• specify the formulations used in the and state which batches are identical to those proposed for registration in Australia; • state whether the batches used in the study were laboratory, pilot or production batches; • specify the size of each batch (eg. 50 kg) • clearly describe the packaging used in the and confirm whether it is identical to the pack which will be used in Australia; • present stability data on at least two batches of the product; • specify the temperature, lighting and humidity conditions applied during the study; • describe all test methods and sample sizes; • provide validation of analytical methods (and include copies of relevant chromatograms); • provide quantitative results where possible (in preference to “passes test” or similar wording); • where possible, include quantitative or semi-quantitative determinations of the content of degradation products • do not use an HPLC procedure to detect impurities without validation for this purpose. HPLC assay procedures as used for determination of the active ingredient may be unsuitable for separation and detection of impurities if they use too short a run time. Such a procedure would be acceptable if validated for impurity detection (note, however, that long run times do not in themselves ensure good separation); • comment or conduct additional where there is a lack of balance between the formation of degradation products and the loss of the active substance. For example, are the assay procedures sufficiently specific? Is the active ingredient volatile? Is it adsorbed onto the container wall? • consider additional tests to investigate the significance of obvious alterations in the characteristics of the product (eg. a distinct change in the colour of the product may necessitate additional investigation for degradation products); • include relevant information on the physical characteristics of the product during storage, such as dissolution characteristics, homogeneity, particle size etc; • include stability studies conditions of high humidity for products which are to be registered in moisture-permeable containers, and especially for those which are potentially labile to moisture; • provide results from sufficient time stations to allow assessment of any trends in the parameters; • provide results for individual dosage where these are available (eg. dissolution profiles).
Names that have been accepted to date include ‘Chemists’ Own’, ‘XX Chemists’, ‘Health Care Chemist’, ‘XXX Pharmacy’, ‘Pharmacist’, ‘Pharmacist Formula’, ‘Pharmacy Formula’, ‘Pharmacy Health’ and ‘Pharmacist Advice’.
9. MEC guidelines This Chapter represents a summary of the views of the TGA and the Medicines Evaluation Committee (MEC) with respect to OTC medicines (including new substances) at the time of publication and is intended to assist sponsors in submitting acceptable applications for registration of OTC medicines. Products are assessed according to the best clinical and scientific information at the time of evaluation. If you believe that a particular application warrants a departure from the Guidelines, a justification should be submitted with the application. The guidelines are not mandatory for existing products. However sponsors of existing products are encouraged to update labels to comply with the relevant guidelines when submitting label variation applications (refer to Chapter 11, , for information on changes to existing products). Suggested statements (for labelling purposes) are written in this chapter of the guideline as dot points and in italics. Comments relating to these suggested statements are in normal font and are not intended for inclusion on the labels. Allantoin The absence of convincing evidence that allantoin has a role as a wound healing agent precludes any claims being made for its efficacy in this regard. Alpha hydroxy acids There is evidence to suggest that the use of topical products containing alpha hydroxy acids (such as glycollic acid, lactic acid, citric acid and other fruit acids) may make users more sensitive to sunlight and especially to the ultraviolet (UV) radiation component of sunlight. UV exposure can damage the skin and at high doses, especially over a long period, can cause skin cancer (refer to the FDA Backgrounder – Alpha Hydroxy Acids in Cosmetics, 3 July 1997). The following statements should be included in the labelling of products containing hydroxy acids: • This product may make your skin more sensitive to sunlight; • Sun exposure should be limited by using a sunscreen and by wearing protective clothing; • If you have sensitive skin, test this product on a area of skin before applying it to a large area; • Transient stinging or irritation may occur when using this product. If irritation persists, discontinue use; and • Not recommended for use on children or infants. Anaesthetics, dermal All products containing local anaesthetics for dermal use must contain a statement such as: If irritation occurs, stop use immediately and seek medical advice. See also and
Paediatric dosage recommendations (1 month to 12 years) The dose should be based on 15 mg/kg, with the understanding that dosing with solid dose products for this age group is less flexible than with liquid products. The total daily dose should not exceed 60 mg/kg without medical advice. Doses should be given every four to six hours as required with not more than four doses in 24 hours. The medicine should not be administered for more than 48 hours without seeking medical advice. Administration to children under one month is not recommended. Statements to this effect must appear on labels of the primary pack and the immediate container. Age Average body weight (kg) Single dose (mg) 1 - 3 months 4 – 6 60 - 90 3 - 6 months 6 – 8 90 - 120 6 - 12 months 8 – 10 120 - 150 1 - 2 years 10 – 12 150 - 180 2 - 3 years 12 – 14 180 - 210 3 - 4 years 14 – 16 210 - 240 Age Average body weight (kg) Single dose (mg) 4 - 5 years 16 – 18 240 - 270 5 - 6 years 18 – 20 270 - 300 6 - 7 years 20 – 22 300 - 330 7 - 8 years 22 – 25 330 - 375 8 - 9 years 25 – 28 375 - 420 9 - 10 28 – 32 420 - 480 10 - 11 years 32 – 36 480 - 540 11 - 12 years 36 – 41 540 - 615 Doses must be expressed in whole numbers and should be presented with age, weight and mL unless otherwise justified. The recommended dose should be able to be measured commonly available metric measuring devices. There may be instances where the dose needs to be slightly different than the recommended milligram dose given above, having regard to the paracetamol concentration of the product. Sponsors intending to supply measuring devices with the product should consult Australian Standard AS 2224.2 - 1986. Calibrations on measuring devices should be in metric units and correspond with the doses shown on the label where possible to minimise the need for calculation and guesswork. Product Strength and pack size Sponsors may supply any or all of the following strengths of paracetamol liquid without the need for justification: 24 mg/mL, 48 mg/mL, 50 mg/mL and 100 mg/mL. Deviation from these strengths requires justification. not prohibited, the introduction of pack sizes larger than 200 mL will require justification.
In the case of in vivo carcinogenicity bioassays, a justification for not including long-term studies could be based around issues such as: • the expected pattern of use (identify possible low exposure); • results of mutagenicity studies; • lack of similarity to other molecules with known carcinogenic activity; • low persistence in the skin; • low in vivo absorption; • lack of photosensitisation or phototoxic potential; • proven photostability; • lack of possible adverse effects on the skin (change to epidermis/dermis); • length of submitted repeat dose toxicity studies. Related studies studies that are not currently referenced in EC guidelines may be useful in supporting particular applications. Reference to these studies is included only as a guide. They will not be relevant in all cases, nor should they be seen as a complete list of relevant studies. The following studies may be useful in providing information on the potential of a substance to cause tumours in people: • Studies using a transgenic mouse model to test exposure to the substance (the transgenic mouse is heterozygous for the p53 suppressor gene and tumours develop in a relatively short time frame (6 months) in this strain of mouse); • In vitro human dermal cell cultures exposed to the substance; • In vitro human dermal tumour cell cultures exposed to the substance. The following references may be useful in justifying the use of ingredients with a potential for skin corrosion/irritation: • Non-animal testing strategies for assessment of the skin corrosion and skin irritation potential of ingredients and finished products; M K Robinson et al; Food and Chemical Toxicology, 40(5), pp 573-592, 2002. • OECD/OCDE, Draft TG431, March 2002, OECD Guidelines for the testing of chemicals; in vitro skin corrosion: human skin model test. Chemistry requirements In addition to the requirements stated in Chapter 4B, , sponsors should provide data to establish the UV absorption range of the substance together with data addressing the potential for physical interaction with other commonly used sunscreening agents. New excipients in sunscreens Where a sunscreen contains an excipient ingredient which is not in any product currently included in the Australian Register of Therapeutic Goods (ARTG) for supply in Australia, the excipient must be cleared for use by the TGA. The following information is required:
Aminobenzoic acid 4-Aminobenzoic acid 15% Isoamyl methoxycinnamate (Isoamyl 10% Benzophenone Phenylketone To be determined Benzophenone-2 Benzophenone-2 Methanone To be determined Butyl methoxy dibenzoylmethane 1-(4 tert Avobenzone, BMDM, dibenzoylmethane 5% Cinoxate Cinoxate 6% Dioxybenzone Dioxybenzone Benzophenone 8 3% Ethoxylated ethyl acid PEG25 PABA 10% Padimate O 2-Ethylhexyl dimethyl PABA 8% Octyl methoxycinnamate Octyl methoxycinnamate Ethylhexyl Methoxycinnamate 10% salicylate 2-Ethylhexyl Salicylate 5% Homosalate Homosalate Homomethyl salicylate 15% Isopropylbenzyl salicylate 4-1sopropylbenzyl Salicylate To be determined Menthyl anthranilate Menthyl Anthranilate Methyl 5% 4 Methylbenzylidene camphor 3-(4-Methylbenzylidene)-d-1 camphor 4% Octocrylene 2-cyano-3,3-diphenyl acrylic acid, 2-ethyl hexyl ester diphenylacrylate 10% Octyl triazone 5% acid and its salts 6% (as acid) Oxybenzone Oxybenzone Benzophenone 3 10%
Phenylbenzimidazole sulfonic acid acid and its potassium, sodium and triethanolamine salts 4% anilinium methyl sulphate 6% Salicylic acid salts (potassium, sodium and triethanolamine) To be determined Sulisobenzone 2 Benzophenone 4 10% Sulisobenzone sodium Benzophenone 5 10% Ecamsule Terephthalylidene dicamphor sulfonic acid 10% Titanium dioxide Titanium dioxide 25% Triethanolamine salicylate Trolamine salicylate 12% Zinc oxide 1 Zinc No limit 1 Bemotrizinol 3 Bemotrizinol Tinosorb S 10% Methylene tetramethylbutyl phenol 4 Tinosorb M 10% Drometrizole trisiloxane 5 disiloxanyl]propyl Mexoryl XL 15% Disodium phenyl dibenzimidazole tetrasulfonate 6 2,2'-(1,4-Phenylene) acid, monosodium salt) Bisimidazylate, Neoheliopan AP 10% Polysilicone-157 Dimethicodiethylbenzalmalonate Parsol SLX 10% 1. Maximum concentration for zinc oxide amended 12 December 2003 2. ‘Benzophenone-4’ deleted from column 1 and ‘Sulisobenzone’ from column 2 to column 1, 25 June 2004 3. ‘Bemotrizinol’ added 22 November 2004 4. ‘Methylene bis-benzotriazolyl tetramethylbutyl phenol’ added, 22 November 2004 5. ‘Drometrizole trisiloxane’ added, 6 December 2004 6. ‘Disodium phenyl dibenzimidazole tetrasulfonate’ 31 August 2005 7. ‘Polysilicone’ 18 August 2006
LFO Reformatting of pre-existing text (ie. moving of blocks of text and not rewording – see LIW, LRT) N 5, L _________________________ * A/D = assurances to be and supporting documentation required for the given status to apply. Refer to for an explanation of all codes used. Label changes (including package insert) Status A/D* LRT Rewording of pre-existing text without altering meaning (other than indications or directions for use – see LIW) A - LDT Deletion or addition of text to the label (eg. addition or removal of claims such as clinically proven, fast/rapid action; general claims regarding the product, its nature, mechanism of action, qualifying statements, etc) A - LOC Other changes Ask - Sponsor changes Status A/D* SSP Sponsor name/logo(same sponsor of goods) and/or change to manufacturer/supplier details on label N 5, L SAD Sponsor address Write to OTC - STR Transfer goods to another sponsor N 5, T, L Product detail changes Status A/D* GPN Proprietary name (if grouping applies) A 1, 2, L PIN Proprietary name (if grouping doesn’t apply) NEW - PSZ Pack size – other than liquids/semi-solids (see PLS) or metered dose aerosols (see PMZ) (see also KBT, KGL, KBL and KOT) N 5, 6, 10, L, P PLS Pack size – liquids/semi-solids N 5, 6, 10, 13, L, P PMZ Pack size – metered dose aerosols A - GIN New therapeutic indications (if grouping applies) A 1, 3, L PTI New therapeutic indications (if grouping doesn’t apply) NEW - PDF Dosage form (as defined in TGA Standard Terminology6) NEW - PVI Visual identification N 5, 13, 19 PSL Shelf life – increase (other than in change PSP) A - PSR Shelf life – decrease N 5 PSP Shelf life – increase (in accordance with an approved stability testing protocol for that product) N 5, 11, 20 PPR Approval of a stability testing protocol for a specific product A -