TGA Workshop Tony Manderson Biological Science Section Scientific Evaluation Branch November 2019
Overview • Proposed changes to classification of tissue storage solutions • Assessment of applications from tissue supplied from overseas (products on ARTG) • SAS applications • Gene-therapy regulation • Regulation of FMT • Submission of multiple simultaneous applications • Other TGA updates
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Classification of tissue storage solutions • We have raised your concerns directly with the Medical Devices Branch • Only applies to the solutions the product is supplied in • Will apply to commercially supplied solutions, not those made in-house – these are exempt as there is no commercial supply • Consultation identified issues that require further targeted consultation both within the TGA and with external stakeholders before recommendations on the way forward can be made to government • Scope of proposal is limited to products already considered to be a medical device (and does note seek to broaden the definition of medical device) 3
Evaluation of tissue from overseas Application for inclusion in ARTG • Data requirements and assessment is identical (is the quality and safety sufficient) • GMP inspections for all manufacturing facilities (irradiators, ID testing, principal manufacturing site) • GMP compliance - no reliance on inspections by overseas regulators, regular re- inspections (as per domestic facilities) • Control of collection sites, traceability and critical material control e.g. restricting use of OPO’s to those where control can be demonstrated, testing facilities • Compliance with TGO’s is required (sites may need to establish Aus-specific criteria and processes, not in place previously) • Control and validation of processes generally very high • No comparability is performed to domestic equivalent product 4
Evaluation of tissue from overseas Donor selection and testing Sufficient control over OPOs must be demonstrated • • Compliance with AATB standards and FDA accreditation not considered; must comply with Australian cGMP and TGA standards • Almost all sites have to have Australian-specific requirements to meet compliance with TGO 88 – often requiring donor follow-up • Must comply with requirement for physical assessment; but could be differences between facilities of what this might cover • Includes the requirement for monitoring and action over epidemiological situations • Identical review of donor records to ensure the level of documentation is complete – must be held and evidence of assessment against Australian Std TGA sets the standards to ensure quality and safety of grafts is achieved, we do not compare facilities and may be differences in the level of robustness of donor selection. 5
ARTG for biologicals 6
Assessment of SAS applications – SAS B • Category B is an application pathway that can be accessed by health practitioners • Category B applications must be reviewed and approved by TGA before the unapproved product may be accessed and supplied to the patient: – The application must be completed in full and include the patient diagnosis and indication for which the product is sought. – The application requires a thorough clinical justification for the use of the product, which includes the seriousness of the condition, details of previous treatment and reasons why a therapeutic good currently included in the ARTG cannot be used for the treatment of the individual patient in the particular circumstance. – The application must include sufficient safety and efficacy data to support the proposed use of the product. This may include references to clinical trial results and published peer-reviewed data, or evidence that the product has been approved for an equivalent indication by a national regulatory body with comparable regulatory requirements. – The application should include details of intended monitoring for adverse events and patient response to treatment. 7
Assessment of SAS applications – SAS B • Category B is an application pathway that can be accessed by health practitioners • Category B applications must be reviewed and approved by TGA before the unapproved product may be accessed and supplied to the patient: – The application must be completed in full and include the patient diagnosis and indication for which the product is sought. – The application requires a thorough clinical justification for the use of the product, which includes the seriousness of the condition, details of previous treatment and reasons why a therapeutic good currently included in the ARTG cannot be used for the treatment of the individual patient in the particular circumstance. – The application must include sufficient safety and efficacy data to support the proposed use of the product. This may include references to clinical trial results and published peer-reviewed data, or evidence that the product has been approved for an equivalent indication by a national regulatory body with comparable regulatory requirements. – The application should include details of intended monitoring for adverse events and patient response to treatment. 8
Assessment of SAS applications – SAS B • Must be approved in country of origin and for the claimed intended use • Must be manufactured in an approved facility • Justification that an approved product can not be used • Can consider level of evidence for that individual product use, in that procedure E.g. are all mineralised bone products equivalent? – User points to established clinical trial data that supports the use or a specific product in a procedure – Claim that clinician/dentist have tried multiple and have better outcomes for the unapproved product – Units too large, so cost too high and large wastage 9
Assessment of SAS applications – SAS C • Category C is a notification pathway that allows certain types of health practitioners to supply therapeutic goods that are deemed to have an established history of use. • These goods are specified in a list along with their indications and the type of health practitioner authorised to supply these products for the respective indications. • For example: • All this information and link to the SAS C instrument are available through: https://www.tga.gov.au/form/special-access-scheme 10
Regulation of gene-therapy products • Gene-modified cell therapies are biologicals; gene-therapy vectors alone are medicines • TGA has approved Kymriah and a number of other clinical trials using CAR T cells • TGA often adopt international guidance documents, e.g. EMA guidelines – Adopted guidance on quality, safety and efficacy aspects in cell and gene therapy manufacturing is available on the TGA’s Scientific Guidelines for Biologicals web page. Production and Quality Control of Medicinal Products derived by recombinant DNA Technology Production and Quality Control of Cytokine Products Derived by Biotechnological Processes Gene Therapy Product Quality Aspects in the Production of Vectors and Genetically Modified Somatic Cells Note for Guidance on the Quality, Preclinical and Clinical Aspects of Gene Transfer Medicinal Products Quality, preclinical and clinical aspects of gene therapy medicinal products Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells Human cell-based medicinal products 11
Regulation of Faecal Microbiota Transplants (FMT) • Workshop held in Melbourne on 10 October 2018 • Public consultation held in early 2019 – 22 submissions • Supported most FMT products to be regulated as biologicals (due to need for donor workup) • Changes in place from 1 January 2020, with 12 month transition 12
Regulation of Faecal Microbiota Transplants (FMT) What is a FMT product (biologicals)? means a thing that comprises, contains or is derived from human stool and for a therapeutic use When is FMT products a medicine? When the components of FMT products have been purified and characterized by physiochemical or biological means 13
Class 1 FMT products Class 1 biologicals, if • it is not advertised to consumers; and • collection, manufacturing and release all occurs within a hospital, under the supervision of a medical practitioner • Exempt from GMP requirements • Must comply to applicable standards (TGO 87 and new product-specific standard) • Application for inclusion on ARTG, but no premarket assessment (post-market audit) 14
Class 2 FMT products Class 2 biologicals, if • in the case of minimally manipulated FMT products from appropriately screened donors • manufactured in a facility that is not a hospital or manufactured and used in different hospitals or clinics • GMP licenced facilities • Must comply to applicable standards (TGO 87 and new product-specific standard) • Application for inclusion on ARTG, but with premarket assessment (as per tissue banks) 15
Regulation of Faecal Microbiota Transplants (FMT) • Consultation on new Std for FMT products in next few weeks • Based on TGO 88 and national and international consensus groups (similar structure and content) • Current acceptance rates between 1-10% • Minor changes may be needed to TGO 88 to exclude FMT products • Publish early 2020, implementation following 12 month transition 16
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