Options for reform of the regulatory
framework for pharmacy compounding
Consultation 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 decisionmaking, 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>.
Copyright
© Commonwealth of Australia 2013
This 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
<tga.copyright@tga.gov.au>
Confidentiality
All 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.
Options for reform of the regulatory framework for pharmacy compounding:
V1.0 June 2013
Page 2 of 33
Therapeutic Goods Administration
Version history
Version
Description of change
Author
Effective date
V1.0
Original publication
TGA
June 2013
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 3 of 33
Therapeutic Goods Administration
Contents
Introduction
6
Activities outside the scope of this consultation RIS ___________________ 6
Background
7
Regulatory 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
11
Risks _________________________________________________________________________ 12
Community exposure _____________________________________________________ 14
Options
14
Option 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 _____________________________________________________________________ 22
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 4 of 33
Therapeutic Goods Administration
Summary
23
Making submissions
24
Content 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
Appendix 4: Manufacture that would require a
manufacturing licensed pharmacy under Option C2
31
Appendix 5: Manufacture that would require a
manufacturing licensed pharmacy under Option C3
32
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 5 of 33
Therapeutic Goods Administration
Introduction
This 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)
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 6 of 33
Therapeutic Goods Administration

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
medicine that was previously available is discontinued by the supplier for financial
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 7 of 33
Therapeutic Goods Administration
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
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 8 of 33
Therapeutic Goods Administration
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.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 9 of 33
Therapeutic Goods Administration
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
intention of this legislative arrangement was to allow a pharmacist to continue the longestablished practice of preparing a medicine for an individual patient in response to an
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>
1
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 10 of 33
Therapeutic Goods Administration
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 issues
The 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
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 11 of 33
Therapeutic Goods Administration
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 TGAapproved 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.
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.
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/Medicinesth
atdonotneedalicence/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/compliconform/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>
4
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 12 of 33
Therapeutic Goods Administration
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
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
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/89105/200809301443/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/newengland-compounding-center-product-recall-alert.html>
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/O
RA/ORAElectronicReadingRoom/ucm340853.htm>
7
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 13 of 33
Therapeutic Goods Administration

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.
Options
Three 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.
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>
13
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 14 of 33
Therapeutic Goods Administration
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
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.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 15 of 33
Therapeutic Goods Administration
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.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 16 of 33
Therapeutic Goods Administration
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.
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
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
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>
15
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 17 of 33
Therapeutic Goods Administration
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 2 – Therapeutic
goods
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:
5
[contract manufacturer
exemption]
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
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.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 18 of 33
Therapeutic Goods Administration
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
(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,
(c) on the premises of a private hospital;
for supply (other than by wholesale) on or from those premises

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.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 19 of 33
Therapeutic Goods Administration
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 suboptions relate to sterile medicines, other complex formulations, and quantities.
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.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 20 of 33
Therapeutic Goods Administration
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
See Division 1, clause (3) of the Therapeutic Goods (Manufacturing Principles) Determination No.
1 of 2013.
16
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 21 of 33
Therapeutic Goods Administration
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.

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.
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>
17
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 22 of 33
Therapeutic Goods Administration
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:
(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
(c) on the premises of a private hospital;
for supply (other than by wholesale) on or from those premises

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
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 23 of 33
Therapeutic Goods Administration

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).
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 24 of 33
Therapeutic Goods Administration
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
pharmacy.manufacture@tga.gov.au. 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 Section
Office of Scientific Evaluation
Therapeutic Goods Administration
PO Box 100
WODEN 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 pharmacy.manufacture@tga.gov.au or by telephone to 02 6232 8623.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 25 of 33
Therapeutic Goods Administration
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)
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 26 of 33
Therapeutic Goods Administration
Term
Definition
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
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.
(from section 3 of the Act)
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.
(from section 2 of the Act)
pharmaceutical a Commonwealth pharmaceutical benefit under the National
benefit
Health Act 1953 or the Veterans’ Entitlements Act 1986
(from regulation 2 of the Regulations)
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 27 of 33
Therapeutic Goods Administration
Appendix 2: Previous consultations
In 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 nonhospital 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.
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
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 28 of 33
Therapeutic Goods Administration
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.
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 29 of 33
Therapeutic Goods Administration
Appendix 3: Manufacture that would
require a manufacturing licensed
pharmacy under Option C1
Medicine type
Need licence?
Eye preparations:
- eye drops
No
- eye lotions
No
- powders for eye drops and powders for eye lotions
No
- semi-solid eye preparations
No
- ophthalmic inserts
Yes
Parenteral preparations:
- implants.
Yes
Parenteral preparations, such as:
- injections
Yes, except if:
- infusions
- single use only, and
- concentrates for injections or infusions
- for immediate supply, and
- powders for injections or infusions
- for immediate use
- gels for injections
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 30 of 33
Therapeutic Goods Administration
Appendix 4: Manufacture that would
require a manufacturing licensed
pharmacy under Option C2
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
Medicines that may not be interchangeable when
made by different pharmacies / manufacturers
sustained release medicine
nitrogen blanketing
modified release medicine
liposomal products
medicines with low
therapeutic index
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 31 of 33
Therapeutic Goods Administration
Appendix 5: Manufacture that would
require a manufacturing licensed
pharmacy under Option C3
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
Options for reform of the regulatory framework for pharmacy compounding
V1.0 June 2013
Page 32 of 33
Therapeutic Goods Administration
PO Box 100 Woden ACT 2606 Australia
Email: info@tga.gov.au Phone: 1800 020 653 Fax: 02 6232 8605
www.tga.gov.au
Reference/Publication #