PHARMACEUTICAL FORM'.>

3 PHARMACEUTICAL FORM

• Presentation of the medicine, including information about:
  • dosage form; and
  • any other information relevant to the presentation or appearance of the medicine.

Note 5: The pharmaceutical form should be described by the AAN, together with a visual description of the appearance of the product (colour, markings, tablet scoring etc). In the case of products to be reconstituted before use, a reference to the appearance before reconstitution should be included.

4 CLINICAL PARTICULARS

4.1 THERAPEUTIC INDICATIONS

• The therapeutic indications of the medicine.

Note 6: The specific therapeutic uses should be stated clearly and concisely, and should define the target disease or condition, distinguishing between treatment (symptomatic, curative or modifying the evolution or progression of the disease), prevention (primary or secondary) and diagnostic indications. Mandatory conditions of product usage, where relevant, should also be included if not covered more appropriately in other parts of the PI.

4.2 DOSE AND METHOD OF ADMINISTRATION

• Dosage (dose and interval)
• Method of administration
• Dosage adjustment <(if applicable)> in:
  • renal impairment
  • hepatic impairment
  • dialysis
  • concomitant disease.
• <If relevant,> the maximum tolerated daily dose and the maximum dose for an entire course of therapy.
• Monitoring advice.
• Other relevant information such as relationship to meals and compatibility with other medicines and fluids.

4.3 CONTRAINDICATIONS

• A description of situations in which persons:
  • should never be treated with the medicine; and
  • should generally not be treated with the medicine.

Note 7: Situations where life threatening or fatal adverse reactions may occur can also be referred to.

4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Note 8: The circumstances where caution is required in relation to the medicine should be described. The actions the health care professional should take should also be described. Information on <special warnings and> precautions should include, but not be limited to, information of the kind listed below. Additional information can also be provided if appropriate.

Note 9: Examples of the circumstances where caution is required could be in relation to particular population groups or clinical situations where dosage adjustment is required.

Note 10: An example of the actions the health care professional should take could be to specify particular investigations that may need to be carried out.

Identified precautions

• <Include identified precautions and special warnings specific to the use of the medicine under relevant sub-headings.
• If not relevant, this sub-heading may be deleted from this section of the PI.

Note 11: Example sub-headings include 'Hepatotoxicity', 'QT prolongation' etc. These should replace the term 'identified precautions' which is not intended as a sub-heading in the PI.>

Use in hepatic impairment

• <If relevant, include a precaution regarding use of the medicine in persons with hepatic impairment.
• If not relevant, this sub-heading may be deleted from this section of the PI.>

Use in renal impairment

• <If relevant, include a precaution regarding use of the medicine in persons with renal impairment.
• If not relevant, this sub-heading may be deleted from this section of the PI.>

Use in the elderly

• *This subheading is mandatory standard text. If no data are available, then a cross-reference to another relevant section or the following optional standard text may be included: 'No data available'.*

Paediatric use

• *This subheading is mandatory standard text. If no data are available, then a cross-reference to another relevant section or the following optional standard text may be included: 'No data available'.*

Effects on laboratory tests

• *This subheading is mandatory standard text. If no data are available, then a cross-reference to another relevant section or the following optional standard text may be included: 'No data available'.*

4.5 INTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS

Note 12: In relation to interactions with other medicines <or other forms of interaction (such as with food)>, include known clinically relevant interactions and other potentially serious interactions. Interactions should be grouped according to outcome, for example, potentiation or reduction of effect, and the mechanism of action should also be explained where this is known.

Note 13: If relevant, a cross-reference to 'Section 6.2 - Incompatibilities' may be included.

4.6 FERTILITY, PREGNANCY AND LACTATION

Note 14: The following subheadings are mandatory *standard text*. If no data are available, then the following optional standard text may be included: 'No data available'.

Effects on fertility

Use in pregnancy

Note 15: Include a proposed or approved Australian Pregnancy Categorisation, any relevant standard text for the class of medicine and other information consistent with this categorisation, as well as effects on labour and delivery.

Use in lactation

4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

• Extent to which the medicine influences the ability of persons to drive or use machines.

Note 16: <Medicines listed in Appendix K to the current Poisons Standard should include a sedation warning in this section.

Note 17: If the medicine was registered prior to 1 January 2018 and there is currently no statement regarding effects of ability to drive and use machines, then the following optional standard text may be included: 'The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration'.>

4.8 ADVERSE EFFECTS (UNDESIRABLE EFFECTS)

• Severity, clinical importance and frequency of adverse effects.

Note 18: For clarity and consistency, the following format is preferred:

Note 19: <following mandatory standard text must be included in this section:

4.9 OVERDOSE

• Symptoms, signs and recommended treatment of overdose or accidental poisoning.

Note 20: The following mandatory standard text <must be> included under this heading:

Note 21: For all overdoses, the mainstay of treatment is supportive and symptomatic care. This should be emphasised before discussion of specific antidotes. Information on serious toxicity, Tmax, elimination half-life (in the setting of overdose) and the effectiveness of haemodialysis and repeated doses of activated charcoal in removing the medicine are very useful in the management of overdose. Any available information on these issues, including animal data, should be considered for inclusion.

Note 22: If activated charcoal is considered to be potentially useful in the management of overdose of the medicine, then a suitable statement for inclusion would be:

Note 23: Whole bowel irrigation may be useful in the management of overdose of slow release preparations with significant toxicity (eg. slow release calcium channel blockers) or medicine not absorbed by charcoal (eg. iron, lithium). If whole bowel irrigation is considered to be potentially useful in the management of overdose of the medicine, then a suitable statement for inclusion would be:

Note 24: Syrup of Ipecac and gastric lavage are no longer considered to be standard therapy for gut decontamination. Reference to these interventions therefore need not routinely be included.

Note 25: It is generally inappropriate to include LD50 values from any animal studies.

5 PHARMACOLOGICAL PROPERTIES

Note 26: *The following subheadings are mandatory standard text.*

5.1 PHARMACODYNAMIC PROPERTIES

Mechanism of action

• The pharmacology and pharmacological actions of the medicine, especially in humans.

Clinical trials

• Clinical trials related to the indications, both positive and negative.

Note 27: If the medicine was registered prior to 1991 and there have been no applications to the Therapeutic Goods Administration requiring the advice of either the Australian Drug Evaluation Committee (ADEC) or the Advisory Committee on Prescription Medicines (ACPM) since then, it is unlikely that suitable clinical trial data will be available. In that case, the Clinical Trials section may include the optional standard text 'No data available'.

Note 28: For over the counter medicines not registered on the basis of clinical trial data, the Clinical Trials section may include the optional standard text 'No data available'.

5.2 PHARMACOKINETIC PROPERTIES

• Pharmacokinetics, especially in humans, with subheadings *(if relevant)* in the order shown below.

Absorption

Distribution

Metabolism

Excretion

5.3 PRECLINICAL SAFETY DATA

• <Preclinical safety data with subheadings in the order shown below.>

Genotoxicity

• *This subheading is mandatory standard text. If no data are available, then the following optional standard text may be included: 'No data available'.*

Carcinogenicity

• *This subheading is mandatory standard text. If no data are available, then the following optional standard text may be included: 'No data available'.*

6 PHARMACEUTICAL PARTICULARS

6.1 LIST OF EXCIPIENTS

• Complete list of excipients, including those listed in section 2.

Note 29: Australian Approved Names should be used for the excipients.

Note 30: <If the medicine was registered prior to 1 January 2018, the following optional standard text may be used in this section: 'Refer to Section 2 - Qualitative and quantitative composition.'>

6.2 INCOMPATIBILITIES

• Information on physical and chemical incompatibilities of the medicine with other products with which it is likely to be mixed or co-administered.

Note 31: <If the medicine was registered prior to 1 January 2018 and the approved PI did not require a statement on incompatibilities, then the following optional standard text may be used in this section: 'Incompatibilities were either not assessed or not identified as part of the registration of this medicine.'

Note 32: If relevant, a cross-reference to 'Section 4.5 - Interactions with other medicines and other forms of interactions' may be included.>

6.3 SHELF LIFE

• Duration of approved shelf-life

Note 33: <The following optional standard text may be used in place of the shelf-life information in this section: 'In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.'

Note 34: If relevant, information on the in-use shelf life may be included in this section of the PI.>

6.4 SPECIAL PRECAUTIONS FOR STORAGE

• Storage conditions.

6.5 NATURE AND CONTENTS OF CONTAINER

• Container type.
• Pack sizes.

Note 35: Reference should be made to the immediate container for the medicine using the AAN and the material of construction of the immediate container (for example, "glass vial", "PVC/Aluminium blisters"). Any other component of the product should be listed (for example, needles, swabs, measuring spoons, syringes or inhaler devices). The container of any solvent provided with the medicine should also be described.

Note 36: All pack sizes should be listed. Pack sizes mentioned should include the number of units, total weight or volume of the immediate container (as appropriate) and the number of containers present in any outer carton.

6.6 SPECIAL PRECAUTIONS FOR DISPOSAL

Note 37: <If there are no special precautions for disposal, then *one or the other of* the following optional standard text may be used in this section: 'In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.'>

*'In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.'*

6.7 PHYSICOCHEMICAL PROPERTIES

Chemical structure

• The chemical structure of each therapeutically active ingredient, except in the case of therapeutically active ingredients that are:
  • inorganic salts or simple organic compounds where a molecular formula may be included;
  • complex biological molecules such as large peptides and proteins, where a simpler schematic presentation of the structure may be included; and
  • substances where the structure is not defined.

CAS number

• The Chemical Abstracts Service (CAS) Registry Number of the medicine.

7 MEDICINE SCHEDULE (POISONS STANDARD)

• The schedule of the current Poisons Standard in which the medicine is included (if applicable).

8 SPONSOR

• Name, street address <and contact details> of the sponsor of the medicine.

Note 38: <It is recommended that the PI include contact details such as an email address, phone number and/or website address for the sponsor.

Note 39: If the medicine was registered prior to 1 January 2018 and the approved PI did not include these details, then inclusion of the sponsor name and street address only is acceptable.>

9 DATE OF FIRST APPROVAL

• Date of first inclusion in the Australian Register of Therapeutic Goods.

Note 40: To be completed when the medicine is included in the ARTG.

10 DATE OF REVISION

• Date of the most recent TGA approved changes to an approved PI.

Note 41: To be completed at the time of any approval of change(s) to the approved PI, including changes to tradenames or approval of additional tradenames.

Summary table of changes