Biopharmaceutics Classification System (BCS)-based ...



6540512700TGA use onlyThis form, when completed, will be classified as 'For official use only'.For guidance on how your information will be treated by the TGA see: Treatment of information provided to the TGA at < Classification System (BCS)-based biowaiver templateRefer to guidance document ‘Completing the biowaiver templates’ when completing this template.Do not include any text in fields or text boxes indicated for “TGA use only”.For more information, refer to TGA website regarding bioequivalence data summary templatesAdministrative informationActive Pharmaceutical Ingredient (API) in Australian Approved Name format FORMTEXT ?????Dosage form and strength(s) FORMTEXT ?????Daily dose FORMTEXT ?????Final (test) product manufacturer name and address FORMTEXT ?????Dissolution testing laboratory name and address FORMTEXT ?????Test product details: batch size and batch number FORMTEXT ?????Reference product name, sponsor, and country of procurement FORMTEXT ?????Summary of requirements and outcomesSelect the finding in the outcome column that applies to your proposed products (test products)RequirementsOutcomeTherapeutic range (and dose) FORMCHECKBOX Narrow FORMCHECKBOX Non-narrowSolubility FORMCHECKBOX High FORMCHECKBOX LowStable drug substance throughout in vitro testing FORMCHECKBOX Yes FORMCHECKBOX NoHuman absorption FORMCHECKBOX >85% FORMCHECKBOX <85%Permeability FORMCHECKBOX High FORMCHECKBOX LowBCS class FORMCHECKBOX I FORMCHECKBOX II FORMCHECKBOX III FORMCHECKBOX IVDosage form characteristics FORMCHECKBOX Oral FORMCHECKBOX Systemically acting FORMCHECKBOX Immediate release (Note, all three must apply)Comparison of excipients in the formulations between test and reference products FORMCHECKBOX Quantitatively - and qualitatively identical FORMCHECKBOX Qualitatively identical but not quantitatively identical FORMCHECKBOX Neither quantitatively nor qualitatively identical (only applicable for BCS class I)Dissolution profiles FORMCHECKBOX Similar and very rapidly dissolving FORMCHECKBOX Similar and rapidly dissolving FORMCHECKBOX Non-similar FORMCHECKBOX Non-very rapidly dissolving FORMCHECKBOX Non-rapidly dissolvingCertificates of Analysis (CoAs)Difference between test and reference product assays within 5% FORMCHECKBOX Yes FORMCHECKBOX NoTGA use only - Comments for Section 2Benefit risk summary FORMCHECKBOX Acceptable FORMCHECKBOX Not acceptableConclusion FORMCHECKBOX Acceptable FORMCHECKBOX Not acceptableIntroductionProvide brief introduction of the drug substance and the proposed finished drug products (test products) FORMTEXT ?????Is the Active Pharmaceutical Ingredient (API) a narrow therapeutic index (NTI) drug substance?Yes FORMCHECKBOX Stop The drug substance should not belong to the group of narrow therapeutic index drugs. Please discuss suitability of a BCS-based biowaiver with TGA if you wish to proceed further. To contact TGA, see TGA contact details for enquiries about prescription medicines.Provide location in the dossier of TGA correspondence regarding the suitability of a BCS-based biowaiver (if any): FORMTEXT ?????No FORMCHECKBOX Provide evidence to support the API is not a NTI below. FORMTEXT ?????3.1Application objectiveReason for application of biowaiver and BCS Classification FORMTEXT ?????Were the drug substance and test product used in the studies for the BCS-based biowaiver justification:manufactured by the same proposed drug substance and drug product manufacturers listed in Module 3, andmanufactured in the same manner as proposed for marketing purposes?Yes FORMCHECKBOX Go to section 3.2 No FORMCHECKBOX State the difference in the formulation proposed for marketing and those used for comparative dissolution studies and justify below why a BCS-based biowaiver can be applied: FORMTEXT ?????3.2Comparison between the test and reference productsWhat were the similarities and differences between the test and reference products? FORMTEXT ?????3.3Basic pharmacokinetic informationWas the mass balance and absolute BA studies conducted on the highest strength dose?Yes FORMCHECKBOX Go to section 4No FORMCHECKBOX Go to next question in this sectionWere linear pharmacokinetics observed over the dose range?Yes FORMCHECKBOX Provide source of the evidence: FORMTEXT ?????No FORMCHECKBOX Please discuss suitability of a BCS-based biowaiver with TGA if you wish to proceed further. To contact TGA, see TGA contact details for enquiries about prescription medicines.Provide location in the dossier of TGA correspondence regarding the suitability of a BCS-based biowaiver (if any): FORMTEXT ?????TGA use only - Comments from review of Section 3 FORMTEXT ?????BCS biowaiver assessment4.1SolubilityLocation of the informationStudy report FORMTEXT ?????Study protocol FORMTEXT ?????Description of solubility method and conditions FORMTEXT ?????Description and validation of the stability-indicating analytical method FORMTEXT ?????Dates of the study FORMTEXT ?????Name and address of the study site FORMTEXT ?????4.1.1Solubility methodApparatus FORMTEXT ?????Volume FORMTEXT ?????Time FORMTEXT ?????Dose/ amount FORMTEXT ?????Temperature FORMTEXT ?????pH values FORMTEXT ?????Buffer composition FORMTEXT ?????4.1.2Solubility at different pH values and replicatesTheoretical pHRepeatObserved pHAdjusted pHIndividual concentration at saturation (Cs) valuesCs (mean)Quantity dissolved in 250 mlpH 1.21 FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????2 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????3 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????Intermediate pH: FORMTEXT ?????1 FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????2 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????3 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH 4.51 FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????2 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????3 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????Intermediate pH: FORMTEXT ?????1 FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????2 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????3 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH 6.81 FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????2 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????3 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????Other intermediate pH values**: FORMTEXT ?????1 FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????2 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????3 FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????** Other intermediate pH values e.g. pKa, pKa-1, pKa+1Insert the solubility (concentration at saturation) vs. pH plots based on the data provided in the table above to identify the pH of minimum solubility below. FORMTEXT ?????TGA use only - Comments from review of Section 4.1 FORMTEXT ?????4.2Human absorption (methods and results)4.2.1Absolute bioavailability (BA) (in human)Reference citation of the absolute BA data source FORMTEXT ?????Oral dose FORMTEXT ?????Intravenous dose FORMTEXT ?????Number of subjects FORMTEXT ?????Absolute BA result FORMTEXT ?????4.2.2Mass balance (in human)Reference citation of the mass balance data source FORMTEXT ?????Dose FORMTEXT ?????Number of subjects FORMTEXT ?????Mass balance result FORMTEXT ?????4.2.3In vivo or in vitro permeabilityTest system FORMTEXT ?????Concentration FORMTEXT ?????Result FORMTEXT ?????4.2.4Other informationInfluence of the transporters to absorption FORMTEXT ?????TGA use only - Comments from review of Section 4.2 FORMTEXT ?????4.3Comparison of test and reference formulations / excipientsIngredientFunctionTest product quantityReference product quantity (if known) FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????TGA use only - Comments from review of Section 4.3 FORMTEXT ?????4.4In vitro dissolution comparisonLocation of the informationStudy report FORMTEXT ?????Study protocol FORMTEXT ?????Batch information on test and reference batches including certificates of analysis (CoAs) FORMTEXT ?????Validation of experimental analytical methods FORMTEXT ?????Individual and mean results and respective summary statistics FORMTEXT ?????Dates of the study FORMTEXT ?????Name and address of the study site FORMTEXT ?????4.4.1Summary of dissolution test method parametersApparatus FORMTEXT ?????Are sinkers used? FORMCHECKBOX Yes FORMCHECKBOX NoRate of operation FORMCHECKBOX 50 rpm for paddle FORMCHECKBOX 100 rpm for basket FORMCHECKBOX other system: FORMTEXT ?????If other system was selected, provide explanation: FORMTEXT ?????Dissolution media FORMTEXT ?????Volume FORMTEXT ?????Temperature FORMTEXT ?????Sampling times FORMTEXT ?????Number of Dosage Units FORMTEXT ?????Sample handling and storage FORMTEXT ?????Filtration methods (e.g. in-line filtration or immediately after sampling) FORMTEXT ?????De-aeration method FORMTEXT ?????4.4.1.1Test batch dissolution resultsBatch number: FORMTEXT ?????n = FORMTEXT ????? dosage units/ pH medium npH of medium% Label Claim Released FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins)pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH of minimum solubility: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????Batch number: FORMTEXT ?????n = FORMTEXT ????? dosage units/ pH medium npH of medium% Label Claim Released FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins)pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH of minimum solubility: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????Provide the mean dissolution results of the above test batches below:Mean of the dissolution resultsn pH of medium% Label Claim Released FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins)pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH of minimum solubility: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????4.4.1.2Reference batch dissolution resultsBatch number: FORMTEXT ?????n = FORMTEXT ????? dosage units/ pH medium npH of medium% Label Claim Released FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins)pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH of minimum solubility: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????Batch number: FORMTEXT ?????n = FORMTEXT ????? dosage units/ pH medium npH of medium% Label Claim Released FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins)pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH of minimum solubility: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????Provide the mean dissolution results of the above reference batches below:Mean of the dissolution resultsn pH of medium% Label Claim Released FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins) FORMTEXT ????? (Mins)pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????pH of minimum solubility: FORMTEXT ?????Mean FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????%RSD FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????4.4.2Dissolution profile comparisonStrength: FORMTEXT ?????Test product batch number: FORMTEXT ?????Reference product batch number: FORMTEXT ?????pHSimilarity factor (f2)Time points used for f2 calculationDiscussion of dissolution profile similarity* FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????* Discussion provided must not be in terms of clinical/therapeutical relevance (i.e. in vitro in vivo correlation).TGA use only - Comments from review of Section 4.4 FORMTEXT ?????4.5Testing laboratory4.5.1Audit(s)Name of testing facilityLocation of internal quality assurance methods and results FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????4.5.2GLP compliance/certificationName of the testing facilityLocation of the monitoring, auditing or inspection reportsLocation of the compliance certifications/accreditations FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ????? FORMTEXT ?????TGA use only - Comments from review of Section 4.5 FORMTEXT ?????Essential similarity/appropriateness of drug product specification (if applicable)What are your proposed drug product dissolution specifications? FORMTEXT ?????Do the proposed drug product dissolution specifications reflect the dissolution profile characteristics in this BCS-based biowaiver?Yes FORMCHECKBOX ?Go to section 6No FORMCHECKBOX ?Justify why wider dissolution specifications are proposed: FORMTEXT ?????TGA use only - Comments from review of Section 5 FORMTEXT ?????References of relevant regulatory guidelines and scientific papers FORMTEXT ?????List of questions to the applicantTGA use only – List of questions FORMTEXT ?????Applicant’s response to the list of questions FORMTEXT ?????TGA’s assessment and conclusionTGA’s assessment of applicant’s responsesTGA use only – Assessment of applicant’s answers to the list of questions FORMTEXT ?????TGA’s overall conclusion and recommendationsTGA use only – Conclusion and recommendations FORMTEXT ????? ................
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