therapeutic goods committee · the tgc noted that the resolutions and minutes of the 33rd tgc...

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Therapeutic Goods Committee

34TH MEETING (13 MAY 2009)

INFORMATION FOR STAKEHOLDERS – REPORT ON MEETING

The 34th meeting of the Therapeutic Goods Committee (TGC) was held in Meeting Room 6, TGA Building, Narrabundah Lane, Symonston on 13 May 2009, between the hours of 10 am and 4 pm. Attendance: Chairperson: Associate Professor Loraine Holley Members: Mr David Clayton Dr Geoffrey Higgins Mr Alan Leslie Ms Anthea Steans Ms Diane Walsh Dr Meera Verma Apologies: Mr Michael Gepp Dr Karen Hapgood Professor Klaus Schindhelm Observers: Ms Kristy Roberts TGA officers: Ms Vivienne Christ Dr Kevin Eager (part-meeting) Ms Hongxia Jin (part-meeting) Dr Mayada Kayali (part-meeting) Ms Terry Lee (part-meeting) Dr Chong Loh (part-meeting) Dr Mark McDonald (part-meeting) Ms Michelle McLaughlin (part-meeting) Dr Michael Pass (part-meeting) Dr David Sinclair (part-meeting) Secretariat: Ms Margaret Joy Ms Lyn Lewis (Secretary)

Therapeutic Goods Committee – 34th Meeting (13 May 2009) Information for Stakeholders – Report on Meeting

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AGENDA AND COMMITTEE ADMINISTRATION OPENING OF MEETING The Chairperson opened the Meeting at 10 am and welcomed Members, observers and TGA staff. Apologies were noted. Members noted the Committee’s functions, composition and provisions relating to tenure of office as given in Regulation 34 of The Therapeutic Goods Regulations 1990, and submitted their completed Disclosure of Interest Declarations in accordance with Committee procedures. No conflicts of interest relevant to the agenda for the Meeting were declared by Members, although Ms Roberts (present as an observer) declared potential conflicts of interest for several agenda items. The Committee noted the agenda and agreed to vary the order of considerations to allow early discussion of several major issues. MINUTES OF THE 33RD MEETING OF THE TGC The TGC noted that the Resolutions and Minutes of the 33rd TGC Meeting, held on 15-16 October 2008, had been ratified out-of-session in accordance with usual processes, and that key resolutions from that Meeting and a report for stakeholders were subsequently posted on the TGA internet site. RESOLUTION:

The Therapeutic Goods Committee (TGC) NOTES that:

1. The Minutes of the 33rd Meeting of the TGC held on 15-16 October 2008 were

ratified out-of-session in December 2008 as a true and accurate record of that Meeting; and

2. The documents Summary of Key Resolutions and Information For Stakeholders –

Report On Meeting were published on the TGA website in October and December 2008 respectively,

in accordance with usual practice.

STATUS REPORT OF ACTION ARISING FROM THE 33RD TGC MEETING Members noted the report summarising the status of action arising from the 33rd TGC Meeting that had been held on 15-16 October 2008. A number of the actions requested by the Committee had resulted in items for consideration at the present Meeting. SUBCOMMITTEE REPORTS Subcommittee on Biologicals The TGC noted that a meeting of this Subcommittee would be needed in the near future, when the Subcommittee would be requested to review a revised draft of the proposed standard relating to the


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minimisation of infectious disease transmission via human tissue-based products, and to commence consideration of other related standards. Subcommittee on Packaging Requirements for Therapeutic Goods The TGC noted that, at its previous Meeting, a report had been provided on the establishment of this Subcommittee and its role in providing advice on matters relating to the packaging of therapeutic goods for human use. The particular tasks given to the Subcommittee were noted to be: • the development of a best practice guideline on non-reclosable forms of packaging, such as

blister or foil strip packaging, that would assist sponsors to improve the effectiveness of this style of packaging in reducing the potential for children to be accidentally poisoned by medicines packaged in this way;

• a review of the Code of Practice for the Tamper-Evident Packaging (TEP) of Therapeutic Goods (TEP Code of Practice) to determine whether it reflected current packaging technologies and stakeholder needs; and

• a review the relevance of Australian Standard AS 2216-1997 Packaging for Poisonous Substances to therapeutic goods and development of a draft Therapeutic Goods Order that would effect the transfer of container requirements for therapeutic goods for human use from the Standard for the Uniform Scheduling of Drugs and Poisons (SUSDP) to therapeutic goods legislation, as recommended by the National Competition Policy review of drugs, poisons and controlled substances legislation.

The TGC was advised now that this Subcommittee had met twice – initially on Friday 7 November 2008 and then on Friday 20 March 2009. The Ratified Report on Meeting 1 was accepted and it was noted that the Report of Meeting 2 was in preparation. The TGC was advised of progress by the Subcommittee against all three tasks, and it was observed that the proposed structure and content of the guideline on non-reclosable packaging was sound and technically robust. Noting that documents prepared by the Subcommittee would need to undergo stakeholder consultation prior to their referral to the TGC for finalisation, Members requested that they be provided with a copy of any consultation drafts out-of-session. RESOLUTION: The Therapeutic Goods Committee (TGC) NOTES: 1. That the first meeting of the TGC’s Subcommittee on Packaging Requirements for

Therapeutic Goods for Human Use was held on Friday 7 November 2008 and the second Meeting was held on Friday 20 March 2009;

2. The outline of the document A Guideline on Improving the Performance of Non-

Reclosable Packaging for Medicines as a Barrier to Children developed by the Subcommittee and that further work on this document is to be undertaken;

3. The Subcommittee has considered comments from stakeholders on the adequacy of the

technical content of the document Code of Practice for the Tamper-Evident Packaging of Therapeutic Goods (TEP Code of Practice) and will be preparing a revised document for stakeholder consultation; and


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4. That the Subcommittee will undertake further work to develop an effective order which

will transfer container requirements for therapeutic goods from the Standard for the Uniform Scheduling of Drugs and Poisons to the control of the Therapeutic Goods Administration.

SUMMARY AND STATUS OF THERAPEUTIC GOODS ORDERS The TGC received a report on the status of Therapeutic Goods Orders (TGOs) made under the Therapeutic Goods Act 1989 and it was noted that, since the October 2008 Meeting of the TGC, three new TGOs and one amendment to an existing TGO had been registered on the Federal Register of Therapeutic Goods. The new TGOs were: • Therapeutic Goods Order No. 78 General Requirements for Tablets and Capsules; • Therapeutic Goods Order No. 81 Standards for Blood and Blood Components; and • Therapeutic Goods Order No. 82 Standard for Tampons – Menstrual. The Order amending an existing TGO was Therapeutic Goods Order No. TGO 69C Amendment to Therapeutic Goods Order No. 69 General requirements for labels for medicines. MEDICINAL PRODUCTS STATUS REPORT ON ADOPTION OF MULTIPLE PHARMACOPOEIAS AS DEFAULT STANDARDS The TGC was informed of the status of the proposed regulatory reform to recognise the European Pharmacopoeia (Ph Eur) and the United States Pharmacopeia-National Formulary (USP-NF) in addition to the British Pharmacopoeia (BP), as equal default standards under the Therapeutic Goods Act 1989 (the Act). The TGC recalled that the issue of standards for medicines and other therapeutic goods that were not medical devices, in the absence of any specific Therapeutic Goods Order (TGO), had been considered by the Committee a number of times previously. For example, at its 32nd Meeting, following postponement of the proposed joint regulatory scheme with New Zealand, the TGC had recommended that Australia should move forward with changes to the Act that would give equal recognition to the BP, the Ph Eur and the USP-NF, as interpreted by the general notices in the applicable pharmacopoeia, with new editions of each pharmacopoeia becoming effective at the same time as the new edition became effective in its region of origin. The TGC was advised now that the Therapeutic Goods Amendment (Medical Devices and Other Measures) Bill 2008 was introduced to the Senate by Senator the Hon Jan McLucas on 3 December 2008 and the Bill had been passed by the Senate without amendment on 20 March 2009. It was, at the time of the Meeting, before the House of Representatives for consideration. The relevant content of the Bill and its Explanatory Memorandum were noted. The TGC noted that the TGA proposed to publish, on its internet site, a ‘Question and Answer’ document to provide information for stakeholders on the additional default standards and their application by the TGA. The TGC supported the publication of this information.


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RESOLUTION: The Therapeutic Goods Committee: 1. NOTES that amendments to the Therapeutic Goods Act 1989 to adopt the British

Pharmacopoeia, the European Pharmacopoeia and United States Pharmacopeia-National Formulary as default standards for medicines and other therapeutic goods that are not medical devices are under consideration by the Australian Parliament; and

2. SUPPORTS the publication of information for stakeholders on the implementation of

the additional default standards legislation. BRITISH PHARMACOPOEIA 2009 The TGC was informed that an order giving effect to the March 2009 (out-of-session) recommendation of the TGC, that British Pharmacopoeia 2009 (BP 2009) should be specified as the edition of that standard in force under the Therapeutic Goods Act 1989 (the Act) with effect 1 June 2009, had been signed by the Delegate of the Minister for Health and Ageing, and had been entered on the Federal Register of Legislative Instruments on 8 May 2009. The Committee recalled that, at its 33rd Meeting (October 2008), consultation with stakeholders on the adoption of BP 2009 as the default standard under the Act had been recommended, notwithstanding the planned recognition of multiple pharmacopoeias ‘as amended from time to time’ as equal standards under the Act. The Committee had considered it important to avoid a superseded edition of the BP remaining the default standard for an extended time if there was a delay in the passage by Parliament of the planned amendments to the Act to recognise multiple pharmacopoeias. Furthermore, it became apparent subsequently that although the amendments to the Act relating to the BP would provide for the automatic update of editions of the BP in the future, the revised definition of ‘British Pharmacopoeia’ would not give recognition to BP 2009 which had already been published. In order to seek a recommendation from the Committee, TGC Members were provided in March 2009 with a copy of the TGA website notice advising stakeholders of the intention of the Delegate of the Minister for Health and Ageing to make an order under the current Act to specify that BP 2009 would become the edition in force with effect 1 June 2009, together with stakeholder responses. The TGC noted that the resulting recommendation was as follows:

The Therapeutic Goods Committee RECOMMENDS that British Pharmacopoeia 2009 should be specified in an Order made under the definition of 'British Pharmacopoeia' at subsection 3(1) of the Therapeutic Goods Act 1989 as the edition of that standard in force with effect 1 June 2009.

RESOLUTION: The Therapeutic Goods Committee NOTES: 1. Its recommendation made out-of-session in March 2009 that the British Pharmacopoeia

2009 should be specified in an order made under the definition of ‘British Pharmacopoeia’ at subsection 3(1) of the Therapeutic Goods Act 1989 (the Act) as the edition of that standard in force with effect 1 June 2009; and


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2. That an order giving effect to this amendment to the edition of the British Pharmacopoeia in effect under the Act has been made by the Delegate of the Minister for Health and Ageing, and duly registered on the Federal Register of Legislative Instruments.

STANDARDS FOR ANTHROPOSOPHIC AND HOMOEOPATHIC MEDICINES A potential conflict of interest was declared by Ms Roberts. However as the purpose of the agenda item was only to provide the TGC with an update on progress in the matter, and Ms Roberts was present as an observer only, no conflict of interest was seen to exist. The TGC was provided with an update on the proposed changes to the Therapeutic Goods Act 1989 (the Act) relating to standards for homoeopathic and anthroposophic medicines. Members were advised that the Therapeutic Goods Amendment (2009 Measures No. 1) Bill 2009 had been introduced into the House of Representatives by the Hon Justine Elliot MP on Thursday 19 March 2009 and this Bill proposed changes to the Act relating to the regulation of homoeopathic and anthroposophic medicines. In particular, the proposed changes to the Act included the specification of standards for homoeopathic and anthroposophic medicines which, together with Good Manufacturing Practice (GMP) requirements, would perform a pivotal role in their regulation. It was noted that the proposed commencement date for the Act changes was 1 July 2011, and the Act changes would need to be supported by amendments to the Regulations and the relevant Therapeutic Goods Orders, such as Therapeutic Goods Order No. 69 General requirements for labels for medicines (TGO 69). The Committee was informed that the proposed regulations for homoeopathic and anthroposophic medicines, as presented to stakeholders in the September 2008 consultation paper Regulation of Homoeopathic and Anthroposophic Medicines in Australia were currently undergoing further development. This was in order to ensure that: • GMP requirements would be met; • appropriate standards were followed; • consumers would be given adequate information to make an informed decision with respect to

use of these products; • the TGA would not be seen to be endorsing unsubstantiated claims or assessing unreliable

evidence; and • products would be easily traceable to ensure rapid identification and correction of non-

compliance issues. Members were also asked to note that changes to TGO 69 were likely to be needed to overcome a perceived lack of understanding in the community of homoeopathic and anthroposophic medicines and their use in accordance with homoeopathic and anthroposophic principles. The TGC was advised that the TGA intended to conduct further stakeholder consultation to invite comment on revisions to the previously proposed regulatory framework. As this consultation would address a broad range of matters, the TGA proposed to seek stakeholder comments on associated labelling changes at the same time. Those comments would be provided to the TGC for consideration and a recommendation in relation to an amendment to TGO 69. Committee discussion centred on the reasons for reliance on GMP requirements, and compliance with standards, to regulate homoeopathic and anthroposophic medicines, and the nature of evidence


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supporting their efficacy and use. It was noted that GMP and compliance with standards were critical to the starting material being sound. RESOLUTION: The Therapeutic Goods Committee (TGC) NOTES that: 1. The Therapeutic Goods Amendment (2009 Measures No. 1) Bill 2009 introduced into the

House of Representatives on 19 March 2009 includes proposed changes to the Therapeutic Goods Act 1989 (the Act) relating to the regulation of homoeopathic and anthroposophic medicines;

2. These changes to the Act are planned to commence on 1 July 2011 and will be supported

by amendments to the Therapeutic Goods Regulations 1990 and various Orders; 3. The proposed Regulations for homoeopathic and anthroposophic medicines, as

presented to stakeholders in the Therapeutic Goods Administration (TGA) September 2008 consultation paper Regulation of Homoeopathic and Anthroposophic Medicines in Australia, are currently undergoing further development;

4. Changes to Therapeutic Goods Order No. 69 General Requirements for Labels for

Medicines relating to labelling requirements for homoeopathic and anthroposophic medicines are likely to be necessary; and

5. Appropriate stakeholder consultation regarding the proposed changes will be

undertaken by the TGA prior to their consideration by the TGC. MEDICINE LABELLING – LABELLING OF TRANSDERMAL PATCHES The TGC was requested to consider the labelling of transdermal patches and specifically whether there was justification for a new mandatory requirement for identifying information to be included on the actual patch. Members recalled that this issue had first been raised with the TGC at its 32nd Meeting (April 2008), when concerns raised by the Medicines Evaluation Committee (MEC) over the lack of identifying information on some transdermal patches had been brought to its attention. Those concerns had arisen from reports of patients entering hospital in a confused or unconscious state or being anaesthetised for surgery whilst wearing a transdermal patch that had no identifying markings. The difficulty in identifying such patches was compounded by there being no consolidated list of patches and descriptions generally available. At the TGC’s 33rd Meeting, the Committee received further information on the potential for confusion in the clinical setting in the identification of transdermal patches, consequential difficulties in determining appropriate treatments, and cases of serious adverse events or reduced therapeutic efficacy resulting from interactions between drugs administered and those in patches that patients were wearing. The Committee was advised also that there were approximately 100 transdermal patches registered or listed in Australia, the vast majority being prescription products, although there were a number of non-prescription products and a smaller number of patches delivering various complementary medicines. Labelling on the actual patches varied, ranging from full identification with brand name, active ingredient name and strength, through to a code number or nothing at all. The TGC discussed general issues surrounding the labelling of transdermal patches, including privacy considerations for patients wearing patches and the balance of this


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against safety considerations. It was noted also that many transdermal patches were manufactured overseas, and hence the consideration of whether a labelling requirement for transdermal patches was feasible needed to take that into account. At the present (34th) Meeting, the TGC noted information provided by the Office of Prescription Medicines (OPM), Office of Non-Prescription Medicines (ONPM) and the Office of Complementary Medicines (OCM), as well as the Adverse Drug Reactions Committee (ADRAC), concerning transdermal patches currently marketed in Australia including information on their labelling that had been gathered from sponsors. It was noted that no stakeholder consultation relating to the labelling of transdermal patches had as yet been undertaken. The Committee discussed the importance of transdermal patches being identifiable after application to a patient. It was agreed that it was essential for patient safety in emergency situations for health professionals to be able to identify any medications being delivered to a patient from a transdermal patch. Amendment of TGO 69 to require appropriate markings on transdermal patches was therefore supported. Members noted that many transdermal patches already included identifying markings of some kind, and that there appeared to be no reason why the remaining transdermal patches could not do so also. As the number of transdermal patches on the market had increased considerably in recent years, reliance on shape to identify a patch was not a valid alternative. Also, as the problem being addressed was the correct identification of patches by health professionals in emergency situations, the inclusion of descriptive information in product literature was not an adequate solution either. The TGC considered the form of markings that should be required on transdermal patches, discussing whether an identifying mark such as a product code would be sufficient, or whether the product name and/or active ingredient together with strength should be required. While standardisation of the labelling of transdermal patches would be desirable in the longer term and labelling with explicit information such as the product or active ingredient name was the preferred option, the TGC considered that, in the short term, the important issue was to ensure that all transdermal patches had unique markings of some kind. There were a number of labelling options that would achieve this goal, including unique codes, product names (with strength when more than one strength was marketed), and active ingredient names (with delivery rate). The TGC concluded that allowing options for the labelling of transdermal patches may mean that fewer patches would need to change their labelling in the short term and it was recommended therefore that stakeholders should be consulted on a range of labelling options. As the feasibility of using unique codes to identify transdermal patches would depend on both the uniqueness of the code itself, and the existence of a suitable repository of information, the TGA was requested to explore whether the publishers of MIMS would be prepared to include in that publication diagrams or photographs of transdermal patches that would assist in their identification. The TGC noted that any transition period would need to take into account that most transdermal patches were manufactured overseas for world-wide supply, and much of the backing material was pre-printed. However as this was a safety related proposal, a two year transition period was considered to be reasonable for those patches which currently had inadequate markings.


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RESOLUTION: The Therapeutic Goods Committee RECOMMENDS that: 1. For safety reasons, transdermal patches should have markings which will make each

patch uniquely identifiable after application to a patient; 2. The Therapeutic Goods Administration (TGA) consult with stakeholders on the

proposal that Therapeutic Goods Order No. 69 General requirements for labels for medicines be amended to require that transdermal patches be labelled with: (a) a code or other markings that are unique to the product and its strength; or (b) the product name, and where there is more than one strength of that product, an

indicator of the strength; or (c) the name of the active ingredient together with a statement of the quantity of

active ingredient released in a stated time. 3. A transition period of two years be allowed for those transdermal patches which

currently have inadequate or no identification markings for compliance with this requirement; and

4. The TGA inform the publishers of the reference document MIMS of the intent to

require markings on transdermal patches and request that the publication include photographs or diagrams of transdermal patches to assist in their identification.

MEDICINE LABELLING – INCLUSION OF BAR CODES ON MEDICINE LABELS Ms Roberts declared a potential conflict of interest in relation to this item. As Ms Roberts was present at the Meeting as an observer only, no conflict of interest was seen to exist. The TGC recalled that, during consideration of matters relating to the labelling of medicines at its 33rd Meeting, the Committee agreed to give high priority to the consideration of bar coding requirements for medicines. This was in response to a submission received by the Committee which proposed that bar coding of medicines should become mandatory, on the basis that this would have potential to reduce dispensing errors and thereby improve patient safety. The TGC was advised that one of the barriers to implementing bar code checking within medication management pathways was non-uniform inclusion of barcodes on pharmaceutical packaging. Members were advised now that, following the 33rd TGC Meeting, the TGA requested the assistance of a number of stakeholders in providing background material on bar coding that would help inform further discussion of this matter by the TGC. The specific matters on which information was sought from the different sectors of the medicines industry included: • current levels of bar coding within the specific medicines sector; • reasons why bar coding might not be used and any particular difficulties experienced in

introducing bar coding; • the extent of use of different bar coding systems [e.g. Health Industry Bar Code (HIBC)

versus Global Trade Item Numbers (GTIN)]; • the product details that were currently encoded in the bar code; • current uses of bar coding and future potential uses; and


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• whether the sector anticipated moving to comprehensive data carriers such as GS1-128 bar codes, the GS1 DataBar or 2D DataMatrix systems in the future.

Similar correspondence to pharmacy organisations was aimed at eliciting information on the ability of pharmacies to scan bar codes, scanner technologies currently in use, the use of bar code information in the dispensing process, the capacity of dispensing programs to interpret bar codes, and estimates of the proportion of medicines which were currently bar coded. Advice was sought also from the Australian Commission on Safety and Quality in Health Care on the information that a bar code should capture in order to reduce medication errors associated with the selection of an incorrect product. The TGC noted that, in response to the requests from the TGA for information on bar coding, a number of submissions had been received, and these submissions revealed that: • A large proportion of medicines in Australia were already bar coded, although a small number

remained without; • The GS1 System in which the GTIN was used to identify different product variants and

package configurations was most commonly used for bar coding medicines; • The GS1 suite of standards had been selected by the National E-Health Transition Authority

Ltd (NEHTA) as the standardised identifier for medicines and other healthcare products included in the National Product Catalogue;

• The GS1 System would lend itself to future developments in the coding of medicines and had formats that would allow inclusion of variable data elements such as batch numbers, expiry dates and serial numbers;

• While there were many commercial reasons for bar coding, at present and in the immediate future, the principal benefit achievable from bar coding relevant to patient safety would be a potential reduction in dispensing errors;

• The data elements to be encoded to realise that benefit were sponsor name, product name, strength, dose form and pack size;

• A mandatory requirement for bar coding which required use of the GS1 system would give certainty to industry in implementing bar coding and in considering future developments; and

• It also would be consistent with international regulatory requirements for medicines, with the GS1 bar codes being applied internationally.

The Committee discussed the potential impact that a mandatory requirement for bar coding would have on the different types of medicines. It was anticipated that the impact on prescription and non-prescription medicines would be minimal as the majority of these were already bar coded. However the impact on complementary medicines may be greater, particularly for those medicines sold other than through commercial outlets. This impact would become clearer through stakeholder consultation. The TGC also discussed the information that would be necessary in a bar code, and its location on the pack, for it to be useful in assuring correct product selection in the dispensing process. The critical information was noted to be product name, strength, pack size and dose form. Although the inclusion of batch numbers and expiry dates would be useful, they were not critical to the prevention of errors associated with incorrect product selection. Furthermore batch numbers and expiry dates were variable data elements and, as such, bar codes containing that information could only be applied on the production line. Implementation of this would involve additional expenditure on capital equipment. The primary pack was considered to be the key location for the bar code.


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Noting that the preferred form of the data carrier within the GS1 System could well change over time with technological innovation, and that some forms of data carrier were more suited to some package types than others, the TGC agreed that any requirement for mandatory bar coding of medicines should not specify the form of data carrier to be used, other than that it encode the GTIN as allocated under the GS1 system. As no stakeholder consultation had been undertaken as yet, the TGC then recommended that this occur. RESOLUTION: The Therapeutic Goods Committee RECOMMENDS that: 1. Stakeholders should be consulted on the proposal that Therapeutic Goods Order No. 69

General requirements for labels for medicines (TGO 69) should be amended to require that the labels of medicines include a machine readable code such as a bar code; and

2. The proposal to be consulted on should include the following elements:

(a) The machine readable code must encode the Global Trade Item Number (GTIN) for the medicine as allocated under the GS1 System;

(b) The machine readable code must identify different product variants and, as a minimum, differentiate between different strengths, pack sizes and dose forms;

(c) Inclusion of additional information such as batch and expiry details should not be prevented;

(d) The format of the machine readable code should not be specified, but sponsors of medicines be permitted to select the format best suited to their particular product and the regulatory environment;

(e) The machine readable code must appear on the primary pack of the medicine; and (f) A transition period of three years should be permitted for compliance.

MEDICINE LABELLING – UNITS OF POTENCY The TGC was requested to consider a proposal for amendment to Therapeutic Goods Order No. 69 General requirements for labels for medicines (TGO 69) to require that, where potency units were used on labels as a measure of activity, the potency must be expressed in terms of International Units (IU) as established by the World Health Organization. Use of United States Pharmacopeia (USP) units of measurement on labels therefore would not be acceptable. It was recalled that this issue had arisen from discussion of the implications of multiple default pharmacopoeias at the Committee’s previous Meeting, and the specific consideration given to labelling implications arising from adoption of the United States Pharmacopeia-National Formulary (USP-NF) as a default standard. One of the issues noted at that time was that USP-NF generally measured potency of biological products against a standardised USP Reference Standard and expressed this in USP Units, not metric or IU. In many cases there was no possible cross-comparison between USP Units and IU. Furthermore, USP-NF monographs for a number of products other than biological products also included assays that were measured against a standardised USP Reference Standard and were expressed in USP Units which differed from IU or metric units. The Committee was concerned that allowing labelling in terms of USP units could result in confusion among health professionals and consumers over product strength and adverse outcomes in clinical practice, as the same active ingredient could be labelled in different units (USP or IU / metric) depending on the manufacturer. Similar concerns applied to dual labelling in USP


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Units and IU / metric units. As TGO 69 only specified that IU were to be used for a limited number of product types, it was suggested that TGO 69 may need to be amended to more generally require the expression of quantities in metric or IU and/or to prohibit the use of USP Units in labelling. At the present Meeting, the TGC noted provisions of TGO 69 that were relevant to the expression of potency on labels and the proposal under consideration. An amendment to TGO 69 that would have the desired effect was identified. The Committee noted that the proposed amendment to TGO 69 would only be relevant to those products which used potency units to express the content of active ingredient, and would not affect the labelling of those which used metric units. Noting that no consultation on this matter had occurred as yet, the TGC recommended that the TGA consult with stakeholders on the proposed amendment to TGO 69. RESOLUTION: The Therapeutic Goods Committee: 1. SUPPORTS amendment of Therapeutic Goods Order No. 69 General requirements for

labels for medicines (TGO 69) to require that, where potency units are used on labels as a measure of activity, the potency must be expressed in terms of International Units (IU) as established by the World Health Organization; and

2. RECOMMENDS that the Therapeutic Goods Administration consult with stakeholders

on an amendment to TGO 69 that would have this effect. MEDICINE LABELLING - DECLARATION OF EXCIPIENTS Ms Roberts declared a potential conflict of interest in relation to this item. As Ms Roberts was present at the Meeting as an observer only, no conflict of interest was seen to exist. The TGC recalled that at its 33rd Meeting, held in October 2008, the Committee had identified the list of excipients included in the First Schedule to Therapeutic Goods Order No. 69 General requirements for labels for medicines (TGO 69) as a matter for further review. This was a result of the Committee’s consideration of stakeholder comments on draft Therapeutic Goods Order No. 79 General Requirements for the Labelling of Medicines [TGO 79 (draft)] which underwent consultation in early 2008 and specifically the proposal to expand the list of excipients that must be declared on labels. Although the TGC had recommended at that time that TGO 79 not be implemented, the Committee had considered that review of the excipient list was clearly safety related and necessary amendments should be progressed through revision of the First Schedule to TGO 69. It was noted that TGO 79 (draft) had proposed that the following additional excipients, if present in a medicine, be declared on labels: crustacea and crustacean products, egg and egg products, fish and fish products, milk and milk products, potassium salts, sesame seed and sesame seed products, soya beans and soya bean products, and tree nuts and tree nut products. A number of other amendments to the First Schedule were also proposed, such as the addition of requirements for statements on the potential for severe allergic reaction to pollen, propolis and royal jelly as well as some editorial changes.


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The proposed amendments to the First Schedule had been based on: • The potential for certain excipients to cause severe, and possibly fatal, adverse reactions in

sensitive individuals; • The desirability for consistency with the requirements of the Australia New Zealand Food

Standards Code (FSC) for the declaration of certain substances when present in food and the associated mandatory advisory statements; and

• The potential for potassium salts (as well as sodium salts) to present a safety issue for a small group of patients, and health professionals often needing to advise patients on the potassium content of medicines and daily intake.

The TGC now noted general comments relating to excipient declarations made by stakeholders in the 2008 consultation on TGO 79 (draft). In general, consumer organisations had been supportive of the intention to expand the list of excipients that required label declaration, on the basis of consistency with food labelling requirements and improving safety for those who may be allergic to particular ingredients, and the contribution of the label to the quality use of medicines. In contrast, industry stakeholders had tended to pose questions relating to specific excipients and the application of the proposed requirements. The TGC reviewed a summary of the changes proposed to First Schedule and the comments relating to individual excipients made by stakeholders. Matters discussed included the following: • Whether the declaration for medicines containing crustacea or crustacean products could refer

to shellfish, shellfish products or ingredients derived from shellfish, rather than crustacea - it was noted that the terms crustacea and crustacean products were required by the FSC on foods containing these ingredients and consumers were therefore familiar with those terms. The difference between shellfish and crustacea was noted, and the Committee considered that the broader term “shellfish” may not clearly signal the presence of ingredients derived from crustacea. This could be misleading for consumers. The Committee questioned whether shellfish were referred to in any other label statements required on medicines, for example through the document Required Advisory Statements for Medicine Labels (RASML) or coded warnings for listed products. If not, consistency with the FSC appeared desirable.

• Whether the declaration for medicines containing fish or fish products could refer to seafood,

seafood products or ingredients derived from seafood rather than fish - it was noted that the terms fish and fish products were required by the FSC on foods containing these ingredients and consumers were therefore familiar with seeing those terms on labels. Seafood had a much broader meaning than fish and may not clearly signal that the ingredient in the medicine was derived from fish, resulting in uncertainty for consumers who may be allergic to fish but not other seafood. Again the Committee questioned whether seafood was referred to in any other label statements required on medicines, for example through the RASML or coded warnings for listed products. If not, consistency with the FSC again appeared desirable.

• Ingredients that would be covered by an entry for milk and milk products – the TGC noted

that this entry would apply to ingredients such as casein, casein variants and whey as well as those that had been listed in the draft TGO and were more obviously derived from milk. It was agreed that including these additional examples in the First Schedule would help clarify the proposed requirement.

• The addition, to the First Schedule entries for pollen, propolis and royal jelly, of requirements

for medicines containing any of these as excipients to have warning statements regarding the potential for severe allergic reactions – the TGC considered that the appropriate reference location for warning statements of this nature would be RASML. The inclusion on labels of


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warning statements specified in RASML was already required by TGO 69, and RASML already required similar warnings on the labels of listed medicines containing propolis or royal jelly. The TGC considered that the proposed warning statements were equally relevant to listed and registered medicines, irrespective of whether the ingredients were included as actives or excipients.

• The proposed inclusion of potassium salts and whether declaration should only be required

above a specified threshold level – the TGC considered comparative requirements in the European Union, noting that the European Commission document Guidelines. Medicinal products for human use. Safety, environment and information. Excipients in the label and package leaflet of medicinal products for human use, dated July 2003, required declaration of potassium in products for oral administration when the potassium content was above 1 millimole per dose and that compliance with these Guidelines was mandatory in Europe under Article 65 of Directive 2001/83/EC of the European Parliament. In view of this and stakeholder comments advising that small amounts of potassium were often present incidentally in medicines, the TGC recommended that there should be a threshold for the declaration of potassium salts when present in medicines for oral administration and this threshold should be consistent with that applied in Europe i.e. 1 mmol (39 mg) of elemental potassium per dose. To aid consumer understanding, the label however should express the potassium content in terms of the milligram amount of elemental potassium per dose.

• The proposed inclusion of sesame seeds and sesame seed products for all routes of

administration, and comments from one stakeholder that such ingredients had a long history of safe use in cosmetic products without there being a need for any special warning statements – the TGC noted advice that sesame seed products may be used in therapeutic goods in higher concentrations than used in cosmetic products, and that application of the label declaration to medicines for any route of administration would be consistent with the European requirement for declaration of sesame oil which was based on its ability to cause severe allergic reactions, albeit rarely.

• The proposed inclusion of soya beans and soya bean products and the comment from one

stakeholder that the proposed declaration would affect all products containing natural vitamin E, which was extracted from vegetable oils including soya oil. The stakeholder drew attention to European Commission Directive 2007/68/EC of 27 November 2007 amending requirements for declaration of soybeans when present in foods to exclude: fully refined soybean oil and fat; natural mixed tocopherols, natural D-alpha tocopherol, natural alpha tocopherol acetate, natural D-alpha tocopherol succinate from soybean sources; vegetable oils derived phytosterols and phytosterol esters from soybean sources; and plant stanol ester produced from vegetable oil sterols from soybean sources. While not opposed to a similar exemption, the TGC noted advice that the current listing system for medicines did not require the source of vitamin E to be stated and manufacturing information rarely declared the origin of vitamin E. Therefore whether the oil had been fully refined for example may be difficult to determine, and correct application of the proposed label requirement may be difficult to verify. Nevertheless, the TGC considered that clarification of the proposed entry for soya beans and soya bean products was warranted, and that the amended entry may assist in making sponsors more aware of the need to be better informed regarding the source and quality of their ingredients.

The TGC noted that many of the other matters raised by stakeholders related to requirements as they currently existed in the First Schedule to TGO 69, for example how the requirement for label declaration should be interpreted when two or more declarations may be relevant to the one ingredient. As these questions related to application of existing requirements by the regulator, the


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TGC considered that such questions would be more appropriately handled on a case by case basis by the product regulator. In relation to other minor or editorial changes to the First Schedule that were proposed in TGO 79 (draft), the TGC agreed that these changes were not warranted at this time. Noting that proposals relating to the declaration of additional excipients on medicine labels had undergone stakeholder consultation on a number of occasions since 2005, the TGC considered that further consultation on the specifics of the proposed changes to the First Schedule appeared unnecessary. It was recommended therefore that stakeholders be advised of the proposed amendments, as agreed at this Meeting, and consulted on a proposed transition period of two years for the changes to labels to be implemented. A two year transition period was considered to be appropriate for label changes that were clearly safety related. RESOLUTION: The Therapeutic Goods Committee: 1. NOTES that proposals relating to the declaration of additional excipients on medicine

labels have undergone stakeholder consultation on a number of occasions since 2005; 2. NOTES that providing information on excipients in medicines that have potential to

cause allergic or other severe adverse effects in sensitive individuals is important for consumer safety;

3. RECOMMENDS that the First Schedule to Therapeutic Goods Order No. 69 General

requirements for labels for medicines should be amended to: (a) Include new entries for:

• crustacean and crustacean products, to be applicable to products for any route of administration;

• egg and egg products, to be applicable to products for any route of administration;

• fish and fish products, to be applicable to products for any route of administration;

• milk and milk products, applicable to products for any route of administration; • potassium salts above the threshold of 1 mmol (39 mg) elemental potassium per

dose, to be applicable to products for oral administration and declared on the label in terms of the milligram amount of elemental potassium per dose;

• sesame seed and sesame seed products, to be applicable to products for any route of administration;

• soya beans & soya bean products, to be applicable to products for any route of administration but excluding

o fully refined soybean oil and fat; o natural mixed tocopherols, natural D-alpha tocopherol, natural

alpha tocopherol acetate, and natural D-alpha tocopherol succinate from soybean sources;

o vegetable oils derived phytosterols and phytosterol esters from soybean sources; and

o plant stanol ester produced from vegetable oil sterols from soybean sources; and

• tree nuts & tree nut products, to be applicable to products for any route of administration.


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(b) Clarify that the existing entry for peanuts and peanut products includes Arachis hypogaea and Arachis (peanut) oil; and

(c) Amend the existing entry for sodium salts to require that the statement of sodium content refer to the milligram amount of elemental sodium per dose.

4. RECOMMENDS that stakeholders be advised of the proposed amendments and

consulted on a proposed transition period of two years for the changes to labels to be implemented; and

5. RECOMMENDS that the proposed warning statements relating to the potential for bee

pollen, propolis and royal jelly to cause severe allergic reactions be included in the document Required Advisory Statements for Medicine Labels and that the required warning statements apply equally to listed and registered medicines irrespective of whether the substance is present as active ingredient or an excipient.

MEDICINE LABELLING - PROMINENCE OF ACTIVE INGREDIENT NAMES Ms Roberts declared a potential conflict of interest in relation to this item. As Ms Roberts was present at the Meeting as an observer only, no conflict of interest was seen to exist. The TGC recalled that, at its previous Meeting, the prominence of active ingredient names on medicine labels had been identified as a matter for further consideration by the Committee. This had resulted from the TGC’s consideration of stakeholder comments on the draft Order on medicine labelling (TGO 79 draft) which underwent consultation in early 2008 and recognition that the display of active ingredient names on the labels of medicines impacted on the quality use of medicines (QUM) and consumer safety. Requirements relating to active ingredient names currently applied through Therapeutic Goods Order No. 69 General requirements for labels for medicines (TGO 69) were noted. Under TGO 69, the minimum letter height was 1.5 millimetres, measured by the height of upper case (capital) letters or lower case letters having an ascender or descender. Qualifications applying to the display of active ingredient names existed, including conditions for the shift of active ingredient names from the main label to a side or back panel. The TGC also noted the changes to the display of active ingredient names that had been proposed through TGO 79 (draft), specifically proposed increases in minimum font size for the display of active ingredient names on registered medicines (from 1.5 mm to 2.0 mm), associated positional requirements and proposed changes to the conditions for the shift of active ingredient names from the main label to a side or back panel. The background to the proposals relating to the display of active ingredient names that had been included in TGO 79 (draft) was reviewed, including the considerations of the Joint Expert Committee on Trans Tasman Labelling Requirements for Medicines in developing a draft labelling order for application under the proposed, but now postponed, joint Australia and New Zealand regulatory scheme for therapeutic goods. As with earlier consultations on the draft joint agency labelling Order, a number of stakeholders responding to the consultation on TGO 79 (draft) had commented on the proposals relating to the display of active ingredient names.


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In general, comments from industry stakeholders had related to the impact across medicines, transition timeframes and practicality, particularly for small containers. Some industry stakeholders questioned whether there was evidence to show that the proposed increase of 0.5 mm in minimum font size for display of active ingredient names on registered medicines would have any benefit for consumers. Consumer organisations, health professional organisations and government agencies had focused on the role of medicine labels in achieving QUM, the need for greater emphasis to be given to generic names, and were supportive of the intention to improve the prominence of active ingredient names on medicine labels. These stakeholders raised a number of issues relating to label legibility and presentation, and the current performance of medicine labels. A number of these stakeholders considered that the changes to the presentation of active ingredient names proposed through TGO 79 (draft) were insufficient to deliver the degree of improvement to medicine labels that was necessary. The TGC was advised that, following its previous Meeting, the TGA had sought further advice from the Australian Commission on Safety and Quality in Healthcare (ACSQHC) on its recommendation that, for prescription medicines at least, product name and active ingredient name(s) be required to be equally prominent on the label. In particular, the ACSQHC was asked for suggestions on how prominence could be defined unambiguously and objectively. The response received from the ACSQHC was noted by the TGC. The ACSQHC advised that the intent of giving equal prominence to product and active ingredient names on prescription medicines labels was to avoid consumer confusion with multiple brands of generic products and therefore reduce the risk of medication errors, such as double dosing with two brands of the same medicine, and associated adverse medicines events. The ACSQHC also considered that equal prominence would reduce the risk of selection errors by health professionals in the dispensing, drug preparation and administering processes in pharmacies, hospitals and residential care facilities, and it also would assist and promote prescribing by generic drug name. Attention was drawn to the National Prescribing Service (NPS) fact sheet Know the active ingredient, and also to a detailed submission from a consumer organisation, both of which had been included as attachments to the ACSQHC response. The submission from the consumer organisation strongly supported greater prominence being given to the active ingredient name(s) on prescription medicine labels, and stated that this would be “an important measure to help consumers avoid adverse medicines events” and was “consistent with the Government’s current emphasis on assisting consumers to self manage their health”. The organisation described a number of situations where lack of knowledge of the name of the active ingredient has had the potential to cause adverse medicines events. In relation to the presentation of active ingredient names on OTC medicines and complementary medicines, the ACSQHC stated that the reasons behind the request for equal prominence of active ingredient names for prescription medicines applied equally to non-prescription medicines such as over-the-counter (OTC) medicines and complementary medicines. With regard to how equal prominence might be defined, the ACSQHC advised that the available literature suggested that size and clarity of font and text were major determinants of readability with large size font, use of sans serif type faces and bold, or semi-bold, type and the use of both upper and lower case letters recommended for improving clarity. Equal size of text was an alternative when equal font size was not a practical option that could be applied universally. Organising text in the same direction and using white space to emphasize important information were also factors that influenced the readability of labels. The ACSQHC acknowledged that there were constraints on the


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font size that could be used on medicine labels, particularly for small containers. It was suggested however that this could be overcome by the use of innovative pack design. The TGC noted the different viewpoints expressed in the consultation responses and the later correspondence from the ACSQHC, and discussed the options for moving forward to improve the prominence of active ingredient names on medicine labels. It was agreed that the current requirement of TGO 69 of a minimum font size of 1.5 mm was not satisfactory, and that the increase to 2.0 mm proposed in TGO 79 (draft) had been a compromise solution that neither satisfied stakeholders nor would provide the level of improvement needed. The Committee then sought to find an alternative proposal, considering in turn various options. Although other factors were important also, font size was considered to be the most important determinant of prominence that could be specified in an Order. The TGC agreed that it would be appropriate for the requirement to be a relational one, with the font size required on the label for the active ingredient name(s) to be related in a specified way to the font size used for the product name. The following options were discussed: • Active ingredient name(s) to have greater prominence than the product name; • Active ingredient name(s) to have equal prominence to the product name; and • Active ingredient name(s) to be in a font size at least half that used for the product name. The TGC considered that the first option, that of requiring active ingredient names to have greater prominence than the product name, was not a practical option that could be mandated, notwithstanding that this had been put forward by the CHF as meeting consumer needs. With regard to the possibility of requiring active ingredient names to have equal prominence to the product name, the Committee noted that this had been supported by the ACSQHC. A Member argued strongly in favour of this option, advising that the recommendation of the Committee should be based on the needs of users of medicines (consumers and health professionals) and the emphasis should be given to safety. Other Members observed that although many of the stakeholders responding to the consultation on TGO 79 (draft) had recommended that the prominence of active ingredient names on labels should be improved, few had suggested that equal font size was necessary. The Committee noted that there were other ways by which prominence could be increased, including use of those features suggested by the ACSQHC. Juxtaposition of the active ingredient name(s) with the product name was suggested as being important also. The TGC next discussed the third option of requiring active ingredient name(s) to be in a font size at least half that used for the product name. Under this option, most active ingredient names may need to increase in font size. Whether this would sufficiently increase prominence and satisfy consumer and health professional needs was considered. Members noted that a similar proposal had been included in the first draft of the joint agency labelling Order that had been consulted on previously, and that it had been opposed by industry stakeholders at that time. However a similar legal requirement existed in the United States for prescription medicines and compliance was achievable there. It was suggested that the key issue for industry in Australia may have been the proposed transition time rather than the proposal itself. As factors other than font size could also be used to improve prominence, the TGC discussed whether any other requirements should be applied in conjunction with an increase in font size. Standardisation of position and/or the use of a box to contain the active ingredient names were put


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forward. It was suggested that a standardised position, such as a top corner of the label, would make it easier for consumers to find active ingredient names and use of a box could facilitate use of a smaller font size while at the same time highlighting the active ingredient names. Noting that containers and primary packs for medicines were of many different forms, shapes and sizes, the Committee concluded that standardisation of the position for display of active ingredient names may not be feasible. However, requiring active ingredient names to appear in a particular relationship to the product name, such as immediately below it and with no intervening text, would have similar effect. This was because the eye would be automatically drawn to the product name and the names of the active ingredients consistently would be immediately below. Although the proposal to require active ingredient names to be in a font size at least half that used for the product name was not prescriptive in specifying any particular font size, the TGC considered that it was necessary to specify an absolute minimum letter height that could be used. This would be important on those packs where, for some reason, the size of the product name appeared in a small font and a letter height half that size may be unreadable. The absolute minimum letter height was recommended to be 2 mm. Summing up the discussion so far, the Chairperson noted that the recommendation the Committee was forming was that TGO 69 should be amended to require that active ingredient names appear in a font size at least half that used for the product name but in any case in a letter size no smaller than 2 mm, and that the active ingredient name(s) should be positioned immediately below the product name and be left aligned with the first letter of the product name. Further discussion followed on: • Whether active ingredient names should be required to be displayed in this manner on

multiple panels and/or every panel on which the product name appeared, and on every occasion that the product name was used – while acknowledging that there may be benefit from this, the TGC noted that proposals consulted on to date, and stakeholder responses, had only related to the display of active ingredient names on the main label. Furthermore TGO 69 currently did not specify that active ingredient names needed to be displayed anywhere other than on the main label and therefore extension of the recommended requirement in this way would be a significant change. The TGC concluded that, if pursued, the proposal would require further broad stakeholder consultation.

• The length of transition period necessary for sponsors to make the required label changes – it

was noted that industry stakeholders had argued for a transition period ranging between three and five years but it was considered that few, if any, sponsors would be holding stock levels that would not be exhausted within three years. As the proposed changes were safety related, the TGC concluded that a transition period no longer than three years would be appropriate.

• Which medicines the recommended changes to requirements relating to the display of active

ingredient names should be applied to – it was noted that proposals previously consulted on had differed depending on the type of medicine, differentiating between prescription medicines, other registered (non-prescription and complementary) medicines, and listed medicines. The changes now recommended were clearly applicable to prescription medicines, and the Committee considered they were equally relevant to registered non-prescription medicines, including registered complementary medicines, as it was just as important for safety reasons for consumers and health professionals to be aware of the ingredients in these medicines. In relation to listed medicines, the Committee noted that no significant safety concerns relating to the display of active ingredient names on the labels had been brought to


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its attention. Also, listed medicines often contained multiple ingredients and/or ingredients with lengthy names such as those for botanical ingredients. For these reasons, the TGC proposed no change to current requirements for the display of active ingredient names on listed medicines at this time.

• What requirements should apply to the display of active ingredient names on registered

medicines when the names were shifted to a side or rear label because of the number of active ingredients in the medicine – the TGC noted that the need to show the names of multiple active ingredients made it impractical to apply the same font size requirements as recommended for the main label. Nevertheless an increase in font size was warranted. It was therefore recommended that, for all registered medicines, where the names of active ingredients were shifted to a side or rear label as permitted by TGO 69, then the minimum letter height should be 2 mm.

Noting that extensive consultation on proposals to increase the prominence of active ingredient names had been undertaken on several occasions, and that further consultation would be unlikely to draw different comments, the TGC then resolved: RESOLUTION: The Therapeutic Goods Committee: 1. NOTES that proposals for an increase in the font size used for active ingredient names

on medicine labels have undergone stakeholder consultation on a number of occasions since 2005;

2. AGREES that clear display on medicine labels of active ingredient names is important

in ensuring the quality use of medicines and for consumer safety; 3. RECOMMENDS that Therapeutic Goods Order No. 69 General requirements for labels

for medicines (TGO 69) be amended to require that: (a) For prescription medicines, the name(s) of active ingredient(s) appearing on the

main label must be: • written in a font size at least half that used for the product name but, in any

case, in a letter height that is not less than 2 millimetres; and • positioned immediately beneath, and left aligned with, the product name;

(b) For registered non-prescription medicines, including registered complementary medicines, the name(s) of active ingredient(s) appearing on the main label must be: • written in a font size at least half that used for the product name but, in any

case, in a letter height that is not less than 2 millimetres; and • positioned immediately beneath, and left aligned with, the product name;

(c) For prescription medicines and registered non-prescription medicines, including registered complementary medicines, where the names of active ingredients are shifted to a side, or rear, panel or label, as permitted by subclauses 3(3)(a) and 3(3)(b) of TGO 69, then the names of the active ingredients must be displayed in a letter height that is not less than 2 millimetres.

4. NOTES that no significant safety concerns relating to the display of active ingredient

names on the labels of listed medicines have been brought to the Committee’s attention, and therefore no change to current requirements for the display of active ingredient names on those medicines is proposed at this time.


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5. RECOMMENDS a transition period of three years for the changes to labels of prescription medicines and registered non-prescription, including registered complementary medicines, to be implemented.

6. RECOMMENDS that stakeholders be advised of the proposed amendments. UPDATE ON HEPARIN STANDARDS – DEVELOPMENT OF A NEW THERAPEUTIC GOODS ORDER At the TGC’s 33rd Meeting, held in October 2008, the Committee had provided advice on the proposal that a Therapeutic Goods Order (TGO) be developed to specify the standard for therapeutic goods containing heparin. The reason for this proposed action was the identification of over-sulphated chondroitin sulphate (OSCS) as a contaminant in a range of heparin products, initially in the USA, and the link between heparin products in which OSCS was present and an observed increase of ‘allergic/ anaphylactoid’ type adverse events associated with the use of heparin for injection. A number of recalls resulted, both in the USA and elsewhere, including Australia where the contaminant OSCS had been identified in a number of heparin products also. The TGA had taken the precaution of making it a condition of listing, registration or inclusion in the Australian Register of Therapeutic Goods (ARTG) for therapeutic goods that contained heparin to comply with monographs of the United States Pharmacopeia-National Formulary (USP-NF) for heparin which had been updated to include tests for OSCS. However it was not possible to apply this condition to therapeutic goods that were exempt from ARTG entry - this included many In Vitro Diagnostic Devices (IVDs) which contained heparin. It was for this reason that the TGA had proposed that, in the longer term, a TGO was the appropriate mechanism to ensure the ongoing purity of heparin used in therapeutic goods supplied in Australia. A preliminary draft of a TGO had been provided to the TGC at its previous Meeting and this TGO had stated that all heparin used in therapeutic goods should be tested in accordance with the requirements given in the monograph for heparin sodium published in the United States Pharmacopeia Revision Bulletin dated 18 June 2008 for the detection of the contaminant OSCS. Two tests were specified: a Nuclear Magnetic Resonance (NMR) spectrometry method, and a Capillary Electrophoresis (CE) method. It was proposed that OSCS should be ‘not detectable’ in samples tested according to either method, and for the purposes of the proposed TGO, not detectable was to be defined by reference to the limit of detection specified in the ICH Guideline Q2B: Validation of Analytical Procedures: Methodology. The TGC was now advised of subsequent developments in the monographs for heparin sodium and heparin calcium in both the European Pharmacopoeia (Ph Eur) and the USP-NF. These developments would influence the requirements proposed for inclusion in the TGO. The Committee was advised that, since the last TGC Meeting, the monographs of the Ph Eur for heparin sodium and heparin calcium had been updated to include the additional requirements for compliance with NMR spectrometry and CE, and the European Directorate for the Quality of Medicines and HealthCare (EDQM) had published detailed procedures for both the NMR and CE methods for detection of OSCS, applying lower limits of detection (LOD) than previously – 0.1% for NMR and 0.5% for CE.


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At that time, Ph Eur / EDQM requirements and methods were superior to those of the USP-NF and the TGA had therefore considered that these were appropriate for adoption in Australia. The TGO had been re-drafted accordingly. The TGA was now aware of further changes proposed for the USP-NF heparin monographs which were intended to again strengthen requirements. These changes were presented in Pharmacopeial Forum 35(2) March-April 2009 as proposed Interim Revision Announcements and were open for public review and comment. The proposed changes to the USP-NF heparin monographs had been discussed in an open microphone web meeting in early May and a number of specific changes were proposed to become official on 1 August 2009. These changes included an expanded 1H Nuclear Magnetic Resonance (NMR) method with specified acceptance criteria and a requirement for the absence of features associated with OSCS, as well as replacement of the previous CE method with Anion Exchange HPLC with the requirement for no peaks corresponding to OSCS. The revision also proposed to apply limits for dermatan sulfate which could be present as an impurity.

The TGC was informed also of symposium on the characterisation of heparin products planned for July 2009. This symposium was being organised by United States Pharmacopeial Convention, the US National Institute for Biological Standards and Control and the EDQM. As one issue for discussion at the symposium was the global harmonisation of compendial tests, it was possible that the Ph Eur would follow the USP-NF and make further amendment to its heparin monographs. In view of this ongoing work to strengthen pharmacopoeial monographs for heparin and improve tests and detection limits for OSCS, Members noted that the proposed TGO may again need revision before its release for stakeholder consultation. Noting that the TGA had not yet had the opportunity to fully consider the changes proposed for the USP-NF heparin monographs or the extent to which the requirements proposed for inclusion in the draft TGO should be amended as a consequence, the TGC agreed to consider the draft TGO out-of-session after it had been amended. It was observed that, although standards for heparin were rapidly developing, sponsors dealing with products containing heparin were keeping informed of the developments.

CLOSE OF MEETING The Committee agreed that its next Meeting should be held on Wednesday 14 October 2009. There being no further business, the Chair closed the Meeting at 4:00pm and thanked Members for their attendance.

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