Notice to Stakeholders - Implementation of Establishment Licensing Requirements for Atypical Active Pharmaceutical Ingredients

January 20, 2020

Health Canada is notifying stakeholders of the interim approach concerning the implementation of Drug Establishment Licensing requirements for certain Active Pharmaceutical Ingredients (APIs) used in the fabrication of human and veterinary pharmaceutical drugs that are also used outside of the pharmaceutical industry. The approach for human pharmaceutical products was communicated as per the Notice to Stakeholders - Implementation of Establishment Licensing Requirements for Atypical Active Pharmaceutical Ingredients issued on November 23, 2017. The approach for veterinary pharmaceutical products was communicated as per the Notice to Stakeholders - Implementation of Establishment Licensing Requirements for Atypical Active Pharmaceutical Ingredients for Veterinary Use issued on July 25, 2018. Health Canada considers atypical APIs for the purpose of this notice, as ingredients used as pharmaceutical excipients, or as ingredients in natural health products (NHPs), veterinary health products (VHPs), foods, cosmetics and that meet recognised standards other than Good Manufacturing Practices (GMPs).

The List of atypical APIs for human use and the List of atypical APIs for veterinary use are appended to this Notice. The list of atypical APIs for human use is applicable to veterinary pharmaceutical drugs; however, the list of atypical APIs for veterinary use is not applicable to human pharmaceutical drugs.

Please refer to the List of atypical APIs regularly, as it may be amended by Health Canada, or at the request of stakeholders. Stakeholders wishing to request an addition or removal of an ingredient to the list of atypical APIs may email hc.api.questions-ipa.sc@canada.ca for instructions and requirements for a supporting rationale.

Please note that a request submitted to Health Canada for the inclusion or exclusion of an ingredient to the List of Atypical APIs does not ensure the addition or removal of the ingredient. Health Canada will review the rationale submitted by the stakeholder in parallel with the information currently available to Health Canada regarding the safety of the ingredient and will notify the stakeholder once a decision has been made.

Importers of the listed atypical APIs and drug in dosage form importers of products formulated using listed atypical APIs, which are fabricated, packaged, labelled and tested against standards other than GMP, can complete the Foreign Building Information Table (Table A) on the Drug Establishment Licence Application: Forms and Instructions (FRM-0033) in accordance with the following instructions:

  1. Column L - Indicate 'Exception' and include the standard that the API is manufactured against (e.g. 'Exception - ISO' or 'Exception - HACCP').
  2. Columns M, N, O and P can be indicated as "Exception".
  3. All other columns should be filled out as per regular Table A instructions.

It is important to note that each lot or batch of the atypical API shall, prior to its availability for sale, be tested against and comply with the specifications for that API.  In cases where there is a pharmacopoeial standard (Schedule B to the Food and Drugs Act) for the atypical API, the API should be manufactured and tested against that standard.

Importers continue to be responsible for having written agreements with foreign buildings and evidence of the foreign building’s compliance to the quality standard indicated. Furthermore, the dosage form fabricator, the DIN-holder and the dosage form importer are responsible to assure the acceptable quality and safety by meeting all applicable requirements of Part C, Division 2 of the Food and Drug Regulations, including Raw Material Testing sections C.02.009 and C.02.010. Should a risk to health be identified, Health Canada will take appropriate compliance and enforcement action proportional to the risk.

This approach will remain in place until Health Canada notifies stakeholders otherwise.

Atypical Active Pharmaceutical Ingredient List for Human Use

  • 1,3-Butanediol
  • Acetic Acid
  • Adenine
  • Allantoin (5-Ureidohydantoin)
  • Almond Oil
  • Aluminum Hydroxide
  • Ammonium Chloride
  • Avobenzone
  • Benzalkonium Chloride
  • Benzethonium Chloride
  • Benzoic Acid
  • Benzophenone-3
  • Benzophenone-4
  • Benzophenone-8
  • Benzyl Alcohol
  • Beta-carotene
  • Bisdisulizole Disodium
  • Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (as Bemotrizinol)
  • Caffeine
  • Calamine
  • Calcium Carbonate
  • Calcium Chloride
  • Calcium Undecylenate
  • Camphor
  • Carbamide
  • Carbonic Acid Monosodium Salt
  • Carboxymethyl Cellulose (sodium salt)
  • Cellulose (as Methylcellulose) and Derivatives
  • Cetylpyridinium Chloride
  • Charcoal (Activated Charcoal)
  • Chlorhexidine Digluconate
  • Chlorhexidine Gluconate
  • Chlorobutanol
  • Chloroxylenol
  • Chlorphenesin
  • Choline Chloride
  • Cinoxate
  • Citric Acid
  • Coal Tar
  • Cocoa Butter
  • Cod Liver Oil
  • Colloidal Oatmeal
  • Copper Undecylenate
  • Corn Starch
  • DEA-Methoxycinnamate
  • Dequalinium Chloride
  • Diethanolamine Methoxycinnamate
  • Dimethicone
  • Dioxybenzone
  • Disodium Edetate
  • Domiphen Bromide
  • Drometrizole Trisiloxane (as Silatrizole or Ecamsule)
  • Dyclonine
  • Ecamsule
  • Egg Yolk Phospolipids
  • Ensulizole
  • Enzacamene (4-Methylbenzylidene camphor)
  • Ethanol (Alcohol Anhydrous)
  • Ethanol (Ethyl Alcohol)
  • Eucalyptol
  • Ferric Oxide
  • Fish Oil
  • Fluoride (as Sodium Fluoride)
  • Gelatin
  • Glucose (as D-Glucose or Dextrose)
  • Glycerol / Glycerine / Glycerin
  • Glycine
  • Glycol
  • Glyoxyldiureide
  • Haloprogin
  • Hard Fat
  • Hexylresorcinol
  • Homomenthyl Salicylate
  • Homosalate
  • Hydrated aluminum silicate
  • Hydrochloric Acid
  • Hydroquinone
  • Iodochlorhydroxyquin
  • Inositol
  • Isopropanol (Isopropyl Alcohol)
  • Kaolin
  • Lactic Acid
  • L-Alanine
  • Lanolin
  • L-Arginine
  • L-Aspartic Acid
  • L-Cysteine
  • L-Glutamic Acid
  • L-Glutathione
  • L-Histidine
  • Lipoic Acid (Alpha Lipoic Acid)
  • L-Isoleucine
  • L-Leucine
  • L-Lysine Acetate
  • L-Methionine
  • L-Phenylalanine
  • L-Proline
  • L-Serine
  • L-Threonine
  • L-Tyrosine
  • L-Valine
  • Magnesium Carbonate
  • Magnesium Chloride
  • Magnesium Hydroxide
  • Magnesium Oxide
  • Mannitol
  • Medium Chain Triglycerides
  • Menthol
  • Menthyl 2-Aminobenzoate
  • Menthyl Anthranilate
  • Meradimate
  • Mineral Oil
  • Nitrofurazone
  • Oat Fibre
  • Octinoxate
  • Octisalate
  • Octocrylene
  • Octyl Methoxycinnamate
  • Octyl Salicylate
  • Oleic Acid
  • Olive Oil
  • Omega-3-Ethyl Esters
  • Oxybenzone (Benzophenone-3)
  • PABA (4-Aminobenzoic Acid)
  • Padimate A
  • Padimate O (Octyl dimethyl PABA)
  • p-Aminobenzoic acid
  • Peanut Oil
  • Pectin
  • Peracetic Acid
  • Petrolatum (Petroleum Jelly)
  • Phenol
  • Phenylbenzimidazole (Ensulizole, Phenylbenzimidazole Sulfonic Acid)
  • Phosphoric Acid
  • Polyaminopropyl Biguanide (PAPB)
  • Polycarbophil Calcium
  • Polyethylene Glycol
  • Polyhexanide
  • Polyvinyl Alcohol
  • Potassium Acetate
  • Potassium Chloride
  • Potassium Citrate
  • Potassium Phosphate
  • Povidone
  • Pramoxine
  • Propyl Alcohol
  • Propylene Glycol
  • Pyrithione Disulfide
  • Pyrithione Zinc
  • Resorcinol
  • Selenium Sulfide
  • Silica (Silicon Dioxide)
  • Silicone
  • Slippery Elm Bark Powder
  • Sodium Acetate
  • Sodium Ascorbate
  • Sodium Bicarbonate
  • Sodium Carbonate
  • Sodium Chloride
  • Sodium Citrate
  • Sodium Gluconate
  • Sodium Glycerophosphate
  • Sodium Hydrogen Carbonate
  • Sodium Hydroxide
  • Sodium Phosphate
  • Sorbitol
  • Soya-Bean Oil (Soybean Oil)
  • Sulfur
  • Sulisobenzone
  • Talc
  • Taurine
  • Terephtalydidene Dicamphor Sulfonic Acid
  • Theobroma Oil
  • Thymol
  • Titanium Dioxide
  • Tolnaftate
  • Topical Starch
  • Triclocarban
  • Triclosan
  • Triethanolamine Salicylate
  • Trolamine Salicylate
  • Tryptophan
  • Undecylenic Acid
  • Urea
  • Vitamin B1 (Thiamine)
  • Vitamin B5 (Pantothenic Acid)
  • Vitamin C (Ascorbic Acid)
  • Vitamin E
  • Wool Fat
  • Zinc Acetate
  • Zinc Carbonate
  • Zinc Chloride
  • Zinc Citrate
  • Zinc Gluconate
  • Zinc Omadine
  • Zinc Oxide
  • Zinc Pyrithione
  • Zinc Sulfate
  • Zinc Undecylenate

 

Atypical Active Pharmaceutical Ingredient List for Veterinary Use

  • Biotin (Vitamin B7)
  • Calcium iodate
  • Calcium Propionate
  • Casein Hydrolysate
  • Chlorhexidine acetate
  • Choline bitartrate
  • Cobalt carbonate
  • Cobalt gluconate
  • Copper gluconate
  • Copper oxide
  • Dexpanthenol (panthotenic acid, B family)
  • Dipiperazine sulfate/piperazine
  • Hydrogen peroxide
  • Inositol
  • Iodine (topical)
  • Linear dodecyl benzene sulfonic acid
  • Magnesium Gluconate
  • Manganese sulphate
  • Menadione sodium bisulfite
  • Neatsfoot Oil
  • Niacinamide (Vit B3)
  • Pine tar
  • Poloxalene
  • Potassium iodide
  • Pyridoxine Hydrochloride (Vitamin B6)
  • Riboflavin (as 5-sodiumphosphate) Vit B2
  • Salicylic acid (topical products for vet use)
  • Sodium chlorite
  • Sodium iodide
  • Sodium linear alkylate sulfonate
  • Sodium propionate
  • Sodium selenite
  • Thiamine Hydrochloride
  • Turpentine
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