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Compositional guideline: Alpha-casozepine enriched hydrolysed milk protein

17 November 2011

Name of the ingredient

alpha (α)-casozepine enriched hydrolysed milk protein (AAN)

Definition of the ingredient

The above named substance is a low-lactose, spray dried powder form of a protein hydrolysate of bovine (Bos taurus) skim milk. Alpha-casozepine is a decapeptide from αS1-casein.

Specific conditions

The milk used in the manufacture of the substance must be sourced either from Australian herds or herds from countries which are considered BSE-free, and which are registered for milk production for human consumption. The milk shall comply with the maximum residue limits for agricultural and veterinary chemicals established for milk in Standard 1.4.2 of the Australia New Zealand Food Standards Code.

Animal origin information would need to be provided with all new applications to list medicines containing α-casozepine enriched hydrolysed milk protein. In some instances further information may be required for evaluation by the TGA in relation to products containing this substance (see Supplementary information on Transmissible Spongiform Encephalopathies (TSEs) regulation).

Table 1: Ingredient specific requirements
Test Method reference Acceptance criteria
Description
Appearance Visual White/cream free flowing powder
Characteristics
Loss on drying IDF 26A (102°C for 2 h) Not more than 5.5%
pH of solution IDF 115 A (pH meter) 5.0-7.5
Ash IDF 27 (550°C, furnace) Not more than 20% (as is)
Identification
Chromatographic profile HPLC1 Profile consistent with that of authenticated reference material
Assay
Content of alpha (α)-casozepine HPLC1 Not less than 1.8%
Protein (as N x 6.38) IDF 20 B (Kjeldahl method) Not less than 73% (as is)
Lactose Enzymatic Not more than 1.0%
Notes
  1. A company method involving solution in water/acetonitrile/trifluoroacetic acid and analysed by HPLC with ultraviolet detection
Table 2: Incidental constituents
Test Method reference Acceptance criteria
Incidental metals and non-metals
Lead AAS Not more than 1 ppm
Arsenic AAS Not more than 3 ppm
Cadmium AAS Not more than 0.05 ppm
Mercury AAS Not more than 0.1 ppm
Sodium Flame spectrometric Not more than 6%
Potassium Flame spectrometric Not more than 0.2%
Calcium AAS Not more than 0.5%
Magnesium AAS Not more than 0.1%
Phophorous Spectrometric Not more than 1%
Other organic or inorganic impurities and toxins
Aflatoxins ISO 14501 Complies
Lysinoalanine2 HPLC Not detected
Nitrite/nitrosamines2 Chromatography Not detected
Microbiology
While substance manufacturers are encouraged to include limits for objectionable microorganisms, it is the product into which those substances are formulated that is subject to a legally binding set of criteria. The Therapeutic Goods Order No. 77 'Microbiological Standards for Medicines' mandates that any finished product that contains the ingredient, alone or in combination with other ingredients, must comply with the microbial acceptance criteria set by Clause 9 of the Order.
Notes
  1. Lysinoalanine is an amino acid sometimes found in alkali treated proteins. Nitrite/nitrosamines originate from the drying gases used in some spray-drying procedures. These tests may be omitted subject to TGA approval.

Key to abbreviations:

AAS = atomic absorption spectroscopy

BP = British Pharmacopoeia

HPLC = high-pressure liquid chromatography

IDF = International Dairy Federation

ISO = International Standards Organization

Ph Eur = European Pharmacopoeia