ARTG requirements for disinfectants and sterilants

The Australian Register of Therapeutic Goods (ARTG) provides a comprehensive data base of information about all therapeutic goods supplied in, or exported from, Australia. For the computer database to fulfil its functions, the data must be entered in an accurate and consistent form.

To include disinfectant and sterilant products in the ARTG each sponsor must complete the appropriate form for each separate and distinct product. This includes provision of the names of active ingredients and excipients in a particular product. The names of active ingredients and excipients must comply with standardised nomenclature. For most substances an official or nonproprietary name known as the "Approved Name" or the "Australian Approved Name (AAN)" <http://www.tga.gov.au/docs/html/aan.htm> is to be used where possible.

Therapeutic Goods Order No 54 <http://www.tga.gov.au/docs/html/tgo/tgo54.htm>, 'Standard for Composition, Packaging, Labelling and Performance of Disinfectants and Sterilants' specifies that the names of active ingredients in the formulation shall appear on the label of the goods. The AAN also has to be used when the name of the substance is included on the label.

Prior to the 1st of July 1997, applications have been accepted from sponsors using non standard terminology. A specific condition of these Registrations or Listings will require the sponsor to upgrade their ARTG details to the AAN standard within one year of entry on the ARTG. Sponsors will be sent application forms to submit the details of the AANs, the propietary ingredients (PIs) and formulation details. Where there is currently no AAN for the substance, sponsors will also be required to propose an appropriate name together with references and any other useful information that will identify the substance and support the assignment of an AAN.

Point to note when submitting a disinfectant or sterilant application

1. Formulations consist of active, excipient and possibly some proprietary ingredients (PI). Whilst most applicants will be able to distinguish between an active or excipient ingredient, the term proprietary ingredient may be new to some sponsors. API is a component of a formulation that is used as a fragrance, perfume, or colour for a product. Where the composition of these components (not a single ingredient) is confidential from the sponsor, the PI supplier can provide this information directly to the TGA on behalf of the sponsor on a 'Notification of a Proprietary Ingredient' form. Once these details are verified an ARTG Proprietary Ingredient number will be assigned to the PI and the supplier notified.
   This number can then be used by the sponsor to describe the same PI in subsequent applications for entry on the ARTG.
2. Formulation details of the active and excipient ingredients must be completed using the Australian Approved Name (AAN). These names are included in the document, 'TGA Approved Terminology for Drugs - July 1995'.
   Where there is currently no AAN a proposal for a new AAN must be submitted to the ARTG on the form in the document and must be accompanied by either a monograph from one of the listed references or manufacturing details of the structure, molecular formula, etc. The minimum information required for each substance is description by a unique Chemicals Abstract number (CAS number). Other acceptable references include Merck Index, Martindale, The Extra Pharmacopoeia, Colour Index (Society of Dyers and Colourists) and the International Cosmetic Ingredient Dictionary.
3. When AAN terminology cannot be determined the substance will be entered with a provisional name classification pending clarification.
4. Standardised terminology for 'dosage forms' and 'route of administration' must also be used when making ARTG application for disinfectants and sterilants.
5. As this process is new to many disinfectant sponsors, the following references available from the TGA Publications Office (Ph: 1800 020 653) will be of assistance.
   • TGA Approved Terminology for Drugs <http://www.tga.gov.au/docs/html/aan.htm>
   • Notification of Proprietary Ingredient Forms <http://www.tga.gov.au/docs/html/forms/notifpi.htm>
   • Information on the procedure to lodge proprietary ingredients/Information on Australian Approved Names can be sought from the TGA

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ARTG notes

Confidentiality

All information supplied to the ARTG is held as 'commercial-in-confidence'. However, information required to appear on the label of goods is considered to be in the "public domain" and may be released in accordance with Regulation 46 of the Therapeutic Goods Act. Details of manufacturer, excipient ingredients and quantities and proprietary ingredient numbers are held in confidence and will only be released to the sponsor of the good, on the request of an 'authorised person'.

Authorised person

All Sponsors are reminded of the need to maintain the 'authorised person' list for their company held by the ARTG. For example, unless names are removed from the list, people remain authorised to amend, delete or submit new applications to the Register. Changes to authorised person's names must be made in writing under the owners/Managers/Partner/Authorised person's signature and sent to TGA PO Box 100 Woden ACT 2606.

Disinfectant regulation update

The final date for lodgement of applications for disinfectant and sterilant products currently being supplied in Australia was the 30th of June 1997. Sponsors proposing to market new products are reminded that they must lodge an application for entry on the ARTG and receive approval from the TGA before supply may commence.

The evaluations of data in support of applications for sterilants and instrument grade disinfectant products will commence in July. AUST R numbers will be allocated by the ARTG as the evaluation of the data for individual products is completed.

A draft document has been developed outlining the procedures to be followed when making changes to products following registration or listing. It allows for sponsors to make a number of changes on the basis of "self assessment". Comments on the draft document have been invited and a final document should be available through the TGA Publications Unit by September.

A draft advertising claims guide is now available and comment is also being sought from industry. Seminars, organised by the PMAA in conjunction with the ACSMA and the TGA, were conducted in Sydney and Melbourne in June.

TGA will pursue coordination of the new national regulatory regime of disinfectants with the NHMRC infection control guidelines. The drug-device distinction list is being revised to incorporate the changes in classifications of devices incorporating antiseptics. Once approved it will be available through the TGA Publications Unit and will apply to all new applications.

It has also been proposed that benchtop and portable sterilisers for medical purposes, that are not permanently plumbed or wired, be incorporated into the Regulation amendments to become listable products. In addition Item 7(e) of Schedule 5 is to be amended to ensure that these devices are not exempt from listing.

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Good manufacturing practice news

Many applications for listing or registration are either delayed or rejected due to inadequate evidence of GMP compliance. To give sponsors greater confidence that applications will not be rejected or delayed due to reasons of GMP, the TGA has decided to offer the opportunity for sponsors to request a non-mandatory preclearance assessment of the GMP evidence for an overseas manufacturer, prior to actually submitting an application. Sponsors who wish to, need to complete a clearance request form for each manufacturing site and forward it to the GMP Audit & Licensing Section (GMPALS) or via the Business Management Unit (if a fee is payable under Section 6AA of the Therapeutic Goods (Charges) Regulations).

No fee is payable for obtaining the clearance other than where GMPALS is required to liaise with other overseas bodies to confirm the status of the manufacturer. GMPALS will then assess the evidence and return the form to the sponsor indicating if the evidence is acceptable, the categories of products or processes it covers and the expiry date of the evidence.

GMPALS will contact the sponsor when additional information or the payment of a fee is required. Once assessed, a copy of the completed form may be submitted as part of an application for entry of a product on the ARTG and used as evidence of GMP compliance. It should not be necessary to re-evaluate this evidence unless additional overseas manufacturers are identified or the product is considered to be outside the scope of the clearance.

A separate clearance form is not required for each application if the evidence can be applied in each case.

When an application is submitted to register or list a product it is essential that the GMP evidence remains valid for at least 6 months.

GMP Newsletter - Issue 17

The GMP Newsletter is published by the GMP Audit & Licensing Section to keep Australian licensed manufacturers informed of GMP developments here and overseas. The most recent issue (Number 17) of this free publication was published in May 1997.

Further reports on latex allergy issues

Allergies to latex medical products are a serious and increasingly common problem that continues to create management problems for health care professionals and their patients. Avoiding patient contact with latex is not always a simple matter. Even indirect contact with latex, such as when drugs are administered via a delivery system containing a latex component, can cause allergic responses in sensitive individuals.

The Therapeutic Device Bulletin has twice published articles on latex allergies. The 3/93 issue summarised regulatory changes proposed by the US Food and Drugs Administration (US FDA). These changes were supported by the TGA who undertook to introduce similar labelling requirements for latex containing products at the same time as the US FDA. The 4/94 issue summarised the world position, gave reasons for the allergies, advised on steps health care professionals could take to minimise the problem and encouraged manufacturers to provide warning information with latex products.

Control of latex sensitisation

Both additives and native proteins in the latex are now recognised as sensitising agents. To date it has not been possible to fully identify these proteins, or to eliminate them entirely through changes in manufacture. Nor has it been possible to set a "safe" level of protein. However it is acknowledged that the measurement of total leachable protein levels correlates with the allergenicity of natural rubber latex. This provides an indication of safety and quality which can be used by manufacturers to help control the protein and chemical levels at the time of production.

Knowing the protein and chemical additive levels assists buyers and users of latex products control the risk of latex sensitisation. Medical personnel need to be able to make informed purchasing decisions, know how to minimise the risk of sensitisation and know how to cope when it occurs. The TGA has been highly active in educating health care professionals and industry in this regard.

Suppliers should provide enough information to enable the buyer to choose a quality latex product or else one that is latex-free. Buyers of latex products should request suppliers to ensure that all appropriate information is provided at the time of purchase.

Other international regulatory organisations are also seeking to inform latex buyers and users:

• Canada (CMBD) has recently published information leaflets for latex device users and for people with a proven sensitisation.
• The UK (Medical Device Agency, UK) recently published an information document (MDA DB 9601, April 1996) titled "Latex Sensitization in the Health Care Setting".

Current international regulatory scene

Proposed legislation by the US FDA (USA) requiring warnings on labels of latex devices has not yet been implemented, however both Canada and Europe have developed medical glove standards.

The Canadian Medical Device Bureau (CMDB) published labelling requirements for all medical gloves in June 1995. These state that glove materials must be suitable for their intended use and the labelling must give sufficient information about the material to determine whether the intended use is appropriate. The primary material of manufacture must be clearly identified. In addition, glove manufacturers are encouraged to label their gloves with the measured levels of natural and artificial substances to which adverse reactions have been reported. This includes latex accelerators such as thiurams as well as latex proteins.

CEN has published a draft standard outlining biocompatibility and labelling requirements for medical gloves in 1995. This standard is the first medical glove standard which identifies both endotoxins and leachable proteins as potential biological hazards. It requires that the manufacturer

• monitor the amount of leachable proteins in the final product,
• label all gloves manufactured from natural rubber latex,
• state whether they are powdered, and
• provide sufficient information to allow a decision to be made whether the biological risks associated with contaminants are acceptable.

TGA is in the process of adopting equivalent device labelling requirements as the European Union which require the inclusion of warnings concerning known hazards. This provision will certainly be applicable to latex medical gloves.

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Bren Milsom transfers

Bren Milson receiving acknowledgement plaque from the
Medical Industry Association of Australia

After seven years involvement with the therapeutic devices program of TGA, Bren Milsom has moved from the CAB to take on a new role as the Secretary of the Australian Drug Evaluation Committee (ADEC).

Bren played a significant role in the negotiations of the mutual recognition agreement on conformity assessment with the European Union. Bren's extensive experience includes working with TDEC and he has indicated his preference for developing a closer working relationship between drug evaluation and device evaluation.

Bren's contribution to device regulation was recognised by industry when the Medical Industry Association of Australia recently presented him with a plaque "acknowledging with gratitude his excellent advice, assistance and support during his time with the TGA devices program".

NCCTG report

The National Coordinating Committee on Therapeutic Goods (NCCTG) comprises representatives from State, Territory and Commonwealth (TGA) health authorities who met on 8 May 1997 to consider a range of issues.

Complementary legislation

The (Commonwealth) Therapeutic Goods Act 1989 provides the basis for a national system for regulating therapeutic goods. State legislation complementary to the Commonwealth Act commenced in Victoria on 23 May 1995 - the Therapeutic Goods (Victoria) Act 1994, and in New South Wales on 23 April 1996 with the passage of the New South Wales Poisons Amendment (Therapeutic Goods) Act 1996 No. 2. Cabinet consideration or drafting instructions for complementary legislation is currently underway in South Australia, Queensland, the Australian Capital Territory, Tasmania and Western Australia.

Supply of medicines via mail order

NCCTG noted that several health authorities had received requests for information concerning the status, in respect of State and Commonwealth law, of a price list which had been distributed by a pharmacy offering a mail order service. Following discussion of this matter, the committee released the following statement:

NCCTG agrees that the provision by a pharmacist of a mere alphabetical price list of Schedule 3, 4 and 8 prescription drugs, at the request of a member of the public, would not be considered to be 'advertising' of those drugs, but would be seen as 'advertising' if:

• the price list contained information concerning the usages (indications) of the drugs; or
• contained photographic or other depictions of the drugs;
• or was unsolicited;
  and in reaching this position NCCTG is aware of:
  • The Council of Australian Government's National Competition Principles Agreement;
  • the development of guidelines for mail order dispensing by pharmacy boards and pharmaceutical societies; and
  • the position of the Australian Pharmaceutical Advisory Council that any dispensing system, including mail order pharmacy, should comply with the principles of the Australian policy on the Quality Use of Medicines.

The vaccine cold chain

The meeting examined a report by the South West Centre for Public Health, NSW, which made a number of recommendations in respect of storage temperatures and storage methods for vaccines to maintain the cold chain from the time of manufacture to the time of vaccination. NCCTG agreed to implement the recommendations in the report, as appropriate, in the States and Territories.

Recalls of therapeutic goods

NCCTG will request the Australian Council on Healthcare Standards to consider including the Uniform Recall Procedure for Therapeutic Goods (URPTG) as a reference document when examining institutions for accreditation and for educational purposes in the information material available through that organisation. This follows NCCTG's consideration of information indicating that hospital protocols for recalling therapeutic goods in response to a company's recall letter, may benefit from periodic review.

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Use of claims of safety

The purpose of the Therapeutic Goods Advertising Code is to ensure that the advertisement and promotion of non-prescription therapeutic goods to the public is conducted in a responsible way.

Clause 7.10 of the Code specifically addresses claims which imply that goods are safe or that their use cannot cause harm. This means that the word 'safe' cannot be used in the labelling or promotion of non-prescription therapeutic goods.

Conformity Assessment Branch seminars

Industry seminar

On March 20 and 21 this year, staff of the CAB in conjunction with the Medical Industry Association of Australia conducted a two day seminar on the future of device regulation in Australia based on the European model. The seminar was sold out in advance and an audience of around 180 filled the Curzon Hall facility. The program included overseas speakers, Karen Howes (European Commission), Robert Allen (UK Medical Devices Agency), Dr Johan Rader (TUV Germany) as well as speakers from the TGA and industry.

The seminar was run to enable sponsors and manufacturers of medical devices to gain a greater understanding of how the European regulatory system works and the process of its implementation in Australia as a result of the Mutual Recognition Agreement.

Tracking symposium

On Saturday 24 May over 150 participants from all states of Australia, including sponsors of implantable devices, gathered in Sydney for a one day symposium to hear about the progress of the national program. Speakers discussed some of the critical issues and coordinators of the pilot studies described their experiences.

For the past three years work has been progressing on the development of a National Implantable Device Tracking System. It is apparent that there is wide agreement on the need for a better approach for recording information about patients receiving permanent implants.

A survey of participants indicated most hospitals had a good understanding of the need for these programs. Responses were evenly divided about whether device tracking and recording should happen at an institutional level. There was general agreement however, that efforts to develop a National Register for a limited number of life sustaining devices should be continued.

Thirty three hospitals have advised that they are now planning to introduce tracking systems.

TGO No.	Title	Gazetted
52 <http://www.tga.gov.au/docs/html/tgo/tgo52.htm>	Gloves for General Medical and Dental use Revokes and replaces TGO 42	18.6.97
53 <http://www.tga.gov.au/docs/html/tgo/tgo53.htm>	Single-use Sterile Surgical Rubber Gloves Adopts "AS/NZS 4197:1997 -Single-use sterile surgical rubber gloves - Specification"	18.6.97
54 <http://www.tga.gov.au/docs/html/tgo/tgo54.htm>	Standard for composition, packaging, labelling and performance of disinfectants and sterilants	13.11.96
54A <http://www.tga.gov.au/docs/html/tgo/tgo54a.htm>	Amendment to TGO 54	9.4.97
55	Amendment to TGO 48 - "GeneralRequirements for Labels for Drug Products". Extends final implementation date for labels for drug products already on ARTG at 1 July 1994 from 1 July 1996 to 1 July 1997.	28.6.96
56 <http://www.tga.gov.au/docs/html/tgo/tgo56.htm>	General standard for tablets, pills and capsulesTakes effect on 1 January 1997 for applications lodged under section 23 of the Act from 1 January 1997. From 1 January 1997 till 31 December 1998, tablets, pills or capsules, other than those for which applications under section 23 have been lodged from 1 January 1997, can comply either with TGO 56 or TGO 35 or TGO 36, as appropriate. Revokes TGO 35 and TGO 36 from 1 January 1999.	16.10.96
57	Dental Materials Revokes and replaces TGO 43	16.4.97
59 <http://www.tga.gov.au/docs/html/tgo/tgo59.htm>	Polymer Urethral Catheters for General Medical Use Revokes and replaces TGO 38	16.4.97
60 <http://www.tga.gov.au/docs/html/tgo/tgo60.htm>	Revocation of Therapeutic Goods Order No. 14 - "General Standard for Metered-Dose Aerosols for Oral Inhalation Revokes TGO 14	18. 6.97

TGOs are available from the TGA Publications Office 1800 020 653

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NCCTG advertising guideline documents

"NCCTG permissible and prohibited advertising claims to the public for therapeutic goods"

Following its recent meeting, the Committee endorsed some minor changes to these Guidelines and agreed to issue a revised, fifth edition of the document (effective 9 May 1997). The changes predominantly relate to the examples of 'permissible' and 'prohibited' claims for sunscreen products and seek to ensure that the Guidelines are consistent with the latest Australian/ New Zealand Standard for Sunscreen Products - AS/NZS 2604:1997.

The Guidelines provide examples of 'permissible' and 'prohibited' claims in terms of the Therapeutic Goods Regulations, which adopt by reference, certain clauses of the Therapeutic Goods Advertising Code. The Guidelines do not constitute an alternate or additional set of requirements, but have been issued at the request of the industry to provide a national (Commonwealth/ State/Territory) interpretation and consensus of the existing requirements.

"NCCTG cosmetic claims guidelines"

The Committee also endorsed a new third edition of the Cosmetic Claims Guidelines <http://www.tga.gov.au/docs/html/cosclaim.htm> (effective 9 May 1997). This revised edition now includes a contact list of the various agencies involved with administering regulations, standards and guidelines concerning cosmetic products in Australia.

Labelling of injection products

The TGA was recently requested to provide comment to the Coroner on the statements of concentration of active ingredient on the labels of a single dose injection product implicated in the death of a patient. Both the ampoule label and the carton label displayed two separate statements: one referred to the amount of active ingredient in the stated volume of the injection in the ampoule, as required by Therapeutic Goods Order (TGO) No.48. The sponsor also included a second statement setting out the amount of active ingredient in one millilitre of the injection.

In this particular case, the person drawing up the injection read the statement referring to the amount of active ingredient in one millilitre of the injection and mistook that to represent the amount of active ingredient in the total volume of injection in the ampoule. Apparently this information was more prominently displayed by the sponsor of the product as it appeared next to the brand name. This incorrect reading of the label led to the administration of a much higher dose than intended.

The requirements for expression of the concentration of active ingredients in injections are specified in subclause 4(7) of TGO 48.

(TGO 48) - "General Requirements for Labels for Drug Products"

Paragraph 4(7)(b) currently requires that the quantity or proportion of active ingredient shall be expressed

"where the injection is intended for multidose use - as the quantity of the active ingredient in one millilitre of the injection or as the quantity in a suitable dose volume of the injection in the container."

and paragraph 4(7)(c) requires that the quantity or proportion of active ingredient shall be expressed -

"where the injection is usually intended for administration as a single dose, other than a large volume injection - as the quantity of active ingredient in the stated volume of the injection in the container."

However TGO 48 specifies minimum requirements for labelling of drug products and there is currently no legal impediment to a sponsor including both statements on the label of an injection product. In view of the safety concerns raised by this case, the TGA is proposing an amendment to the relevant parts of TGO 48, in consultation with industry, to prevent such incidents arising in future.

In the interim, sponsors of single dose and multidose injection products should, at the earliest opportunity, review both the container labels and the carton labels and, if necessary, amend the statements of concentration to ensure that only one type of statement appears as appropriate for the presentation of the product and that this is as specified in TGO 48.

DSEB has advised that this change may be self-assessable subject to the general conditions in Appendix 8 of the AGRD and the specific condition that the change is notified to TGA and copies of the amended and existing labels are supplied.