TGA presentation to industry on phased implementation of PIC/S Version 13.0 and update on the soon to be release PIC/S Annex 1.

1. Updates to Good Manufacturing Practices
PE009-13 Adoption Strategy and Annex 1 Updates
Neale Baldwin
Senior Inspector
Manufacturing Quality Branch
July 2017

2. PIC/S Adoption process overview
Phase 1
Nov 15 – current
Preparatory work
- Complete gap analysis of
changes
- Industry consultation via
TIWGG
- Drafting and development of
guidance and training materials
- Communications internally and
externally
- Legal documents/provisions
approval
Phase 2
12 months
- Go-live planned – date
pending
- Implementation of 12
month phased adoption
strategy
- Update of guidance
documents
- Industry communication
and feedback
Phase 3
post 12 months
- Full implementation of
PE009-13 requirements
- Commence activities for
adoption of PE009-14
adoption
- Continued development
of guidance on as-needs
basis
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3. Activities to date
• Gap analysis PE009-8 vs PE 009-13 (Dec 2016)
– Summary of main changes (drafted for publication)
• Industry consultation via TIWGG (Q4 2016)
• PIC/S issue PE009-13 (Jan 2017)
• Q&A drafting (March 2017)
• Phased adoption strategy (March 2017)
• Internal communications (ongoing)
• Legal aspects concerning implementation (in-progress)
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4. Phase 1 Activities required before “go-live” - Nov 2015 to Date
• Notification of intent to adopt PE009-13 (early 2017)
• Develop/amend web communications for PE009-13 – Q&A
• Phased Implementation Strategy
• APVMA discussions/MOU
• Roadshow for industry (to be confirmed)
• Web notices and second update of intent to adopt (due soon)
Communications
• Legislative provisions for PE009-13 Therapeutic Goods (Manufacturing Principles)
Determination
• Potential application of GMP guide to previously unregulated entities (Annex 2)
Legal Activities
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5. Phased Implementation Strategy (draft examples)
PIC/S GMP Requirement During 1st six months During 2nd 6 months
Beyond 12 month
implementation period
Part I, Chapter 1
Clause 1.6 Management
Reviews
Approved policy
Documented assessment of which
data will be collated and reported.
Commenced amending and drafting
procedures
Commenced training staff in
Management Reviews
Initial management review
meetings held.
Mechanisms for resolving
issues formalised and
implemented
Schedule for management
reviews finalised.
Full implementation of
management reviews
Clause 1.7: Quality Manual Commence drafting of Quality
Manual (ICH Q10)
Approved Quality Manual in
place.
Full Implementation
• Summary document (to be published) also outlines how deficiencies will be
reported by the TGA 4

6. Phase 2 Following “go-live” (during 12 month Implementation Phase)
• Inspect against “Adoption Strategy”
• Encourage feedback from manufacturers
Inspection Activities
• Update guidance documents (14 identified to date) with TIWGs
• Ongoing consultation with impacted entities (Annex 2 related)
Communications
• Review existing determinations/technical decisions in QMS
Quality Management System
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7. Phase 3 Following “full implementation” (post implementation phase)
• Future PIC/S changes (Ch 3, 5 & 8, Annex 1, Annex 16)
• Ongoing management of feedback from industry (TIWG’s, TIWGG, etc.)
Communications
• SOP updates/development
• Inspector training (medicines, devices and specialists)
Quality Management System
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8. Annex 1 - Key reasons for update
• Original version revised in 1996, 2003, 2005, 2007 and 2009; no complete
review of the document since originally issued
• Introducing principles of Quality Risk Management
• Provide guidance for new technologies:
• Reinforcing the need of manufacturers to keep up with current technologies
• Single use closed systems
• Disposable systems
• Innovative technologies, processing and testing
• Monograph on WFI
• ISO 14644 updates
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9. Annex 1 update - process
• Joint working group between PIC/S and EMA (and WHO)
• Drafted by IWG throughout 2016
• Draft Annex 1 circulated to PIC/S members and IWG Feb 2017
• Comments received and reviewed
• Updated draft referred to the May IWG
• Public consultation on the draft is due out soon!
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10. Annex 1 – new structure (1)
Section Number General overview
1.Scope New section to link to other annexes and chapters
Additional areas (other than sterile medicinal products) where the general principles of
the annex can be applied.
2.Principles General principles as applied to the manufacture of medicinal products.
3. Pharmaceutical Quality System
(PQS)
Highlights the specific requirements of the PQS when applied to sterile medicinal
products.
Re-enforcing the process of quality risk management.
Re-enforcing the process of Root Cause Analysis and product impact assessment
4. Personnel Guidance on the requirements for specific training, knowledge and skills. Also gives
guidance to the qualification of personnel.
Goggles (face coverings)
5. Premises General guidance regarding the specific needs for premises design and also guidance
on the qualification of premises including the use of barrier technology. 9

11. Annex 1 – new structure (2)
Section Number General overview
6. Equipment General guidance on the design and operation of equipment.
7. Utilities Guidance with regards to the special requirements of utilities such as water, air and
vacuum.
WFI by RO; Biofilms
8. Production and specific
technologies
Discusses the approaches to be taken with regards to aseptic and terminal sterilisation
processes. Also discusses different technologies such as lyophilisation and BFS where
specific requirements may be required. Discusses approaches to sterilization of products,
equipment and packaging components.
9. Viable and non viable
environmental and process
monitoring
This section differs from guidance given in section 5 in that the guidance here applies to
ongoing routine monitoring with regards to the setting of alert limits and reviewing trend
data.
The section also gives guidance on the requirements of Aseptic Process Simulation.
10. Quality control Give guidance on some of the specific Quality Control requirements relating to sterile
medicinal products.
11. Glossary Explanation of specific terminology. 10

12. Areas of Clarity or ambiguity
• Pre-Use, Post Sterilization Integrity Test of Product Sterilising Filters
(PUPSIT)
Requirement retained “as is”
No coherent case against the risk of omitting PUPSIT
Supported by all IWG members
• Grade A Supply Air?
Now defined in glossary: “Grade A air – Air which is passed through a filter qualified as capable of
producing Grade A, non-viable quality air, but where there is no requirement to continuously
perform non-viable monitoring or meet Grade A viable monitoring limits.”
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13. Areas of Clarity or ambiguity
• CCIT
– Clause 117. Containers should be closed by appropriately
validated methods. Containers closed by fusion, e.g. glass or
plastic ampoules should be subject to 100% integrity testing.
– Samples of other containers should be checked for integrity
according to appropriate procedures.
 TGA expects batch specific sampling and testing of these
containers, following QRM.
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14. Areas of Clarity or ambiguity
• Cleanroom classification/monitoring
– Updates regarding 5.0µm classification made in
accordance with ISO 14644.1 – 2015
– ISO 14644 referenced, not mandated
– New section on routine monitoring specifies both 0.5 and 5.0µm continuous
monitoring.
– Expectations regarding classification frequency included in new draft
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15. Areas of Clarity or ambiguity
• Media fills:
– Batches can be 10s of thousands so why is low level
contamination in media fills accepted?
– The intent is zero
– Anything else needs to be:
 Investigated
 Corrected
 Possibly revalidated
 Revalidation, the magic number?
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16. Areas of Clarity or ambiguity
• Settle plate Averages
– Same locations, different session?
– Same session, different locations?
– Different locations, different sessions?
– Reference to averaging has been removed from Annex 1
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17. Questions?
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