LAWS90003 Biotechnology Regulation Lecture 13 & 14 PDF

LAWS90003 Regulation of Biotechnology Lecture 13 & 14. APVMA/FDA/EU regulations Michelle McNamara Dr Daniel Czech  WARNING This material has been reproduced and communicated to you by or on behalf of the University of Melbourne in accordance with section 113...

LAWS90003 Regulation of Biotechnology Lecture 13 & 14. APVMA/FDA/EU regulations Michelle McNamara Dr Daniel Czech  WARNING This material has been reproduced and communicated to you by or on behalf of the University of Melbourne in accordance with section 113P of the Copyright Act 1968 (Act). The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice Acknowledgement of Country The University of Melbourne acknowledges the Traditional Owners of the unceded land on which we work, learn and live: the Wurundjeri Woi-wurrung and Bunurong peoples (Burnley, Fishermans Bend, Parkville, Southbank and Werribee campuses), the Yorta Yorta Nation (Dookie and Shepparton campuses), and the Dja Dja Wurrung people (Creswick campus). The University also acknowledges and is grateful to the Traditional Owners, Elders and Knowledge Holders of all Indigenous nations and clans who have been instrumental in our reconciliation journey. We recognise the unique place held by Aboriginal and Torres Strait Islander peoples as the original owners and custodians of the lands and waterways across the Australian continent, with histories of continuous connection dating back more than 60,000 years. We also acknowledge their enduring cultural practices of caring for Country. We pay respect to Elders past, present and future, and acknowledge the importance of Indigenous knowledge in the Academy. As a community of researchers, teachers, professional staff and students we are privileged to work and learn every day with Indigenous colleagues and partners. Lecture Intended Learning Outcomes On completion of the lecture, students should be able to: Identify the appropriate regulatory body for a particular product and market; Understand the timeframe and technical requirements of the relevant regulatory agency Plan for successfully satisfying the appropriate agency; Relate the stringency and expense of registration to the market and projected sales; and Understand the regulatory steps in international jurisdictions. LAWS90003 Regulation of Biotechnology 4 Biography: Michelle McNamara Over 30 years senior management and leadership experience in multinational agriculture, biotechnology and pharmaceutical companies. Leadership in innovation in the biotech and pharmaceutical sectors with a focus on the development of human therapeutics. Have worked on veterinary, agricultural and horticultural projects. Research interests include small molecule, drug and vaccine delivery involving conventional and nanotechnology approaches. Business experience include commercialisation of new products and development and management of B2B relationships. Senior management and leadership positions in CSL, FH Faulding, Mayne Pharma and Hospira. including R&D Director at Mayne and Hospira and Senior Business and Development Manager at Mayne Pharma. Consultancy in biotech and pharmaceutical areas established in 2009, servicing broad range of biotechnology organisations including therapeutics, medical devices, agriculture and chemical industries. Joined University of Melbourne as an Enterprise Fellow in 2017; now an honorary fellow. LAWS90003 Regulation of Biotechnology Page Lecture 13 Australian agencies regulating biotech AGENCY PURPOSE TGA, Therapeutic Goods Administration Human therapeutic product safety FSANZ, Food safety Australia New Zealand Regulation of food quality and safety NHMRC, Nat Health & Medical Research Funding for medical research and advice to Council Government on health AICIS, Australian Industrial Chemicals Regulation of industrial chemicals Introduction Scheme APVMA Australian Pesticides and Regulation of agricultural chemicals including Veterinary Medicines Authority veterinary therapeutic products (medicines) Biosecurity, Deptartment of Agriculture Regulates importation of organisms and products (Commonwealth) derived from organisms OGTR, Office of the Gene Tech. Regulator Regulates the use of GMOs LAWS90003 Regulation of Biotechnology Page AVPMA and other agencies What is the role of other agencies in regulation of agricultural chemicals and veterinary medicines? Why would other agencies have a role in the regulation of agricultural chemicals and veterinary medicines? What would those roles be? Are there any agencies on the list without a role? LAWS90003 Regulation of Biotechnology Page Do any of these agencies contribute to the APVMA’s role? AGENCY PURPOSE CONTRIBUTION TO APVMA TGA Human therapeutic product safety ? FSANZ Regulation of food quality and safety ? NHMRC Funding for medical research and ? advice to Government on health AICIS Regulation of industrial chemicals ? APVMA Regulation of agricultural chemicals (ACs) including veterinary therapeutic products (veterinary medicines, VMs) Biosecurity Regulates importation of organisms and ? products derived from organisms OGTR Regulates the use of GMOs ? LAWS90003 Regulation of Biotechnology Page Do any of these contribute to APVMA’s areas? AGENCY PURPOSE CONTRIBUTION TO APVMA TGA Human therapeutic product safety Use of antibiotics and hormones in livestock animals- potential human risk. Knowledge of human safety FSANZ Regulation of food quality and safety Effect of use in food chain, plants and animals on human safety NHMRC Funding for medical research and As for TGA but evaluation of quality of research particularly advice to Government on health health related research AICIS Regulation of industrial chemicals Many ACs are new industrial chemicals and need approval before they are introduced to Australia APVMA Regulation of agricultural chemicals Regulation of agricultural chemicals including veterinary including veterinary therapeutic products therapeutic products (veterinary medicines) (veterinary medicines) Biosecurity Regulates importation of organisms and VMs can present biosecurity risk and so Biosecurity needs to be products derived from organisms consulted. OGTR Regulates the use of GMOs Some AC and VM products will be products of gene tech LAWS90003 Regulation of Biotechnology Page Why should we regulate? Law is the history of human failure. Regulation is also like that although now risk management is taking a much stronger role with agencies being proactive – preventing failure. Companies are also taking proactive roles - preventing failures and lawsuits. Let’s now look at the history of regulation of pesticides; ‒ First in the US. ‒ Then in Australia. LAWS90003 Regulation of Biotechnology Page Regulation of pesticides - USA Federal Insecticide Act (1910) protected from fraudulent or adulterated products. Federal Insecticide, Fungicide and Rodenticide Act (1947) gave control to Department of the interior and Department of Agriculture (DoA) controlled pesticides in USA. Pesticides Control Amendment (1954) first to establish safe limits. ‒ FDA oversees this amendment. The Food Additives Amendment (1958) prohibited carcinogenic pesticide residues or natural additives in foods. In 1959, pesticides registration introduced – DoA responsible. LAWS90003 Regulation of Biotechnology Page Regulation of pesticides - USA EPA created (1970) – took control of pesticide regulation from FDA. Federal Environmental Pesticides Control Act (1972) required proof of a lack of "unreasonable adverse effects" on human health or the environment. Today EPA must consider before approval: ‒ ingredients of the pesticide; ‒ the particular site or crop on which it is to be used; ‒ the amount, frequency, and timing of its use; ‒ and storage and disposal practices. The potential human health and environmental effects might be associated with the use of the pesticide. LAWS90003 Regulation of Biotechnology Page The beginnging of US pesticide regulation http://i114.photobucket.com/albums/n271/harpo516/2007-2008/Tidbits/Untitled-18.jpg http://www.safarisamblog.com/wp-content/uploads/2011/11/Bald_Eagle_holding_pink_salmon_discoveryed-665x1024.jpg After world war 2 the use of chemicals increased dramatically including DDT in the 1950s. Sixty years ago, the bald eagle - USA national symbol was in danger of extinction throughout most of its range. Habitat destruction and degradation, illegal shooting, and the contamination of its food source by DDT, decimated the eagle population. DDT entered the food chain from farms washed into rivers to fish to eagle. DDT is an endocrine disruptor produces a weak eggshell. DDT (dichloro-diphenyl-trichloroethane) LAWS90003 Regulation of Biotechnology Page Silent Spring and foundation of the US EPA Rachel Carson worked for US Bureau of Fisheries in the 1940s. Aware of the effect of pesticides on fisheries. Published Silent Spring in 1962 → Increased public awareness of dangers of pesticides Lead to campaign to ban DDT: ‒ Lead to formation of US EPA in 1970 ‒ DDT finally banned in the US in 1972 Regulation of pesticides in US strengthened – push back from lobby groups have diminished this strength. In 2012 Silent Spring was designated a National Historic Chemical Landmark by the American Chemical Society for its role in the development of the modern environmental movement. LAWS90003 Regulation of Biotechnology Page Pesticides and the US EPA today Environment Protection Agency (EPA) is responsible for regulating pesticides. ‒ under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA); ‒ and the Food Quality Protection Act (FQPA). Must be safe to use and effective against the intended pest(s). No adverse effects to humans or the environment. United States Department of Agriculture (USDA) and the United States Food and Drug Administration (FDA); ‒ set standards for the level of pesticide residue that is allowed on or in crops. LAWS90003 Regulation of Biotechnology Page Pesticides and the US EPA today Environment Protection Agency must consider before approval; ‒ "ingredients of the pesticide; ‒ the particular site or crop on which it is to be used; ‒ the amount, frequency, and timing of its use; ‒ and storage and disposal practices." Also the potential human health and environmental effects associated with use. LAWS90003 Regulation of Biotechnology Page Veterinary medicines in the US Governed by the Center for Veterinary Medicine (CVM). Department of the FDA. Its mission: “Protecting Human and Animal Health.” To achieve this broad mission, CVM: Makes sure an animal drug is safe and effective before approving it. https://www.fda.gov/about-fda/fda-organization/center-veterinary-medicine LAWS90003 Regulation of Biotechnology Page Role of the CVM If the drug is for a food-producing animal, before approving it, the center also makes sure that food products made from treated animals—meat, milk, and eggs—are safe for people to eat; Monitors the safety and effectiveness of animal drugs on the market; Makes sure food for animals—which includes animal feed, pet food, and pet treats—is safe, made under sanitary conditions, and properly labelled; Makes sure a food additive for use in food for animals is safe and effective before approving it; Conducts research that helps FDA ensure the safety of animal drugs, food for animals, and food products made from animals. LAWS90003 Regulation of Biotechnology Page Pesticides in the EU Pesticides authorised by the European Parliament under Regulation 1107/2009. Active substances authorised by the European Union, Products by Member states. Following risk assessment by the European Food Safety Authority. Pesticides must not have: ‒ Unacceptable effects on plants; ‒ Damaging effects on human or animal health; and ‒ Damaging effects on groundwater or the environment in general. Authorisation is valid for 10 years and is subject to renewal. EU divided into 4 biogeographic zones (N,S,E,W). New authorisation required for each zone. At a review in 2009: 25% actives authorised, 66% eliminated (withdrawn, etc.), 7% failed review. LAWS90003 Regulation of Biotechnology Page Veterinary medicines in the EU Veterinary medicines approved by the European Medicines Authority in EU since mid 1990s. Follows an approach similar to human medicines; subject to cGMP for manufacture. Authorisation and monitoring of veterinary medicinal products are laid down in Directive 2001/82/EC and in Regulation (EC) No 726/2004. Protection against harm to human or animal health or the environment. Protected against potentially harmful effects as a result of exposure to residues from veterinary medicinal products in food products. Strong focus on antibiotic and hormone use. LAWS90003 Regulation of Biotechnology Page History of pesticide regulation in Australia Before 1990s regulation of pesticides was a state and territory responsibility. 1992 National Registration Scheme established under responsibility of National Registration Authority. Responsible to the Department of Agriculture for ensuring agricultural and veterinary chemicals are: ‒ safe when exposed to humans and non-target species including direct exposure of residues in food; ‒ not a risk to the environment; ‒ effective on target species; and ‒ labelled and packaged correctly. LAWS90003 Regulation of Biotechnology Page What is the APVMA? Australian Pesticides and Veterinary Medicines Authority (APVMA). Australian government statutory authority. Established in June1993, now nearly 30 years old. Centralised the registration of all agricultural and veterinary chemicals. APVMA Vision: Australians have confidence that agricultural and veterinary chemicals are safe to use. APVMA Mission: ‒ To protect the health and safety of Australia – ‒ its people, animals and environment; and ‒ support Australian agriculture by taking a scientific and risk-based approach to regulating agricultural and veterinary chemicals. LAWS90003 Regulation of Biotechnology Page What does the APVMA regulate? The APVMA regulates agricultural chemicals and veterinary therapeutic products. “Agvet chemicals”, whether used by farmers, pest controllers, veterinarians or other home or professional users - are regulated by the APVMA. This includes: ‒ agricultural chemicals such as pesticides, herbicides, biocides, insecticides and seed treatments; ‒ veterinary chemicals such as medicines, antibiotics, hormonal treatments and some stockfeed and petfood, and; ‒ other chemicals such as insect repellents, garden sprays and pool chemicals. See video at https://youtu.be/03Noa0_Xpds URL: https://apvma.gov.au/node/15866 LAWS90003 Regulation of Biotechnology Page What does the APVMA regulate? APVMA regulates products up to and including point of sale (POS). What happens after point of sale? State and Territory authorities such as the Victorian Department of Primary Industries regulate after the point of sale. Note they do not regulate at the point of sale. LAWS90003 Regulation of Biotechnology Page What does the APVMA regulate? Ongoing focus in this subject is the Australian system. Details of US and European regulatory systems are different but.. ‒ Aim of protecting the human population and the environment the same. ‒ Australia is different – APVMA must “support Australian agriculture”. All 3 regulatory systems use the tool of risk analysis, to balance risk with benefits. Also implement measures to control and mitigate risk. LAWS90003 Regulation of Biotechnology Page Lecture 14 How does APVMA regulate new products? The APVMA must be satisfied that… human health and safety are protected will not prejudice international trade product is effective for the purpose product is adequately labelled will not harm the environment will not harm animals LAWS90003 Regulation of Biotechnology Page How does APVMA regulate new products? For a new agricultural or veterinary (agvet) chemical product Active constituent glyphosate that contains a new active constituent. APVMA must approve the active constituent before we register the product. Once approved, the active constituent may be used in new agvet chemical products for registration. Each registered product must have a label containing the Product – Roundup instructions approved by the APVMA: What you need to know about a popular weed killer's alleged link... ‒ for the safe and effective use of the product; ‒ for its storage, handling and disposal. Products cannot legally be supplied without having a label containing these instructions attached to their containers. LAWS90003 Regulation of Biotechnology Page How does APVMA regulate new products? Satisfying the statutory criteria You must indicate in your application how you expect us to be satisfied that the statutory criteria relevant to your application have been addressed, by using one, or a combination, of the methods below: ‒ Providing relevant data; ‒ Using a reference product; ‒ Providing a valid scientific argument; ‒ Submitting previously provided reports from the Australian Pesticides and Veterinary Medicines Authority (APVMA); ‒ Using overseas data assessments and decisions – relevance to the Australian agricultural environment must be explained. Testimonials or anecdotal evidence on their own are not acceptable methods of satisfying the statutory criteria and are generally given little weight but may be used as additional supporting information. LAWS90003 Regulation of Biotechnology Page How does APVMA regulate new products? Chemical product For a chemical product, the APVMA must be satisfied that the product meets the safety criteria, the efficacy criteria, the trade criteria, and the labelling criteria (see the hyperlinks for details of each). Safety criteria - Details of how we determine that a product meets relevant safety criteria (safe for humans, animals and plants and the environment). Efficacy criteria - Details of how we determine that a product meets relevant efficacy criteria (works as intended). Trade criteria - Details of how we determine that a product meets relevant trade criteria (does not prejudice international trade). Labelling criteria - Details of how we determine that a product meets relevant labelling criteria. (adequate to control risks with intended use). LAWS90003 Regulation of Biotechnology Page APVMA criteria APVMA Safety criteria A product will meet the APVMA’s safety criteria if it is not: an undue hazard to the safety of people exposed to the product during its handling or people using anything containing its residues; and likely to have an effect that is harmful to human beings; and likely to have an unintended effect that is harmful to animals, plants or things or to the environment. LAWS90003 Regulation of Biotechnology Page APVMA Safety criteria The submission should include information on: 1. The toxicity of the product, residues, metabolites and degradation products, to organisms and ecosystems, including humans. 2. The relevant poison classification of the product as determined under the law in this jurisdiction. 3. How the product is formulated. 4. The composition and form of the constituents of the product. 5. Any relevant particulars that are, or would be, entered in the Register for the product. 6. Whether the product conforms, or would conform, to any standard made for the product, to the extent that the standard relates to the safety of the product. LAWS90003 Regulation of Biotechnology Page APVMA Safety criteria 7. Any matters prescribed by the Agvet Code Regulations, including: ‒ for all chemical products, the method of analysis (if any) of the chemical composition and form of the constituents of the chemical product. ‒ compliance with a code of Good Manufacturing practice and; ‒ other requirements for specific product classes. LAWS90003 Regulation of Biotechnology Page APVMA Safety criteria The APVMA will consider; 1. The acceptable daily intake of each constituent contained in the product. 2. Any dietary exposure assessment. 3. Any trials or laboratory experiments to determine the residues of the product in relation to the limits. 4. The stability of the product. 5. The specifications for containers for the product. 6. Other matters as we think relevant. LAWS90003 Regulation of Biotechnology Page APVMA Efficacy criteria APVMA must have regard to the following for the purposes of being satisfied as to whether a chemical product meets the efficacy criteria: 1. whether any trials or laboratory experiments have been carried out to determine the efficacy of the product and, if so, the results of those trials or experiments; 2. any conditions to which its registration is, or would be, subject; 3. any relevant particulars that are, or would be, entered in the Register for the product; 4. whether the product conforms, or would conform, to any standard made for the product; 5. any matters prescribed by the Agvet Code Regulations. LAWS90003 Regulation of Biotechnology Page APVMA Trade criteria APVMA must have regard to the following for the purposes of being satisfied whether a chemical product meets the trade criteria: 1. any conditions to which its registration is, or would be, subject; 2. any relevant particulars that are, or would be, entered in the register for the product; 3. whether the product conforms, or would conform, to any standard made for the product; 4. any matters prescribed by the Regulations. LAWS90003 Regulation of Biotechnology Page APVMA Trade criteria The extent to which the APVMA must have regard to trade criteria matters is prescribed by the Agvet Code Regulations to be: in full where it can be reasonably expected that the chemical product will be used in relation to: ‒ a crop or animal, a product of which might be provided to a place outside Australia; ‒ a crop that will be fed to an animal, a product of which might be provided to a place outside Australia. in any other case, to the extent that the APVMA thinks is relevant. LAWS90003 Regulation of Biotechnology Page What are international trade issues? APVMA must be satisfied that the international trade issues arising from the use of the chemical on produce are manageable. Different food standards and maximum residue limits (MRLs) apply in different countries. An MRL is the highest level of a pesticide residue that is legally tolerated in or on food or feed when pesticides are applied correctly in accordance with Good Agricultural Practice (GAP). Different MRLs reflect different agricultural practices. Need to meet the standards of the importing country. Producers must consider MRLs when making chemical selections. LAWS90003 Regulation of Biotechnology Page What trade deals are being negotiated? http://www.theage.com.au/business/the-economy/tpp- what-the-trade-pact-means-for-australia-20151005- gk20h9.html http://www.afr.com/news/uk-foreign-secretary-boris- johnson-promises-a-great-trade-deal-with-australia- 20170727-gxjub6 http://www.agriculture.gov.au/market-access- trade/fta/ftas-signed-under-negotiation http://dfat.gov.au/trade/agreements/Pages/trade- agreements.aspx https://www.dfat.gov.au/trade/agreements/negotiations/ aukfta LAWS90003 Regulation of Biotechnology Page Maximum Residual Limit (MRL) The maximum concentration of a residue resulting from the approved use of an agricultural or veterinary chemical. Which is legally permitted or recognised as acceptable to be present in or on a food, agricultural commodity or animal feed. Varies from country to country; may vary from crop to crop. Not needed in non-food situations e.g., ornamental plant or companion animal. APVMA makes a trade assessment only where there is significant international trade. Assessment involves comparing the level of residues that may occur in treated produce with the known residue standards in major export markets for that commodity; and with the international standards for residues set by the Codex Alimentarius Commission (Codex). LAWS90003 Regulation of Biotechnology Page APVMA Labelling criteria A chemical product meets the labelling criteria if the label contains adequate instructions relating to the following as appropriate: 1. The circumstances in which the product should be used. 2. How the product should be used. 3. The times when the product should be used. 4. The frequency of the use of the product. 5. The withholding period after the use of the product. 6. The re-entry period after the use of the product. X 7. The disposal of the product when it is no longer required. 8. The disposal of containers of the product. LAWS90003 Regulation of Biotechnology Page APVMA Labelling criteria A chemical product meets the labelling criteria if the label contains adequate instructions relating to the following as appropriate: 1. The circumstances in which the product should be used. 2. How the product should be used. 3. The times when the product should be used. 4. The frequency of the use of the product. 5. The withholding period after the use of the product. 6. The re-entry period after the use of the product. X 7. The disposal of the product when it is no longer required. 8. The disposal of containers of the product. LAWS90003 Regulation of Biotechnology Page APVMA Labelling criteria 9. The safe handling of the product and first aid in the event of an accident caused by the handling of the product. 10. Any matters prescribed by the Agvet Code Regulations, including: the prevention of undue prejudice to trade or commerce between Australia and places outside Australia; the appropriate signal words (if any) required by the current Poisons Standard; for a chemical product that is a date-controlled chemical product, the storage of containers for the product. LAWS90003 Regulation of Biotechnology Page Multiple tiers of risk management Risk assessment of new chemicals and uses. National Control the supply of chemicals. Control National policies for chemical management. National Maintain access to markets and facilitate trade. and State Control how chemicals are used. Enforce controls that protect the environment and the State health of consumers, the community and farm workers. Control LAWS90003 Regulation of Biotechnology Page Regulatory approvals – general principles Approval is based on benefits relative to risks. Benefit is the effectiveness of the product and flow-on effects. Risks are the hazards that are intrinsic to the product multiplied by the exposure to the product. Risk = Hazard x Exposure LAWS90003 Regulation of Biotechnology Page How does APVMA regulate new products? The APVMA must be satisfied that… human health and safety are protected - RISK will not prejudice international trade product is effective - RISK for the purpose product is - BENEFIT adequately labelled - RISK will not harm the environment will not - RISK harm animals - RISK LAWS90003 Regulation of Biotechnology Page How does APVMA regulate new products? Risk = Hazard x Exposure Hazard = intrinsic properties of chemical or formulation – evaluate from lab and field studies in regulatory submission. Exposure = direct or indirect contact with product. Control by use instructions i.e., “the label”. Critical for safe and effective use. LAWS90003 Regulation of Biotechnology Page Risk management matrix Risk = Hazard x Exposure but also Risk = Likelihood x Consequence Almost certain 9 - 10 Moderate Major Critical Critical Critical (e.g., >90% chance) Likely 7-8 Moderate Major Major Critical Critical (e.g., between 50% - 90% chance) Likelihood Possible 5-6 Moderate Moderate Major Major Critical (e.g., between 10% and 50% chance) Unlikely 3-4 Minor Moderate Moderate Major Critical (e.g., between 3% and 10% chance) Rare 1-2 Minor Minor Moderate Moderate Major (e.g.,