Information of Submitted Person Additives

สิ่งที่ส่งมาด้ว ย 2 Form for Public Hearing

(Draft) Ministry of Public Health’s Notification number ... B.E. .... For Enzyme for processing aid in Food use Information of submitted person Name – Surname .Patrick Fox ....Position...Secretary General Organization/ and Address…....AMFEP. 188A, Avenue de Tervueren, 1150 Brussels, Belgium...... Tel ... +32 2 761 16 77 Fax......

These comments are being submitted on behalf of AMFEP, ETA and IFAC

1. Having Enzyme for processing aid to be classified as Food additive which is Special Control Food according to the Law today  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) Enzymes may be regulated, but should not be classified, as Food Additives because they are almost exclusively used as Processing Aids in accordance with the CODEX definitions and guidelines1: Processing Aid means any substance or material, not including apparatus or utensils, and not consumed as a food ingredient by itself, intentionally used in the processing of raw materials, foods or its ingredients, to fulfil a certain technological purpose during treatment or processing and which may result in the non- intentional but unavoidable presence of residues or derivatives in the final product. Scope: Provisions for the use of processing aids (e.g. most enzyme preparations, clarifying and filtering aids, extraction solvents) are not included in the General Standard for Food Additives.

1 According to the Codex Alimentarius Commission, Procedural Manual, Section I, Definitions for the purpose of the Codex Alimentarius and Section II: Elaboration of Codex texts Thus, we propose to change Clause 1 to read: “Enzymes used in the food production process are food processing aids which are controlled foods.”

2. Definition of “Enzyme”, “Enzyme Preparation” and “Immobilized Enzyme” according to Article 2 in the draft  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

3. 3.1 Enzyme for processing aid in Food use must be from Plants, Animals or Microorganisms that listed in the Annex 1 or as determined in Codex Advisory Specification for the Identity and Purity of Food Additive according to paragraph 1 of Article 3 of the draft.  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) Reference to Codex Advisory Specification for the Identity and Purity of Food Additive should not be included because a) enzymes are almost exclusively used as Processing Aids as outlined in comment item 1 above and b) all enzymes mentioned in the list of Codex Advisory Specification for the Identity and Purity of Food Additive are already included in Annex 1.

Instead it is suggested to make reference to the JECFA Combined Compendium of Food Additive Specifications. It is noted that almost all enzymes mentioned in Annex 1 are already included in the list of enzymes that have been evaluated by JECFA, however a few JECFA evaluated enzymes are not included in Annex 1. JECFA evaluated enzymes should be incorporated in Annex 1 by reference.

A limited number of enzymes that are not JECFA evaluated are included in Annex 1. It should be clarified what criteria were used for their inclusion in Annex 1 and additional enzymes should be added into Annex 1 based on recognition with other countries’ safety assessments.

3.2 In the case that enzyme is not on the list in Annex 1, Supplier or Importer shall submit Food and Drug Committee a safety assessment report for permission according to suggestion of Food committee in paragraph 2 Article 3 of the draft.  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) In case the enzyme is not listed in Annex 1, it is required to submit a safety assessment report to the Food and Drug Committee. It should be sufficient that such safety assessment report is the result of a JECFA evaluation or other countries’ safety assessments. Only in case there are no safety evaluation or assessment report available, it is appropriate to request data for FDA consideration by provision of documents listed in Annex 2.

4. Enzyme for processing aid in Food use must have quality and specification (Article 4 in the draft) 4.1 Enzyme efficiency by activity must not less than 85% of enzyme activity as specified (Article 4 (1) in the draft)  Agree  Required improvement of enzyme activity value as (Please identify area for suggestion and attach the documents support or having explanation)  Agree that no need to determine it because (Please indicate the reason or attach the supporting documents) In general, internal company specific methods should be accepted for all analyses required to document quality specifications.

4.2 Not detected genetic-modified microorganism in 1 g in the case that enzyme is produced by genetic-modified microorganism (Article 4 (2) in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) In general, internal company specific methods should be accepted for all analyses required to document quality specifications.

4.3 Required to have other qualities or other standards according to one of either conditions as following (1) Codex Advisory Specification for the Identity and Purity of Food Additive or (2) General specification and considerations for enzyme preparations used in food processing or (3) Notification of Food and Drug Administrative by approval of Food and Drug committee (Article 4 (3) in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) In general, internal company specific methods should be accepted for all analyses required to document quality specifications.

5. Using enzyme for processing aid must be used according to one of either conditions as following (1) functional use as stated in Annex 1 or as determined in the most update version of Codex Advisory Specification for the Identity and Purity of Food Additives or (2) as determined in Ministry of Public Health Notification on Food additives or the most update version on general standard of Codex General Standard for Food Additives (Article 5 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) Reference to Codex Advisory Specification for the Identity and Purity of Food Additive or Codex General Standard for Food Additives should not be included because enzymes are almost exclusively used as Processing Aids and not included in the GSFA as outlined in comment item 1 above.

Enzymes used as Processing Aids for food or food ingredient production will not have a technological function in the final food because they are typically removed and/or denatured during the manufacture process. Use of enzymes in food production depend on the reaction they catalyze and availability of substrate, and thus are characterized by food and food ingredient production processes and not by final food categories.

Accordingly, the limitation of the enzyme uses to specific Food category in Annex 1 should be deleted which is appropriate taking the Not specified for ADI and As Appropriate for Maximum use permission into account.

6. Using Food additives in enzyme, it shall be allowed to be used according to the list and conditions determined in Annex 4. In the case, that Food additive is not in the list of Annex 4, it shall have supplier or importer submit safety assessment report of that Food additive as required by the Notification of Food additive and shall have Food and Drug Administrative consider for permission according to approval granted by Food and Drug Committee (Article 6 paragraph 2 in the draft).  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

7. Determined the use of other ingredients such as water, salt, flour which are not food additives, in enzyme, they must be safe (Article 7 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

8. Determined method of analysis according to Annex 5 (Article 8 in the draft) Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) Internal company specific methods should be accepted for all analyses required to document quality specifications.

9. Required suppler or importer of processing aid enzyme for sale to be complied to Ministry of Public Health Notification on Equipment for Food Production and Storage Method (Article 9 of the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

10. Processing aid enzyme’s container must be complied to Ministry of Public Health Notification on Container (Article 10 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

11. Processing aid enzyme’s Supplier or Importer for sale must present evidences or information to Food producers to manage the use as determined in (Article 11 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

12. Label for processing aid enzyme must be complied to Ministry of Public Health Notification for Food Additives (Article 12 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

13. Required processing aid enzyme suppliers or importers who obtained permission before enforcement of this Notification, must be complied to this Notification within 2 years after enforcement (Article 13 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) It is not clear which situations are foreseen by Article 13, since it is assumed that all existing approvals for enzymes used in food are included in Annex 1 and in compliance with this Notification.

14. This Notification shall not be implemented for (1) enzyme which is an ingredient in Food for any nutrition or health objectives and (2) enzyme using to produce Food additive (Article 14 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

15. Determined that this notification would be enforced the date after announced in the Royal Gazette (Article 15 in the draft)  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) Change to 180 days after announced in the Royal Gazette, so industry will have more time to understand and comply with the regulation.

The enzymes currently on the market should be given the opportunity to stay on the market, and market disruption should be prevented.

16. List of permitted enzymes to be used as processing aid would be contained functional use, Food category, ADI for each enzyme in Annex 1  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) Almost all enzymes mentioned in Annex 1 are already included in the list of enzymes that have been evaluated by JECFA, however a few JECFA evaluated enzymes are not included in Annex 1. JECFA evaluated enzymes should be incorporated in Annex 1 by reference.

Additional enzymes should be added into Annex 1 based on recognition with other countries’ safety assessments. We suggest extending Annex 1 List of permitted Enzymes for Food production with food enzymes that have been approved and/or recognized in other countries, such as France, Denmark, EU, Brazil, USA, Canada, and/or Australia/New Zealand. A non-exhaustive list of enzymes which are recognized or have approval status is provided in Appendix A of this document. AMFEP, ETA and IFAC are happy to provide further information on request.

Accordingly, for “Functional Use”, the wording should say Processing Aid for all enzymes, and the limitation of the enzyme uses to specific Food category in Annex 1 should be deleted or changed to read all food processes. For “Acceptable Daily Intake (ADI)”, the wording should be consolidated to Not specified for ADI.

Additional comments: We propose to correct the IUBMB number of Bromelain from Ananas comosus and Ananas bracteatus (L). EC 3.4.22.4 has been transferred to EC 3.4.22.32 (stem bromelain) and EC 3.4.22.33 (fruit bromelain).

17. List of documents required for safety assessment in Annex 2 Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) In case the enzyme is not listed in Annex 1, it is required to submit a safety assessment report to the Food and Drug Committee. It should be sufficient that such safety assessment report is the result of a JECFA evaluation or other countries’ safety assessments. Only in case there are no safety evaluation or assessment report available, it is appropriate to request data for FDA consideration by provision of documents listed in Annex 2.

For enzymes produced by a GMM (item 3.1 in Annex 2) it is appropriate to provide information on the GMM, including recipient/host, donor, genetic modification, characteristics and purification, but the exhaustive list of items listed should only serve as guidance and can be omitted when not relevant. Further details are provided in the table below.

The criteria for exemption of providing safety data (item 4.1 in Annex 2) should be amended to cover all enzymes with safe use history, e.g. enzymes which are recognised / approved and used in other countries.

We propose to add consideration for exemption for enzyme that is produced by a GM strain from a safe strain lineage. When strains from a certain strain lineage have been assessed for their safety, used for several years for the production of food enzymes, and further improved by e.g. mutagenesis or deleting genes, then one can conclude that a strain from this strain lineage can be declared safe for use, thus, removing the need for further toxicological testing.

We propose to add a new case, Case 4.4, for extension of use of enzyme that is listed in Annex 1 or meets other conditions under Article 5. When the safety of enzyme as processing aid has been evaluated, it is unnecessary to re-evaluate the enzyme for extension of use to other application. Only dietary exposure is relevant for this case.

Business confidentiality should be guaranteed. The applicant should be allowed to indicate which parts are business confidential, and these should be kept as such at all costs. The applicant shall be shown a draft of the opinion, with a chance to comment and indicate which parts are business sensitive, before the final opinion is given.

Detailed comments on ANNEX 2 2.2 Numeric code of We propose to remove CAS number as it is not enzyme based on relevant for food enzymes used as processing aids international system 2.3 Enzyme structure We propose to apply this requirement only for (3) Amino acid GMM-derived enzyme. Amino acid sequences of sequence non-GMM derived enzymes is often not determined. Alternatively, the enzyme structure available in publicly available databases has to be accepted. 2.7 Stability We propose to remove this requirement. Stability is not related to the safety of enzyme, but to the stability of the formulated enzyme during storage. It is the interest of food enzyme manufacturer/user and is part of the quality insurance of the enzyme product. 2.9 Specification of We consider that the requirements mentioned enzyme under sub-paragraph 6 is adequately ensured by (6) Contamination adherence to the General Specifications and conditions Considerations for Enzyme Preparations used in Food Processing (JECFA specifications). 3.1 Enzyme source Please clarify the strain information that needs to be (3) Case that enzyme is provided. from microorganism 3.1(4).3.1.4 The donor is most likely not specifically registered in Accession number for an international storage database. The donor donor microorganism sequence can be directly multiplied from the DNA, the donor organism is not needed, therefore this information is not needed.

3.1(4).3.1.6 Genotype of The DNA sequence from the donor is the only the donor. sequence needed. The donor organism is not needed and is not present in the enzyme preparation and not used during the enzyme production. Therefore the phenotype of the donor organism is not relevant, and there is no need to assess all possible toxins, antibiotics etc which could be present in the donor organism. In total, all the information in subsection 3.1.6 is not relevant for the safety assessment of the produced enzyme. 3.1(4). 6.1. The presence of rDNA is not relevant if there are no sequences of concern (eg antibiotic resistance markers). Therefore, the absence of rDNA should only be shown if there are sequences of concern present in the production organism. Subsection 4.1. It should be made clear that all the experiments mentioned under 4.1 are not needed when the production organism has a history of safe use and/or is QPS. This should also be extended to GMM’s, if shown that the inserted sequences do not shown any reason for concern. 4.1.3 Allergenicity or anti- Anti-nutrient is not relevant for enzymes used as nutrients processing aid. Therefore, we propose to remove this requirement. In addition, allergenicity check based on one most updated database shall be sufficient. 4.1.4 Dietary exposure Industry can only use publicly available databases and risk to perform the exposure assessment. - Consumption data This section needs much more specific information. Please identify which food consumption database specific for Thailand needs to be used. Is there a database from the government of Thailand which can be used? If not, it should be allowed to use the Budget method for calculating the exposure. Also clarify which 7 age ranges should be used. The upper limit of 95 percentile should be sufficient, instead of 97,5. 4.1.5 Margin of exposure The margin of exposure should be calculated using the generally accepted 10x interspecies safety factor and 10x-intraspecies safety factor, resulting in a total safety level of 100 (instead of the chosen 250 times). 4.2 Case that enzyme has We assume that scientific papers and scientific history of consumption or books can be considered as sufficient evidences. food production 4.2.2 Microorganisms When a micro-organism qualifies for QPS, it should be made clear which parts of the risk assessment are no longer needed. This should also be extended to GMM’s, if shown that the inserted sequences do not shown any reason for concern. When QPS is shown, no (or very limited) further risk assessment should be needed. Subsection 5.1. Safety The following competent authorities can be added assessment by other to the list: France, Brazil, Mexico, Denmark. It competent authorities. should also be made clear which part of the risk assessment is no longer needed if a positive assessment from one of these countries can be provided. Suggest a direct mutual recognition of the safety if there is a risk assessment available from one of the mentioned countries and remove the need for a full risk assessment.

18. Information to consider the need for production technology in Annex 3  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) Enzymes used as Processing Aids for food or food ingredient production will not have a technological function in the final food because they are typically removed and/or denatured during the manufacture process. Use of enzymes in food production depend on the reaction they catalyze and availability of substrate, and thus are characterized by food and food ingredient production processes and not by final food categories. Accordingly, item 3.1 of Annex 3 should be deleted since there is no technological function in final food and thus no justification for that needed. Appropriate information on the enzyme use is already required under the other items in Annex 3.

19. List of permitted enzymes to be used as Food Additive and Residue conditions in beverages and other foods in Annex 4.  Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents)

20. Method of Analysis for processing aid enzyme in Annex 5 Agree  Required improvement as (Please identify area for suggestion and attach the documents support or having explanation)  Not agree because (Please indicate the reason or attach the supporting documents) We propose that food enzyme manufacturer can use any validated methods, including company specific methods, or internationally accepted analytical methods to fulfill the above requirements.

21. Other comments or suggestions

Name: Patrick Fox (AMFEP, Ann Begley (ETA), Robert Rankin (IFAC) (20 December 2018)