Session A03: Hints and Tips for Acceptance of your Prescription - - PowerPoint PPT Presentation
Session A03: Hints and Tips for Acceptance of your Prescription Medicines Submission(s) Melissa Quinn B.Pharm (Hons) Director & Senior Pharmacist - Application Management & Exports Section Prescription Medicines Authorisation Branch
Melissa Quinn B.Pharm (Hons) Director & Senior Pharmacist - Application Management & Exports Section Prescription Medicines Authorisation Branch Medicines Regulation Division Therapeutic Goods Administration
ARCS 21 August 2018
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Things this presenter is not: An IT or legal expert! – When you encounter issues with forms or IT systems, please always give feedback so we can resolve as quickly as possible. – Resolutions for existing IT problems will not be provided in this talk but I am happy to take a list of questions on notice! – Many legislation related queries are very situation specific and the TGA generally cannot provide external stakeholders with legal advice, but can provide some direction/guidance when appropriate. – It is important for you to understand the relevant legislation and seek your own legal advice as required.
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Pharmaceutical Benefits Division
Product Billing & Industry Assistance Section
Regulatory Practice & Support Division
Scheduling & Committee Support Section
Medicines Regulation Division Medical Devices & Product Quality Division PM Registration Processes
Prescription Medicines Authorisation Branch Scientific Evaluation Branch Pharmacovigilance and Special Access Branch Laboratories Branch Manufacturing Quality Branch
CEU 1
Behavioural disorders
CEU 2
disease
media)
radiopharmaceuticals and contrast media use
therapeutic)
(diagnostic)
CEU 3
disorders
reproductive system
disorders
CEU 4
functioning carcinoid neoplasms
solid tumours (therapeutic)
CEU 5
reproductive system
disorders
paranasal sinuses & upper airway CEU 6
disorders, including haematological malignancies
cancer (therapeutic)
(plasma products)
Further information can be found in Guidance 4 of the Australian Guidelines for Prescription Medicines (ARGPM)
Application Entry Team Application Support Team Exports FOI requests Retrospective performance reporting KPI reporting Sponsor Pipeline Reporting (Forecasting) Business improvements and solutions eCTD reform B2B Portal Premier Replacement External evaluator procurement Reforms implementation Associated legislative and guidance change Change management AusPAR preparation and publication
Business Systems Review & Reporting
aet.application.entry.team@health.gov.au ast.application.support.team@health.gov.au
Application Entry, Support & Exports Transparency Reforms & Evaluation Support Application & Advisory Management
Case Management Media and ministerial enquiries Secretary of Advisory Committee for Medicines International work-sharing Streamlined Submission Review Pre-submission meetings
streamlinedsubmission@health.gov.au
Application received and application fees paid
Date = 40 working day start
Application screened by AESE (administrative) and assigned to a case manager for further technical screening Application has minor deficiencies Opportunity to remedy minor deficiencies
Deficiencies unresolved
Application has critical issues/ unresolved deficiencies Notice of refusal sent
Deficiencies resolved
Application acceptable Notice of acceptance sent Payment of evaluation fees
CMES 7
Phase Description
Applicant provides necessary information on scope and scale of application. Assists resource planning
TGA completes activities in preparation for application evaluation. Letter of application
Evaluators assess the dossier 4 Consolidated Section 31 requests TGA will consolidate all questions from evaluators and send to applicant. Stop Clock. Rolling questions used for Priority
TGA evaluators assess the application in view of the response to questions
Delegate may seek independent advice after considering all evaluation reports 7 TGA Decision TGA delegate makes a decision
Administrative and regulatory activities are completed
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Registration Designation
MS2 MS7 220 255 20
priority, provisional (if required)
−40
legislated timeframe (except for COR) application submitted
MS1
(optional) dossier submitted TGA clock in working days for decision timing ('Milestone 7') for the different pathways
120 150 175
STOP-CLOCK, s.31 questions to sponsor TGA clock STARTS
MS3 MS4
Round 1 evaluation
MS5
Round 2 evaluation ACM expert advice (optional) TGA clock STOPS
MS6 155 COR-A priority COR-B generic provisional non-generic and
Priority Review (Jul 2017) = substantial evidence & complete data dossier Provisional Approval (Mar 2018) = early clinical safety & efficacy data Comparable Overseas Regulator (COR) report-based process (Jan 2018)
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A submission to register a new prescription medicine is supported by:
(i.e. the extent and rate of release from the dosage form: in vivo or sometime in vitro)
Data required outlined in the Australian Regulatory Guidelines for Prescription Medicines (ARGPM)
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– Section 9C – request for copy of ARTG entry – Section 9D – request to vary information about an ARTG entry – Section 14 – exemption from compliance with a standard – Section 23 – registration or listing (in this case each application results in a single registration or listing
– Section 61 (6) – request for information from ARTG – Regulation 14 – transfer of goods registered/listed – Regulation 14A – reassignment of registration/listing numbers
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– An application for a new medicine or a change to a medicine constitutes a Category 1 application if it does not meet the requirements of Category 3
– Implemented on 2 Jan 2018 as part of MMDR reforms – Builds on previous Category 2 process.
– Changes to quality data of a medicine already in the ARTG
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– Prescription medicines applications are lodged via the TBS portal. – Applicants need to be set up in the TGA client database in order to lodge applications.
database.
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– Look at how to propose a new ingredient name https://www.tga.gov.au/proposing-new-ingredient- name
– Look at requirements outlined in pre-submission planning form www.tga.gov.au/form/pre-submission-planning-form-ppf
– Product Information: New format as of 2 January 2018 – Consumer Medicine Information (CMI) – Patent certification and data exclusivity
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New chemical/biological entity or biosimilar medicine OR Change(s) to an existing good that MAY create a separate and distinct good on the ARTG
– applications for new dosage forms – new fixed–dose combinations – new strengths and new generic products – extensions of indications – amendments to the Product Information (type J, otherwise 9D) – Additional trade names (45 working days, no longer Cat 1) – Changes to product information
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a) the strength, as recorded in the entry in the Register; or b) the dosage, the recommended dose regimen or the maximum daily dose; or c) the dosage form; or d) the route of administration; or e) the intended patient group f) some types of minor variations (type G and H) Requires evaluation of clinical, pre-clinical and/or bioequivalence data.
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COUNTRY OR JURISDICTION REGULATORY AUTHORITY Countries Canada Health Canada Singapore Health Science Authority Singapore (HSA) Switzerland SwissMedic United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) United States Food and Drug Administration (FDA) Jurisdictions European Union European Medicines Agency (EMA) - centralised and decentralised processes
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Open to applications where the medicine has received full overseas marketing approval following a de novo evaluation. COR approach A (target time frame of 120 working days)
Manufacturing Practice (GMP)
required.
COR approach B (target time frame of 175 working days)
processed under the COR-B approach or as a Category 1 application.
support the proposed indication.
See: https://www.tga.gov.au/publication/comparable-overseas-regulators-cors-prescription-medicines
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a major variation) to: a) the formulation, composition or design specification; or b) the container for the goods; c) any other attribute of the goods that results in the goods being separate and distinct
– Correction of an ARTG entry that is incomplete or incorrect – Safety-related requests (SRR), with and without data, Self Assessable Request (SAR) – Minor editorial Change (MEC), Notifications More notifiable changes (enhancements) are coming in 2019/2020
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Launched July 2017
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– Checks that application fee is paid
– Notifying letter of acceptability and evaluation fee invoice sent to sponsor – Statutory evaluation period applies – Application lapses if evaluation fee is not paid by due date
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– A set of specifications for a dossier for the registration of medicines.
www.tga.gov.au/publication/general-dossier-requirements
www.tga.gov.au/book-page/ectd-preparation-tools
www.tga.gov.au/book/organising-nees-submissions
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for prescription medicines
guidelines-prescription-medicines
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– Technical data requirements (Appendix A – specific mandatory requirements https://www.tga.gov.au/book-page/appendix- specific-mandatory-requirements) – Australian and adopted international guidelines
Note: – There are no “secret guidelines” but a section can determine that there are other matters which are relevant to an application, relevant to best practice and risk-management for use in an Australian population – Post-market experience may not be specific enough to manage an identified risk with an application.
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ITEM REQUIREMENT
Language All information must be in English and readable Measurements Units of measurement must use the metric system (or other appropriate units, such as those generally accepted in clinical practice e.g. SI) Provision of Module 1 All application dossiers must include Module 1. Electronic Data Must be submitted in either the eCTD or NeeS format* * note: TGA will likely be moving to eCTD only in the next 2-3 years. Are you ready? Applications that have previously been rejected by the TGA or withdrawn by the applicant before a decision by the TGA Delegate.
been addressed.
must provide:
application should be used for the current application.
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ITEM REQUIREMENT
Cover Letter Must be included in Module 1.0.1 for all regulatory activities (submissions) and for each sequence associated with that regulatory activity. Lifecycle management tracking table Must be included in Module 1.0.2 for all regulatory activities and for each sequence associated with that regulatory activity provided in the eCTD format. Table of Contents Must be included for all regulatory activities and for each sequence associated with that regulatory activity provided in the NeeS format Letter of Authorisation If an applicant is acting on behalf of another applicant, a letter of authorisation must be provided. Where the applicant is using another company's name and/or livery on labels, a letter of authorisation from the company owning the name/livery must be provided. Application Form Must be included in Module 1.2.1 for all applications Literature-based submission documents If your application partially or completely relies on a literature-based data set include either:
approved by the TGA; OR
Information must be included in Module 1.5.1 in these instances. Designation applications – supporting documents To be eligible for the relevant pathway, applicants must provide a copy of the priority or provisional determination letter that was issued by the TGA. The determination must be in force at the time of making the section 23 application. To be eligible for a waiver of the section 23 application and evaluation fees, applicants must provide a copy of the Orphan drug designation letter that was issued by the TGA. The designation must be in force at the time of making the application. Information must be included in Module 1.5.2 in these instances.
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ITEM REQUIREMENT
Declaration of compliance with Pre- submission planning form and planning letter
PPF (including attachments) and planning letter.
application. Risk Management plan for Australia Include in all regulatory activities for:
activities. Include an RMP under certain circumstances for other applications as descripted in Risk management plans for medicines and biologicals. The Risk Management Plan must be the current, unaltered EU-RMP and an Australian Specific Annex should be included. An alternative to the EU RMP is acceptable only if there is no current EU-RMP. Include in Module 1.8.2. Justification for not providing appropriate biopharmaceutic studies A justification within Module 1.11.2 is required when:
Such a justification must consist of a document that:
submitting biopharmaceutic data
bioequivalence CPMP/QWP/EWP/1401/98 Rev 1).
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Category 1/category 2 applications - Module 2 TGA's application fee type is … A - NCE B - New Combination C – Extension of indication D – New generic medicine Applying for a … New chemical entity New salt or ester of existing active ingredient Similar biological medicinal product Module 2.1 Table of contents Mandatory Mandatory Mandatory Mandatory Mandatory Mandatory Module 2.2 Introduction Mandatory Mandatory Mandatory Mandatory Mandatory Mandatory Module 2.3 Quality overall summary Mandatory Mandatory Mandatory Mandatory Not required Mandatory Module 2.4 Nonclinical
Mandatory Mandatory Mandatory Mandatory May be required* May be required* Module 2.5 Clinical overview Mandatory Mandatory Mandatory Mandatory Mandatory Mandatory Module 2.6 Nonclinical
Mandatory Mandatory Mandatory May be required* May be required* May be required* Module 2.7 Clinical overview Mandatory Mandatory Mandatory Mandatory Mandatory May be required* *Refer to Module 1 requirements.
https://www.tga.gov.au/dossier-documents-matrix-module-2-5
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Category 1/category 2 applications - Module 2 TGA's application fee type is … F - Major variation E - Additional tradename J - PI Change requiring evaluation Applying for a … New strength New dosage form New route of administration Change in patient group (not decrease) Change of dosage Module 2.1 Table of contents Mandatory Mandatory Mandatory Mandatory Mandatory Not required May be required.* Module 2.2 Introduction Mandatory Mandatory Mandatory Mandatory Mandatory Not required May be required.* Module 2.3 Quality overall summary Mandatory Mandatory May be required.* Not required Not required Not required May be required.* Module 2.4 Nonclinical
May be required.* May be required.* May be required.* May be required.* May be required.* Not required May be required.* Module 2.5 Clinical overview Mandatory Mandatory Mandatory Mandatory Mandatory Not required May be required.* Module 2.6 Nonclinical
May be required.* May be required.* May be required.* May be required.* May be required.* Not required May be required.* Module 2.7 Clinical overview May be required.* Mandatory Mandatory Mandatory Mandatory Not required May be required.*
*Refer to Module 1 requirements. https://www.tga.gov.au/dossier-documents-matrix-module-2-5
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TGA's application fee type is … G - Minor variation, new Register entry H - Minor variation, not resulting in a new Register Entry Applying for a … Change of formulation New container type Change of tradename Module 2.1 Table of contents May be required* May be required* Not required May be required* Module 2.2 Introduction May be required* May be required* Not required May be required* Module 2.3 Quality overall summary Mandatory Mandatory Not required Mandatory Module 2.4 Nonclinical overview Not required Not required Not required Not required Module 2.5 Clinical overview Not required Not required Not required Not required Module 2.6 Nonclinical overview Not required Not required Not required Not required Module 2.7 Clinical overview Not required Not required Not required Not required
*Refer to Module 1 requirements. https://www.tga.gov.au/dossier-documents-matrix-module-2-5
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Category 1/category 2 applications - other modules TGA's application fee type is … A - NCE B - New Combination C – Extension of indication D – New generic medicine Applying for a … New chemical entity New salt or ester of existing active ingredient Similar biological medicinal product Module 3—Quality Mandatory Mandatory Mandatory Mandatory Not required Mandatory Module 4—Nonclinical Mandatory Mandatory Mandatory May be required* May be required* May be required* Module 5—Clinical Mandatory Mandatory Mandatory Mandatory Mandatory May be required* Module 5.3.1 Reports
studies May be required* May be required* May be required* May be required* Not required May be required* Module 5.3.2 Pharmacokinetic studies using human biomaterials May be required* May be required* May be required* May be required* May be required* Not required
*Refer to Module 1 requirements. https://www.tga.gov.au/dossier-documents-matrix-module-2-5
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Category 1/category 2 applications - other modules TGA's application fee type is … F - Major variation E - Additional tradename J - PI Change requiring evaluation Applying for a … New strength New dosage form New route of administration Change in patient group (not decrese) Change of dosage Module 3—Quality Mandatory Mandatory May be required* Not required Not required Not required Not required Module 4— Nonclinical May be required* May be required* May be required* May be required* May be required* Not required May be required* Module 5—Clinical May be required* Mandatory Mandatory Mandatory Mandatory Not required May be required* Module 5.3.1 Reports of biopharmaceutic studies May be required* May be required* May be required* Not required May be required* Not required May be required* Module 5.3.2 Pharmacokinetic studies using human biomaterials May be required* May be required* May be required* May be required* May be required* Not required May be required*
*Refer to Module 1 requirements. https://www.tga.gov.au/dossier-documents-matrix-module-2-5
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TGA's application fee type is … G - Minor variation, new Register entry H - Minor variation, not resulting in a new Register Entry Applying for a … Change of formulation New container type Change of tradename Module 3—Quality Mandatory Mandatory Not required Mandatory Module 4—Nonclinical Not required Not required Not required Not required Module 5—Clinical Not required Not required Not required Not required Module 5.3.1 Reports of biopharmaceutic studies Not required Not required Not required Not required Module 5.3.2 Pharmacokinetic studies using human biomaterials Not required Not required Not required Not required
https://www.tga.gov.au/dossier-documents-matrix-module-2-5
supported by clinical, nonclinical or bioavailability data (Cat 1/2) or not (Cat 3).
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– A fee is charged for a service e.g. evaluation of an application – A charge is a form of tax applied per financial year
Goods (Charges) Regulations 1990.
www.tga.gov.au/book-page/prescription-medicines-2
AET.application.entry.team@tga.gov.au
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associated with that service
example, A, B or C application types).
– new chemical entity – new indication or major variation.
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A: New chemical or biological entity, biosimilar medicine or New salt/ester of previously approved active ingredients B: New combination of previously approved active ingredients C: Extension of indications D: New Generic medicines E: Major Variation – Additional trade name F: Major variation – New strength, new dosage form, new route of administration, change/increase in patient group, change in dosage J: Change to Product information requiring the evaluation of clinical, non clinical or bioequivalence data
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– Summaries/unpublished manuscripts instead of full study reports – Documents not in English – Unacceptable dossier format(s)
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https://www.tga.gov.au/publication/australian-regulatory-guidelines-prescription-medicines-argpm
– https://www.tga.gov.au/standards-guidelines-prescription-medicines – https://www.tga.gov.au/prescription-medicines-registration-process – https://www.tga.gov.au/publication/common-technical-document-ctd
https://www.tga.gov.au/forms-prescription-medicine-sponsors
https://www.tga.gov.au/regulatory-decisions-and-notices-prescription-medicines
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guideline
rejection at the entry stage
annotations)
Secretary (as enshrined in recent legislative amendments)
any IT related issues being experienced where possible
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sponsor
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