Regulatory guidelines of

Australia

Presented By: Guided By:

Nandini Warier(14MPH806) Dr. Charmy Kothari
Semester-II
Nirma University
 Content
What is TGA, its role & objectives?
TGA structure
TGA guidelines for clinical trials.
TGA Guidelines for Drugs
How the drugs are listed?
Phases of prescription drug registration.
TGA drug approval of OTC & Complementary
Drugs.
 What is TGA??

The Therapeutic Goods Administration (TGA) is

a unit of the Australian Government Department
of Health and Ageing, is responsible for
administering the Act.
Which came into effect on 15 February 1991.
Responsibility for the regulatory controls lies with
the Therapeutic Goods Administration (TGA) as the
national regulatory authority for therapeutic goods.
 OBJECTIVES OF TGA
To provide a national framework for the
regulation of therapeutic goods in Australia to
ensure the quality, safety and efficacy of
medicines and ensure the quality, safety and
performance of medical devices
Essentially therapeutic goods must be entered
on the Australian Register of Therapeutic
Goods (ARTG) before they can be supplied in
Australia
 ROLE OF TGA
The TGA carries out an overall control through five
main processes:

Pre-market evaluation and approval of registered

products intended for supply in Australia;
Development, maintenance and monitoring of the
systems for listing of medicines;
Licensing of manufacturers in accordance with
international standards of GMPs
Post-market monitoring, through sampling, adverse
event reporting, surveillance activities, and response to
public inquiries.
The assessment of medicines for export.
TGA STRUCTURE:
 REGULATION OF CLINICAL TRIALS BY TGA
Clinical trials of medicines and medical devices conducted in
Australia are subject to Commonwealth Government regulation
administered by the Therapeutic Goods Administration (TGA).

There are two schemes to conduct clinical trials

A. Clinical Trial Exemption (CTX) Scheme: Trial sponsor notifies

the TGA of their intention to conduct a clinical trial using an
unapproved therapeutic good.
B. Clinical Trial Notification(CTN) Scheme: The TGA does not
review any data relating to the clinical trial. The CTN Form is
submitted by the investigator on behalf of the sponsor to the
HREC and to the Approving Authority. Once the sponsor, the
principal investigator, the Chairman of the HREC and the person
responsible from the Approving Authority have signed the CTN
Form, it is submitted by the sponsor of the trial to the TGA along
with the appropriate notification fee.
ROLE OF STAKEHOLDERS IN CTN/CTX
Difference between CTN/CTX Scheme
As per the TGA act regulations all type of goods are divided in
to medicines and devices. Medicines are again divided in to
I. Prescription medicines,
ii. Non-prescription medicines and
iii. Export only medicines
Prescription medicines (PM):
High-risk medicines
Ingredients described in Standard for the Uniform Scheduling
of Drugs and Poisons (SUSDP) and are available by
prescription only.
The Drug Safety Evaluation Board (DSEB) evaluates the
majority of prescription medicine applications. Ex: insulin for
diabetics.
Must be registered in TGA.
Non-prescription medicines (NPM):
classified in to two categories that are,
A. OTC Medicines-The Non-prescription Medicines Branch
(NPMB) is responsible for evaluating OTC medicines.
B. Complementary medicines-One or more designated active
ingredients, each of which has a clearly established identity
and for traditional use.
The Office of Complementary Medicines (OCM) is responsible
for the evaluation of complementary medicines at the TGA.
 CONTD..
Export only medicines:
Products containing substances, quantities of
substances or labels without mandatory warning
statements required for listing for supply in Australia
which would require registration for domestic supply
will be assessed under Section 26 of the Act.
Ex:
1. Commercial export of medicines.
2. Export of medicines for donation or humanitarian
purposes.
3. Export of human body fluids/ tissue.
4. Export of medical devices.
 Medicine registration/Listing.
As per the TGA regulations high risk medicines should
be registered and low risk medicine need to list at ARTG
for marketing the drug products in Australian region.
After approving the medicine, it can get the assigned
number either an AUST R number (registered) or AUST
L number (listed medicines).
AUS R Medicines:
Registered medicines
Registered medicines are assessed by the TGA for quality, safety and efficacy.

Includes all prescription drugs & some OTC drugs like for pains,cough,fever etc
Prescription only medicines do not display their purpose on labels for which it lies with the
doctor
AUS L Medicines:
Listed medicines are assessed by TGA for quality & safety but not efficacy.

They are used for minor health problems-example. Sunscreens, vitamins, herbals, minerals.
How the medicines are listed??
 Prescription Drugs
Classified into 3 category applications
1)Category 1:Application includes
New chemical entities.
New dosage forms.
New strengths and new generic products.
Significant variations to an existing application.
2)Category2:Can only be utilized when an application has been
previously accepted in two countries. Requires shorter time frame
for evaluation.
3)Category 3:Involve changes to the quality data of medicines
already included on the ARTG.
Do not need to be supported by clinical, non-clinical or
bioequivalence data.
Example: The shelf life and storage conditions, labeling and
packaging, replacement trade name, Minor changes in formulation
Category 1 & 2 application evaluation process
Category 3 application evaluation process
 Time period
Application Form Required working days
Category 1 applications
Application submission to acceptance for
40
evaluation
Evaluation time 255
Category 2 applications
Application submission to acceptance for 20
evaluation
Evaluation time 175

Fees & charges for Evaluation

Category Fees $
New Chemical Entities 170,200
New Generics 65,000
New Indications 101,200
Product Information Changes 65,900
Additional Trade Names Only 10,700
 Key groups in Prescription medicine
registration
1) Drug Safety & Evaluation Branch(DSEB)-They give priority
evaluation status to Category 1 &2 applications.
The DSEB requires the submission of all relevant quality data,,
non-clinical data, and clinical data to support the application.
2) Financial Services Group (FSG)-Accounts for the fees paid to
TGA for the application.
3) The Application Entry Team (AET)-Will conduct an
administrative screen of the application before the dossier is
accepted for evaluation to ensure that there are no
deficiencies that would render the application un-evaluable.
4) TGA Delegates-The TGA may contract external evaluators to
review aspects of the data. A TGA Delegate will coordinate
the evaluation with the external evaluator. The identity of
external evaluators is generally kept confidential.
 S31 requests..
The TGA may request information additional to that provided in
the dossier, or may seek clarification of information provided.
Such requests are referred to as Section 31 requests.
For an application, these requests may be issued at any time
from submission of the application to marketing approval.
The evaluation clock is stopped until a full response to the S31
request is submitted.
All (S31) requests are identified with a unique identification
number, a S31 Request Number. This number should be quoted
in the heading of any response to the request.
If a sponsor considers that a S31 request is unreasonable they
should discuss this with the Delegate who issued the request.
If the sponsor is not satisfied with the outcome, the sponsor
may request a review of the issue by the Standing Arbitration
Committee (SAC) or Pharmaceutical Sub-Committee (PSC)
 Registration phases of Prescription drugs
Phase 1-Pre-Submission Phase:
Applies to Category 1 & 2 applications
It begins with lodging Pre-submission Planning
Form(PPF).
Once a PPF has been considered complete and
acceptable, the TGA begins the process of
securing appropriate evaluators for the dossier.
Contains quality, clinical, non clinical evidence
included in dossier.
PPF acceptable-A TGA Planning letter sent to
applicant with expected dossier lodgment date,
and target dates.
DSEB application form 15 & sponsor application
letter sent to FSG along with the fees.
The Planning letter is sent 15th of the month, following the month in which
PPF is processed.
Requirements of Pre-Submission:
PPF , Module 2 data, Certificate by applicant, Application fees, Changes in
Pre-submission , Key dates.
 Phase 2- Submission Phase
Dossier submission is done in eCTD format.
Submission phases involve processing activities.
This phase starts with receipt of dossier & ends
when TGA sends applicant Notification Letter .
Dossier must be received by TGA on 7th of
month following receipt of Planning Letter.
Notification letter sent to the application within
end of the month in which dossier was lodged.
Notification letter advises the applicant whether
the application is accepted or not.
An application is considered effective if:
i. The dossier arrives by expected date.
ii. It satisfies TGA regulatory requirements
iii. It is completed form.
The full evaluation fees should be paid after receiving the letter, within 2
months.
Applicant can withdraw the application, but if Module 3,4,5 evaluation is
over, then 25% of remaining evaluation fees is to be paid.
Phase 3-First round assessment phase
All the data provided by the dossier are considered
by the evaluators during this phase.
1st round assessment starts with Notification letter
& ends with Milestone 3 Letter
Applicant will be sent Milestone 3 Letter including:
i. S31 requests for information or documents
required.
ii. Copies of the first round assessment reports
prepared by the quality, nonclinical, clinical and
evaluators.
1st round evaluation requires
i. 3 months for generic application
ii. 4 months for other applications.
TGA Delegate, Evaluators, DSEB can further send evaluation reports to ADEC
for advice in complicated applications.
 Phase 4-S31 Response Phase.
Applicant prepare a response and send the
response to the TGA.
The S31 request response phase ends on the
date by which the applicant is required to
respond to the S31 as identified in the section
31 request letter .
Proposed S31 response time-30-60 days.
The S31 request response period does not
count within the 255 working day period for
evaluation.
The evaluation clock stops till the request
response are obtained.
The response to S31 request containing
information & documents should be in CTD
format-hard & electronic copy formats.
 Phase 5-2nd round assessment Phase
Evaluators will consider the response obtained by
applicant & complete evaluation of data.

This phase starts event though the S31 request

response is not obtained.

TGA will complete the 2nd assessment report:

i. Within 2 months for generics
ii. Within 1 month for other applications.

Applicant will be given 14 calender days after

the TGA issues the final evaluation report, in
which to review & advice the TGA of any errors
occurred.
 Phase-6-Expert Advisory Review Phase
After phase 5-evaluation report is considered by
delegate. The delegate may seek advice by various
committees.
The major advisory committee are ACPM (Advisory
Committee on Prescription Medicines)
The expert advisory review phase begins on the day
of Delegates request to ACPM.
The applicant is notified of the ACPM meeting &
the applicant ensures that a pre-ACPM response is
received by committee 13 days before the meeting.
Delegate sends a copy of the request to the
applicant prior to the ACPM meeting to allow the
applicant to compile a Pre-ACPM response. The
Pre-ACPM response is the applicants opportunity
to provide final comment on the application .
The ACPM advice is published in Australian public
assessment report (AusPAR)
 Phase-7 Decision phase.
TGA Delegate will determine whether the
application is to be approved or not.

The applicant will be notified in writing of the

decision within 28 days of it being made .

The decision Phase begins when the ACPM advice

is sent to the applicant on the 15th of the month
of the ACPM meeting.

The decision phase is completed when the

applicant is notified of the delegates decision 6
weeks after the ACPM meeting.
 Phase 8-Post decision Phase
At this Phase the Administration & regulatory
activities are completed.
Post-decision phase begins when applicant is
notified of the Delegates decision.
The phase is completed by the end of the month
following the delegates decision.
A new Registry entry can be included on ARTG
once applicant provides Patent Certificate or
notice to the TGA.
The provisional ARTG record will become ARTG
Record of Registration.
The applicant notifies actual commencement
date of the marketing
OTC DRUG APPROVAL PROCESS
COMPLEMENTARY DRUGS APPROVAL
PROCESS
 REFERENCES
Guidance document Prescription medicine
registration process by TGA, Version-2.0,May
2013.
Pharmaceutical Drug products approval process
in Australia by Usnei Reddy Mallu,June- Vol 2011
Dossier submission to TGA for Prescription
medicines by M.M Gupta
Australian Clinical Trial Handbook by TGA,2006