BIOTECHNOLOGY REGULATIONS

Transcription

1 PowerPoint Lectures for Introduction to Biotechnology, Second Edition William J.Thieman and Michael A.Palladino BIOTECHNOLOGY REGULATIONS Lectures by Lara Dowland

2 Government Oversight USDA EU Regulatory Agencies FDA APHIS EPA

3 Regulatory Agencies 1. United States Department of Agriculture (USDA) Responsible for oversight on nearly all genetically modified organisms Sets most policy regarding genetically modified organisms.

4 Regulatory Agencies 2. Food & Drug Administration (FDA) US regulatory agency responsible for ensuring the safety of genetically modified foods. Genetically modified foods DO NOT need to be labeled in the US- as long as they are not SIGNIFICANTLY different than traditional foods. Agrimedicines produced in GMO s (through the process of pharming) fall under the same regulations as traditional medicines.

5 Regulatory Agencies 3. Animal & Plant Health Inspection Service (APHIS) Responsible for ensuring the safety of introducing a new genetically modified organism to the environment and existing populations. Specifically monitor all field trials for genetically modified organisms.

6 Regulatory Agencies 4. Environmental Protection Agency (EPA) Plays varying roles in monitoring the use of genetically modified organisms. Monitors the use of GMO s in pest management and environmental science.

7 Regulatory Agencies 5. European Union forms legislation governing the regulation of genetically modified foods and biotechnology techniques in western Europe

8 Regulatory Issues 1. Unexpected results from the release of genetically modified organisms have been extremely rare. A recent study indicated that monarch butterflies were being killed by pollen from Bt corn. The study upon reexamination was proven FALSE.

9 Regulatory Issues 2. In 2004, 56 genetically engineered products were approved for human consumption in the United States. The number has been increasing each year, though Bt corn and Bt soybeans are by far the most common.

10 Regulatory Issues 3. The successful development of a genetically modified organism usually takes between 6-12 years and costs between $50-$300 million dollars.

11 Regulatory Issues 4. Bans on GMO foods in many foreign countries (particularly in Europe and Africa). African nations have even declined or destroyed food aid during crises rather than allow consumption of GMO s. Though economics could be a sub context, food safety is the primary concern.

12 Specific GMO Regulations 1. In the US, GMO foods must only be labeled if they are NOT SUBSTANTIALLY EQUIVILANT to normal products. 2. Any GMO can be certified organic in North Carolina and many other states.

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14 Safety issues over GMO Classic toxicity testing Substantial equivalence Pre-cautionary principal vs risk benefit Identity preservation labeling

15 Poisonous or Deleterious Substances general toxicity carcinogens mutagens teratogens

16 Food Drug and Cosmetic Act 402(a)(1) - a food is adulterated if it contains any poisonous or deleterious substance which may render the food injurious to health

17 Food Drug and Cosmetic Act 402(a)(1) - a food is adulterated if it contains any poisonous or deleterious substance which may render the food injurious to health Microbial example : pathogens such as E. coli O157:H7

18 Food Drug and Cosmetic Act 402(a)(1) - a food is adulterated if it contains any poisonous or deleterious substance which may render the food injurious to health Chemical examples : lead, PCBs, dioxin, mercury, radio-nucleotides, pesticides

19 Food Drug and Cosmetic Act 402(a)(1) - a food is adulterated if it contains any poisonous or deleterious substance which may render the food injurious to health Relates to unapproved substances added by man intentionally or non-intentionally

20 Food Drug and Cosmetic Act 402(a)(1) - however if not added*, the food is not adulterated if the quantity would not ordinarily render injurious to health example - solanine in potatoes New level of consumption More susceptible population * meaning naturally present So could apply to a GMO

21 GMO analytical Needs Problems in evaluating %GMO On farm or at commercial silo Mixing in transport Cost of test Time to do Sample size and reliability

22 Allergen analysis failure Problems extraction denaturation +/- need for specific ELISA not available for most allergens except peanuts and egg (Neogen)

23 Starlink Corn Starlink corn with Cry9C based Bt toxin protein 63FR28258 Bacillus Thuringiensis Subspecies tolworthi Cry9C Protein and the Genetic Material Necessary for its Production in Corn; Exemption from the Requirement of a Tolerance May 22, 1998

24 EPA allergenicity evaluation 1. Homology - EPA says no known homology of the 8 amino acid sequence - but not all known 2. Cry9c is resistant to digestion 3. Cry9c is stable to thermal processing 4. MW (68 kd) is in upper range for allergens Thus EPA warned in approval that may be linked to allergens Other EPA arguments to allow approval Abundance of protein low but patent argues high toxicity Low environmental exposure but what about corn dust

25 Elisa Test Developed

26 Starlink Corn problem Starlink corn produced by Adventis Corp (Research Triangle NC ) with Cry9c Bt toxin protein Approval given by EPA in 1998 but restricted to animal feed as noted by potential for allergenic response in humans based on four criteria September 2000 Consumer group (FOE) analyzes taco shells and finds Cry9c Bt protein. Sept 11, 2000 calls on EPA to remove Taco Bell begins recall of tacos from supermarkets, as does Safeway product made by Kraft

27 Seeds of Dissent The next step : Wednesday, October 11, :48 PM EST WASHINGTON (Reuters) - A biotech corn variety found last month in Taco Bell taco shells and intended only for use as a livestock feed has been detected in a second human food product, a consumer advocacy group said on Wednesday. Genetically Engineered Food Alert, a coalition of health, consumer and environmental groups, said it would announce the product at a news conference on Thursday. ``It'll be a product that people have heard about,'' said Matt Rand, biotechnology specialist for the National Environmental Trust and co-coordinator of the GE Food Alert campaign. The group's announcement last month that Taco Bell taco shells sold in grocery stores contained the Starlink corn variety prompted manufacturer Kraft Foods, a unit of Philip Morris Cos. Inc. (MO.N), to announce a voluntary recall. Starlink corn, which is made by Aventis SA (AVEP.PA), has been approved for animal feed but not for use in human food because of concerns about the potential for allergic reactions. The U.S. Agriculture Department has said it would buy all of the estimated 45 million bushels of Starlink corn produced this year to get it off the market. Aventis will reimburse the department for the expected $90 to $100 million cost of that action.

28 Starlink Corn problem Kellogg s shuts down corn flakes cereal plant ( 10/18/2000) as precaution against potential for allergenic response 10/19/00 Adventis says problem is farmers comingled corn into human food destined corn. Of 260 grain elevators, about 106 sent out to food processors which is 12% of Starlink corn or 9 million bushels

29 Millers and Grocers Reuters 10/10/00 Kroger and Albertsons remove cereal and tacos Mission Foods recalls all Tacos (largest US maker) Azteca Milling will take back all yellow 2 corn flour ConAgra stops operations at Kansas corn flour mill - will not disclose customers Nov 3 FDA announces over 300 products with potential risk

30 FDA Regulation of GMO s

31 CASE STUDY Examine ethical issues concerning the use of genetic manipulation to improve the agricultural productivity of living organisms. * Frankenfoods???

32 Labeling - Informed Consent basis the consumer s right to know so they can protect themselves from harm Voluntary serious warnings allergens

33 Labeling - Informed Consent basis the consumer s right to know so they can have a freedom of choice Voluntary warnings Non-GMO

34 Chapter Contents 12.1 The Regulatory Framework 12.2 U.S. Department of Agriculture 12.3 The Environmental Protection Agency 12.4 Food and Drug Administration 12.5 Legislation and Regulation: The Ongoing Role of Government 12.6 Introduction to Patents 12.7 Biotechnology Products in the Global Marketplace

35 12.1 The Regulatory Framework NIH was the first federal agency to assume regulatory responsibility over biotechnology In 1974, NIH published research guidelines for recombinant DNA techniques Continued monitoring until 1984 Government published the Coordinated Framework for Regulation of Biotechnology Joint responsibility of the NIH, the USDA (United stated Department of Agriculture), and the EPA (Environmental Protection Agency) Established as formal policy in 1986 Biotechnology products would not pose regulatory and scientific issues that are substantially different from those posed by traditional products

36 12.1 The Regulatory Framework

37 12.2 U.S. Department of Agriculture Created in 1862 Advancement and Regulations of Agriculture Regulating plant pests, plants, and veterinary biologics Biologics any medical preparation made from living organisms or their products

38 12.2 U.S. Department of Agriculture Animal and Plant Health Inspection Service (APHIS) Branch of USDA responsible for protecting agriculture from pests and diseases Genetically engineered plants and insects are potentially invasive so are treated as plant pests

39 12.2 U.S. Department of Agriculture Permitting Process Requires several years of field trials to investigate everything about the plant Disease resistance, drought tolerance, reproductive rates Precautions must be taken to prevent accidental crosspollination

40 12.2 U.S. Department of Agriculture Ultimate objective for grower is to harvest a marketable product Petition APHIS for deregulated status Three broad areas to evaluate the petition Plant pest consequences Risks to other organisms Weed consequences

41 12.2 U.S. Department of Agriculture Alternative system to fast-track some new agricultural products called notification Six criteria must be met The new agricultural product must be one of only a limited number of eligible plant species The new genetic material must be confined to the nucleus of the new plant The function of the genes being introduced must be known If to be used for food, the new genes cannot cause the production of a toxin, an infectious disease, or any substance used medically If the gene is derived from a plant virus, it cannot have the potential to create a new virus The new genetic material must not be derived from animal or human viruses

42 12.3 The Environmental Protection Agency Established in 1970 with responsibilities including Protecting endangered species Establishing emission standards for cars Regulating pesticides and herbicides Regulates any plant that is genetically engineered to express proteins that provide pest control Supervising the use of herbicide-tolerant plants

43 12.3 The Environmental Protection Agency Experimental Use Permits If field test will involve 10 acres or more of land or 1 acre or more of water, then need an experimental use permit (EUP) First EUP issued in July 1985 to Advanced Genetic Sciences for use of two genetically altered strains of naturally occurring bacteria that could potentially protect crops from frost damage

44 12.3 The Environmental Protection Agency Deregulation and Commercialization EPA spends about one year reviewing the data collected, concentrating on four areas of concern: Source of gene, how it is expressed, and the nature of the pesticide-protein produced Health effects of the bioengineered plant The environmental fate of the pesticide protein The effects on nontarget species

45 12.4 Food and Drug Administration Charged with making sure that the foods we eat and the medicines we use are safe and effective Food and Food Additives FDA serves as a consultant Studies focus on Unexpected or undesirable effects Evaluation of the protein to see if it is substantially the same as naturally occurring proteins in food If food additive poses no foreseeable threat, FDA can grant generally-recognized-as-safe (GRAS) status

46 12.4 Food and Drug Administration The Drug Approval Process Investigational new drug (IND) application FDA considers results of previous experiments, the nature of the substance itself, and the plans for additional testing Good Laboratory Practice (GLP) and Good Manufacturing Practice (GMP) Regulations instituted by FDA to govern animal studies of pharmaceutical products Follow written protocols, have adequate facilities, provide proper animal care, record data properly, and conduct valid toxicity tests

47 12.4 Food and Drug Administration Phase Testing of Drugs Phase I (safety) between 20 and 80 healthy volunteers take the medicine Phase II (efficacy) test new treatment on patients who actually have the illness Phase III (comparative benefit to other current drugs) testing on 1,000-3,000 patients in double-blinded tests FDA approval as an NDA (new drug authorization)

48 12.4 Food and Drug Administration

49 12.4 Food and Drug Administration Biotech company will file for a Biological License Agreement (BLA) If seeking approval of a biologically derived product such as a viral therapy, blood compound, vaccine, or protein derived from animals FDA reviews information that goes on label and inspects the facilities where drug will be manufactured as part of approval process

50 12.4 Food and Drug Administration Exceptions to Phase Testing Procedure FDA allows approval of drugs and vaccines intended to counter biological, chemical, and nuclear terrorism without first proving their safety and worth in Phase II and Phase III trials Also true for orphan drugs drugs with a small number of beneficiaries but with great benefit

51 12.5 Legislation and Regulation: The Ongoing Role of Government Regulation of biotechnology, like other industries, is a matter of politics as well as science Stem cells Labeling of foods that contain GMOs

52 12.5 Legislation and Regulation: The Ongoing Role of Government

53 12.6 Introduction to Patents A patent gives an inventor or researcher exclusive rights to a product and prohibits others from making, using, or selling the product for a certain number of years Regulated by the U.S. Patent and Trademark Office (USPTO) 1980 first patent for a bacterium with a unique gene sequence 2,000 patents granted since for plant, animal, and human genes

54 12.6 Introduction to Patents To win a patent, discovery Must be novel Must be nonobvious Must have some utility Patents are enforced for up to 20 years from earliest date of filing Must file an application that Adequately describes the product Discloses the best use of the product

55 12.6 Introduction to Patents Patenting DNA Sequences Applicants must assert a utility for the claimed invention that is specific, substantial, and credible Specific utility must know exactly what the DNA sequence does Substantial utility defines a real-world use Credible utility must convince the patent office that the application is backed by sound science

56 12.7 Biotechnology Products in the Global Marketplace Biotechnology Is a Global Enterprise World community is still in preliminary negotiations about the regulation of biotechnology products As a model, the European Union (EU) has created the European Agency for the Evaluation of Medicinal Products (EMEA) Once a product is approved, can be marketed in all 15 countries in the EU

57 PowerPoint Lectures for Introduction to Biotechnology, Second Edition William J.Thieman and Michael A.Palladino ETHNICS and BIOTECHNOLOGY Lectures by Lara Dowland

58 Chapter Contents 13.1 What Is Ethics? 13.2 Biotechnology and Nature 13.3 Economics, The Role of Science, and Communication

59 Defining Ethics 1. Ethics are a theory or system of moral values and principles that govern interactions in society. Vary between cultures and religious groups - often conflicting in the US. Many times ethical decisions are not absolutely right or wrong, but somewhere in the middle.

60 Defining Ethics 2. Ethic is the discipline dealing with what is good and bad and with moral duty and obligation.

61 Ethical Examples 1. The use of embryonic stem cells in research. Positives- because of the ability of stem cells to differentiate, research could result in tremendous medical breakthroughs. Producing spare organs, skin for grafts, and other biological products for medical treatments. Negatives- requires the destruction of developing human embryos for the collection of genetic information.

62 Ethical Examples 2. The process of cloning. Occurs naturally in many varieties of plants through processes like layering, rhizomes and division. Usually (the exception is identical twins) requires human intervention in animals. Often damages embryos, resulting in the death of developing baby- highly objectionable in animals and humans.

63 Ethical Examples 3. MOST BIOTECHNOLOGY TECHNIQUES & PRODUCTS DO NOT POSE AN ETHICAL DILLEMNA FOR A MAJORITY OF PEOPLE IN DEVELOPED NATIONS. Ethical objections remain the most common objection for the use of biotechnology in agriculture especially for uninformed. Despite concerns over food safety, increasing use of biotechnology has occurred as a result of demands for increased production.

64 3. MOST BIOTECHNOLOGY TECHNIQUES & PRODUCTS continued Objections are centered more around the human element as to who makes decisions that life is expendable in one case and not in another. Misuse is at the center of ethical objections. Objections to products focus on the uncertainty as to what long-term effects the use of genetically modified materials might have in the absence of long-term records. Will genetically modified foods have a chronic effect on the animals that consume them? Will Bt crops create super pests that adapt over a period of time? Will Bt products lose their effectiveness over time?

65 13.1 What Is Ethics? Ethics identifies a code of values for our actions Bioethics area of ethics that deals with the implications of biological research and biotechnological applications, especially regarding medicine Ask Should this be done? not Can this be done?

66 13.1 What Is Ethics? Approaches to Ethical Decision Making Two main viewpoints Utilitarian approach states that something is good if it is useful, and an action is moral if it maximizes pleasure among humans; greatest good for the greatest number Deontological approach (Kantian approach or duty ethics) focuses on certain imperatives, or absolute principles, which we should follow out of a sense of duty and which should dictate our actions

67 13.1 What Is Ethics? Modern Bioethics Primarily the work of two ethicists in the 1970s Joseph Fletcher and Paul Ramsey Refined the utilitarian and deontological approaches

68 13.2 Biotechnology and Nature Scientists met at conference in Asilomar, CA, in 1975 to discuss the safety and possible consequences of recombinant DNA techniques Established guidelines for different levels of biosafety containment

69 13.2 Biotechnology and Nature Cells and Products Issues of safety Issue of efficacy (effectiveness) Humane treatment of animals

70 13.2 Biotechnology and Nature GM Crops: Are You What You Eat? Several areas of concern The plant itself (species integrity) Possible effect of altered plants on the ecosystem and on overall biodiversity Effects on nontarget species How will the crop be used? Is it safe to feed to animals? Is it safe for humans? Consideration of other genes or products present in the GM crop

71 13.2 Biotechnology and Nature GM Crops: Are You What You Eat? Social and economic questions arise Statistical Probability The likelihood of an event; what chance exists for a bad event to happen Risk Assessment Considers the likelihood that something harmful or unintended will happen in making a decision

72 13.2 Biotechnology and Nature Animal Husbandry or Animal Tinkering Raises same ethical questions as genetic modification of plants The Human Question Informed consent patients have the right to be informed fully of the potential effects of the experimental treatment, both good and bad Placebos a safe but non-effective treatment Double-blind trials: An experimental procedure in which neither the subjects of the experiment nor the persons administering the experiment know In a double-blind experiment, neither the individuals nor the researchers know who belongs to the control group and the experimental group ; "a double-blind procedure is used to guard against both experimenter bias and placebo effects"

73 13.2 Biotechnology and Nature What Does It Mean to Be Human? Many ethical debates revolve around the moral status of the human embryo Is it ethical to destroy early-stage human embryos for research that may potentially treat thousands of patients? Personhood used to define an entity that qualifies for protection based not on an intrinsic value but rather on certain attributes, such as self-awareness

74 13.2 Biotechnology and Nature Spare Embryos for Research Versus Creating Embryos for Research Primary source of embryos for research is excess embryos from in vitro fertilization Another potential source is the creation of embryos for research purposes

75 13.2 Biotechnology and Nature Cloning Raises many of the same questions, with the added complexity of the technique and the potential identity of the clone Is creating a cloned embryo with the intent of initiating a pregnancy another type of assisted reproductive technology?

76 13.2 Biotechnology and Nature Cloning Ethical considerations of a human clone include How lack of relatedness to one parent might change kinship and family relationships Expectations put on a clone once born to live a better life than the person who was cloned Expectation to live up to a legacy achieved by the donor of the genetic material When someone creates a clone from a dead dear one.

77 13.2 Biotechnology and Nature Cloning Creation of human embryos could lead to matched embryonic cells for patients Could this lead to human commercialization, making human life a commodity to be bought, sold, and used?

78 13.2 Biotechnology and Nature Patient Rights and Biological Materials Physicians do have a duty to disclose the physician s personal interest in research and potential economic matters unrelated to patient treatment Courts have ruled that donors of cells and other biological materials do not have ownership rights of their biological materials

79 13.2 Biotechnology and Nature Regulations in Flux August 9, 2001, ban on using federal funds for embryo creation or destruction Some states have enacted their own laws 2009: The Government approved the use of embryonic cells for research (In particular stem cells research) (Embryos from in vitro fertilization only) Stem cells: Un programmed cells that can continue dividing forever and can change into other types of cells (bone, muscle, cartilage, etc), so they have the potential to treat many diseases, including Parkinson's, Alzheimer's, diabetes and cancer, and repairing damage in other organs - such as the liver, kidneys, heart, etc

80 13.2 Biotechnology and Nature Your Genes, Your Self Concern over the privacy of DNA information How genetic information could be used negatively by employers, insurance companies, governmental agencies, or through perceptions by the general public 2008, the Genetic Information Nondiscrimination Act was passed into law Prohibits discrimination based on genetics and the improper use of genetic information in health insurance and employment

81 13.2 Biotechnology and Nature More or Less Human? Ethical considerations of gene therapy Informed consent, safety, and efficacy What about treatment of the possibility of genetic disease?

82 13.3 Economics, The Role of Science, and Communication Money plays a major role in research decisions Patenting of intellectual property may be lucrative, but may also pose ethical and scientific problems Limited scientific access to gene for other researchers Should scientists have unlimited freedom for research? Accurate, honest communication is vital to the success of science

83 13.2 Biotechnology and Nature

84 What Are the Public Concerns? Economics Are we changing the economics on the farm? Environmental Are we irreversibly modifying the environment? Globalization Is technology becoming centralized in too few hands? Social Will we develop a class of genetic outcasts? Religious Are we playing God?

85 Microbial Biotechnology Plant Biotechnology Animal Biotechnology Aquatic Biotechnology Medical Biotechnology