EXPLANATORY STATEMENT
THERAPEUTIC GOODS (LISTING) NOTICE 2008 (No. 6)
Dimethyl sulfone and Vegetable oil phytosterol esters
Section 9A(5), Therapeutic Goods Act 1989
OUTLINE
Therapeutic Goods (Listing) Notice 2008 (No. 6) (‘the Listing Notice’) is a notice made by the delegate of the Minister for Health and Ageing under subsection 9A(5) of the Therapeutic Goods Act 1989 (‘the Act’).
The Listing Notice has the effect of permitting the use of dimethyl sulfone and vegetable oil phytosterol esters as active ingredients in listed medicines for oral use. Products containing vegetable oil phytosterol esters are subject to the inclusion of additional advisory statements on the label.
The Listing Notice commenced on the day after it was registered on the Federal Register of Legislative Instruments (‘FRLI’).
BACKGROUND
The Act provides for the establishment and maintenance of a national system of controls for the quality, safety, efficacy and timely availability of therapeutic goods that are used in Australia or exported from Australia. The Therapeutic Goods Administration (‘TGA’) is responsible for administering the Act.
Unless specifically exempted or authorised under the Act, therapeutic goods are required to be included in the Australian Register of Therapeutic Goods (‘ARTG’) before being supplied in, imported into, manufactured in, or exported from Australia (sections 19B and 19D of the Act). Medicines are registered or listed in the ARTG, depending on the ingredients they contain and the therapeutic claims that are being made.
In Australia, products that contain low risk ingredients are referred to as listed medicines. Most listed medicines are considered to be of relatively low risk compared to other types of medicines, such as prescription and over-the-counter medicines, as they may only contain ingredients that have been approved by the TGA as being of low risk and may only make limited therapeutic claims.
Schedule 4 of the Therapeutic Goods Regulations 1990 (‘the Regulations’) sets out those therapeutic goods that are required to be included in the part of the ARTG for listed medicines. Part 5 of Schedule 4 specifies substances other than vitamins, minerals and plant material that are for use in listed medicines. Division 1 of Part 5 specifies substances not mentioned in Division 2 or 3 that may be ingredients of preparations. At present, Schedule 4 of the Regulations does not include a reference to either dimethyl sulfone or vegetable oil phytosterol esters but it is anticipated that Division 1 of Part 5 Schedule 4 of the Regulations will include a reference to dimethyl sulfone and vegetable oil phytosterol esters when the Regulations are next amended.
In order to facilitate the timely approval of new listable substances, subsection 9A(5) of the Act allows the Minister for Health and Ageing to publish a notice that has the effect of permitting the use of particular substances in listed medicines subject to any specified conditions.
Pursuant to subsection 9A(6) of the Act, when Schedule 4 of the Regulations is amended to include reference to a substance that has been the subject of the Listing Notice, the Listing Notice ceases to have effect.
Dimethyl sulfone
Dimethyl sulfone is present at relatively low levels in a range of dietary sources, including plants and animal tissues. It is currently supplied (as methylsulfonyl methane – MSM) in many countries including the USA, Canada, and New Zealand as an ingredient in dietary supplements.
Dimethyl sulfone has a relatively short history of use as a therapeutic agent, starting from the mid to late 1970s. A number of anecdotal reports have shown positive effects in a range of inflammatory disorders. The typical recommended daily doses are relatively large at up to 3 grams per day, but there is little evidence that such a pattern of use is associated with serious toxicity or adverse reactions.
In the lead up to the establishment of the Australia New Zealand Therapeutic Products Authority (‘ANZTPA’), the Permitted Ingredients List Project Team reviewed the suitability of dimethyl sulfone for use as an active ingredient in low risk “Class 1” medicines. This review was considered by the Interim Joint Expert Advisory Committee on Complementary Medicines (‘IJEACCM’) which recommended that “dimethyl sulfone is suitable for use in Class 1 medicines” and “that practitioners should be made aware of the widespread use of MSM in the community”.
Following the postponement of the ANZTPA, the TGA was asked to reconsider the suitability of dimethyl sulfone for use as an active ingredient in listed medicines. This review was carried out by the Over-The-Counter Medicines Evaluation Section, which recommended approval of dimethyl sulfone for use in listed medicines.
Vegetable oil phytosterol esters
Vegetable oil phytosterol esters consist mainly of a mix of fatty acid esters combined with plant oil-derived steroid alcohols. They have been extensively used, initially in vegetable spreads and more recently (for approximately a decade) in so-called ‘functional foods’ (high-fibre breakfast cereals, low-fat milk and low-fat yoghurt products). A typical dietary intake of phytosterol esters has been estimated to be about 200-300 milligrams per day, with a higher intake (300-450 mg/day) in vegetarians.
Most of the complaints made in Europe during the first year of marketing of vegetable oil spreads containing 14% phytosterol esters were of gastrointestinal symptoms (diarrhoea and constipation) or skin conditions (e.g. rash, urticaria and itching). There are no reports of adverse reactions in the Australian Adverse Reactions database for therapeutic products containing a similar active ingredient.
The Medicines Evaluation Committee (‘MEC’) considered the application for this substance at its meeting in June 2008. The MEC recommended approval of the substance for use in listed medicines for oral use subject to the inclusion of particular advisory statements on the product labels.
The Complementary Medicines Evaluation Committee (‘CMEC’) subsequently considered the advisory statements recommended by the MEC and recommended that the labels of products containing phytosterols as an active ingredient should include the following advisory statements:
- “There is no benefit from taking more than 3g/day of phytosterols from all sources”; and
- “Not suitable for pregnant or lactating women”.
CONSULTATION
Although no consultation is required in relation to the Listing Notice, as the regulation change is minor and machinery in nature, the TGA has consulted the IJEACCM in relation to the approval of dimethyl sulfone and the MEC and CMEC in relation to the approval of vegetable oil phytosterol esters.
REGULATION IMPACT STATEMENT
No Regulation Impact Statement is necessary in relation to the Listing Notice as the listing of the ingredients dimethyl sulfone and vegetable oil phytosterol esters is minor and machinery in nature with no or low compliance costs and impact on business, individuals or the economy.