Updates to Good Manufacturing Practices

PE009-13 Adoption Strategy and Annex 1 Updates

Neale Baldwin

Senior Inspector

Manufacturing Quality Branch

July 2017

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

1

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)

2

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

3

Phased Implementation Strategy (draft examples)

PIC/S GMP Requirement During 1st six months During 2nd 6 monthsBeyond 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

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

5

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

6

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

7

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!

8

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

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

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.”

11

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.

12

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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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?

14

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

15

Questions?

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