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Drugs and Health Products

Monograph: Protease, Fungal

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient. Notes: (i) Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's discretion. (ii) The solidus (/) indicates that the terms and/or the statements are synonymous. Either term or statement may be selected by the applicant.

Date: 2014-03-11

NHPID Name

Fungal protease (NHPD 2007a)

Proper Name(s)

Fungal protease ( FCC 8 )

Common Name(s)

Source Material


Route Of Administration

Oral

Dosage Form(s)

  • The acceptable pharmaceutical dosage forms include, but are not limited to capsules, chewables (e.g. gummies, tablets), liquids, powders, strips or tablets.
  • This monograph is not intended to include foods or food-like dosage forms such as bars, chewing gums or beverages.

Use(s) or Purpose(s)

Statement(s) to the effect of:

Dose(s)

Adults:

Dose(s): not to exceed 680000 FCC hemoglobin units on the tyrosine basis per day
Directions For Use:
  • Enteric coated products: Swallow whole/Do not crush or chew (CPS 2008)
  • Take with food/meal

Dose(s): not to exceed 6800 FCC spectrophotometric acid protease units per day
Directions For Use:
  • Enteric coated products: Swallow whole/Do not crush or chew (CPS 2008)
  • Take with food/meal


  • Dose unit information must include the quantities of both the enzyme preparation (mg or ml) and its enzymatic activity (FCC or USP units). When submitting by ePLA, please put the enzymatic activity quantity in the Quantity/Unit fields (field 77) and the quantity of enzyme preparation in mg or ml in the Additional Quantity/Unit fields.
  • Enzymatic activity can be either in FCC hemoglobin units on the tyrosine basis per day and/or in FCC spectrophometric acid protease units per day.
  • FCC 8: One hemoglobin unit on the tyrosine basis (HUT) of proteolytic (protease) activity is defined as that amount of enzyme that produces, in 1 minute under the conditions of the assay, a hydrolysate whose absorbance at 275 nm is the same as that of a solution containing 1.10 mcg/mL of tyrosine in 0.006 N hydrochloric acid.
  • FCC 8: One spectrophotometric acid protease unit (SAP) is that activity that will liberate 1 micromol of tyrosine per minute under the conditions of the assay.
  • For multi-ingredient products containing protease from A. niger and protease from A. oryzae, the maximum proteolytic activity from both sources cannot exceed 680000 FCC HUT per day and/or 6800 FCCSAP per day (FCC 8).

Duration of use

For prolonged use, consult a health care practitioner.

Risk Information

Statement(s) to the effect of:

Caution(s) and Warning(s):
  • If you are pregnant or breastfeeding, consult a health care practitioner prior to use
  • If you have a gastrointestinal lesion/ulcer, are taking an anticoagulant/ blood thinner or an anti-inflammatory, or are having surgery, consult a health care practitioner prior to use.

Contraindication(s):
No statement is required

Known Adverse Reaction(s):
Hypersensitivity/allergy has been known to occur; in which case, discontinue use

Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database and must meet the limitations outlined in the database.

Specifications

  • The finished product specifications must be established in accordance with the requirements described in the NHPD Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredient Database (NHPID).
  • Details of the manufacturing of the enzyme at the raw material stage should include fermentation medium and the isolation process of the medicinal ingredient.
  • No traces of any antibiotics or their residues should be detectable in the finished product.
  • The finished product specifications must be established in accordance with the requirements described in the NHPD Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredients Database (NHPID)
  • The specifications must include testing for enzymatic activity of the medicinal ingredient at appropriate stages of formulation and manufacturing using the assay outlined in the current Food Chemicals Codex (FCC): PROTEOLYTIC ACTIVITY, FUNGAL (HUT) and PROTEOLYTIC ACTIVITY, FUNGAL (SAP).
  • Where published methods are not suitable for use, manufacturers will use due diligence to ensure that the enzymes remain active to the end of the shelf life indicated on the product label.

References cited

  • Bisby F, Roskov Y, Orrell T, Nicolson D, Paglinawan L, Bailly N, Kirk P, Bourgoin T, Baillargeon G, Ouvrard D, editors. Species 2000 & ITIS Catalogue of Life, 15th March 2012 [Internet]. Reading (GB): Species 2000. [Source database Species Fungorum, 9.0, Sep 2010; Accessed 2012 March 28]. Available from: http://www.catalogueoflife.org
  • Brown SA, Coimbra M, Coberly DM, Chao JJ, Rohrich RJ. Oral nutritional supplementation accelerates skin wound healing: a randomized, placebo-controlled, double-arm, crossover study. Plastic and Reconstructive Surgery 2004;114(1):237-244.
  • CABI 2012: Centre for Agriculture and Bioscience International. Index Fungorum [Internet]. Wallingford (GB): CABI (Centre for Agriculture and Bioscience International); 2012. [Accessed 2012 March 30]. Available from: http://www.speciesfungorum.org
  • CPS 2008: Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals. Ottawa (ON): Canadian Pharmacists Association; 2008.
  • FCC 8: Food Chemicals Codex, Eighth edition. Rockville (MD): The United States Pharmacopeial Convention; 2012.
  • IUBMB 1992: IUBMB Enzyme Nomenclature [Internet]. London (GB): Queen Mary, University of London. [aspergillopepsin I: other name Aspergillus acid protease, CAS 9025-49-4, EC 3.4.23.18 created 1992; Accessed 2012 March 16]. Available from: http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/18.html
  • Murray MT. Encyclopedia of Nutritional Supplements: The Essential Guide for Improving Your Health Naturally. New York (NY): Three Rivers Press; 1996.
  • Oben J, Kothari SC, Anderson ML. An open label study to determine the effects of an oral proteolytic enzyme system on when protein concentrate metabolism in health males. Journal of the International Society of Sports Nutrition 2008;5:10.

References reviewed

  • Cichoke AJ. Pancreatic Enzymes. In: Pizzorno JE, Murray MT, editors. Textbook of Natural Medicine, Third edition, volume 1. St. Louis (MI): Churchill Livingstone Elsevier; 2006 p. 1131-1146.
  • Evidence for Quality of Finished Natural Health Products, Version 2.0 [Internet]. Ottawa (ON): Natural Health Products Directorate, Health Canada. 2007. [Accessed 2012 March 28]. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/eq-paq-eng.php
  • Martindale 2011: Sweetman SC, editor. Martindale: The Complete Drug Reference [Internet]. London (GB): Pharmaceutical Press; 2011. [Pancreatic enzymes latest modification 09-Apr-2011; Accessed 2012 March 28]. Available from: http://www.medicinescomplete.com