LAWS90003 Regulation of Biotechnology Lecture 15 & 16 PDF

LAWS90003 Regulation of Biotechnology Lecture 15 & 16. 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 15 & 16. 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: Discuss the implications of the 4Corners glyphosate program; Describe the political oversight of the APVMA and the role of the incumbent CEO; Evaluate evidence about whether glyphosate is a probable carcinogen from different agency perspectives; Analyse the composition of glyphosate and the role of the label in mitigating risk; and Consider the role of risk management in the use of hazardous products. LAWS90003 Regulation of Biotechnology 4 Notice about the discussion board Please use the Canvas discussion board if you have specific questions about Module 4. There is a specific discussion topic for this at: https://canvas.lms.unimelb.edu.au/course s/187797/discussion_topics/1269286 Michelle will be monitoring the discussion board for about the next two weeks. General enquiries about the subject should be sent to: [email protected] LAWS90003 Regulation of Biotechnology Page Lecture 15 What will we cover in Lecture 15? Fallout from 4 Corners program. AVPMA governance and structure: Political oversight – Senate questions and inquiry. 2016 move and following inquiries. CEO changes. Other staff changes. Is glyphosate a Carcinogen? What are carcinogens/probable carcinogens? IARC evidence. APVMA position. Other regulatory agencies. LAWS90003 Regulation of Biotechnology Page The Monsanto Papers Fallout from 4Corners program. First aired in October 2018. Watch the Monsanto Papers here. LAWS90003 Regulation of Biotechnology Page Is the APVMA/Government response to Glyphosate Compromised? Four Corners program led to Senate inquiry into the governance of APVMA and the registration of Glyphosate. From the Weekly Times Feb 8, 2019 “The senate report calls the APVMA’s review of glyphosate ‘robust’, even though the agency decided not to conduct a formal reconsideration of the chemical despite the APVMA’s chief executive agreeing that glyphosate is a probable carcinogen,” Senator Green (sic – actually Senator Rice, Greens party) said. https://www.weeklytimesnow.com.au/agribusiness/cropping/inquiry-into-australias-agricultural- chemical-management-in-question/news-story/08c77a2ae8a6c72bbd162c4c5c00cb12 LAWS90003 Regulation of Biotechnology Page Fallout from 4 Corners program “The Monsanto Papers” Four Corners program led to Senate inquiry into the governance of APVMA and the registration of glyphosate Inquiry into Australia’s agricultural chemical management in question MADELEINE STUCHBERY, The Weekly Times February 8, 2019 12:00am Subscriber only THE independence of an inquiry in Australia’s agricultural chemical management has been called into question. The Greens cast a shadow over the finding of a senate inquiry into the Australian Pesticides and Veterinary Medicines Authority because of political donations to the major political parties. Last week’s release of the political donor list coincided with the inquiry’s findings. The inquiry examined the effectiveness of the APVMA’s process for reviewing and reassessing the safety of agricultural chemicals, including glyphosate. It recommended the development of a national plan for agricultural and veterinary pest control innovation and an independent assessment of the cost of registration of minor-use chemicals. LAWS90003 Regulation of Biotechnology Page Does funding of APVMA by companies influence their regulatory decisions? Applicants pay fees to APVMA for assessing their applications. Could this compromise their independence? Senate report - Cost recovery funding model is comparable to the funding models of other national and international regulators. LAWS90003 Regulation of Biotechnology Page Other regulatory agencies Another industry example Does funding of FDA by pharma influence their regulatory decisions? FDA has had user fees (PDUFA) for 30 years now. Introduced to speed review of new drugs (in 1988 took 26months down to 12 months now). PDUFA regularly reviewed and renewed by congress. Applicants pay fees to FDA for assessing their applications. Some debate about the way this may compromise their independence See https://www.forbes.com/sites/johnlamattina/2013/08/07/is-the-fda-being-compromised-by- pharma-payments/?sh=4d57c7c42830 TGA and EMEA also have user fees – a globally accepted funding mechanism. LAWS90003 Regulation of Biotechnology Page Is the APVMA/Government response to glyphosate compromised? From the Weekly Times Feb 8, 2019 Do Donations influence the outcome? “It’s also clear from the donations data released… that the independence of this Senate inquiry and indeed the APVMA is under a cloud.” CropLife Australia and chemical company Bayer, which produces the glyphosate- based weed killer Roundup, donated to both federal Labor and the Coalition Government in 2017-18. Bayer donated $40,600 to Labor, $27,840 to the Nationals and $14,700 to the Liberals. CropLife Australia donated $34,271 to Labor and $22,300 to the Nationals. CropLife Australia chief executive Matthew Cossey said the inquiry was sparked by “sensationalised and baseless media reporting” and said the weight of evidence had confirmed why the community should have confidence in the decisions of the APVMA. LAWS90003 Regulation of Biotechnology Page Senate Report - 1 Relocation to Armidale created staff shortages. More staff needed to fulfil regulatory responsibilities. Lacks a robust quality control framework and a fit-for- purpose workflow management system. Cost recovery funding model is comparable to the funding models of other national and international regulators. Industry does not unduly influence the decisions of the regulator. LAWS90003 Regulation of Biotechnology Page Senate Report - 2 Concerned by delays to review of chemicals. ‒ Particularly those grandfathered into the NRS. Risk based approach acceptable. Regarding Glyphosate: ‒ Considers the APVMA's scientific processes to be robust, noting that all 264 of the studies referenced in the IARC report were independently evaluated. ‒ Further addressed in APVMA’s report: ‒ APVMA Report (2019) → LAWS90003 Regulation of Biotechnology Page Senate Report – Dissenting responses The committee had a majority of Labor Party members. Coalition did not agree with criticism of the relocation. Greens: Agreed with: The effect of relocation. Disagreed with: Independence of the APVMA. The support for glyphosate. Increase in the hazard of glyphosate (now a probable carcinogen) leads to an increase in risk. LAWS90003 Regulation of Biotechnology Page APVMA response to the 4 Corners program The APVMA “considered the evidence presented in the Californian case and found no grounds to take regulatory action in Australia.” “The manner in which the APVMA is funded bears no influence on our independent regulatory activities “ “We hold industry to account and take action when a risk is identified.” In the past 12 months, the APVMA has acted to change label directions for 2,4-D, and fined manufacturers: ‒ When products did not meet specification ‒ suspended registrations where products no longer met safety requirements. “Australian’s can have confidence in the decisions of the APVMA and that our regulation will continue to protect the health and safety of people, animals and the environment.” LAWS90003 Regulation of Biotechnology Page APVMA governance and structure Political oversight. 2016 move and following inquiries. CEO changes. Other staff changes. LAWS90003 Regulation of Biotechnology Page Australian government statutory bodies Statutory Authorities Governed independently of the political system e.g., by a board or advisory body. Headed by a CEO (or similar). Usually answerable to a responsible minister (with a relevant portfolio) and government. Accountable to the parliament of Australia and the law. APVMA Transitioned from an advisory body to a governing board in 2022. Responsible to the Agriculture Minister. Have an acting CEO and acting board currently after massive turmoil. LAWS90003 Regulation of Biotechnology Page Australian political system Federation of 6 states and 2 territories. Party % of 2022 Seats House Seats Vote of Reps (MHR) Senate Constitution established Commonwealth of Australia in 1901. States ceded some of their powers to 33% 77 26 the Commonwealth. Bicameral (2 houses) system with 36% 58 31 House of Representatives and Senate. (Nationals (Nationals 10) (Nationals 4) 4%) 4 Major political parties (above 10% of the vote), labour, greens, Liberals and 2022 Vote 4 11 nationals (last 2 in a coalition). 12% Nationals (formerly Country Party) Total including 151 members represent rural and regional Australia minor parties and 100% MHR 76 Senators independents LAWS90003 Regulation of Biotechnology Page Key political figures Representing Roles Reason for leaving role Impact on APVMA Barnaby Joyce Minister for Agriculture to Demoted to backbench Moved APVMA to Armidale 2016. MHR for New England Dec 2017; Deputy PM due to sex scandal involving a staff member. David Littleproud Minister Agriculture to Became Deputy Leader Labor calls on Minister to reverse move MHR for Maranoa 2019 of Nationals. to Armidale. Bill to introduce governance board blocked in Senate 2019. Bridget McKenzie Minister for Agriculture Resigned due to sports Opened Armidale office 2019. New Senator for Victoria 2019 to 2020 rorts affair breached board implemented CropLife objected. ministerial standards. David Littleproud Minister for Agriculture Liberal National coalition Review report 2021 MHR for Maranoa 2020-2022 lost 2022 election. Statement of Expectations for APVMA March 2022. Murray Watt Senator Minister for Agriculture Appointed following 2022 Inquiry led to resignation of board chair for Queensland 2022- July 2024 election. and CEO July 2023. New APVMA strategy. LAWS90003 Regulation of Biotechnology Page Current Minister for Agriculture The Hon Julie Collins MP was sworn in as Minister for Agriculture, Fisheries and Forestry on 29 July 2024. Labor MP representing Franklin in Tasmania. Replaced Murray Watt in a reshuffle where Murray Watt was appointed Minister of Home Affairs. LAWS90003 Regulation of Biotechnology Page APVMA move to Armidale Sydney Morning Herald article on the Public servants told it's Armidale or find new jobs June 10 2016 move to Armidale (2016). The Canberra Times Hundreds of Canberra public servants have been told they will be moving to northern NSW or looking for new jobs if the Coalition wins the election. Agriculture Minister Barnaby Joyce said the veterinary medicines authority was going to move to Armidale in Mr Joyce's electorate of New England and the public servants who work at the agency better get used to the idea. LAWS90003 Regulation of Biotechnology Page How did the APVMA relocation go? Moving APVMA to a Rural and regional area appears to make some sense. APVMA do primarily service the agricultural industry. However,… Survey showed 70 per cent of staff did not wish to relocate. Staff working from the Armidale McDonalds due to a lack of office space → Ultimately only 17 of 170 staff relocated to Armidale. LAWS90003 Regulation of Biotechnology Page APVMA CEO changes APVMA CEO Commentary (i.e. what happened) In early 2017 CEO Kareena Arthy quit as the move to Armidale began. New CEO Chris Parker quit in 2019 (cited personal reasons), 2 years into a 5-year contract. In 12 months to June half of the staff were replaced. CEO Lisa Croft deputy CEO appointed CEO 2020 went on leave in Feb 2023 following Senate estimates pending inquiry by Clayton Utz; Resigns July 2023 following Clayton Utz report release. Nicola Hinder on secondment from Dept Ag; interim CEO Feb 2023 for duration of Clayton Utz inquiry; In July 2023 Clayton Utz inquiry recommends further inquiry conducted by Ken Matthews. Melissa McKewon appointed acting CEO July 2023 for 12 months to manage implementation of inquiries recommendations. Matthews report extension to 27 October. LAWS90003 Regulation of Biotechnology Page New CEO appointed for a 5-year contract - July 2024! “Performance has not really been APVMA’s problem, with the committed regulatory and scientific staff often applauded for their commitment and dedication to processing applications as efficiently as their antiquated systems and complex regulatory framework would allow, and the vast majority of applications processed on time. However, the failed myAPVMA project that was to replace the clunky online application system, as well as a reportedly toxic workplace environment on the administrative side of the building, often hampered that ongoing good work and caused significant staff turnover, ultimately resulting in the ministerial investigation and wholesale change of the organisation’s leadership.” “The APVMA were unable to advise if Mr Hansen would be based in Armidale”. New England Times (2024) LAWS90003 Regulation of Biotechnology Page APVMA Inquiries - Staff issues - 1 In November 2022, the Brennan inquiry initiated by Minister Senator Watt following Senate estimates evidence; Sexual harassment complaints. Senior male staff member allegedly urinated on colleagues; Interim report referred to police. In March 2023, Minister Watt requested that the APVMA board conduct a strategic review. Board commissioned Clayton Utz to conduct review; report released in July 2023. Minister Watt then commissioned public servant Ken Matthews to conduct further review on the operation of the APVMA. LAWS90003 Regulation of Biotechnology Page APVMA Inquiries - Staff issues - 1 Clayton Utz found: Serious allegations of poor governance, poor workplace culture and poor leadership. Potential noncompliance with commonwealth procurement rules of the APVMA. Very high staff turnover and unacceptably higher number of workplace complaints. Formal HR complaint recorded every four to six weeks for the past five years. Employed 129 people June 2022 – recorded 56 personnel-related complaints between 2018 and 2023. ‒ 21 were allegations of inappropriate behaviour. Some of the complaints were very serious - little if any reporting of these matters to the board. Move to Armidale led to: A loss of corporate knowledge, a loss of corporate culture. And a loss of experience and knowledge of public sector values. LAWS90003 Regulation of Biotechnology Page APVMA Inquiry – Regulatory issues Clayton Utz also found: APVMA had focused on timeframes for registering AgVet chemicals. ‒ At the expense of undertaking monitoring and compliance activities. ‒ Over half of ongoing chemical reviews in progress for nearly two decades. ‒ Compliance targets of 100% unrealistic, do not reflect best regulator practice and may contribute to a reduction in regulatory performance. APVMA's current timeframe targets do not align with realistic regulatory best practice. ‒ Impacts the capacity and workload for the APVMA's staff. LAWS90003 Regulation of Biotechnology Page APVMA Inquiry – Regulatory issues Clayton Utz also found: APVMA’s regulation “appears to align with industry interests”. ‒ Embedded into the APVMA's regulatory priorities and culture. And this alignment “appears to be embedded into the APVMA's regulatory priorities and culture”. An “educational approach” to enforcing regulations. ‒ Rather than applying stronger penalties. Minister Watt is reported to take “firm action” on the inquiry findings; appointed Ken Matthews a former public servant to conduct a further review – report due 27 October 2023 released April 2024. LAWS90003 Regulation of Biotechnology Page Matthew’s inquiry recommendations overview Mathew’s key recommendation was that APVMA be abolished. APVMA be moved into the Department of Agriculture, Fisheries and Forestry. Returned to Canberra. Minister of Agriculture rejected key recommendation and stated that he implemented: ‒ A new Ministerial Statement of Expectations for the APVMA. ‒ Expediting eight long-running chemical reconsiderations. ‒ The APVMA Strategy 2030, which provides clear strategic direction. ‒ A new APVMA Values Statement and updated APVMA Board Charter. ‒ Locations in Armidale and Canberra to be maintained. LAWS90003 Regulation of Biotechnology Page APVMA strategy 2030: 5 themes LAWS90003 Regulation of Biotechnology Page The APVMA’s approach to chemical risk - glyphosate All glyphosate products registered have been through a robust chemical risk assessment process. Are safe to use, provided they are used as per the label instructions. APVMA considers all relevant scientific information including human health and worker safety. Glyphosate if used according to label instructions does not result in a level of exposure that poses an unacceptable risk. Uses a risk-based, weight-of-evidence assessment. Minimises human risk through instructions for use and safety directions. LAWS90003 Regulation of Biotechnology Page Lecture 16 What will we cover in Lecture 16? Glyphosate in Use: Glyphosate – product versus active agent. Glyphosate labelling. Adherence to the label in use. Management of Risk: General aspects of risk management. Chemical risk, hazard and exposure. What is hazard? What is exposure? How do we combine these? How do we eliminate/mitigate risk? Risk management applied to glyphosate. Updates on regulatory and legal actions LAWS90003 Regulation of Biotechnology Page Is glyphosate a Carcinogen? What are carcinogens/probable carcinogens? IARC evidence. APVMA position. Other regulatory agencies. Judicial decisions. LAWS90003 Regulation of Biotechnology Page WHO classification of carcinogenicity Group 1 Group 2A Group 2B Group 3 Group 4 Carcinogenic to Probably Possibly Not classifiable Probably not Humans Carcinogenic to Carcinogenic to Carcinogenic to Humans Humans Humans Sufficient evidence of Limited evidence of Limited evidence of Inadequate evidence of Evidence suggesting carcinogenicity in carcinogenicity in carcinogenicity in carcinogenicity in lack of carcinogenicity humans and in humans and sufficient humans and humans and in in humans and in experimental animals evidence of insufficient evidence of experimental animals experimental animals carcinogenicity in carcinogenicity in experimental animals experimental animals 11 agents, including 8 65 agents, including 3 274 agents, including 6 504 agents, including 5 1 agent, no biological biological agents: biological agents: biological agents: biological agents: agent - Epstein-Barr virus - Human - BK polyomavirus - Human - Helicobacter pylori papillomavirus papillomavirus genus beta LAWS90003 Regulation of Biotechnology Page Spot the carcinogen LAWS90003 Regulation of Biotechnology Page WHO classification of carcinogenicity Tobacco smoke and smokeless Group 1. Tea Group 3 (but very hot liquids group 2A). Coffee Group 2B. Processed meats Group 1. Red meat Group 2A. Gas stoves and fires emit Group 1 particulates. Solar radiation Group 1. Mobile phones Group 2B. Alcoholic beverages Group 1. Magnetic fields Group 2B/Group 3. Group 4 was deleted from IARC carcinogen list in 2019. LAWS90003 Regulation of Biotechnology Page IARC Monograph on glyphosate IARC Q&A on its Monograph in IARC News in 2019 In March 2015, IARC classified glyphosate as “probably carcinogenic to humans” (Group 2A). Based on “limited” evidence of cancer in humans (from real-world exposures that actually occurred). And “sufficient” evidence of cancer in experimental animals (from studies of “pure” glyphosate). “Strong” evidence for genotoxicity, both for “pure” glyphosate and its formulations. LAWS90003 Regulation of Biotechnology Page IARC Monograph on glyphosate IARC Q&A on its Monograph in IARC News in 2017 The Agricultural Health Study (AHS) incorrectly described as the “most powerful” study. AHS collected data on cancer and pesticide use in more than 50,000 users in 2 US states over 5 phases. Only short follow up - fewer cases of cancer would have had time to appear. ‒ Limit's ability of the study to detect an association if one truly exists. Although the AHS is a large, well-conducted study its results on glyphosate and non-Hodgkin lymphoma risk do not outweigh other studies. The IARC Working Group also conducted an objective statistical analysis of the results of all the studies on glyphosate and non-Hodgkin lymphoma (included AHS) and all case-control studies. The combined data show a statistically significant association between non-Hodgkin lymphoma and exposure to glyphosate. LAWS90003 Regulation of Biotechnology Page Agricultural Health Study The Agricultural Health Study (AHS) is a prospective study of cancer and other health outcomes in a cohort of licensed pesticide applicators and their spouses from Iowa and North Carolina funded by NIH and EPA. 52,394 licensed private pesticide applicators (mostly farmers) and 32,345 spouses. 2021 updated meta-analysis reinforces a lack of an association between exposure to glyphosate and risk of NHL overall – not directly linked to Bayer but one researcher glyphosate industry funded. LAWS90003 Regulation of Biotechnology Page Agricultural Health Study Graphic showing the 5 phases of the study. Phase 1 (1993-1997), Phase 2 (1999-2003), Phase 3 (2005-2010), Phase 4 (2013-2015), Phase 5 (2019-2021). LAWS90003 Regulation of Biotechnology Page IARC Monograph on Glyphosate Regulatory Authorities compared with IARC Many regulatory agencies rely primarily on industry data from toxicological studies that are not available in the public domain. In contrast, IARC systematically assembles and evaluates all relevant evidence available in the public domain for independent scientific review. In the interests of transparency, IARC evaluations rely only on data that are in the public domain and available for independent scientific review. The IARC Working Group’s evaluation of glyphosate included any industry studies that met these criteria. However, they did not include data from summary tables in online supplements to published articles, which did not provide enough detail for independent assessment. This was the case with some of the industry studies of cancer in experimental animals. LAWS90003 Regulation of Biotechnology Page Joint FAO/WHO Meeting on Pesticide Residues (JMPR 2016) Food and Agriculture Organisation (FAO). World Health Organisation (WHO) The Joint Meeting on Pesticide Residues (JMPR) is an expert ad hoc body administered jointly by FAO and WHO. Meeting held May 2016. For the purpose of harmonizing the requirement and the risk assessment on the pesticide residues. Placed on agenda due to the recent studies suggesting toxicity. LAWS90003 Regulation of Biotechnology Page JMPR conclusions LAWS90003 Regulation of Biotechnology Page APVMA position on IARC glyphosate report The Australian Pesticides and Veterinary Medicines Authority (APVMA) has completed several scientific assessments of glyphosate since it was first registered: 1996 Reconsideration of Glyphosate – restricted use in areas with sensitive waterways In response to an EPA request – study showed acute toxicity to tadpoles Proposed regulatory position report – September 2016 Review of IARC Monograph 112 (Glyphosate): Tier 1 – September 2016 Review of IARC Monograph 112 (Glyphosate): Tier 2 – September 2016 Final regulatory position: Consideration of the evidence for a formal reconsideration of glyphosate – March 2017 Reconsideration of a registered product is a formal process and APVMA concluded it was not needed for glyphosate. Current position can be found at https://www.apvma.gov.au/resources/chemicals-news/glyphosate LAWS90003 Regulation of Biotechnology Page APVMA position on IARC assessment of glyphosate The APVMA conducted a weight-of-evidence evaluation including Department of Health review – APVMA does not need to formally reconsider registration. APVMA keeps a close watch on new scientific studies that may indicate whether this position should be revised. In the weight-of-evidence assessment used by regulators, relevant observations are validated because different investigators reproduce them independently. A weight-of-evidence assessment considers both the number of studies reporting a particular conclusion and the quality of the study design and data analysis. A strength-of-evidence assessment can be based on a single study, even if the study protocol has limitations or does not comply with internationally accepted regulatory protocols, or if the results are not consistent with observations made in other well-designed studies. Regulators do not use strength-of-evidence assessments. LAWS90003 Regulation of Biotechnology Page APVMA’s approach to chemical risk - glyphosate The Joint FAO/WHO Meeting on Pesticide Residues (JMPR, May 2016) concluded that there was some evidence for a positive correlation between occupational glyphosate exposure and non-Hodgkin lymphoma in some studies while… ‒ The only well-designed large cohort study (AHS) found no association at any exposure level. APVMA weight of evidence approach put more emphasis on the latter study. List of publications reviewed by APVMA is at https://apvma.gov.au/node/47421. LAWS90003 Regulation of Biotechnology Page APVMA position on IARC assessment of glyphosate Exposure to glyphosate does not pose a carcinogenic or genotoxic risk to humans. There is no scientific basis for changing the view on glyphosate and that it: ‒ would not be an undue hazard to the safety of people exposed to it; ‒ would not be likely to have an effect that is harmful to human beings; X ‒ would not be likely to have an unintended effect that is harmful to animals, plants or things or to the environment; ‒ would be effective; and ‒ would not unduly prejudice trade. There are no scientific grounds for placing glyphosate and products containing glyphosate under formal reconsideration. The APVMA will continue to maintain a close focus on any new assessment reports or studies that indicate that this position should be revised. LAWS90003 Regulation of Biotechnology Page Quality Control of Studies IARC rely on published studies Quality control of study validity is by: ‒ Researchers are bound by research ethics eg NHMRC code for responsible conduct of research. ‒ Peer review of published papers. ‒ Fraud happens – other researchers fail to replicate and then investigate initial study. LAWS90003 Regulation of Biotechnology Page Quality Control of Studies Regulatory Authorities e.g. APVMA Rely on toxicology studies provided by the company submitting the data Quality Control of study validity is by: ‒ Ethics of the toxicologists performing the studies eg board certification in US. ‒ Codes of Good Laboratory Practice. ‒ FDA cGLP in USA. ‒ OECD code of GLP in the rest of the world. ‒ Audit and certification process for registered laboratories. ‒ Fraud uncovered during audit process. LAWS90003 Regulation of Biotechnology Page Glyphosate – product versus active agent Recap Active agent in glyphosate products is the chemical with the structure. The product in the drum has a number of other agents to help disperse glyphosate. Extensive studies have shown that the carcinogenicity hazard lies in the active agent. Product is the one in use and it is the one to which the hazard applies, and risk is controlled by the label. LAWS90003 Regulation of Biotechnology Page Labelling of pesticides LAWS90003 Regulation of Biotechnology Page Reducing the exposure – the “label” Labels must be consistent with the Globally Harmonised system of classification and labelling, in English, and contain: 1. Signal heading 13. ‘Trade advice’ statements 2. Product name 14. General instructions 3. Constituent statements 15. Resistance warnings 4. ‘Mode of action’ indicator 16. Compatibility statements 5. Statement of claims for use 17. ‘Precaution’ statements 6. Restricted chemical product statements 18. ‘Protection’ statements 7. ‘Net contents’ statement 19. ‘Storage and disposal’ statements 8. Name and address of person primarily responsible 20. Safety directions for marketing the product 21. First aid instructions 9. Directions for use 22. Batch number 10. ‘Not to be used’ statement 23. Date of manufacture and/or expiry date of product 11. Other limitations and prohibitions 24. APVMA label approval number 12. ‘Withholding period’ statements 25. Dangerous goods and worker safety legislative requirements LAWS90003 Regulation of Biotechnology Page Information required on labels The Agvet Code stipulates that a label must contain adequate instructions relating to such of the following as are appropriate: The circumstances in which the product should be used. How the product should be used. The times when the product should be used. The frequency of the use of the product. The withholding period after the use of the product. Limiting Exposure The re-entry period after the use of the product. The disposal of the product when it is no longer required. The disposal of the product’s containers. The safe handling of the product and first aid. LAWS90003 Regulation of Biotechnology Page Information required on labels The Agvet Code stipulates that a label must contain adequate instructions relating to such of the following as are appropriate: Any matters prescribed by the Agvet Code Regulations, which include: 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. The storage of containers for the product (for a chemical product that is a date-controlled chemical product). Any other matter determined by the APVMA Chief Executive Officer (CEO). LAWS90003 Regulation of Biotechnology Page Dept of Agriculture and AVPMA Multicultural Access and Equity Policy 2013-2015 Key languages are supported by translation services, with educational and awareness material relating to quarantine, animal and plant health, and the use of farm chemicals. The APVMA has launched a booklet and poster titled ‘Understanding Pesticide Chemical Labels’, which was designed for farmers, market gardeners and home pesticide users in English. Industry contacts subsequently suggested that the APVMA develop a Vietnamese translation as a pilot edition. Further translations in Chinese, Arabic and Khmer languages are under development for the APVMA website. Is it surprising that these have not developed earlier? https://archive.apvma.gov.au/use_safely/docs/understanding_labels_ booklet.pdf LAWS90003 Regulation of Biotechnology Page  WHAT ABOUT THE OFF-LABEL USE OF AGRICULTURAL CHEMICALS?  What does “off-label” mean?  When the use is not “the recommended use”  off label uses can involve significant risks  any off label uses must be assessed and approved  off-label uses are assessed against the same criteria as registered on-label use patterns and subject to approval  residue data required for new crops to set MRL  off label approval can be issued for  minor uses including minor crops  emergency uses, or  for research purposes  APVMA does not regulate use by farmers - Dept of Ag in each state does  Most off label use is unregulated – usually “more is better”, some times “we will get away with less”  WHAT ABOUT THE OFF-LABEL USE OF AGRICULTURAL CHEMICALS?  In Australia, to apply for an off-label permit, you must submit an application to the APVMA  including field and laboratory data that supports the use on efficacy, safety and trade grounds.  There is a category for pesticides and agricultural chemicals called restricted which prevents applications for off-label use  A search of the APVMA websites reveals 461 permits for off-label use of glyposate  See https://apvma.gov.au/node/611  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 ie “the label” Critical for safe and effective use  Risk Management Matrix http://www.drservices.com.au/images/tramatrix.jpg Risk Minimum Category Action Extreme Eliminate/strong mitigation High Eliminate/strong mitigation Moderate Mitigate Low Monitor In general, elimination is the best option if no other adverse effects 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.,