implementing tgo 101 · ph. eur. monograph 2619) elemental impurities: bp and ep (general chapter...
TRANSCRIPT
Implementing TGO 101
Standard for tablets, capsules and pills
TGA – Industry workshop 13 May 2019
1
Outline
How we got here
Technical requirements
Implementation
Implementing TGO 101 2
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Previous scoping done however TGO 78 was not remade or repealed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
3
The conundrum…
• • •
Complexities of USP monographs, if mandatoryIndustry wanting certainty for medicines without monographsConfusion 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?
4
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31st March 2019 TGO 101 commenced TGO 78 repealed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
What’s changed? For medicines following an applicable monograph ü
Choice of pharmacopoeia
ü Monograph being followed can be changed with a variation
ü Order clarifies that general monographs and chapters are part of the applicable monograph
TGO 78 requirements, including folic acid dissolution requirements, retained.
6
What’s changed? For medicines not following an applicable monograph ü
This option can be chosen even where there is an applicable monograph
ü Default active ingredient assay values now 90.0-110.0% ü Registered medicines containing vitamins, minerals and probiotics may
use USP dietary supplement overages ü Impurity requirements clarified
TGO 78 requirements, including folic acid dissolution requirements, retained
7
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
Implementing TGO 101 8
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
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.
10
Any questions so far?
11
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
Any questions so far?
13
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.
Implementing TGO 101 14
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.
Implementing TGO 101 15
Elemental impurities
From the EP/BP principles of risk management
From USP<2232> a risk-based approach
From ICH Q3D risk-based control strategy
From TGO 101 guidance
Implementing TGO 101 16
In many cases, existing controls on impurities in the ingredients included in the medicine and compliance with GMP requirements may be sufficient
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.
17
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.
Implementing TGO 101 18
Any questions so far?
19
20
