Consultation: Options for reform of the regulatory … · Web view< In 2012, the PBS prescription volume was 195 million prescriptions Australian Government Department of Health and

Therapeutic Goods Administration

Options for reform of the regulatory framework for pharmacy compoundingConsultation regulation impact statement

Version 1.0, 5 June 2013

About the Therapeutic Goods Administration (TGA) The Therapeutic Goods Administration (TGA) is part of the Australian Government

Department of Health and Ageing, and is responsible for regulating medicines and medical devices.

The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary.

The work of the TGA is based on applying scientific and clinical expertise to decision-making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices.

The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action.

To report a problem with a medicine or medical device, please see the information on the TGA website <www.tga.gov.au>.

Document title Page 2 of 34V1.0 Month 2012

http://www.tga.gov.au/


Copyright© Commonwealth of Australia 2013This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to <[email protected]>

ConfidentialityAll submissions received will be placed on the TGA’s Internet site, unless marked confidential. Any confidential material contained within your submission should be provided under a separate cover and clearly marked “IN CONFIDENCE”. Reasons for a claim to confidentiality must be included in the space provided on the TGA submission coversheet. For submission made by individuals, all personal details, other than your name, will be removed from your submission before it is published on the TGA’s Internet site. In addition, a list of parties making submissions will be published. If you do not wish to be identified with your submission you must specifically request this in the space provided on the submission coversheet.

Version history

Version Description of change Author Effective date

V1.0 Original publication TGA June 2013

Document title Page 3 of 34V1.0 Month 2012

mailto:[email protected]


ContentsIntroduction 6

Activities outside the scope of this consultation RIS_____________________6

Background 7Regulatory requirements for medicines___________________________________7

Regulatory requirements for manufacturers_____________________________8

Pharmacists____________________________________________________________________9

Pharmacies____________________________________________________________________10

Regulatory interface between professional practice and therapeutic goods regulations____________________________________________________________10

Joint agency with New Zealand____________________________________________11

The issues 11Risks___________________________________________________________________________12

Community exposure________________________________________________________14

Options 14Option A – status quo________________________________________________________15

Maintain professional practice standards_______________________________________________15

Existing regulation under the Act and Regulations____________________________________15

Option B – enhance co-regulation and update legislation_____________16

Amendments regarding the ARTG exemption__________________________________________16

Amendments regarding the manufacturing exemption________________________________18

Option C – manufacturing licence for specified manufacture in pharmacies____________________________________________________________________19

Option C1 Sterile medicines______________________________________________________________20

Option C2 Other complex formulations_________________________________________________20

Option C3 Quantity limits________________________________________________________________20

Manufacturing licences for pharmacies, if Option C supported_______________________21

Costs of manufacturing licences for pharmacies, if Option C supported______________21

Transition periods________________________________________________________________________22Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 4 of 34


Summary 23

Making submissions 24Content of submissions_____________________________________________________24

How to respond______________________________________________________________25

What will happen____________________________________________________________25

Confidentiality________________________________________________________________25

Enquiries______________________________________________________________________25

Appendix 1: Glossary 26

Appendix 2: Previous consultations 28

Appendix 3: Manufacture that would require a manufacturing licensed pharmacy under Option C1 30



Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 5 of 34


IntroductionThis consultation regulatory impact statement (RIS) has been prepared by the Therapeutic Goods Administration (TGA).

There are concerns among regulators and health care professionals locally and overseas regarding the complexity and scale of manufacture in pharmacies that was not envisaged when the current regulatory arrangements were originally put in place. The expansion of manufacture in pharmacies in Australia reflects international trends. The purpose of the paper is to assist Australian Government decision making on how to address concerns that the current regulatory framework for the manufacture of extemporaneous preparations in pharmacies (‘extemporaneously compounded medicines’) does not provide adequate assurance that medicines manufactured in this way will meet acceptable standards of quality and safety.

Consultation feedback will be used to inform the development of advice to the Australian Government on the need for changes to the regulatory framework.

This consultation RIS has been structured to provide background on the current regulatory environment for extemporaneously compounded medicines in Australia, including previous consultations and publications by the TGA. This is followed by a description of issues with the safety and quality of compounded medicines. The document then canvasses three options to address the safety and quality issues.

To minimise confusion, terms used in this document that may have different meanings for other stakeholders have been included in Appendix 1: Glossary.

Activities outside the scope of this consultation RIS

The scope of this consultation RIS does not extend to:

the traditional role of a pharmacist in preparing medicine for a known particular patient

– For clarity, this includes the reconstitution of a TGA-approved medicine in accordance with the directions in the TGA-approved Product Information document.

veterinary medicines. These medicines are not regulated by the TGA

therapeutic goods such as medical devices or biologicals

manufacture of medicines in a public hospital or a public institution, for supply in hospitals or public institutions in the same state or territory (see Item 3 of Schedule 8 of the Therapeutic Goods Regulations 1990 (the Regulations))

contract manufacture, performed by a manufacturer licensed to comply with good manufacturing practice (GMP) standards, of a medicine for a patient in a private hospital, public hospital or public institution, where there is no medicine on the Australian Register of Therapeutic Goods (ARTG) that, in all relevant respects, is substantially similar (see Item 5 of Schedule 5A of the Regulations)



manufacture of medicines by pharmacists in Queensland, Western Australia or the Northern Territory where the medicine is supplied within that jurisdiction and is not supplied as a pharmaceutical benefit.

– The Commonwealth Therapeutic Goods Act 1989 applies to corporations. It also applies to natural persons (such as a pharmacist or other individual) whose business is not a corporation and the person is supplying medicines in another jurisdiction or as a pharmaceutical benefit. Since the commencement of the Act and Regulations, five jurisdictions have enacted legislation that has been declared to be ‘corresponding State law’ under the Therapeutic Goods Act 1989. Where a ‘corresponding State law’ exists, the Commonwealth legislation treats a natural person in the same way, whether or not the medicine is supplied locally or interstate, or as a pharmaceutical benefit or as a private prescription. As there is no ‘corresponding State law’ for Queensland, Western Australia and the Northern Territory, the Commonwealth legislation has no effect on natural persons supplying only within the jurisdiction and not as pharmaceutical benefits.

Background

Regulatory requirements for medicines

Medicines are regulated to ensure acceptable quality, safety and efficacy for consumers.

The TGA administers the following legislation and requirements that regulate medicines:

Therapeutic Goods Act 1989 (the Act)

Therapeutic Goods Regulations 1990 (the Regulations)

Therapeutic Goods Orders (which detail technical requirements for specific groups of products)

Therapeutic Goods (Manufacturing Principles) Determination No. 1 of 2013 (which adopts the PIC/S Guide to Good Manufacturing Practice for Medicinal Products, PE 009-8)

Part 3-2 of the Act relates to the registration and listing of therapeutic goods, other than medical devices. The Act requires that prescription medicines are registered in the Australian Register of Therapeutic Goods (ARTG) after a sponsor submits a dossier that includes detailed scientific and clinical information about the medicine. The dossier is assessed by the TGA against relevant standards and guidelines, for example, compliance with specifications stated in pharmacopoeias. For non-prescription medicines, the type and extent of the information required is dependent on the level of risk associated with the medicine. Once approved for use in the Australian market, post-market regulation may include collection and assessment of adverse event reports, approval of advertising copy, monitoring of manufacturing standards and laboratory testing of product samples.

There are several thousand different medicines on the ARTG for supply in Australia. Despite this, in clinical practice there are a number of situations where no suitable medicine is on the ARTG and commercially available. For example, a patient with an allergy may need a preservative-free medicine, or a child may require a liquid medicine when the commercially available medicine is a tablet. There are also occasions where a


http://www.tga.gov.au/industry/manuf-pics-gmp-medicines.htm


medicine that was previously available is discontinued by the supplier for financial reasons, not safety or efficacy reasons. To satisfy the clinical need in these situations, a medicine may be prepared to meet the patient’s individual requirements. The legal mechanism for the supply of such medicines without the prior approval of the medicine by the TGA is Schedule 5 of the Therapeutic Goods Regulations 1990, which exempts such medicines from being included in the ARTG, as shown in Table 1.

Table 1

Extract from Schedule 5 of the Therapeutic Goods Regulations 1990 - Therapeutic goods exempt from the operation of Parts 3-2 and 3-2A of the Act

Column 1 – Item

Column 2 – Therapeutic goods

6 medicines (other than medicines used for gene therapy) that are dispensed, or extemporaneously compounded, for a particular person for therapeutic application to that person

The states and territories also have a role in the regulatory arrangements for medicines, through their drugs and poisons legislation. State and territory legislation provides for controls over the supply, distribution, possession and use of drugs and poisons, including access to these.

Regulatory requirements for manufacturers

The vast majority of medicines supplied in Australia by community pharmacy are manufactured by pharmaceutical manufacturers regulated by the TGA.

Part 3-3 of the Act relates to the manufacturing of therapeutic goods. Good manufacturing practice (GMP) is a generally accepted term that describes the set of principles and procedures that, when followed by manufacturers of therapeutic goods, help ensure that the products manufactured will possess the required safety and quality in a consistent and reproducible manner. Australian medicine manufacturers must hold a manufacturing licence issued by the TGA. A licence to manufacture will only be issued if the applicant demonstrates the ability to comply with relevant manufacturing principles and has adequate facilities for the steps in manufacture they wished to be licensed for. The TGA usually assesses this by conducting an inspection of the manufacturing site. Manufacture of a medicine is usually a multi-step activity that involves several manufacturers. The manufacturing licence authorises the types of products (e.g. sterile medicines; antibiotics; liquids) and the steps in manufacture (e.g. manufacture of dosage form; release for supply; microbiological testing) that the manufacturer can undertake.

Schedule 8 of the Therapeutic Goods Regulations 1990 allows certain persons to act as manufacturers without requiring a licence from the TGA. The exemptions for pharmacists are shown in Table 2.



Table 2

Extract from Schedule 8 of the Therapeutic Goods Regulations 1990 - Persons exempt from the operation of Part 3-3 of the Act

Column 1 – Item

Column 2 - Persons

Column 3 – Matter in relation to which person is exempted

2 Pharmacist the manufacture of therapeutic goods, other than biologicals, produced by the pharmacist:

(a) in a pharmacy where the pharmacist practices and the pharmacy is open to the public; or

(b) on the premises of a dispensary conducted by a Friendly Society; or

(c) on the premises of a private hospital;

for supply (other than by wholesale) on or from those premises

3 Biomedical engineers, radiochemists and pharmacists in public hospitals

the manufacture of therapeutic goods, other than biologicals, by the person when employed by a public hospital or a public institution and produced by that person for supply in hospitals or public institutions in the same State or Territory

The definition and regulation of wholesaling of medicines is a state and territory responsibility under drugs and poisons legislation. State and territory legislation may permit a pharmacist to sell by wholesale a medicine to another pharmacist for lawful use by the second pharmacist.

Pharmacists

A pharmacist must be registered to practise by the Pharmacy Board of Australia. The Pharmacy Board of Australia has a range of roles including: registering pharmacists and pharmacy students; developing standards, codes and guidelines for the pharmacy profession; handling notifications, complaints, investigations and disciplinary hearings; assessing overseas trained practitioners who wish to practise in Australia; and approving accreditation standards and accredited courses of study.

Like other professionals, pharmacists are expected to know the extent of their competence and to not practise beyond their skills. The National Competency Standards Framework for Pharmacists in Australia 2010 provides the competency framework for pharmacists in Australia and addresses both scope of practice and performance level.

The Pharmaceutical Society of Australia Ltd (PSA) is a national professional pharmacy organisation and the publisher of the Professional Practice Standards.

The Pharmacy Guild of Australia is a national peak body representing community pharmacy as a pharmacy owners’ organisation.


http://www.psa.org.au/supporting-practice/national-competency-standards

http://www.psa.org.au/supporting-practice/national-competency-standards


Pharmacies

States and territories regulate the workplaces where community pharmacists provide goods and services. Approval of pharmacy premises is required for community pharmacies, and (in some jurisdictions) pharmacies in private hospitals and pharmacy departments in public hospitals. State and territory regulation may include the specification of the size and facilities of the premises, and the publications and equipment that must be present in the pharmacy.

States and territories also regulate the ownership arrangements for pharmacies. This is generally that pharmacies are required to be owned by pharmacists.

In April 2011, the Pharmacy Guild of Australia’s Quality Care Pharmacy Program (QCPP) was republished as Australian Standard S 85000:2011 Quality Care Pharmacy Standard - quality management system for pharmacies in Australia. This standard includes the statement that pharmacies should maintain and follow a system for compounding (extemporaneous dispensing). Compliance with this standard is voluntary; for pharmacies wishing to demonstrate compliance with the Australian Standard, there is an external audit every two years conducted by QCPP licensed assessors within the QCPP arrangements. According to the Pharmacy Guild, over 92% of pharmacies across Australia are accredited under the QCPP.1

Industry figures suggest that 6-10% of pharmacies advertise or claim some degree of specialisation in compounding. An Australian survey2 found that in pharmacies not specialising in compounding on average three compounded products were prepared each week. In the sample of 26 pharmacies claiming to specialise in compounding, the average number of compounded products per week was 25.

There are a small number of pharmacies that are ‘compounding only’ pharmacies that supply few, if any, medicines produced by other manufacturers.

There are pharmacies that specialise in the reconstitution and manufacture of chemotherapy (oncology) medicines. Due to its complex nature and need for specialist skills and equipment, the Pharmacy Guild has stated that fewer than 10 community pharmacies in Australia have the facilities to compound these medicines.3

Regulatory interface between professional practice and therapeutic goods regulations

Since 1990, exemptions have been in place that mean that compounded medicines do not require TGA approval and pharmacists do not require a TGA manufacturing licence. The

1 Pharmacy Guild of Australia. What is QCPP? Viewed 10 May 2013.

<http://www.guild.org.au/QCPP/About_QCPP/What+is+QCPP/What+is+QCPP.page>

2 Giam J, McLachlan A, Krass I “Specialised compounding – practices and opinions of Australian community pharmacists”, J Pharm Pract Res 2007; 37, 260-264.

3 Senate Standing Committees on Community Affairs. Supply of chemotherapy drugs such as Docetaxel. Submission Number 25. Viewed 10 May 2013. <http://www.aph.gov.au/Parliamentary_Business/Committees/Senate_Committees?url=clac_ctte/completed_inquiries/2010-13/chemotherapy_drugs/submissions.htm>Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 10 of 34

http://www.aph.gov.au/Parliamentary_Business/Committees/Senate_Committees?url=clac_ctte/completed_inquiries/2010-13/chemotherapy_drugs/submissions.htm

http://www.aph.gov.au/Parliamentary_Business/Committees/Senate_Committees?url=clac_ctte/completed_inquiries/2010-13/chemotherapy_drugs/submissions.htm

http://www.guild.org.au/QCPP/About_QCPP/What+is+QCPP/What+is+QCPP.page


intention of this legislative arrangement was to allow a pharmacist to continue the long-established practice of preparing a medicine for an individual patient in response to an identified need of that patient. The exemptions recognised the one-off nature of such medicines and the professional training of the pharmacist to prepare the medicine.

Joint agency with New Zealand

In June 2011, the Australian and New Zealand Governments announced their agreement to proceed with a joint scheme for regulation of therapeutic goods. The new joint agency, the Australian New Zealand Therapeutic Products Agency (ANZTPA), is expected to be operational by 2016.

New Zealand government, healthcare, consumer and industry groups will particularly be invited to participate in this consultation to ensure alignment with future joint regulatory arrangements. General consultation on the regulatory system to apply in Australia and New Zealand will also be undertaken in the development of the ANZTPA.

Currently, pharmacists are the health professionals in New Zealand who may compound medicines, and preparing pharmaceutical products (non-sterile) is one of the seven Competence Standards required of entry-level pharmacists.

The issuesThe TGA notes the well established role of pharmacists in preparing medicines for individual patients in a community pharmacy setting where such medicines are prepared using formulations from established formularies such as the Australian Pharmaceutical Formulary. Compounding in community pharmacy is generally of a non-sterile medicine, such as a skin preparation or an oral medicine.

There are concerns among regulators and health care professionals locally and overseas regarding the complexity and scale of manufacture in pharmacies that was not envisaged when the current regulatory arrangements were originally put in place. The expansion of manufacture in pharmacies in Australia reflects international trends.

Contrary to the intent of the regulatory exemptions, TGA is aware that identical medicines may be produced for a number of customers simultaneously, or in large overall quantities, and the medicines may be promoted or supplied by distance dispensing or through a number of outlets. Pharmacies publish price lists detailing the active ingredient, strength, pack size and price for compounded prescription-only medicines, indicative of routine supply. It is primarily the practices of these pharmacies that are viewed as a regulatory concern. Such pharmacies appear to be manufacturing and supplying medicines in a manner comparable to licensed manufacturers, but without comparable regulatory oversight and standards of manufacture.

In Australia, current regulatory exemptions do not discriminate between simple compounded medicines and ones that are technically more complex to produce and that have a higher risk associated with their use. For example, there is nothing in current regulations to prevent a pharmacist in a community pharmacy from producing sterile injectable medicines, or ones that are required to have modified release properties or ones that contain very small, but accurately measured, amounts of highly potent active ingredients.



In 2005, the Australian Health Ministers' Advisory Council (AHMAC) acknowledged that public health concerns existed regarding extemporaneous compounding and endorsed development of an appropriate regulatory response for managing health and safety risks of extemporaneously compounded therapeutic goods. Appendix 2 provides a summary of previous consultation activities.

Internationally, there are a range of regulatory responses to manufacturing occurring in pharmacies. The New Zealand Standard 8134.7:2010 Health and Disability Services: Pharmacy Services Standard allows a pharmacy to compound small batches of non-sterile medicines. In the UK, the manufacturer of a ‘special’ must hold a manufacturer's (specials) licence issued by the Medicines and Healthcare Products Regulatory Agency (MHRA); a ‘special’ is an unlicensed relevant medicinal product for an individual patient.4 In Canada, there is a policy guidance document nominating criteria to be considered in differentiating usual pharmacy practice from manufacturing.5 In the USA, the national and state legislatures and the U.S. Food and Drug Administration (FDA) are actively reviewing the oversight of compounding pharmacies.6

Risks

The public health risks from compounded medicines are difficult to quantify, as community exposure to compounded medicines is difficult to estimate (see below). There is no legal obligation for prescribers and pharmacists to report clinically significant adverse drug reactions to a regulator, unlike the manufacturers and sponsors of TGA-approved medicines. The former Australian Adverse Drug Reactions Advisory Committee provided advice to the TGA on this point:

ADRAC is concerned that there may be substantial under-reporting of adverse drug reactions to unregulated extemporaneously prepared products as a result of widespread promotional claims that play down potential risks and thus lead to under–recognition of adverse reactions.

The TGA’s Database of Adverse Event Notifications (DAEN) contains around 251,000 cases of adverse events reported since 1971. The DAEN includes fewer than 20 cases associated with compounded medicines as the suspected medicine, noting that inclusion of a case report in DAEN does not confirm a causal association. Of these reports, a small number refer to endometrial cancer and breast cancer for which oral and/or topical compounded hormones were the suspected medicines.

4 Medicines and Healthcare Products Regulatory Agency. Medicines that do not need a licence (Exemptions from licensing) Last modified 17 December 2012. Viewed 10 May 2013 <http://www.mhra.gov.uk/Howweregulate/Medicines/Doesmyproductneedalicence/Medicinesthatdonotneedalicence/index.htm>

5 Health Canada. Policy on Manufacturing and Compounding Drug Products in Canada (POL-0051). Last modified 6 February 2009. Viewed 10 May 2013. <http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/docs/pol_0051-eng.php#a9>

6 For example, FDA. Pharmacy Compounding. Last modified 12 April 2013. Viewed 10 May 2013. <http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm>


http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm

http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/docs/pol_0051-eng.php

http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/docs/pol_0051-eng.php

http://www.mhra.gov.uk/Howweregulate/Medicines/Doesmyproductneedalicence/Medicinesthatdonotneedalicence/index.htm

http://www.mhra.gov.uk/Howweregulate/Medicines/Doesmyproductneedalicence/Medicinesthatdonotneedalicence/index.htm


Manufacturing within pharmacies is subject to a similar range of risks to those required to be managed by TGA-licensed pharmaceutical manufacturers: weighing errors; cross contamination between products; mis-identified or deteriorated starting materials; starting materials of unassured quality; and production problems for complex dosage forms (e.g. very dilute preparations). The preparation of sterile medicines adds special requirements for equipment, training and processes, and the compounding of sterile medicines that are cytotoxic (for treatment of cancer) requires particular care.

State and territory pharmacy inspectorates in Australia have reported incidents relating to quality and safety of compounding in pharmacies:

on analysis, one sample provided to the Board showed no active ingredient at all7

ingredients for extemporaneous preparations which appear to ... not have any expiry date on them or have been transferred to a “bulk” container8

balances and scales in, what could well be described, as “poor state of repair”9

Observations of these types have been managed as professional practice issues, or as actions under state and territory drugs and poisons legislation, including professional misconduct.

Overseas, the Missouri Board of Pharmacy continues to report unsatisfactory results related to potency in over 10% of sampled compounded medicines, including medicines with 3.3% and 226.6% of the claimed quantity of active ingredient.10

Recently there have been over 50 fatalities from contaminated steroid injections prepared by the New England Compounding Center in the USA. The site was a licensed pharmacy allowed by the state regulator to compound sterile medicines. Apart from regulatory infractions (e.g. illegal supply interstate), an on-going investigation into this pharmacy has found failures to comply with the compounding standards of the United States Pharmacopeia, which are applicable to compounding pharmacies in the USA, and failure to provide sanitary conditions that ought to be provided irrespective of status as a pharmacy or a manufacturer.11

7 Pharmacy Board of New South Wales Newsletter March 2008. ‘Compounding – a respected art – a professional responsibility’, page 2. Viewed 29 May 2013.

<http://pandora.nla.gov.au/pan/89105/20080930-1443/www.pbnsw.org.au/pdf/NewsletterMarch2008.pdf>

8 Pharmacy Board of New South Wales Newsletter March 2009. ‘The Inspectors’ say ... out of date – out of mind’, page 4.

9 Pharmacy Board of New South Wales Newsletter March 2010. ‘The Inspectors’ say ... weight is right! Or is it?’, page 4.

10 Missouri Board of Pharmacy. 2012 Annual Report. Compounded drug testing , page 20. Last modified 24 April 2013. Viewed 10 May 2013.

<http://pr.mo.gov/pharmacists-annual-reports.asp>

11 Commonwealth of Massachusetts. Fungal Meningitis Outbreak (NECC). NECC Preliminary Investigation Report 23/10/2012. Viewed 10 May 2013.

<http://www.mass.gov/eohhs/gov/departments/dph/programs/hcq/dhpl/pharmacy/new-england-compounding-center-product-recall-alert.html>Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 13 of 34

http://www.mass.gov/eohhs/gov/departments/dph/programs/hcq/dhpl/pharmacy/new-england-compounding-center-product-recall-alert.html

http://pr.mo.gov/pharmacists-annual-reports.asp


The U.S. Food and Drug Administration has published reports of their inspections of pharmacy compounding facilities, which disclose a range of deficiencies including:12

procedures designed to prevent microbiological contamination of medicines purporting to be sterile did not include validation of the sterilisation process

control systems necessary to prevent contamination or mix-up were deficient

clothing of personnel engaged in the processing of medicine were not appropriate for the duties they performed

formulation worksheets were not sufficiently reviewed to ensure accurate and complete information was recorded

equipment and utensils were not maintained at appropriate intervals to prevent malfunctions and contamination that would alter the safety, identity, strength, quality or purity of the medicine.

Community exposure

The majority of compounded medicines are not supplied as pharmaceutical benefits. These medicines include hormone replacement therapies, women and men’s health products, and ingredients approved overseas but not in Australia. There is no single database on the number and range of private prescriptions, including compounded medicines, supplied in Australia. For example, current and previous editions of Australian Statistics on Medicines advise that some extemporaneously prepared items may not be included in that report.13

In 2012, the PBS prescription volume was 195 million prescriptions14, including approximately 300,000 extemporaneously compounded medicines. The extemporaneously compounded medicines subsidised by the PBS are generally long established formulations with a small range of active ingredients, mostly for dermatological use or oral liquids. The only compounded sterile medicines in the PBS are for application to the eye.

12 U.S. Food and Drug Administration. 2013 Pharmacy Inspections. Last updated 29 April 2013. Viewed 10 May 2013.

<http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/ucm340853.htm>

13 Australian Government Department of Health and Ageing. Pharmaceutical Benefits Scheme (PBS) - Australian Statistics on Medicines 2010. Viewed 10 May 2013.

<http://www.pbs.gov.au/info/browse/statistics>

14 Australian Government Department of Health and Ageing. Pharmaceutical Benefits Scheme (PBS) - Expenditure and Prescriptions twelve months to 30 June 2012 . Viewed 10 May 2013. <http://www.pbs.gov.au/info/statistics/expenditure-and-prescriptions-30-06-2012>Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 14 of 34

http://www.pbs.gov.au/info/statistics/expenditure-and-prescriptions-30-06-2012

http://www.pbs.gov.au/info/statistics/expenditure-and-prescriptions-30-06-2012

http://www.pbs.gov.au/info/statistics/asm/asm-2010

http://www.pbs.gov.au/info/statistics/asm/asm-2010

http://www.fda.gov/AboutFDA/CentersOffices/OfficeofGlobalRegulatoryOperationsandPolicy/ORA/ORAElectronicReadingRoom/ucm340853.htm


OptionsThree Options are proposed to address the concerns that current regulatory arrangements do not provide adequate public protection regarding compounded medicines.

The Options are not mutually exclusive and contain sub-options. Submissions to this consultation, and the outcome from this consultation process, may propose that specific elements from different Options be combined.

The options are described below.

A. Maintain the status quo, based on professional practice standards and guidelines, and existing regulation under the Act and Regulations

B. Enhance co-regulation with pharmacy and pharmacist regulators by amendments to Commonwealth legislation to reference the role of professional oversight and requirements, including pharmacy approvals, and clearer requirements regarding medicines exempt from TGA processes.

C. Require that specified manufacturing activity in a pharmacy requires the pharmacy to hold a manufacturing licence from the TGA. There are three sub-options, based on either sterility or complexity of the medicine, or scale of manufacturing activity.

Option A – status quo

Option A would maintain the status quo. This Option would involve continued reliance on:

professional practice standards

existing regulations under the Act

state and territory pharmacy inspection arrangements

Maintain professional practice standards

Current arrangements for professional practice rely on:

Pharmacy Board of Australia Guidelines for dispensing of medicines, Guidelines on practice-specific issues, Guidelines for advertising of regulated health services, and Code of conduct for registered health practitioners

Professional Practice Standards 2006 and 2010, published by the Pharmaceutical Society of Australia Ltd.

National Health (Pharmaceutical Benefits) (Conditions of approval for approved pharmacists) Determination 2007, which requires compliance with the Pharmaceutical Society of Australia’s Professional Practice Standards 2006 in the provision of medicines supplied as pharmaceutical benefits.

Professional practice guidelines and standards are developed and reviewed by the relevant organisations. Adoption and implementation of the guidelines and standards depends on the governance arrangements within the relevant organisation.

Existing regulation under the Act and Regulations


http://www.comlaw.gov.au/Details/F2007L02703

http://www.comlaw.gov.au/Details/F2007L02703


Medicines compounded by pharmacists are subject to the following regulatory arrangements.

Quality standards

The current exemptions in the Act relate to Part 3-2 (Registration and listing of therapeutic goods) and Part 3-3 (Manufacturing of therapeutic goods). Significantly, compounded medicines are not excluded from Part 3-1(Standards) of the Act. Broadly, Part 3-1 requires medicines to comply with Therapeutic Goods Orders and the standards for ingredients (including water) and medicines in the British, European or US pharmacopoeias, including sterility requirements for medicines.

Advertising

The advertising of therapeutic goods to consumers and health practitioners is controlled by a combination of statutory measures administered by the TGA and self-regulation through Codes of Practice administered by the relevant therapeutic goods industry associations. In general, prescription medicines and many Pharmacist only (Schedule 3 of Poisons Standard) medicines may not be advertised and advertisements for other medicine are required to undergo a pre-approval process.

Product recalls

Compounded medicines may be recalled (‘product recovery’) under Section 30EA(1) of the Act, where the goods do not conform with a standard applicable to the goods.

The TGA encourages pharmacists, and other healthcare providers, to voluntarily report adverse events to the TGA. This complements the statutory obligations to report adverse events that apply to licensed manufacturers (section 40 of the Act) and sponsors of medicines (via conditions of registration or listing on the ARTG).

Are there other risks and benefits of the continuation of existing regulatory arrangements that have not been identified in this consultation paper?

Note: Submissions to this consultation, and the outcome from this consultation process, may propose that specific elements from different Options be combined.

Option B – enhance co-regulation and update legislation

Option B would:

amend regulatory arrangements to:

– require compounded medicines to be identified as such on their labels. This could be via a condition on exemption (amendments to Schedule 5A of the Therapeutic Goods Regulation 1990) or a requirement to comply with a standard (a new Therapeutic Goods Order)

– reflect that, where a pharmacist is not required to hold a manufacturing licence, a specified edition of the Pharmacy Board guidelines on compounding apply to



pharmacists manufacturing medicines, via amendments to Schedule 8 of the Therapeutic Goods Regulation 1990

– exempt compounded medicines from inclusion in the ARTG only when there is no suitable and available medicine on the ARTG, via amendments to Schedule 5A of the Therapeutic Goods Regulation 1990

– allow the Secretary to request information about exempt compounded medicines, via amendments to Schedule 5A of the Therapeutic Goods Regulation 1990

– reflect state and territory legislation on pharmacy premises, via amendments to Schedule 8 of the Therapeutic Goods Regulation 1990

continue TGA liaison with pharmacy inspectors in states and territories, using available communication channels.

Amendments regarding the ARTG exemption

The Regulations would distinguish ‘dispensed’ and ‘extemporaneously compounded’, which are different professional activities.

To ensure that the regulatory status of compounded medicines is clear to patients, extemporaneously compounded medicines would be labelled to the effect that the medicine has been compounded and is not a TGA approved product. Possible wording for labels are:

“This is a compounded medicine”

“Compounded medicine. Not TGA approved” (for scheduled medicines)

“Compounded medicine. Discuss with your pharmacist”

The exemption in Schedule 5A of the Regulations for contract manufacturers includes the condition that there are no listed goods or registered goods that, in all relevant respects, are substantially similar to the goods manufactured. A similar condition would be applied to extemporaneously compounded medicines. This is consistent with the Pharmacy Board of Australia’s current guidance, which says:

An extemporaneous preparation should be used only in circumstances where a commercial product is unavailable or unsuitable.15

A verification process would be included in the Regulations to allow the Secretary to request information about an exempt medicine, such as active ingredient, formulation, shelf life, sterilisation process and labelling.

Possible amendments to Schedules 5 and 5A of the Therapeutic Goods Regulations 1990 with indicative wording are shown in tables 3 and 3A; indicative additions are shown in red italic text and indicative deletions are shown in strikethrough.

15 Pharmacy Board of Australia. Codes and Guidelines. Pharmacy Guidelines for dispensing of medicines. Viewed 10 May 2013.

<http://www.pharmacyboard.gov.au/documents/default.aspx?record=WD10%2f2951&dbid=AP&chksum=WMyYdhKfX3%2bWGPiGUCLsMw%3d%3d>Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 17 of 34

http://www.pharmacyboard.gov.au/Codes-Guidelines.aspx


Table 3

Possible amendment to the Therapeutic Goods Regulations 1990, Schedule 5 ‘Therapeutic goods exempt from the operation of Parts 3-2 and 3-2A of the Act’.

Column 1 – Item


6 medicines (other than medicines used for gene therapy) that are dispensed, or extemporaneously compounded, for a particular person for therapeutic application to that person



Table 3A

Possible amendment to the Therapeutic Goods Regulations 1990, Schedule 5A ‘Therapeutic goods exempt from the operation of Parts 3-2 and 3-2A of the Act subject to conditions’.

Column 1 – Item


Column 3 - Conditions

13 medicines (other than medicines used for gene therapy) that are extemporaneously compounded for a particular person for therapeutic application to that person

a) the medicine is labelled <to the effect that the medicine is compounded>

b) where there is no listed or registered medicine suitable and available for the particular patient for whom the medicine is being compounded

c) the manufacturer must:

i. keep records relating to the manufacture of the medicine;

ii. keep records relating to adverse reactions or similar experiences related to the medicine

iii. if requested by the Secretary — supply records to the Secretary

5 [contract manufacturer exemption]

Add:

the medicine is labelled <to the effect that the medicine is compounded>

Amendments regarding the manufacturing exemption

Where pharmacists are exempt from the requirement to hold a TGA manufacturing licence, the Act is silent on what manufacturing standard applies in the place of pharmaceutical GMP requirements. This would be addressed by reference to the Pharmacy Board of Australia Guidelines on compounding.

Friendly Societies operate a particular ownership model for pharmacies. State and territory regulations on pharmacies do not differentiate the professional activities allowed to be conducted in Friendly Society dispensaries compared to other pharmacies. The continuation of a special mention of the premises of a dispensary conducted by a Friendly Society appears to be no longer required.

The manufacturing exemption does not specify ‘for immediate supply’, indicating that the pharmacist can manufacture to have stock-on-hand for eventual supply (subject to the expiry date of the goods as allocated by the pharmacist).

Option B could be implemented via amendments to Schedules 5, 5A and 8 of the Therapeutic Goods Regulations 1990, with indicative wording as in tables 3, 3A and 4; indicative additions are shown in red italic text and indicative deletions are shown in strikethrough.



Table 4

Possible amendment to Schedule 8 of the Therapeutic Goods Regulations 1990 under Option B

Persons Matter in relation to which person is exempted

Pharmacist the manufacture of therapeutic goods, other than:

i. biologicals

ii. medicines for which there are listed or registered medicines suitable and available for the particular patient for whom the medicine is being manufactured

produced by the pharmacist in compliance with the Pharmacy Board of Australia guidelines for compounding (as at <date>):

in premises where the pharmacist practises

and the premises are approved in accordance with state or territory legislation on pharmacies or are


(b) on the premises of a dispensary conducted by a Friendly Society,



What are the risks and benefits of Option B?

Do you have any views on how Option B could be improved?

What wording should be used on medicine labels to highlight that the medicine is compounded?

Note: Submissions to this consultation, and the outcome from this consultation process, may propose that specific elements from different Options be combined.

Option C – manufacturing licence for specified manufacture in pharmacies

Option C would require the workplace where a pharmacist manufactures to hold a licence as a manufacturing site in a wider range of circumstances. Already, the pharmacy must hold a licence when medicines are supplied by wholesale.

This Option includes three sub-options proposing different sets of circumstances that would require the pharmacy to hold a manufacturing licence from the TGA. The sub-options relate to sterile medicines, other complex formulations, and quantities.Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 20 of 34


The Options are:

Option C1 - require a pharmacy where the pharmacist works to hold a manufacturing licence before manufacture of the sterile dosage forms nominated in Appendix 3, via amendments to Schedule 8 of the Therapeutic Goods Regulation 1990, and/or

Option C2 - require a pharmacy where the pharmacist works to hold a manufacturing licence before manufacture of ‘complex formulations’ nominated in Appendix 4, via amendments to Schedule 8 of the Therapeutic Goods Regulation 1990, and/or

Option C3 - require a pharmacy where the pharmacist works to hold a manufacturing licence before manufacture of quantities exceeding the limits in Appendix 5, via amendments to Schedule 8 of the Therapeutic Goods Regulation 1990.

There would also be a transition period for pharmacists operating affected pharmacies to obtain a manufacturing licence, via the commencement date of the changes to the Regulations and amendment to Regulation 18.

Option C1 Sterile medicines

Sterile medicines pose a higher intrinsic risk to consumers than non-sterile medicines, because of the increased risk of transmission of harmful microbial agents, particularly in vulnerable populations such as those who are already ill, children and the elderly.

Under Option C1, the manufacture in pharmacies of the sterile dosage forms nominated in Appendix 3 would become licensable activities.

Current practices of compounding sterile medicines that are topical products (such as eye drops and topical irrigation solutions for burns) and single use injections for immediate supply and immediate use could continue and a manufacturing licence from the TGA would not be required. These sterile medicines are occasionally required from a range of pharmacies, usually in emergency situations, and the making of these medicines would remain guided by the pharmacist’s professional competence and responsibilities.

Option C2 Other complex formulations

In addition to sterile medicines, there are other medicines the preparation of which requires special competencies, equipment, processes or facilities. A common descriptive term is ‘complex compounding’. Generally, these medicines can be described by reference to dosage form (e.g. micro-dose dosage forms, modified-release preparations) and ingredients (e.g. cytotoxics, hormones).

Appendix 4 describes the types of medicines that are considered to be complex to prepare, and gives some examples.

Option C3 Quantity limits

Appendix 5 describes two variants for applying quantitative limits, to recognise that manufacturing beyond small-scale batch manufacture should be regulated as manufacturing.

The quantitative limits based on batch size are from New Zealand Standard 8134.7:2010 Health and Disability Services: Pharmacy services Standard.

The quantitative limit of 500 compounded prescriptions per month reflects a previous consultation proposal.



Manufacturing licences for pharmacies, if Option C supported

The holder of a manufacturing licence is required to demonstrate compliance with minimum standards for matters such as personnel, premises, equipment, documentation, production processes and quality control. The code of good manufacturing practice that is proposed to be adopted is the PIC/S Guide to Good Manufacturing Practice - 15 January 2009, PE 009-8, supplemented with interpretive guidance notes specific to Australian pharmacies, where appropriate.

Manufacturing licences would authorise the specific types of medicines that could be manufactured in pharmacies that come within the scope of Option C.

Under Option C, pharmacy owners of affected pharmacies would need to prepare for, seek and obtain a manufacturing licence from the TGA. The effect of requiring manufacturing licences will vary between pharmacies, depending on:

which sterile medicines and/or complex formulations are manufactured (e.g. methods of manufacture)

level of compliance with existing professional standards. If a pharmacy already has clean rooms and anteroom that meet Australian standards, as is expected by the Pharmaceutical Society of Australia Professional Practice Standards 2010, the compliance gap would be smaller than if the pharmacy is not already compliant with this professional standard

level of compliance with the proposed manufacturing principles.

Because of this variability, the TGA is unable to undertake a meaningful ‘gap analysis’ between present practice and GMP requirements under Option C for a notional pharmacy currently manufacturing sterile medicines and/or complex formulations.

Manufacturing principles describe benchmark practices that should be followed, but permit alternative approaches provided it can be demonstrated to the inspector that the intent of the GMP requirements is met in a timely and effective manner.16

Costs of manufacturing licences for pharmacies, if Option C supported

Commonwealth legislation is in place that defines the inspection fees and annual charges that apply to medicine manufacturers. The existing TGA regulatory fees applicable to manufacturers are outlined in TGA Fees & payments information. No different fees or inspections would be introduced. TGA manufacturing licences are issued without expiry dates but licence holders are subject to periodic re-inspection. The Act allows for conditions to be applied to licences and for actions such as suspension and revocation to be undertaken.

Typical costs could reflect the following matters.

TGA fees and charges. The current costs associated with a manufacturing licence include an $890 application fee and $10,900 for annual charges for sterile manufacture. The annual charge includes 48 inspection hours, over a three year cycle. Once these hours are exceeded a charge of $580 per hour per inspector applies.

Capital investment, if required, in order to comply with the requirements of the manufacturing licence. These could include purchase of duplicated equipment to prevent cross-contamination, and improvements to air and water handling.

16 See Division 1, clause (3) of the Therapeutic Goods (Manufacturing Principles) Determination No. 1 of 2013.Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 22 of 34

http://www.tga.gov.au/about/fees.htm

http://www.comlaw.gov.au/Details/F2013L00855/Download

http://www.comlaw.gov.au/Details/F2013L00855/Download


On-going costs, if required, in order to comply with the requirements of the manufacturing licence. These could include the purchase of higher grade materials and external services (e.g. for microbiological testing).

As a new cost recovery impact statement documenting cost recovery arrangements for good manufacturing practice licences will be prepared for commencement on 1 July 2013, the above costs should be regarded as indicative.17

Option C could be implemented via amendments to Schedule 8 of the Therapeutic Goods Regulations 1990, as shown in Table 5; indicative additions are shown in red italic text and indicative deletions are shown in strikethrough.

Transition periods

The changes to the Regulations described above would take effect on a proclaimed date; this effectively provides a transition period for affected parties to prepare for the new arrangements. A two year period is proposed.

Option C3 would require additional transition arrangements, as the time at which a pharmacy exceeds the quantity limit in Option C3 would not be predictable. Similarly to Regulation 17, Regulation 18 would be amended to allow a transition period for pharmacists who apply for a manufacturing licence before crossing the quantity limit. In these cases, the transition period is the time from formal application to the TGA for the manufacturing licence until the application is determined.

Table 5

Possible amendment to Schedule 8 of the Therapeutic Goods Regulations 1990, under Option C

Persons Matter in relation to which person is exempted

Pharmacist the manufacture of therapeutic goods, other than:

i. biologicals

ii. medicines that are <as described in Appendix 3, 4 or 5>

produced by the pharmacist:


(b) on the premises of a dispensary conducted by a Friendly Society



17 Australian Government Department of Health and Ageing Therapeutic Goods Administration. Fees & payments. Webpage last updated 21 August 2012. Viewed 10 May 2013.

<http://www.tga.gov.au/about/fees-cris-gmp-120629.htm>Options for reform of the regulatory framework for pharmacy compoundingV1.0 June 2013 Page 23 of 34

http://www.tga.gov.au/about/fees.htm


What are the risks and benefits of Option C?

Do you have any views on how Option C could be improved?

If your business would be affected by this proposal, what would be the financial impact on your business and flow-on impact on consumers, if any?

Do you support sub-option C1, C2 or C3, or a combination or hybrid of these options?

In sub-option C3, which means of controlling quantity do you support?

Are there other mechanisms that can discriminate using quantities between traditional and commercial scale compounding?

At the commencement of any new requirement for requiring a manufacturing licence, would a two year transition time be sufficient?

Summary The options in this consultation RIS relate to the protection of public health, via:

appropriate regulation of compounding of medicines

appropriate regulation of manufacture undertaken in certain pharmacies

maintenance of the professional practice of pharmacy

risk management of the types of medicines (dosage forms, ingredients) suited to the level of professional competence and regulatory oversight

manufacturing principles/standards for non-hospital pharmacies that manufacture medicines, with compliance monitored and appropriate regulatory actions in the event of non-compliance

use of approved medicines in preference to unapproved medicines manufactured by unlicensed pharmacies.

Submissions to this consultation, and the outcome from this consultation process, may propose that specific elements from different Options be combined.

Which Option, or combination of Options or parts thereof, do you favour and why?



Making submissions

Content of submissions

Submissions may address any, or all, of the proposed changes to arrangements for manufacture in pharmacies.

Throughout this document there are a number of boxes like this one. These include questions which you may wish to use as prompts in preparing your submission.

In addition, submissions might include:

suggested improvements or alternatives to proposed changes

whether or not you support the specific proposals or combinations of proposals. If you do not support the proposals you may make suggestions for an alternative acceptable to you

an assessment of how the proposed change will impact on you. That is, what do you see as the likely benefits or costs to you (these may be financial or non-financial). If possible, please attempt to quantify these costs and benefits. Any comments you can make will assist in developing the Regulation Impact Statement (RIS).

How to respond

All submissions should be accompanied by a TGA submission cover sheet. Submissions must include full personal or organisational contact details (including address, telephone number and email).

Electronic submissions are preferred and should be emailed to [email protected]. Please include your name/name of organisation in the subject line of the email.

Alternatively, hard copy submissions may be mailed to:

Management and Coordination SectionOffice of Scientific EvaluationTherapeutic Goods AdministrationPO Box 100WODEN ACT 2606

What will happen

Submissions will be reviewed by the TGA and feedback on submissions will be provided through the TGA's Internet site.



Consultation feedback will be used to inform the development of advice to the Australian Government on the need for changes to the regulatory framework.

Confidentiality

All submissions will be placed on the TGA website unless marked confidential. Any confidential material contained within your submission should be provided under a separate cover and clearly marked 'IN CONFIDENCE'. Reasons for a claim to confidentiality must be included in the space provided on the TGA submission coversheet.

For submissions made by individuals, all personal details other than your name will be removed from your submission before it is published on the TGA's website.

In addition, a list of parties making submissions will be published. If you do not wish to be identified with your submission you must specifically request this in the space provided on the submission coversheet.

Enquiries

Questions relating to submissions should be directed to the consultation project officer by email to [email protected] or by telephone to 02 6232 8623.



Appendix 1: Glossary

Term Definition

batch batch means a quantity of a product that is:

(a) uniform in composition, method of manufacture and probability of chemical or microbial contamination; and

(b) made in one cycle of manufacture and, in the case of a product that is sterilised or freeze dried, sterilised or freeze dried in one cycle.

(from section 3 of the Act)

complex compounding

The preparation and supply of a single ‘unit of issue’ of a therapeutic product which is intended for immediate use by a specific patient that requires or involved special competencies, equipment, processes or facilities. Examples include sterile products, preparations containing ingredients which pose an occupational health and safety hazard, such as cytotoxics or hormones, micro-dose single unit dosage forms, and sustained or other modified release preparations.

(from Australian Pharmaceutical Formulary, Edition 22)

Note: “Micro-dose single unit dosage forms” is a term that is not used by the TGA. Current pharmacopoeial standards for a capsule require Uniformity of Dosage Units to be demonstrated by content uniformity (assay of the individual contents of active substance(s) of a number of dosage units to determine whether the individual contents are within the limits set) where the content of the active ingredient is less than 25 mg or 25% of the total capsule mass.

GMP good manufacturing practice: The acronym GMP is used internationally to describe a set of principles and procedures which, when followed by manufacturers of therapeutic goods, helps ensure that the products manufactured will have the required quality. A basic tenet of GMP is that quality cannot be tested into a batch of product but must be built into each batch of product during all stages of the manufacturing process.

(from TGA website)

immediate use Within 24 hours, in relation to aseptically prepared products without sterility tests

(from The Society of Hospital Pharmacists of Australia Guidelines for Medicines Prepared in Australian Hospital



Term Definition

Pharmacy Departments, which states, regarding Aseptic Prepared Products, that due to the risk of microbial contamination the default expiry date for aseptic products without sterility tests should be 24 hours.)

manufacture manufacture, in relation to therapeutic goods that are not medical devices, means:

(a) to produce the goods; or

(b) to engage in any part of the process of producing the goods or of bringing the goods to their final state, including engaging in the processing, assembling, packaging, labelling, storage, sterilising, testing or releasing for supply of the goods or of any component or ingredient of the goods as part of that process.


manufacturing site

manufacturing site means premises:

(a) that are for use in the manufacture of a particular kind of therapeutic goods; and

(b) at which the same persons have control of the management of the production of the goods and the procedures for quality control.


pharmaceutical benefit

a Commonwealth pharmaceutical benefit under the National Health Act 1953 or the Veterans’ Entitlements Act 1986

(from regulation 2 of the Regulations)



Appendix 2: Previous consultationsIn late 2004, the TGA commissioned a review by Oceania Health Consulting on the growth in the practice of extemporaneous compounding and the concerns noted by the National Coordinating Committee on Therapeutic Goods (NCCTG). The report was published as Review of the need for further regulation of extemporaneous compounding in September 2005.

The report was reviewed by the Australian Health Ministers' Advisory Council (AHMAC). The AHMAC acknowledged that public health concerns existed and endorsed continued development by the NCCTG, in consultation with stakeholders, of an appropriate regulatory response for managing health and safety risks of extemporaneously compounded therapeutic goods.

The TGA hosted two round table discussions with key stakeholders in September 2005 and October 2006.

A discussion paper on regulation of extemporaneously prepared medicines in non-hospital pharmacies authored by the NCCTG, was published April 2008 for public consultation. Submissions were received from 26 groups (including regulators, medical and pharmacy professional groups, health advocacy groups, and pharmaceutical manufacturers), individual pharmacists, individual medical practitioners (of which dermatologists were a significant group), and individual consumers. This consultation attracted divergent responses. Two proposals were particularly contentious:

The use of quantitative limits to differentiate the level of regulation. Some submissions argued that the then-proposed limit was excessive and that tighter regulation should cut-in at a lower level of compounding. Other submissions argued that a quantitative limit was irrelevant to risk management.

The prohibition of use of ingredients unapproved by the TGA. Some submissions argued that this interfered with prescribers’ rights to prescribe unapproved ingredients, the process of ‘informed consent’, and continuity of care of existing customers. Other submissions supported the proposal as the various mechanisms for supply of unapproved products, including extemporaneously compounded medicines, are intended to be temporary mechanisms for supply, rather than advocated and promoted.

In November 2009 the Australian Government House of Representatives Standing Committee on Health and Ageing Roundtable forum on impotence medications released its report on the health impacts of impotence medications in Australia. In relation to extemporaneous compounding of these medications, the Committee commented on:

the lack of consumer awareness that compounded medicines have not been subject to clinical trials

the compounding by some pharmacies of significant quantities of individual treatments that verged on mass production.

The House of Representatives’ Committee supported the development and speedy implementation of the NCCTG’s [2008] proposals to strengthen regulation around compounding.


http://www.aph.gov.au/Parliamentary_Business/Committees/House_of_Representatives_Committees?url=/haa/impotence/hearings.htm

http://www.tga.gov.au/archive/consult-ncctg-compounding-080410.htm

http://www.tga.gov.au/archive/consult-ncctg-compounding-080410.htm

http://www.tga.gov.au/archive/review-ncctg-compounding-050921.htm


In mid 2010, the NCCTG updated its 2008 proposal and removed several elements: limits on the range of active ingredients used in compounding, prior approval of compounded medicines, and differentiation of 'Class 1' from 'Class 2' pharmacies. The NCCTG proposal was that pharmacies that manufacture medicines would require a manufacturing licence from the TGA in two situations:

where the pharmacy compounds sterile medicines other than topical sterile medicines and single-use injections (which may be subject to further qualification)

where the pharmacy compounds in excess of a specified quantitative limit; this proposed limit was 500 prescriptions/month.

In order to obtain information to support development of regulation, the NCCTG published Seeking information from compounding pharmacies. Specific information was sought regarding quantities of compounded medicines produced, and types of sterile medicines compounded.

From late 2012, the TGA has been in direct consultation with peak bodies, including the Pharmaceutical Society of Australia, the Pharmacy Guild of Australia, the Society of Hospital Pharmacists of Australia, the Australian College of Pharmacy, the Medicines Australia Compounding Manufacturers' Advisory Group, and the Pharmacy Board of Australia Compounding Working Party.


http://www.tga.gov.au/newsroom/consult-ncctg-compounding-100610.htm


Appendix 3: Manufacture that would require a manufacturing licensed pharmacy under Option C1

Medicine type Need licence?

Eye preparations:

- eye drops

- eye lotions

- powders for eye drops and powders for eye lotions

- semi-solid eye preparations

- ophthalmic inserts

No

No

No

No

Yes

Parenteral preparations:

- implants. Yes

Parenteral preparations, such as:

- injections

- infusions

- concentrates for injections or infusions

- powders for injections or infusions

- gels for injections

Yes, except if:

- single use only, and

- for immediate supply, and

- for immediate use




Medicine type Examples

Dosage forms required to comply with a sterility standard

terminally sterilised medicines

aseptic compounding

total parenteral nutrition

Radiopharmaceuticals

Dosage forms required to comply with Uniformity of Dosage Units standard using Content Uniformity

micro dose products

Medicines where segregation of activities is required penicillins

cytotoxics

hormones

Medicines where special facilities/equipment are needed to maintain efficacy of the product

special lighting arrangements

nitrogen blanketing

Medicines that may not be interchangeable when made by different pharmacies / manufacturers

sustained release medicine

modified release medicine

liposomal products

medicines with low therapeutic index




Manufacturing activity above the following limits

Non-sterile medicines in excess of:

Five litres of an oral or topical liquid

Five kilograms of a cream, ointment or gel

300 grams of loose powder blend or capsule powder blend

More than 300 grams and less and 5 kilograms of loose powder blend, or capsule powder blend for encapsulation only if there is demonstrated validation of the process (including testing) completed prior to the sale or supply of the product

100 suppositories or other single solid dose forms, excluding capsules

Any sterile medicine

500 compounded medicines per month


Therapeutic Goods AdministrationPO Box 100 Woden ACT 2606 Australia

Email: [email protected] Phone: 1800 020 653 Fax: 02 6232 8605www.tga.gov.au

Reference/Publication #

http://www.tga.gov.au/

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