Vol. 146, No. 6 — March 14, 2012

Registration

SOR/2012-26 March 2, 2012

FOOD AND DRUGS ACT

Regulations Amending the Food and Drug Regulations (1611 — Asparaginase)

P.C. 2012-219 March 1, 2012

His Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to subsection 30(1) (see footnote a) of the Food and Drugs Act (see footnote b), hereby makes the annexed Regulations Amending the Food and Drug Regulations (1611 — Asparaginase).

REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS
(1611 — ASPARAGINASE)

AMENDMENTS

1. Subparagraph B.13.001(e)(iii) of the Food and Drug Regulations (see footnote 1) is replaced by the following:

1. (iii) amylase, amylase (maltogenic), asparaginase, bromelain, glucoamylase, glucose oxidase, lactase, lipase, lipoxidase, pentosanase, protease, pullulanase or xylanase,

2. Subparagraph B.13.005(d)(iii) of the Regulations is replaced by the following:

1. (iii) amylase, amylase (maltogenic), asparaginase, bromelain, glucoamylase, glucose oxidase, lactase, lipase, lipoxidase, pentosanase, protease, pullulanase or xylanase,

3. Paragraph B.13.021(h) of the Regulations is replaced by the following:

1. (h) amylase, amylase (maltogenic), asparaginase, bromelain, glucoamylase, glucose oxidase, lactase, lipase, lipoxidase, pentosanase, protease, pullulanase or xylanase;
   

4. Table V to section B.16.100 of the Regulations is amended by adding the following after item A.2:

Item No.	Column I Additive	Column II Permitted Source	Column III Permitted in or Upon	Column IV Maximum Level of Use
A.3	Asparaginase	Aspergillus niger ASP72; Aspergillus oryzae (pCaHj621/BECh2#10)	(1) Bread; Flour; Whole wheat flour (2) Unstandardized foods	(1) Good Manufacturing Practice (2) Good Manufacturing Practice

COMING INTO FORCE

5. These Regulations come into force on the day on which they are registered.

REGULATORY IMPACT ANALYSIS STATEMENT

(This statement is not part of the Regulations.)

Executive summary

Issue

Health Canada has received submissions from industry requesting that Table V to section B.16.100 of the Food and Drug Regulations (“the Regulations”) be amended to permit the use of the enzyme asparaginase from the following new genetically modified sources of micro-organisms: Aspergillus oryzae (pCaHj621/BECh2#10) and Aspergillus niger ASP72. These amendments permit the use of asparaginase in the production of bread, flour, whole wheat flour and unstandardized foods, all at a maximum level of use consistent with good manufacturing practice (GMP).

Asparaginase is an enzyme that hydrolyzes an amino acid, asparagine, to aspartic acid. The purpose for using asparaginase in food manufacture is to reduce the amount of asparagine in food, thereby reducing the formation of acrylamide in baked or fried food products. Acrylamide is an industrial chemical and can also naturally form in certain foods, particularly plant-based foods that are rich in carbohydrates and low in protein, during processing or cooking at high temperatures. The greatest source of exposure of the general population to acrylamide is the diet. The highest concentrations of acrylamide have been detected in potato chips and French fries, although it has been found in other foods as well. Acrylamide is the product of a chemical reaction between asparagine and reducing sugars that takes place when certain foods are baked or fried at temperatures exceeding 120°C. Both asparagine and reducing sugars are commonly found in many raw food materials.

Dietary exposure to acrylamide has been identified as a potential human health concern by JECFA. (see footnote 3) Therefore, acrylamide was considered a high priority for assessment of risk to human health by the Government of Canada due to its high potential for exposure to consumers. Acrylamide was included in one of the priority groups of chemical substances under the Government of Canada Chemicals Management Plan. A science-based screening assessment of acrylamide conducted by the Government of Canada concluded that acrylamide is potentially harmful to human health. Additional research is being undertaken in order to fully understand the risks acrylamide poses to human health.

The enzyme asparaginase meets the definition of a food additive under the Regulations. Prescriptive regulations set out in Division 16 of Part B of the Regulations control the sale and use of food additives in Canada. The Tables to section B.16.100 list each permitted food additive according to their purpose of use and specify in which foods and at what levels they may be incorporated. Table V to section B.16.100 lists food enzymes that may be used as food additives. Asparaginase is not currently listed in Table V. Therefore, amendments to Part B of the Regulations are required to enable the use of asparaginase as a food additive.

Objectives

A screening assessment of acrylamide (see footnote 4) was completed in 2009 as part of the federal government’s Chemicals Management Plan, in which detailed information about uses of acrylamide, its environmental impacts, and its potential risks to ecological and human health was presented. The release of the Government of Canada’s screening assessment to minimize consumers’ exposure to acrylamide from food sources reaffirmed Health Canada’s approach: (1) to press the food industry towards the development and implementation of acrylamide reduction strategies by food processors and the food service industry; (2) to update and reissue its consumption advice to consumers on how to limit their exposure to acrylamide from food sources, based on new scientific findings; and (3) to coordinate its risk communication efforts with key international food regulatory partners. On August 22, 2009, the Minister of Health announced that acrylamide may pose a risk to human health and recommended that acrylamide be added to Schedule 1 (List of Toxic Substances) of the Canadian Environmental Protection Act, 1999. The proposed Order to add acrylamide to Schedule 1 was published in Part Ⅰ of the Canada Gazette (see footnote 5) on October 3, 2009. The regulatory amendments permitting the use of the enzyme asparaginase address the risk management approach adopted by Health Canada to reduce consumers’ exposure to acrylamide from food sources.

Health Canada has conducted a safety and efficacy assessment of asparaginase for the uses described above. The evaluation considered the toxicological aspects of the use of the food additive, as well as relevant microbiological and nutritional factors. Asparaginase has been determined to be effective for its intended purpose, that is in reducing the amount of asparagine in foods such as bread, crackers and cookies, and cut potato products, sliced potato products and potato chips, thereby reducing the formation of acrylamide in these products. When used as described above, asparaginase does not pose a hazard to the health of the consumer. Further, Health Canada has concluded that the sources of micro-organisms mentioned above have a history of safe use and have been shown not to present toxicological concerns.

The enzyme asparaginase from the sources of micro-organisms mentioned above complies with international specifications established at the 68th and 69th JECFA meetings, (see footnote 6),(see footnote 7) confirming that asparaginase is a substance of very low toxicity. The enzyme asparaginase from the sources of micro-organisms noted above also meets the general and additional requirements for enzymes as outlined in the Fifth Edition of the Food Chemicals Codex (see footnote 8) and the First Supplement to the Fifth Edition. Based on its safety and efficacy assessment and in accordance with section B.16.003, the Minister recommends that amendments be made to the Regulations to enable the uses of asparaginase as described above.

Description

The amendments enable the use of the enzyme asparaginase produced from the genetically modified sources of micro-organisms as described above. Table V to section B.16.100 of the Regulations is amended to permit the use of asparaginase in the production of bread, flour, whole wheat flour and unstandardized foods, all at a maximum level of use consistent with GMP. The standards for flour, whole wheat flour and bread in Division 13, Grain and Bakery Products, are also amended to permit the use of the enzyme asparaginase in the foods mentioned above.

Regulatory and non-regulatory options considered

Under the Regulations, the use of food additives in foods sold in Canada is controlled through prescriptive regulations. Specifically, Division 16 of Part B of the Regulations sets out specific requirements for food additive submissions and requires that the Minister notify the person filing the submission whether or not she intends to recommend to the Governor in Council that the Regulations be amended. Evaluation of available data supports the safety and effectiveness of the enzyme asparaginase produced from the genetically modified sources of micro-organisms Aspergillus oryzae (pCaHj621/BECh2#10) and Aspergillus niger ASP72, in the above specified uses.

The only regulatory options available to address these submissions are for the Minister to recommend or not to the Governor in Council that the Regulations be amended to permit the uses as described above for this food additive. Based on its safety and efficacy assessment, the Minister recommends that the uses for this food additive be enabled.

Rationale

There is no anticipated increase in cost to government from the administration of these amendments to the Regulations. Furthermore, compliance costs incurred by the manufacturers are not considered to be a factor because the use of food additives is optional.

These amendments benefit consumers by reducing the formation of acrylamide in some processed foods, thereby reducing the levels of acrylamide in the food supply and helping to protect the health and safety of consumers. In addition, these amendments provide some food manufacturers with a safe option to reduce acrylamide formation in certain foods without compromising the quality, flavour or other characteristics of the food.

Consultation

The amendments permit the use of this food additive in certain foods for which there are standards set out in Division 13, Grain and Bakery Products, of the Regulations. The Baking Association of Canada and the Canadian Food Inspection Agency (CFIA) were consulted during the development of this regulatory project and neither expressed any objection to the use of this food additive as described above.

Two public consultations on the proposal to amend the Regulations to permit the use of asparaginase in certain food products were conducted through postings on Health Canada’s Web site in 2009. The final consultation closed on February 21, 2010, although comments received after this date were accepted.

Health Canada received more than 600 comments from consumers, health professionals, health organizations, food and agricultural organizations, and from a parliamentarian. The majority of the comments did not support Health Canada’s proposal. However many comments were based on misconceptions and inaccuracies about how asparaginase would be used as a food additive. In response to the large volume of questions that were received, Health Canada has prepared a document entitled Questions and Answers Regarding Health Canada’s Proposal to Amend the Food and Drug Regulations to Permit the Use of the Enzyme Asparaginase in Certain Food Products. This document provides responses to the most common questions that were posed during the consultation periods and also attempts to address the misconceptions and correct the inaccuracies about how asparaginase would be used as a food additive. Health Canada has sent responses to all those who submitted comments during the consultations. The responses included a notification that the Questions and Answers document is available on Health Canada’s Web site at www.hc-sc.gc.ca/fn-an/securit/addit/asparaginase_ qs_as-eng.php.

Comments received fell into six key categories:

1. Clarification of information
2. Asparaginase and human health
3. Health Canada’s approach to mitigating the risks posed by acrylamide in food
4. Food additive regulation and use in Canada
5. Questions about the online proposal and consultation
6. Informing the public of the use of asparaginase in foods

1. Clarification of information

A number of comments raised concerns to the effect that Health Canada was proposing to add a chemotherapeutic prescription drug to junk food as a strategy for cancer prevention. Some comments asked for clarification about possible side effects on human health, including allergic reactions, of the use of asparaginase in foods, while others questioned the use of genetically modified organisms to our foods or the use of enzymes in food processing.

Enzymes have been used in food production for centuries. Most of the enzymes that are used today by the food industry are isolated from sources of micro-organisms, some of which are genetically modified to optimize the production of the desired enzyme. The enzyme asparaginase itself does not contain any genetically modified material; however, the micro-organism that produces it has been genetically modified.

Any confusion about the use of asparaginase may have resulted from the fact that it is also used as an injectable prescription drug to treat some forms of cancer. However, it should be emphasized that it is not possible for asparaginase, when used in food, to have a therapeutic effect on the human body. In order to act as a chemotherapeutic agent, asparaginase must be in its active form to be effective and it must be injected into muscle or veins and not given orally. When used in manufacturing food, asparaginase exerts its effect before the food is cooked. The heat from cooking inactivates the enzyme asparaginase that is present. Inactive asparaginase, consumed as part of a food, would be digested in the stomach like other proteins (including other enzymes) in food and would not have any therapeutic effects on the body. When used in food processing, asparaginase can only act on the food to which it has been added. Asparaginase would be used in certain foods in order to reduce the amount of the amino acid asparagine that is already present in foods. Under specific cooking conditions, asparagine can react with certain carbohydrates in the food to form acrylamide, a potential human carcinogen. Reducing the amount of asparagine in the food prior to cooking or processing would reduce the amount of acrylamide that can be formed.

It is very unlikely that the consumption of residual asparaginase in food would cause an allergic reaction or hypersensitivities. Based on an internationally accepted approach to determine the potential allergenicity of proteins (including enzymes), there was no evidence of any similarity between the asparaginase protein sequence with known toxins or food allergens. Asparaginase has been used in other jurisdictions (European Union, United States, Australia and New Zealand) with a history of safe use.

2. Asparaginase and human health

Comments were received which questioned Health Canada’s role in conducting toxicity studies for asparaginase. Health Canada does not conduct toxicity studies for food additive submissions from industry. Pursuant to the Regulations, when industry makes a request that a food additive be added to, or a change made in, the Tables to section B.16.100 of the Regulations, the request shall be accompanied by a submission in which data and detailed reports are submitted for review by Health Canada’s scientists. Health Canada’s scientists review all safety studies provided as part of the submission, as well as any available studies published in the scientific literature. If insufficient safety data or other deficiencies in the submitted data are identified, additional information or studies are requested by Health Canada. Health Canada will consider making a regulatory amendment to permit the use of a food additive, under specified conditions, if Health Canada’s scientists are satisfied that the food additive is safe and does not pose a hazard to the health of the consumer and is effective for the intended purpose of use.

Health Canada received comments expressing concern about the effects of asparaginase or its breakdown products on human health. Various toxicity studies were evaluated. There are no known health risks associated with the breakdown products of asparagine from the enzymatic reaction that takes place during food processing. The enzyme asparaginase is added to foods prior to the frying and baking process in order to reduce acrylamide formation during processing and cooking at high temperatures. As mentioned above, the enzyme asparaginase is inactivated when the food to which it has been added is cooked; therefore, no active enzyme remains in food products when they are consumed. Further, the residual inactive asparaginase, as for any other protein, would be broken down by acid and digestive enzymes in the human gastrointestinal tract and eliminated through the digestive system.

3. Health Canada’s approach to mitigating the risks posed by acrylamide in food

Other comments questioned the real benefits to human health to using asparaginase to reduce acrylamide levels in foods. JECFA has determined that the estimated dietary exposure of acrylamide from certain foods may be a human health concern and has called for strategies to reduce exposure to acrylamide. (see footnote 9) Health Canada’s scientists concur with JECFA’s recommendations. Health Canada is proactively responding to JECFA’s recommendation to reduce exposure to foodborne acrylamide and has strongly encouraged the food industry to develop and implement acrylamide reduction strategies. Some food processors, in Canada and internationally, have adjusted their cooking instructions to ensure that acrylamide levels are reduced in their food products, whether prepared at home or in a restaurant. The use of asparaginase in food processing is another option for reducing acrylamide formation in food that the food industry has proposed.

It is difficult to determine if past exposure to acrylamide in food in Canada has had a detrimental effect on human health. However, it is well known that the diet has changed over the years to include more carbohydrate-rich foods that are baked or fried, thus exposure to acrylamide has likely increased over time. Since acrylamide is a known carcinogen in laboratory animals, Health Canada is working proactively to reduce human exposure to acrylamide from food. Allowing for the use of asparaginase in certain foods is considered one of several options available to reduce dietary exposure to acrylamide, including the continued promotion of a healthy diet in accordance with Health Canada’s Eating Well with Canada’s Food Guide (www.hc-sc.gc.ca/fn-an/food-guide-aliment/index-eng.php).

4. Food additive regulation and use in Canada

A number of comments requested information on how Health Canada would regulate the level of use of asparaginase in foods and how it would ensure that this enzyme would not be used in additional foods. If the food industry wishes to use asparaginase in additional foods in the future, a new submission would have to be sent and a new safety and efficacy assessment would have to be undertaken before an amendment could be made to the food additive tables in the Regulations. All enzymes that are used as food additives in Canada, including the new enzyme asparaginase, have a permitted maximum level of use that is consistent with GMP. The Regulations define “Good Manufacturing Practice” as the amount of a food additive that does not exceed the amount that is required to accomplish the purpose for which that food additive is permitted. Since the use of enzymes or other food additives add to the food manufacturer’s costs, there is no motivation on the part of the food manufacturer to add a greater concentration of a food additive than is necessary to achieve the desired technical effect.

5. Questions about the online proposal and consultation

Some comments requested the publication of the names of the petitioners. A petitioner is a company who sends a submission requesting that a food additive be added to or a change made in the Tables to section B.16.100 of the Regulations. For confidentiality and privacy reasons, Health Canada does not release this type of information.

6. Informing the public of the use of asparaginase in foods

Other comments requested clarification on whether asparaginase would be labelled on prepackaged food products so that consumers can avoid the products containing asparaginase if they choose. Pursuant to the Regulations, most prepackaged products containing more than one ingredient must carry a list of all ingredients, including components, if any, subject to the exceptions set out in Regulations. A consumer may therefore have to inquire with retailers to determine if their products contain asparaginase.

Implementation, enforcement and service standards

The CFIA is responsible for the enforcement of the Food and Drugs Act and the Regulations with respect to foods. The CFIA uses a science-based risk management approach to set its food safety priorities. Using this approach as its foundation, the CFIA plans its inspection and testing programs for foods, taking into account the degree of risk associated with a particular sector and concentrates its resources where risk is the greatest. Each CFIA commodity inspection program performs ingredient verifications at which time inspectors compare formulation, list of ingredients and perform on-site verification of the manufacture of the product. The frequency of inspection depends on the history of compliance of a particular product, the history of compliance of the manufacturer and the food safety risk.

Contact

Barbara Lee
Director
Bureau of Chemical Safety
Health Canada
251 Sir Frederick Banting Driveway
Tunney’s Pasture
Address Locator: 2203B
Ottawa, Ontario
K1A 0K9
Telephone: 613-957-0973
Fax: 613-954-4674
Email: sche-ann@hc-sc.gc.ca

Footnote a
S.C. 2005, c. 42, s. 2

Footnote b
R.S., c. F-27

Footnote 1
C.R.C., c. 870

Footnote 2
Joint FAO/WHO Expert Committee on Food Additives. Seventy-second meeting (Rome, 16-25 February, 2010). Summary and Conclusion (issued March 16, 2010).

Footnote 3
Joint FAO/WHO Expert Committee on Food Additives. Seventy-second meeting (Rome, 16-25 February, 2010). Summary and Conclusion (issued March 16, 2010).

Footnote 4
Environment Canada and Health Canada. August 2009. Screening Assessment for the Challenge. 2-Propenamide (Acrylamide). Chemical Abstracts Service Registry Number 79-06-1. (www.ec.gc.ca/substances/ese/eng/challenge/batch5/batch5_79-06-1.cfm)

Footnote 5
Canada Gazette, Volume 143, Number 40, October 3, 2009.

Footnote 6
Joint FAO/WHO Expert Committee on Food Additives, Sixty-eighth meeting, Geneva, 19-28 June 2007 — Summary and Conclusion, issued on July 12, 2007.

Footnote 7
Joint FAO/WHO Expert Committee on Food Additives, Sixty-ninth meeting, Rome, Italy, 17-26 June 2008 — Summary and Conclusion, issued on July 4, 2008.

Footnote 8
Food Chemicals Codex, Fifth Edition, 2003, and the First Supplement to the Fifth Edition, 2006, published by the National Academy of Sciences, Washington, D.C., United States.

Footnote 9
Joint FAO/WHO Expert Committee on Food Additives. Seventy-second meeting (Rome, 16-25 February, 2010). Summary and Conclusion (issued March 16, 2010).