This presentation highlights some of the changes in Therapeutic Goods (Standard for Tablets, Capsules and Pills) (TGO 101) Order 2019, compared to the previous Order, Therapeutic Goods Order No. 78 – Standard for tablets and capsules.

1. Implementing TGO 101
Standard for tablets, capsules and pills
TGA – Industry workshop
13 May 2019

2. Outline
How we got here
Technical requirements
Implementation
Implementing TGO 101 2

3. TGO 101: How we got here
• Previous scoping done however TGO 78 was not remade or
repealed
• Recognition of multiple default standards
• TGO 78 remake - industry agreed the Order was needed but
amendment required
TGO 78 sunsetting on 1 April 2019
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4. The conundrum…
• Complexities of USP monographs, if mandatory
• Industry wanting certainty for medicines without monographs
• Confusion about the operation of the general monographs/chapters in the USP,
BP, EP
How do you re-make the Order to align internationally without significant
change to regulatory burden?
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5. Introduction of requirements
• 31st March 2019
– TGO 101 commenced
– TGO 78 repealed
• Two year transition periods
– Section 16
impurities where a monograph is not followed
– Part 3 - Pills
Implementing TGO 101 5

6. What’s changed?
For medicines following an applicable monograph
 Choice of pharmacopoeia
 Monograph being followed can be changed with a variation
 Order clarifies that general monographs and chapters are part of the
applicable monograph
TGO 78 requirements, including folic acid dissolution requirements,
retained.
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7. What’s changed?
For medicines not following an applicable monograph
 This option can be chosen even where there is an applicable
monograph
 Default active ingredient assay values now 90.0-110.0%
 Registered medicines containing vitamins, minerals and probiotics may
use USP dietary supplement overages
 Impurity requirements clarified
TGO 78 requirements, including folic acid dissolution requirements,
retained
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8. What’s changed?
Pills
– Pills were included in TGO 56 (1996)
but omitted from TGO 78
– All pills on the ARTG are listed
Traditional Chinese Medicines
– Default standards are largely silent
on pills
– TGO 101 requirements and tests
aligned with the Chinese
Pharmacopeia
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9. Standards recognised in the Act
• Ministerial standards
– Orders created under section 10
• Default standards
– Defined in section 3 as monographs in the
British, European or United States
Pharmacopeias.
‘subject to one or more monographs’
this means both specific/individual AND general
monographs.
Implementing TGO 101 9

10. Legal operation of default standards
Subsection 13(2) -
If a ministerial standard applies
AND
applicable requirements are also in a default standard
AND
the requirements are in conflict
THEN
requirements in default standard are disregarded
Where a ministerial and a default standard do not
conflict, then both sets of requirements are applicable.
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11. Any questions so far?
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12. Dissolution
TGO 78 required a test for dissolution
when:
 A BP monograph required it; or
 The medicine contained more
than 100 micrograms of folic acid;
or
 Was modified release; or
 Is a registered medicine, with an
active ingredient which is subject
to a dissolution test in the USP.
TGO 101 requires a test for dissolution
when:
 A monograph requires it; or
 The medicine contained more
than 100 micrograms of folic acid;
or
 Is modified release; or
 Is a registered medicine, not
following a monograph, but a
monograph for the same dosage
form with any of the same active
ingredients requires it.
No test for dissolution required for listed medicines that do not claim to be modified
release or do not contain folic acid, unless they choose to follow a monograph that
requires it. 12

13. Any questions so far?
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14. Elemental impurities
EP and BP cover impurities in Pharmaceutical Preparations General
Monograph (Ph. Eur. Monograph 2619)
Elemental Impurities:
• BP and EP (general chapter 5.20) effectively defer to ICH Q3D.
• USP<232> is the equivalent for non-dietary supplements
• USP<2232> covers dietary supplements (aligns closely with ICH Q3D
but only covers the ‘big four’ heavy metals)
Following a specific monograph which has heavy metal limits takes
precedence over the general chapter.
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15. Elemental impurities
TGO 101 s16 allows either
• ICHQ3D
• USP 2232
approach to elemental impurity control to be used if a monograph is not
being followed.
Batchwise testing for elemental
impurities is not expected.
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16. Elemental impurities
From the EP/BP principles of risk management
a risk-based approach
risk-based control strategyFrom ICH Q3D
From USP<2232>
From TGO 101
guidance
In many cases, existing controls
on impurities in the ingredients
included in the medicine and
compliance with GMP
requirements may be sufficient
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17. From the guidance
• Compliance with TGO 101 is not necessarily sufficient to demonstrate
quality, safety or efficacy for the purposes of registering or listing a
medicine. Additional requirements may be applied, for example, as
conditions of listing or conditions of registration.
• In some instances, compliance with TGO 101 may not be sufficient to
establish the safe use of medicines. Sponsors will need to further
consider the intended patient population, size of the recommended
daily dose, etc. to ensure that their medicines are safe for the purpose
for which they are to be used.
• Consideration must also be given to any other relevant standards.
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18. GMP requirements
• Inspectors inspect against the code of GMP, not
TGOs.
• GMP code requires manufacturers to know and
produce products that comply with marketing
authorisation.
• Inspectors will interrogate quality systems to
ensure they can achieve this.
• This will include consideration of relevant TGOs,
especially if ‘release for supply’ is a step of
manufacture.
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19. Any questions so far?
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21. Questions?
TGO78.remake@tga.gov.au
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