Notifications for prescription medicines (non-biological medicines)

• The API must not be sterile.
• The material of the container/closure must be either unchanged or is changed to a more protective material.
• The thickness of the material must be either unchanged or increased.
• There must either be no change in retest period/storage conditions, or a decrease in retest period and/or more stringent storage conditions are applied in the new container/closure system.

You must submit:

• Details of the new container/closure system.
• Details of the new retest period or storage conditions, if changed.

You must generate the following:

• Relevant comparative moisture permeability data for the current and proposed material demonstrating either equivalent or better moisture protection.
• Initial stability testing data of the API in the new container/closure system conducted in accordance with relevant stability testing guidelines.

• The API must not be manufactured wholly or substantially by fermentation.
• The API must not be a synthetic polypeptide.
• The API must not be manufactured as a sterile drug substance.
• The current CEP must have been approved previously by the TGA.
• The revised CEP must be the next issued version from that approved by the TGA. Additional consecutive updates can be included if:
  • they follow the 5 year renewal (with no other changes) and/or
  • the changes are for minor administrative updates and/or
  • the drug substance has not been used to manufacture any drug products supplied in Australia.
  • Where changes to the API specification are involved (including test parameters, limits and test methods), the same changes must be adopted by the product sponsor and/or drug product manufacturer, and any new test methods must be validated as suitable for use.
• Where the change to the CEP is a change to the site of API manufacture, the site must have either:
  • a licence to manufacture the API (if the site is in Australia) or
  • sponsor-specific GMP clearance (if the site is overseas) that is valid at the time of the application.

You must submit:

• Documentary evidence that the current CEP has been previously approved by the TGA.
• The updated CEP, including any annexes, or a declaration from the EDQM that, due to the nature of the changes, an updated CEP was not issued.
• A summary of the changes made to the API that resulted in the revision of the CEP.
• A declaration that any test requirements in addition to those in the CEP that were previously approved by the TGA will continue to apply.
• A declaration that no significant changes to the API have been made since the revised CEP was issued. If minor changes have been made, a flow diagram or outline of the revised route of synthesis of the API must also be submitted.

You must generate the following data:

• Relevant comparative data for pre-change and post-change batches of the API (if the revision to the CEP is due to changes to the method of synthesis that involve using different crystallisation solvents, a different purification process, or micronisation of the final drug substance).
• Comparative data using validated test methods to show that:
  • there is no change in the crystalline (polymorphic) form of the final substance (if relevant) and
  • the particle size distribution profiles (tested by a laser diffraction or other equivalent method) remain comparable and within the same ranges as the pre-change API. Alternatively comparative dissolution profiles must be generated.
• Comparative batch data from at least one production-scale batch of the final drug substance manufactured or tested according to the changed process, which demonstrate compliance with any revised API specification.

• Any increase in batch size must be less than 10 fold from that last evaluated by the TGA.
• There must be no change in route of synthesis (including solvents used in the final purification of the API), other than any necessary adjustment to processing conditions or use of different equipment.
• The change must not be due to unexpected events arising during manufacture or to stability concerns.
• The API must not be a sterile substance.

You must submit:

• Details of the new manufacturing batch size.

You must generate the following data:

• Comparative batch data demonstrating there is no significant difference in the tested parameters, particularly particle size distribution, polymorphism and impurity profiles.

• There must be at least one other registered site of manufacture for the API.

You must submit:

• The name and address of the manufacturer to be ceased.
• A current TGA Business Services printout for the product or a copy of the TGA approval showing that at least one registered site of manufacture of the API remains to perform the relevant steps of manufacture.

• The change must be consistent with any applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products.
• The change must not be due to adverse events during manufacture.
• The change must result in equivalent or improved quality of the final isolated material.
• The specifications of the API and/or intermediates may only be changed in ways permitted in other parts of this guidance document or remain unchanged.
• The new test method must not be a biological method.

You must submit:

• Details of the new in-process control tests and limits.

You must generate the following data:

• Appropriate validation data for the in-process control test method.
• Batch analytical data from testing of three batches using the current and proposed methods demonstrating the results are within the same ranges.

• The change must be consistent with any applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products.
• The synthetic route must remain the same, and no new reagents, solvents or catalysts are to be used in the amended process.
• The change must not involve any sterilising steps.
• The specifications of the API, starting materials and intermediates may only be changed in ways permitted in other parts of this document or remain unchanged.

You must submit:

• Details of the amended manufacturing process, including the synthesis flowchart.

You must generate the following data:

• Comparative batch data for the API/starting material/intermediate demonstrating there are no significant differences in the purity profiles or physicochemical properties.

• The intermediates must be isolated chemical species and be at least three steps back in the synthetic scheme from the API (purification procedures do not count as steps of synthesis).
• The synthetic route must remain the same, and no new reagents, solvents or catalysts are to be used at the new site.
• The specification limits of starting materials or intermediates must be the same or tighter.
• For intermediates prepared wholly or partially by fermentation:
  • there must be either no change in the strain of the producer organism used or, where there is a change, details of the new producer organism must be provided and the component profiles of the final fermentation broth at harvest made from the new and old strain must be the same.
  • there must be no changes to the scale of operation of the fermentation tank and fermentation processes.
  • there must be no changes to the nature of the media ingredients, particularly precursors, activators or components of biological or animal origin (although changes to the quantities used are acceptable, provided that they are not a result of a change in scale of operation).

You must submit:

• The name and site address of the new manufacturer(s) of the starting material(s) or intermediate(s).
• The route of synthesis of the API.
• The name or code number of the intermediates for which the alternative site of manufacture is sought.

You must generate the following data:

• Comparative batch data (including impurity levels) for the starting material(s) or intermediate(s) manufactured at the current and proposed sites using validated test methods demonstrating that there are no significant differences in purity profiles.
• Comparative batch data for API synthesised using starting material(s) or intermediate(s) from the current and proposed sites demonstrating that there are no significant differences in purity profiles.

• The API must be prepared by chemical synthesis or isolated from a natural source as pure chemical entities.
• The API must not be prepared wholly or partially by fermentation, and must not be sterile.
• There must be no change to the existing method of synthesis, including to any intermediates and any solvents or reagents used in the synthesis and purification of the drug substance (the API), or any other aspect of manufacture and specifications.

• The manufacturing batch size remains unchanged or smaller.

• The new site must have either:
  • a current manufacturing licence issued by the TGA for this type of manufacture (if the site is in Australia) or
  • a sponsor-specific GMP clearance (if the site is overseas) that is valid at the time of the application for this type of manufacture.

You must submit:

• The name and address of the new manufacturing site and GMP clearance number.
• The flowchart of the route of synthesis from the existing site and the new site of manufacture.
• The manufacturing batch size at the new site.

You must generate the following data:

• Comparative batch data for three batches of the API from the proposed site. This data must demonstrate that all results (including impurity profiles, particle size distribution and polymorphic forms) are either:
  • within the same range as three batches manufactured at the current site (that is, no new impurities or polymorphic forms are present) or
  • remain unchanged.

• The proposed method must not be a biological method.
• Validation data from the proposed method must demonstrate either:
  • an improvement in at least one of precision, accuracy or specificity, without a reduction in the other parameters or
  • an improvement in specificity or accuracy with reduced precision (while precision remains within the specified limits).

You must submit:

• A summary description of the change and details of the new method.

You must generate the following data:

• Validation data for the proposed method.
• Data for three batches of the API tested using the current and proposed methods demonstrating equivalency of both methods.

• The change should not be the result of unexpected events arising during manufacture or because of stability concerns.

You must submit:

• Reasons for the change.
• Details of the new retest period and/or storage conditions.
• An assurance that you possess adequate stability data for at least three production-scale batches of the API to support the new retest period and/or storage conditions.

• The changes to identification tests must:
  • be from a less specific to a more specific identification test (for example, from an ultraviolet/visible spectrophotometric or chromatographic method, such as thin layer chromatography, gas chromatography or high-performance liquid chromatography (HPLC), to a conventional infrared spectroscopic method) and/or
  • vary the existing identification test (for example, an HPLC test that has been shown to improve or at least maintain the specificity of the method) and/or
  • replace an existing identification test with a near infrared spectroscopic identification test and/or
  • include a new identification test in addition to an existing identification test.
• Any additional identification test must not serve as an alternative identification test.
• For near infrared spectroscopy tests, the method development and other data requirements (including data collection, establishment of the spectral reference library, calibration and validation of the method) must comply with the currently adopted European Medicines Agency (EMA) guideline on the use of near-infrared spectroscopy.

You must submit:

• The revised set of specifications.
• Details of the identification test method.

• The proposed limits must be consistent with any applicable official standard or adopted guidelines.

• The grade of material must not change (for example, unmicronised to micronised material).

You must submit:

• The revised set of specifications for the starting materials, intermediates or API (as applicable).

You must generate the following data:

• Data for at least three production-scale batches demonstrating compliance with the proposed test and limits.

• The change must not result from an altered method of manufacture that changes the material’s quality characteristics (such as micronisation).
• The proposed method must be validated.
• Applied limits must be based on batch analytical data, and comply with any applicable official standard or adopted guidelines.
• The change must not involve a genotoxic impurity.

You must submit:

• Details of the new method.
• The revised set of specifications for the starting materials, intermediates or API (as applicable).

You must generate the following data:

• Comparative batch data for at least three commercial batches demonstrating compliance with the proposed test and limit.

• The test limit must either remain unchanged or be more stringent.
• The amended method must have been validated or deemed comparable.
• The test principle must remain unchanged.

You must submit:

• Details of the new method together with a summary description of the change.

You must generate the following data:

• Appropriate validation data or comparison data for the new method.

• The API must already be tested to the existing pharmacopoeial or TGO requirements.
• The requirements applied from one pharmacopoeia must not be changed to another (e.g. changing from the BP to the USP requires the submission of data for evaluation).
• The new pharmacopoeial monograph or amended TGO must be applicable to the API.
• Any tests that were performed in addition to those of the pharmacopoeial monograph must continue to be applied, except where the test was removed going from the old monograph to the new one.

You must submit:

• The revised set of specifications for the API.

• The change must not be an increase in batch size for sterile products or products manufactured under sterile conditions.
• For sterile products, a decrease in manufacturing batch size must be either:
  • not accompanied by any change in sterile manufacturing process or
  • where there has been a change in sterile manufacturing process, the specific conditions in DMSE: Drug product manufacture - changes to manufacturing method and/or equipment of sterile dosage forms that are not modified release have been met.
• The product must not be a modified-release dosage form. This includes enteric-coated tablets, enteric capsules and transdermal patches.
• The new manufacturing batch size must be validated in accordance with applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products and any relevant guidelines adopted by the TGA.

You must submit:

• Details of the new manufacturing batch size, with the revised batch manufacturing formula.

You must generate the following data:

• Additional validation data as required for the dosage form, as appropriate:
  • For semi-solid/liquid dosage forms, see DMEL: Drug product manufacture - changes to manufacturing method and/or equipment of semi-solid/liquid dosage forms that are not modified release.
  • For oral/nasal inhalation dosage forms, see DMEO: Drug product manufacture - changes to manufacturing method and/or equipment of oral/nasal inhalation dosage forms that are not modified release.
  • For solid dosage forms, see DMES: Drug product manufacture - changes to manufacturing method and/or equipment of solid dosage forms that are not modified release.
  • For sterile dosage forms, see DMSE: Drug product manufacture - changes to manufacturing method and/or equipment of sterile dosage forms that are not modified release.

• The product must not be a modified-release dosage form (including enteric-coated tablets, enteric capsules and transdermal patches) or sterile.
• The new manufacturing method and equipment must be validated consistent with applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products and any relevant guidelines adopted by the TGA on at least one production-scale batch of the product.

You must submit:

• Details of the revised method of manufacture and/or equipment, and any relevant flow diagram of the new process.

You must generate the following data:

• Comparative batch data that demonstrates all results are comparable and within the same range as those obtained previously, as well as meeting currently approved drug product release specifications.
• For semi-solid and liquid products (for example, ointments, creams, lotions, oral liquids, moulded suppositories and pessaries), comparative batch data using appropriate current methodology demonstrating that there has been no change to the particle size distribution and polymorphic form of the API in suspension. These data are not required if the API is in solution for the drug product, or if it is in solution as liquid globules.

• The product must not be a modified-release dosage form (including enteric-coated tablets, enteric capsules and transdermal patches) or sterile.
• The new manufacturing method and equipment must be validated consistent with applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products and any relevant guidelines adopted by the TGA on at least one production-scale batch of the product.

You must submit:

• Details of the revised method of manufacture and/or equipment, and any relevant flow diagram of the new process.

You must generate comparative batch data:

• That demonstrates all results are comparable and within the same range as those obtained previously, as well as meeting currently approved drug product release specifications.
• For the drug mass aerodynamic particle size distribution of the aerosol emitted by the drug product (for metered-dose pressurised inhalations, metered-dose nasal spray solutions, and dry powders for oral or nasal inhalation) that demonstrates that results are in the same range as previously obtained, as measured by either a multi-stage liquid impinger or a multi- stage cascade impactor (Andersen type).

• The product must not be a modified-release dosage form (including enteric-coated tablets, enteric capsules and transdermal patches) or sterile.
• The new manufacturing method and equipment must be validated consistent with applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products and any relevant guidelines adopted by the TGA on at least one production-scale batch of the product.

You must submit:

• Details of the revised method of manufacture and/or equipment, and any relevant flow diagram of the new process.

You must generate the following data:

• Comparative batch data that demonstrates all results are comparable and within the same range as those obtained previously, as well as meeting currently approved drug product release specifications.
• All solid dosage forms (for example, tablets, capsules, compressed suppositories and pessaries) must have similar comparative dissolution profiles - that is, the similarity factor, f2, should be between 50 and 100. These data are not required if the API is in solution for the drug product, or if it is in solution as liquid globules.

• The change must not relate to the parametric release of sterile products.

• The change must be consistent with applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products.
• Any changes to in-process control test methods must be validated appropriately.
• The change must result in either improved quality or no change in the quality of the drug product.

You must submit:

• Details of the changes proposed, and the revised set of in-process control tests and limits. Test method details are not required.

You must generate the following data:

• Comparative batch data with the results within the same range as previously obtained.

• Any excipient involved must not be an antioxidant or another ingredient whose function (at least in part) involves being ‘consumed’ over time.
• Manufacture of the product with reduced overage must be appropriately validated.
• The TGA must be notified as a priority if the results of supporting stability data fail to meet the specifications. The TGA reserves the right to withdraw the product from the market if this requirement is not met.

You must submit:

• The revised manufacturing formula.

You must generate the following data:

• Comparative batch data to demonstrate that the results are comparable to those obtained previously (allowing for the reduction in overage).
• Stability data on at least one production batch of the post-variation product (with at least two more production batches to be similarly tested) should have been initiated.

• The product must not be a modified-release dosage form.
• The new manufacturing method and equipment must be validated consistent with applicable principles of the Guide to Good Manufacturing Practice for Medicinal Products on at least one production-scale batch of the product.
• Other changes to ensure sterility are permitted, provided that:
  • the technology to be used already exists at the manufacturing site and is in use for other TGA-approved products.
  • there are no changes to (or there are improvements in) microbiological environmental standards, bioburden specifications, the sterilisation cycle or its parameters, and sterility assurance levels.

You must submit:

• Details of the revised method of manufacture and/or equipment, and any relevant flow diagram of the new process.
• Validated process times.

You must generate the following data:

• Comparative batch data that demonstrates all results are comparable and within the same range as those obtained previously, as well as meeting currently approved drug product release specifications.
• The new method of manufacture (including sterilisation of containers or container components, and use of a second filter in a filling line) or new manufacturing equipment (such as introduction of a similar filling line) must not affect the final sterility of the product.
• All of the dosage-specific data requirements described in the following change types must be certified as having been met, as appropriate:
• • For solid dosage forms, see DMES: Drug product manufacture - changes to manufacturing method and/or equipment of solid dosage forms that are not modified release.
  • For semi-solid/liquid dosage forms, see DMEL: Drug product manufacture - changes to manufacturing method and/or equipment of semi-solid/liquid dosage forms that are not modified release.
  • For oral/nasal inhalation dosage forms, see DMEO: Drug product manufacture - changes to manufacturing method and/or equipment of oral/nasal inhalation dosage forms that are not modified release.

• This change is applicable to all medicines, including sterile products and modified-release dosage forms.
• There must be at least one other site that performs the same steps of manufacture as the ceased site, or that performs the deleted step of manufacture.

You must submit:

• The name and address of the manufacturer to be ceased.
• Details of the manufacturing step(s) to be deleted, as relevant.
• Documentary evidence to show that there is at least one registered site of manufacture performing the same step of manufacture as the ceased site.

• A change in, or addition of an alternative, site of primary packaging operations may relate to any product except products that are sterile or are manufactured under sterile conditions.
• A change in, or addition of an alternative, site of secondary packaging operations may relate to any product, including sterile products and products manufactured under sterile conditions.
• The new site must have either:
  • a current manufacturing licence issued by the TGA (Australian manufacturers) for this type of manufacture or
  • a current GMP clearance issued by the TGA and valid at the time of this application (overseas manufacturers) for this type of manufacture.
• Apart from the change in site of manufacture, there must be no change to any aspect of the quality data other than changes to manufacturing equipment.
  • Where a change in manufacturing equipment is made, this must be validated in accordance with the principles of GMP.

You must submit:

• The name and address of the new manufacturer and licence/clearance number.
• Details of the manufacturing step(s) undertaken at the new site of manufacture.

• Applies to sites of manufacture of the final drug product only, not sites performing in- process steps.
• The product must not be sterile or manufactured under sterile conditions.
• The product must not be a modified-release dosage form. This includes enteric-coated tablets, enteric capsules and transdermal patches.
• The new site must either have:
  • a current manufacturing licence issued by the TGA (Australian manufacturers) for this type of manufacture or
  • a current GMP clearance issued by the TGA and valid at the time of this application (overseas manufacturers) for this type of manufacture.
  • There must be no changes to any aspect of the quality data other than changes to manufacturing equipment or method at the new site of manufacture and
  • The changes to the manufacturing methods are only those necessitated by scale-up or downscaling, e.g. use of different-sized equipment or
  • The change does not adversely affect the reproducibility of the process and it is not the result of unexpected events arising during manufacture or because of stability concerns.
  • Where a change in manufacturing equipment or method is made, this must have been validated at the new manufacturing site in accordance with the principles of GMP and/or any relevant guidelines adopted by the TGA.

You must submit:

• The name and address of the new manufacturer and licence/clearance number.
• Details of the manufacturing step(s) undertaken at the new site of manufacture.
• A summary of the change in manufacturing equipment or manufacturing method at the new site, if relevant.

You must generate the following data:

• Comparative batch data demonstrating all results are comparable and within the same range as those obtained previously, as well as meeting currently approved drug product release specifications.
• For semi-solid and liquid products (for example, ointments, creams, lotions, oral liquids, moulded suppositories and pessaries), comparative batch data using appropriate current methodology demonstrating that there has been no change to the particle size distribution and polymorphic form of the API in suspension. These data are not required if the API is in solution at any stage during manufacture of the drug product or if it is in solution in the drug product or present as liquid globules.

• Applies to sites of manufacture of the final drug product only, not sites performing in- process steps. For changes to the site of manufacture not involving the final product see:
  • EMMP: Excipients (not of animal or human origin) - changes to the manufacturing process and/or site (same specifications) or
  • CSNS: Non sterile container - changes to the supplier or manufacturer if same material and specification.
• The product must not be sterile or manufactured under sterile conditions.
• The product must not be a modified-release dosage form.
• The new site must either have:
  • a current manufacturing licence issued by the TGA (Australian manufacturers) for this type of manufacture or
  • a current GMP clearance issued by the TGA and valid at the time of this application (overseas manufacturers) for this type of manufacture.
• There must be no changes to any aspect of the quality data other than changes to manufacturing equipment or method at the new site of manufacture.
  • Where a change in manufacturing equipment or method is made, this must have been validated at the new manufacturing site in accordance with the principles of GMP and/or any relevant guidelines adopted by the TGA.

You must submit:

• The name and address of the new manufacturer and licence/clearance number.
• Details of the manufacturing step(s) undertaken at the new site of manufacture.
• A summary of the change in manufacturing equipment or manufacturing method at the new site, if relevant.
• A declaration that the changes to the manufacturing methods are only those necessitated by scaling-up or down, e.g. use of different-sized equipment, that the change does not adversely affect the reproducibility of the process, that it is not the result of unexpected events arising during manufacture or because of stability concerns.

You must generate the following data:

• Comparative batch data demonstrating all results are comparable and within the same range as those obtained previously, as well as meeting currently approved drug product release specifications.
• For metered-dose pressurised inhalations, metered-dose nasal spray solutions, and dry powders for oral or nasal inhalation, the comparative batch data for the drug mass aerodynamic particle size distribution of the aerosol emitted by the drug product demonstrating that results are in the same range as previously obtained, as measured by either a multi-stage liquid impinger or a multi-stage cascade impactor (Andersen type).

• Applies to sites of manufacture of the final drug product only, not sites performing in- process steps.
• The product must not be sterile or manufactured under sterile conditions.
• The product must not be a modified-release dosage form. This includes enteric-coated tablets, enteric capsules and transdermal patches.
• The new site must either have:
  • a current manufacturing licence issued by the TGA (Australian manufacturers) for this type of manufacture or
  • a current GMP clearance issued by the TGA and valid at the time of this application (overseas manufacturers) for this type of manufacture.
• There must be no changes to any aspect of the quality data other than changes to manufacturing equipment or method at the new site of manufacture as outlined under Site of manufacture changes.
  • Where a change in manufacturing equipment or method is made, this must have been validated at the new manufacturing site in accordance with the principles of GMP and/or any relevant guidelines adopted by the TGA.

You must submit:

• The name and address of the new manufacturer and licence/clearance number.
• Details of the manufacturing step(s) undertaken at the new site of manufacture.
• A declaration that the changes to the manufacturing methods are only those necessitated by scaling-up or down, e.g. use of different-sized equipment, that the change does not adversely affect the reproducibility of the process, that it is not the result of unexpected events arising during manufacture or because of stability concerns.

You must generate the following data:

• Comparative batch data demonstrating all results are comparable and within the same range as those obtained previously, as well as meeting currently approved drug product release specifications.
• All solid dosage forms (for example, tablets, capsules, compressed suppositories and pessaries) must have similar comparative dissolution profiles - that is, the similarity factor, f₂, should be between 50 and 100. These data are not required if the API is in solution at any stage during manufacture of the drug product, or if it is in solution in the drug product or present as liquid globules.

• The change applies to sites of manufacture of the final drug product only, not sites performing in-process steps.
• This change is applicable to all medicines, including sterile products and modified-release dosage forms.
• The new site must either have:
  • a current manufacturing licence issued by the TGA (Australian manufacturers) for this type of manufacture or
  • a current GMP clearance issued by the TGA and valid at the time of this application (overseas manufacturers) for this type of manufacture.
• There may not be any changes to the existing test methods used for testing the product, whether or not the test methods have been provided to the TGA previously, except where allowed by DMSL: Drug product site of manufacture - change to site of manufacture of non-sterile semi-solid/liquid dosage forms that are not modified release.

You must submit:

• The name and address of the new manufacturer and licence/clearance number.
• Details of the manufacturing step(s) undertaken at the new site of manufacture.

You must generate the following data:

• Appropriate technology transfer of the approved test methods to the proposed site must have been carried out.

• The product must not be a radiopharmaceutical.
• If the results obtained using the proposed method do not agree with the results obtained during TGA testing, using an official method, the results from the official method will be deemed to be correct.
• The proposed method must not be a biological method.
• The proposed method must not be a test method for impurities, related substances or degradation products.
• Validation data from the proposed method must demonstrate either:
  • an improvement in at least one of precision, accuracy or specificity, without a reduction in the other parameters or
  • an improvement in specificity or accuracy with reduced precision (whilst precision remains within the specified limits).

You must submit:

• Details of the proposed test method.

• You must generate the following data:

• Appropriate validation data for the proposed method.

• The changes to identification tests must:
  • be from a less specific to a more specific identification test (for example, from an ultraviolet/visible spectrophotometric or chromatographic method, such as thin layer chromatography, gas chromatography or high-performance liquid chromatography (HPLC), to a conventional infrared spectroscopic method) and/or
  • vary the existing identification test (for example, an HPLC test that demonstrably improves or at least maintains the specificity of the method) and/or
  • replace an existing identification test with a near infrared spectroscopic identification test and/or
  • include a new identification test in addition to an existing identification test.
• The method must be appropriately validated.
• Any additional identification test included cannot serve as an alternative identification test (this should be submitted as a Category 3 application).
• If near-infrared spectroscopy is used, the method development and other data requirements (including data collection, establishment of the spectral reference library, calibration and validation of the method) must comply with the current EMA guideline on use of near-infrared spectroscopy that has been adopted by the TGA.

You must submit:

• Details of the changes to the existing test or the new identification test.
• The revised set of drug product specifications at release and expiry.

You must generate the following data:

• Appropriate validation data for the identification test.

• Any changes can be made to assay and/or related substances test methods, but not to a dissolution method which requires TGA evaluation of supporting data.
• The method must be appropriately validated.

You must submit:

• A summary description of the change and details of the new method.

You must generate the following data:

• Equivalency of the current and pharmacopoeial test method must be established by testing of three batches of the drug product using the current and proposed methods.

• The proposed limits must be consistent with applicable official standards or adopted guidelines.
• There must be no change in test methods other than those allowed under change types:
  • DSAM: Drug product specification - changes to non-biological assay method for an active or excipient that is not a radiopharmaceutical.
  • DSIP: Drug product specification - changes from an in-house test method to a pharmacopoeial test method.
  • DSPT: Drug product specification - changes resulting from pharmacopoeial or TGO requirements.
  • DSPL: Drug product specification - minor changes to physicochemical test methods and limits.

You must submit:

• A statement of the current and proposed limits.
• The revised set of drug product specifications at release and expiry.

• The proposed method must be validated.
• The proposed limit (release and expiry) of the new test must be based on batch data obtained at product release and on storage for the duration of the shelf life of the product. The limit must comply with any applicable official standard, TGO or adopted guidelines.

You must submit:

• A statement of the new test and limit.
• The revised set of product specifications at release and expiry.
• Details of the test method.

You must generate the following data:

• Appropriate validation data for the test method.

• The test limit should either remain unchanged or be more stringent.
• The amended method should have been validated.

You must submit:

• Details of the new method together with a summary description of the change.

You must generate the following data:

• Appropriate validation data for the new method.

• The products must currently be tested to the existing pharmacopoeial or Therapeutic Goods Order (TGO) requirements.
• Any tests that are performed in addition to those of the pharmacopoeial monograph or TGO must continue to be performed.
• The requirements applied from one pharmacopoeia must not be changed to another, except where the changes are allowed by other sections of this document (e.g. changing from USP to BP is not permitted as a notification).
• The new pharmacopoeial monograph or amended TGO must be applicable to the product and, if necessary, appropriate validation data must be generated.
• If the change involves updating microbiological test requirements for non-sterile products to meet the TGO for microbiological standards for medicines, the product must have undergone a risk assessment for objectionable microorganisms in addition to those specified in the pharmacopoeias that form the basis of the TGO.

You must submit:

• The revised set of drug product specifications (release and expiry), if applicable.
• If the change relates to an update to meet the requirements of the TGO for microbiological standards for medicines, a written assurance that the TGA can review the risk assessment report for objectionable microorganisms other than those specified in the order, if required.

You must generate:

• Appropriate validation data, as required.

• All aspects of the test must comply with the requirements of the internationally harmonised test published in a default pharmacopoeia and as specified in TGO 77 - Microbiological Standards for Medicines.
• The change must comply with the guidelines on particular aspects of the sterility test that are outlined in Guidance 17 - Microbial quality of prescription and over-the-counter medicines.

You must submit:

• Details of the new method together with a summary description of the change.

• The product must only be intended for oral, topical, vaginal, rectal or inhalation routes, with no potential for cross-contamination with higher risk (Category A or B) tissues.
• The product must not be administered by the parenteral, ophthalmic or intra-tracheal routes.
• The change must be from a ruminant-derived source to a plant or other non-animal source.
• No changes to the specifications of the excipients are permitted, except for the changes allowed within the Changes to excipients section.

You must submit:

• Details of the excipients and the proposed changes.
• Where relevant, CEP issued by the EDQM to the manufacturer of the excipient.
• A declaration that the Category IC material has been self-assessed and complies with the TGA’s requirements regarding Transmissible Spongiform Encephalopathies (TSE) risks.
• An assurance that records of compliance will be maintained for future inspection by the TGA.
• The revised specifications, if changes have been made.

• The proposed method must either:
  • improve at least one of precision, accuracy or specificity without a reduction in the other parameters or
  • the proposed method must improve accuracy or specificity with reduced precision if precision remains within the specified limits.

You must submit:

• Details of the new assay method.

You must generate the following data:

• Appropriate validation data for the proposed method.

• Change or addition must only be to test methods for physicochemical parameters (e.g. pH, colour, particle size, particulate matter, density, specific gravity, optical rotation, osmolality, osmolarity and viscosity).
• The change must not result from an altered method of manufacture that changes the material's quality characteristics (such as micronisation).
• Applied limits must be based on batch analytical data, and comply with any applicable official standard (TGO or default standard) or adopted guidelines.
• Any tests that are performed in addition to those of the pharmacopoeial monograph or TGO for critical parameters (e.g. particle size, pH, viscosity) must continue to be performed.

You must submit:

• The revised set of specifications for the excipient.
• A summary description of the change and details of the new method.

You must generate the following data:

• Validation data for the method(s), as required.
• Equivalency of the current and pharmacopoeial test method(s) must be established by testing of three batches using the current and proposed methods.

• The proposed limits must be consistent with any applicable official standard (TGO or default standard) or adopted guidelines.

You must submit:

• A statement of the current and proposed limits.
• The revised set of specifications for the excipient.

• The change must not result from an altered method of manufacture that changes the material's quality characteristics (such as micronisation).
• Applied limits must be based on batch analytical data, and comply with any applicable official standard (TGO or default standard) or adopted guidelines.

You must submit:

• Details of the new test and limit, including the test method.
• The revised set of specifications for the excipient.

You must generate the following data:

• Appropriate validation data for the proposed method.

• The excipient must be tested to the existing pharmacopoeial or TGO requirements.
• Any tests that are performed in addition to those of the pharmacopoeial monograph or TGO must continue to be performed.
• The new pharmacopoeial monograph or TGO must be applicable to the excipient.

You must submit:

• Details of the proposed change.
• The revised set of specifications for the excipient.

• The change is restricted to one or more of the following:
  • a change to, or addition or removal of, the outer carton or other outer primary pack (including changes to size, shape, colour or material thickness); and/or
  • a change to, or addition or removal of, components of the container that are not in direct contact with the product (for example, tamper-evident seal, aluminium flip-off crimps on injection vials, plastic dust-cover disc/top/cap); and/or
  • the inclusion or removal of inert wadding from bottles and other containers containing solid dosage forms; and/or
  • the inclusion of a desiccant in containers of solid dosage forms; and/or
  • the inclusion of, or change to, an outer overwrap designed to prevent ingress or egress of moisture, solvent or gases from a container (including changes to size, shape or colour, or increased material thickness).
• Other than inert wadding and desiccant, the components must not be in direct contact with the product.
• The label of any outer carton or other primary pack that is added or changed must either be identical to the container label or be changed as permitted under:
• • Changes to product labels that are notifications and/or
  • Changes that do not require TGA prior approval (see the TGA minor variations guidance document for chemical entities).
• Where an existing carton or primary pack is removed, the container label must either remain unchanged or be changed as permitted under:
  • Changes to product labels that are notifications and/or
  • Changes that do not require TGA prior approval (see the TGA minor variations guidance document for chemical entities), and must continue to meet all requirements of the TGO that relates to labels.
• No change can be made to the product's shelf life or storage conditions as a notification. For self-assessable (SAR) changes to the shelf life or storage conditions see:
  • DSLE: Shelf life - Extension according to an approved stability-testing protocol and
  • DSLD: Shelf life - Decrease and/or more restrictive storage conditions.
• The TGA must be notified as a priority if the results of supporting stability data fail to meet the specifications. The product in the new container system may be withdrawn from the market at the TGA's discretion.

You must submit:

• Details of the change(s).
• Where a desiccant is included in a container, an assurance that the desiccant is used to improve the existing acceptable stability profile of the product and is not used to overcome stability problems in the existing container.
• Where a desiccant is included in a container, information on the nature of the desiccant, as well as information showing that the desiccant is readily distinguishable from the product, and is appropriately labelled and identified as a desiccant.
• If an overwrap is introduced, the rationale for its inclusion, and details of the material of the overwrap and specification.

You must generate the following data:

• Where applicable, comparative data to demonstrate the removal of inert wadding has not adversely affected the product’s friability and other physical attributes during normal transport.
• If an overwrap is introduced or changed, a stability study of the product with the overwrap to verify the product shelf life must have been initiated on at least one production-scale batch of the product, and should begin on the second and third batches as they are manufactured.

• The change must not result in a change to the container type.
• If the container is a blister pack or strip pack, the change in size or shape must not result in an increase in the headspace volume of the blister-pack or strip-pack pocket.
• If the container is a reclosable package, there must not be an increase in the headspace of the container.
• The material and thickness of the container/closure system must be either unchanged or changed in a manner permitted under change types:
• • CMIT: Container/closure material - increase in thickness for non-sterile solid, semi-solid, semi-liquid or liquid dosage forms and/or
  • CMDT: Container/closure material - decrease in thickness for blister packs, strip packs and sachets for non-sterile solid or semi-solid dosage forms.
• No change can be made to the product’s shelf life or storage conditions as a notification. For self-assessable (SAR) changes to the shelf life or storage conditions see:
  • DSLE: Shelf life - Extension according to an approved stability-testing protocol and
  • DSLD: Shelf life - Decrease and/or more restrictive storage conditions.
• No change can be made to the quantity of products in the new container/closure system.
• The TGA must be notified as a priority if the results of supporting stability data fail to meet the specifications. The product in the new container system may be withdrawn from the market at the TGA’s discretion.

You must submit:

• Details of the new container/closure system, with specifications, if relevant.
• If the closure is a child-resistant cap, or implied by its presentation and construction to be one, a declaration that the reclosable package meets all of the requirements of the current TGO on child-resistant packaging. The declaration must state, in particular, which of the recognised international standards on child-resistant packaging the closure complies with, and include evidence of adequate directions for opening and reclosing the package.

You must generate the following data:

• If the container is a reclosable package and is child-resistant (or is implied by its presentation to be a child-resistant package), data must have been generated to demonstrate that the child-resistant properties of the package and operation of the closure have not been adversely affected by the change in size and shape.
• For solid oral dosage forms, comparative moisture permeability (water-vapour transmission) data must have been generated on the new and current container systems using the current edition of the USP test for containers—permeation (multi-unit or single- unit containers, as appropriate), and the results must show either equivalent or better moisture protection.
• A stability study using the new container/closure system to verify the product shelf life must have been initiated on at least one production-scale batch of the product (with at least two more production batches to be similarly tested).

• There must be no change to container dimensions or components, other than those specified in:
  • CCSS: Container/closure - change to size and shape for non-sterile dosage forms and/or
  • CCCA: Container/closure - change to components.
• The limits applied must be based on batch analytical data, and comply with any applicable official standard or relevant guidelines adopted by the TGA.
• The packaging components must remain compliant with pharmacopoeial requirements and food standards.
• The change does not result from unexpected events arising during manufacture.

You must submit:

• Updated specifications and test methods.

You must generate the following data:

• Validation data for the proposed method demonstrating that the updated test procedure is at least equivalent to the former test procedure.

• The product must be a non-sterile dosage form.
• The material that is decreased in thickness must be either the aluminium foil or, in the case of a laminated aluminium foil, the aluminium foil itself or any non-aluminium polymeric material laminated to it.
• The new aluminium foil thickness or the aluminium component of the laminated foil must be
• at least 20 μm.
• The container/closure material must be unchanged.
• No change should be made to the product’s shelf life or storage conditions. See self- assessable (SAR) changes to the shelf life or storage conditions.
• The TGA must be notified as a priority if the results of supporting stability data fail to meet the specifications. The product in the new container system may be withdrawn from the market at the TGA’s discretion.

You must submit:

• Details of the change in thickness of the container material, with specifications, if relevant.

You must generate the following data:

• Initial stability study data using the new container/closure system to verify the product shelf life must have been initiated on at least one production-scale batch of the product (with at least two more production batches to be similarly tested).

• The container/closure material must be unchanged.
• No change can be made to the product’s shelf life or storage conditions as a notification. For self-assessable (SAR) changes to the shelf life or storage conditions see:
  • DSLE: Shelf life - Extension according to an approved stability-testing protocol and
  • DSLD: Shelf life - Decrease and/or more restrictive storage conditions.
• The TGA must be notified as a priority if the results of supporting stability data fail to meet the specifications. The product in the new container system may be withdrawn from the market at the TGA’s discretion.

You must submit:

• Details of the change in thickness of the container/closure material, with specifications, if relevant.

You must generate the following data:

• A stability study, using the new container/closure system to verify the product shelf life, must have been initiated on at least one production-scale batch of the product (with at least two more production batches to be similarly tested).

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.
• Evidence of the approval of the previous change (such as a TGA submission number).

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.
• The addition or change of a pictogram of a product or its dosage form must only be designed to clarify information about the medicine which is useful for the patient, to the exclusion of any element of a promotional nature.
• The change must not involve removal of information relating to the safe use of the product.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.
• The new name or address must be the same as amended on the register.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.
• The change must not involve removal of information relating to the safe use of the product.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.
• The new text must not be confusing, promotional or contradictory to text on the container or primary pack labels.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.
• All references to PSPs must have the following disclaimer prominently stated - "Patient Support Program complies with the Medicines Australia code of conduct, however it is not authorised or approved by the Therapeutic Goods Administration".

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.
• The link must be to information (e.g. may include CMI or PI documents) that is maintained by an Australian owned and managed company and must not include any element of a promotional nature.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.
• There must be a sufficient period of time that has elapsed to advise the market of the new product.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.
• For changes to labels resulting from other regulatory actions that have been either already notified or approved, appropriate evidence of the notification or approval (such as a TGA submission number).

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.

• There must be no other changes to the label made under this change request.
• The changes must ensure continued compliance with the relevant TGO pertaining to labels and not contravene labelling best practice.

You must submit:

• Copies of the existing labels (with tracked changes) and final copies or mock-ups of the amended labels (for each strength, where applicable) which include any logos, design work or graphics. The copies must be to scale and verify the size/dimensions of the labels and indicate the colours to be used. Where there are multiple pack sizes available, one representative label can be provided for each strength, as long as the only difference between the labels is the pack size.
• For changes to labels resulting from other regulatory actions that have been either already notified or approved, appropriate evidence of the notification or approval (such as a TGA submission number).