This presentation will describe how the TGA undertakes the screening process and will discuss the mandatory requirements for applications, including specific examples of problems commonly encountered.

1. Overcoming the stress of non-prescription medicine
application screening
Complementary medicines
Dr Natasha Kelly
Scientific Evaluator
Complementary Medicines Evaluation Section,
Complementary & OTC Medicines Branch, TGA
ARCS Annual Conference
21 August 2018

2. Overview
• Screening process of complementary medicines evaluated by
Complementary Medicines Evaluation Section (CMES)
– Applications screened
– Workflow and key changes
• Discuss the new mandatory requirements
– Registered complementary medicines (RCM)
– Assessed listed L(A) medicines
• Common pitfalls and how to overcome them
Submit effective applications

3. Applications screened by CMES
Application type Section of Act Evaluation Screened Timeframe Regulation
Applications for new complementary medicine products
RCM Section 23 Quality, Safety
& Efficacy
Yes 40 wd Reg. 16GH
L(A) medicine Section 23 Efficacy Yes 40 wd Reg. 16GH
Other applications
RCM Change/
Variations
Section 23/
Section 9D
Quality, Safety
& Efficacy
Yes 40 wd Reg. 16GH/
Reg. 16GG
Substances for LM Subsection 26BE Quality & Safety Yes 40 wd Reg. 16GI
wd – working days

4. General workflow for screening applications
Application received and application fees paid
Date = 40 working day start
Application screened by CMES
Application has minor
deficiencies
Opportunity to remedy minor
deficiencies
Deficiencies
unresolved
Application has
critical issues/
unresolved deficiencies
Notice of refusal sent
Deficiencies
resolved
Application
acceptable
Notice of acceptance sent
Payment of evaluation fees

5. Key changes
Current Screening Process Previous Screening Process
Application fee Paid upon submission One fee
Evaluation fee Payable after passing preliminary
assessment
Timeframes Yes - 40 working days No timeframe
Information on
data requirements
Guidance in ARGCM
L(A) evidence guidelines
Section 23 Legislative instruments
Guidance in ARGCM

6. Requirements for effective applications
• Legislative requirements of section 23 of the Act
• Mandatory requirements for effective:
– RCM applications
– L(A) applications
• General dossier and CTD module format
• Further information:
– ARGCM for application process
– Assessed listed medicines evidence guidelines
– Australian and adopted international guidelines
 Quality, Safety & Efficacy

7. Mandatory requirements for effective applications
• Separate documents for RCM and
L(A) medicines
• Content structure
– Mandatory requirements
– Appendix A – specific mandatory
requirements
 Application category
 CTD module
RCM - https://www.tga.gov.au/book-page/mandatory-requirements-1
L(A) - https://www.tga.gov.au/book-page/mandatory-requirements-0

8. Mandatory requirements
• Organisation and format
• Content
– Technical data requirements
 Appendix A – specific mandatory requirements
– Australian and adopted international guidelines
• Justification of data gaps
• Administrative requirements

9. Specific requirements for an effective RCM
Requirements for RCM 1 applications:
 CTD Module 1: registered complementary medicines including:
– a letter of authorisation from the sponsor of the fully evaluated originator medicine to access the medicine information in Module 1 under
‘letters of authorisation’ (1.5.5); and
– assurance that all quality aspects of the proposed medicine are identical to the originator medicine, other than differences that are
specifically permitted (as listed in the permitted differences guidance) in Module 1 under ‘Assurances’ (1.5.7)
 If the proposed product includes a new flavour, fragrance or colour (including printing inks), provide the proposed specifications and details of
the test methods for the new flavour/fragrance/colours(s) in Module 3 under ‘control of excipients’ (3.2.P.4).
Application type (more than one
type may apply)
RCM Appln.
level
CTD Module Module 5 Requirement
Applications that include comparative
bioavailability/ bioequivalence reports
RCM4, RCM5,
C4-RCM
5.3.1 Provide bioavailability/bioequivalence study reports in accordance
with requirements detailed in:
 Guidance 15: Biopharmaceutical Studies
Note:
 The Australian originator reference medicine used in the studies
must have been registered on the basis of a full dossier, which may
include chemical, biological, pharmaceutical, pharmacological-
toxicological and clinical data.
 The bioavailability/bioequivalence summary is placed in Module
1.9.1

10. Specific requirements for L(A) medicines
Requirements for L(A)1 applications
 CTD Module 1: Administrative information for assessed listed medicines including:
– Co-marketed medicines declarations (letters of authorisation) (section 1.5.5).
– Assessed listed medicine assurances (section 1.5.7).
Requirements for L(A)2 applications
 CTD Module 1: Administrative information for assessed listed medicines including:
– For applications using the Comparable overseas regulator (COR) report based process, provide the assessment and other information as
described in the document ‘Comparable overseas regulators (CORs) for complementary medicines – guidance for use of COR reports in
Module 1’ (section 1.11).
– For generic based applications, provide Summary of bioavailability or bioequivalence study (section 1.9.1) or Justification for not providing
biopharmaceutic studies (section 1.9.2).
 Module 2 (only for generic based applications)
 Module 5 (only for applications providing biopharmaceutic data).
Requirements for L(A)3 applications
 CTD Module 1: Administrative information for assessed listed medicines
 Module 2
 Module 5

11. Common pitfalls
• Shared queries and deficiencies with OTC
– E.g. accidently omitted documents, literature searches
• Gross deficiency or insufficiency
– E.g. entire module or important component of module
• Lack of justification for gaps in data
• Format of reports
– Summary / unpublished manuscripts instead of full study reports
– Not in English

12. Common pitfalls
• Inadequate safety and/or efficacy data
– E.g. for target population, duration of use, indications
• Bioequivalence and biowavers
– Inadequate justification
– Biowaver not appropriate for the formulation (E.g. prolonged release) or active
ingredients (E.g. ferrous salts plus folic acid)
 Guidance 15: Biopharmaceutic studies
 European Union Guideline on the investigation of bioequivalence
• Application category
– RCM 2 for evaluation of a complementary medicine based on comparable
overseas regulator (COR) reports

13. Substance application categories (subsection 26BE)
Category TGA evaluation Quality data Safety data Timeframe
IN1 Abridged evaluation of quality
and safety.
COR evaluation report COR evaluation report 70 wd
IN2 Abridged evaluation of safety.
Full independent evaluation of
quality.
Full quality data set COR evaluation report 120 wd
IN3 Full independent evaluation of
safety.
Abridged evaluation of quality.
COR evaluation report;
or compliance with a
monograph from a
default standard
Full safety data set 150 wd
IN4 Full independent evaluation of
safety and quality.
Full quality data set Full safety data set 180 wd
COR – comparable overseas regulator; wd – working days

14. More common pitfalls
• Substance not eligible for use in
listed complementary medicines
– Schedule 14 of the Act
– The Poisons Standard
• Data pertaining to combined
substances
• Unacceptable dossier format
– General dossier or CTD module format
– Searchable
Designated Active Ingredients (Schedule 14)
Amino acid Microorganism
Charcoal Mineral
Choline salt Mucopolysaccharide
Essential oil Lipid
Non-human animal material Substance produced by bees
Plant or herbal material (or
synthetic)
Sugar polysaccharide or
carbohydrate
Homoeopathic preparation Vitamin or pro-vitamin

15. Benefits of the CTD format
• General dossier requirements applies to substance applications
• Use of the CTD format is encouraged
– Tracking of communication
– Consistent format/ presentation
– Ease of navigation
Facilitate smooth and efficient evaluations

16. How we can help
• Email – complementary.medicines@health.gov.au
• Pre-submission meetings
• Regulatory affairs consults
• SME Assist hub