Biologicals Regulation in Australia


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Biologicals Regulation in Australia

  1. 1. Biologicals regulation in Australia Evolving perspectives Albert Farrugia Senior Principal Research Scientist Therapeutic Goods Administration Presented to the Second Asian Bio Manufacturing Conference, Kuala Lumpur, Malaysia, November 2007
  2. 2. Current position <ul><li>TGA Act recognises medicines and medical devices as regulated therapeutic goods (no definition of biologicals) </li></ul><ul><li>Products such as blood products, biotechnology medicines, vaccines etc are regulated as prescription medicines </li></ul><ul><li>Products of tissue engineering eg autologous chondrocytes regulated as devices </li></ul><ul><li>Some products eg fresh blood, banked tissues not subject to pre-market review and ARTG so – only regulated outcome is GMP license </li></ul>
  3. 3. Current responsibilities Biologicals <ul><li>DSEB – all registrable biologicals which are medicines eg </li></ul><ul><ul><ul><li>Biotechnology medicines – monoclonal a/bs, recombinant products etc </li></ul></ul></ul><ul><ul><ul><li>Vaccines (including cell based vaccines) </li></ul></ul></ul><ul><ul><ul><li>Plasma derivatives </li></ul></ul></ul><ul><li>ODBT – Devices section – all registrable biologicals which are devices </li></ul><ul><ul><ul><ul><li>Recalls section – advice re blood, blood product and tissue recalls </li></ul></ul></ul></ul><ul><li>MAB – manufacturing license for products subject to the requirement </li></ul>
  4. 4. Role of the Blood and Tissues Unit <ul><li>Situated within the ODBT – historical reasons – link to GMP </li></ul><ul><li>Reviews pre-market data for biotech drugs – plasma products, recombinants etc </li></ul><ul><li>Reviews technical files for fresh blood components, cord blood </li></ul><ul><li>Develops policy for blood, tissues and biologicals </li></ul><ul><li>Provides advice on pathogen safety – viruses, prions </li></ul><ul><li>Interfaces with government(s) on blood and tissue policy issues </li></ul>
  5. 5. International relationships BTU <ul><li>WHO Expert Committee on Biological Standardisation </li></ul><ul><li>Council of Europe Committee of Experts on Blood transfusion </li></ul><ul><li>Council of Europe Committee on cells, tissues and organs </li></ul><ul><li>European Pharmacopeia Group pf Experts 6B – Blood Products </li></ul><ul><li>WHO Global Collaboration for Blood Safety </li></ul><ul><li>[World Federation of Hemophilia Medical Advisory Panel] </li></ul>
  6. 6. Current structure Blood and Tissues Unit <ul><li>Unit head (SPRS) </li></ul><ul><ul><li>Cells and tissues EL2 </li></ul></ul><ul><ul><ul><li>Evaluators EL1 (x 3) </li></ul></ul></ul><ul><ul><li>Blood and Plasma products EL2 </li></ul></ul><ul><ul><ul><li>Evaluators EL1 (x4), APS6 </li></ul></ul></ul><ul><ul><li>Pathogen safety, PMFs EL2 </li></ul></ul><ul><ul><ul><li>Evaluators EL1 (x1), APS6 (x2) </li></ul></ul></ul><ul><ul><li>Operations Manager EL2 </li></ul></ul><ul><ul><ul><li>EA, APS5 </li></ul></ul></ul>Medical Advisor ODBT
  7. 7. Drivers for change Biologicals regulation in Australia <ul><li>Internationally accepted principle </li></ul><ul><li>Difficulties in using traditional paradigms eg medicinal GMPs for biologicals </li></ul><ul><li>High public and political interest </li></ul><ul><li>Publicly funded activities </li></ul>
  8. 8. Regulation of biologicals Proposed approach <ul><li>Scope </li></ul><ul><li>Blood, blood components and blood products </li></ul><ul><li>Biotechnology equivalents of blood, blood components and blood products </li></ul><ul><ul><li>Recombinant clotting factors </li></ul></ul><ul><ul><li>Haemoglobin solutions </li></ul></ul><ul><ul><li>Etc </li></ul></ul><ul><li>Cell and tissue therapies </li></ul><ul><ul><li>Banked “non-viable” tissue </li></ul></ul><ul><ul><li>Cellular therapies </li></ul></ul><ul><ul><li>(under government policy review) solid organs, reproductive tissue </li></ul></ul>
  9. 9. Regulation of biologicals Proposed approach <ul><li>Principles </li></ul><ul><li>All products to be subject to requirements of registration ie pre-market review for safety, quality and efficacy before market entry </li></ul><ul><li>Level of review linked to classification system </li></ul><ul><li>Office of Biologicals established as the Regulator within the agency </li></ul>
  10. 10. Regulation of biologicals Proposed approach <ul><li>Class 1, 2 & 3 - Basis for classification </li></ul><ul><li>Risk-benefit ratio </li></ul><ul><li>Governance arrangements </li></ul><ul><li>Level of manipulation </li></ul><ul><li>Intended use </li></ul>
  11. 11. Regulation of biologicals Proposed approach <ul><li>Class 1 – goods which are </li></ul><ul><ul><li>Governed through medical practice – specific donor-patient r’ship </li></ul></ul><ul><ul><li>Of low risk compared to benefit for individual patient </li></ul></ul><ul><ul><li>Processed with minimal technology – will be defined </li></ul></ul><ul><ul><li>Eg solid organs, autologous/directed HPCs in clinical units, autologous/directed blood, hospital based blood manufacture </li></ul></ul><ul><li>Class 1 will be regulated through Standards established by professional bodies </li></ul><ul><li>Class 1 standards will be overseen and attested by the regulated entity – declaration of conformance or by facility accreditation (NATA) </li></ul><ul><li>The requirements are not “lower” than other Classes – different governance </li></ul>
  12. 12. Regulation of biologicals Proposed approach <ul><li>Class 2 – goods which are </li></ul><ul><ul><li>Governed through manufacturing practice – long term banking </li></ul></ul><ul><ul><li>Of moderate risk compared to benefit – established medical indications, safety profile – for population </li></ul></ul><ul><ul><li>Processed with moderate technology – will be defined – including banking </li></ul></ul><ul><ul><li>Have a homologus function ie same function in recipient as in donor </li></ul></ul><ul><ul><li>Eg banked tissue, banked HPCs detached from medical environment, non-autologous/directed, mainstream blood components </li></ul></ul><ul><li>Class 2 will be regulated through standards for safety and quality in product and manufacture which will be overseen by the agency </li></ul><ul><li>Class 2 efficacy requirements will be minimal and based on established knowledge eg literature, no clinical trials will be solicited </li></ul>
  13. 13. Regulation of biologicals Proposed approach <ul><li>Class 3 – goods which are </li></ul><ul><ul><li>Governed through manufacturing practice </li></ul></ul><ul><ul><li>Of potentially high risk compared to benefit, for population and indvidual </li></ul></ul><ul><ul><li>Processed with industrial technology – will be defined </li></ul></ul><ul><ul><li>Eg plasma derivatives, biotechnology medicines, cellular therapies </li></ul></ul><ul><li>Class 3 cell and tissue products will be further subdivided into 2 types </li></ul><ul><ul><li>Depending on whether function is homologous or not </li></ul></ul><ul><ul><li>Different requirements for clinical trials/efficacy assessment </li></ul></ul><ul><li>Class 3 will be regulated through standards for safety, quality and efficacy in product and manufacture which will be overseen by the agency </li></ul><ul><li>Class 3 efficacy requirements will be based on clinical trials which will be staged on risk based principles </li></ul>
  14. 14. Regulatory model for biologicals <ul><li>Class 1 (many still under policy review) </li></ul><ul><ul><li>Haematopoietic progenitor cells </li></ul></ul><ul><ul><li>Autologous blood transfusions </li></ul></ul><ul><ul><li>Solid organs </li></ul></ul><ul><li>Class 2 </li></ul><ul><ul><li>Mainstream blood components </li></ul></ul><ul><ul><li>Banked cord blood – haematopoietic reconstitution </li></ul></ul><ul><ul><li>Banked tissues </li></ul></ul><ul><li>Class 3 </li></ul><ul><ul><li>Plasma products </li></ul></ul><ul><ul><li>Biotech equivalents of blood products eg rVIII etc </li></ul></ul><ul><ul><li>Cell based vaccines </li></ul></ul>
  15. 15. <ul><li>Class 1 </li></ul><ul><li>Unbanked/unprocessed </li></ul><ul><ul><ul><li>Medical practice governance </li></ul></ul></ul><ul><li>Class 2 </li></ul><ul><li>B anked/unprocessed </li></ul><ul><ul><ul><li>Manufacturing practice governance </li></ul></ul></ul><ul><ul><ul><li>Homologous function </li></ul></ul></ul><ul><li>Class 3 </li></ul><ul><li>B anked/processed </li></ul><ul><ul><ul><li>Manufacturing practice governance </li></ul></ul></ul>Organs Blood Progenitor (stem) cells Hospital based manufacture Banked blood components Banked tissues Processed cells and tissues Manufactured blood products “ Class III” – homologous function “ Class IV” – non-homologous function Plasma products Recombinant plasma products Processed blood components eg virally inactivated platelets Currently exempt Currently regulated through GMP – no ARTG Currently regulated as medicines or therapeutic devices “ listable” Biologicals – no efficacy requirements “ registrable” Biologicals –efficacy requirements Proposed regulatory model for Biologicals
  16. 16. Clinical trial framework Proposed approach <ul><li>Two levels </li></ul><ul><ul><li>CTX – detailed safety data reviewed by regulator </li></ul></ul><ul><ul><li>CTN – less detailed data requirements </li></ul></ul><ul><li>Role of HRECs </li></ul><ul><li>For biologicals – </li></ul><ul><ul><li>Class 3 Cell therapies are CTX </li></ul></ul><ul><ul><li>Gene therapy when vehicled through cell therapies is CTX </li></ul></ul><ul><ul><li>Xenotransplantation is CTX </li></ul></ul><ul><ul><li>New substances may be CTN if overseen by HREC – NHMRC new system </li></ul></ul>
  17. 17. <ul><li>- National minimum dataset of reportable adverse events </li></ul><ul><li>- Agreed definitions of these events, with standards for their investigation </li></ul><ul><li>- Collection within institution or blood establishment </li></ul><ul><li>- Notification to the competent authority (TGA) of any serious adverse events </li></ul><ul><li>and serious adverse reactions </li></ul>Haemovigilance Rapid Report generated by hospital Adverse event in public or private hospital and/or pathology service Health Department Regulator TGA Supplier Rapid validation process