Updating the Manufacturing Principles Adoption of Updates to the - - PowerPoint PPT Presentation

Updating the Manufacturing Principles

Adoption of Updates to the PIC/S Guide to GMP PE009

Matt Davis Senior GMP Inspector Manufacturing Quality Branch 26 June 2018

Overview

• Why adopt updates to GMP?
• Update Processes:

– EMA process – PIC/S process – TGA process

• Future Revisions

– PE009-14 – PE009-??

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Why adopt the latest PIC/S Guide to GMP?

• Australia is highly respected and regarded on an international level due to our

involvement and innovation with respect to GMP

• GMPs are routinely updated in response to identified risks:

– Risks to patient health – Ambiguity leading to misinterpretation and compliance risks

• Relevant to our Mutual Recognition Agreements
• Provides assurance of equivalence to international markets
• GMP, science and innovation never stands still.

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EC/EMA GMP Update Process

Update identified EM A / PIC/ S Concept Paper Consultation (General) Draft Guidance Document Consultation (Participating Authorities) Consolidated comments to PIC/ S / EM A Final draft submitted by EM A GM DP IWG – approval by EC

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PIC/S GMP Update Process

TIWGG M embers: Accord Australia New Zealand Industrial Gas Association (ANZIGA) Active Pharmaceutical Ingredient M anufacturer's Association of Australia (APIM AA) Australian Self M edication Industry (ASM I) Complementary M edicines Australia (CM A) Generic and Biosimilar M edicines Association (GBM A) M edicines Australia (M A).

Update identified

• EC
• SC-H

Draft document in PIC/ S format Draft document submitted to PIC/ S Committee for adoption. Draft paper released to participating authorities for comments TGA consults with TIWGG on draft PIC/ S document Comments considered and final draft provided to PIC/ S Committee Document approved and published with effective date

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TGA GMP Update Process

Establish internal project team Develop gap analysis TGA consults with TIWGG on draft Gap Analysis document Comments considered and final Gap Analysis endorsed Regulatory Impact Statement (OBPR) External communications strategy developed Adoption of new M anufacturing Principles

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Gap Analysis

PE 009-13 PE 009-08 Nature of impact Estimated significance

• f impact
• 1. ORGANISING AND PLANNING FOR QUALIFICATION AND VALIDATION

1.1 All qualification and validation activities should be planned and take the life cycle

• f facilities, equipment, utilities, process and product into consideration.

New clause, but equivalent requirements provided in PE009-8 Annex 15§2. PLANNING FOR VALIDATION

• 2. All validation activities should be planned. The key elements of a

validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent documents. Expanded planning section in PE009-13 However, this section provides additional clarification to that included within PE009-8: Clarification of existing requirements, no change to interpretation. Nil 5.21 A process validation protocol should be prepared which defines the critical process parameters (CPP), critical quality attributes (CQA) and the associated acceptance criteria which should be based on development data or documented process knowledge. New clause, but equivalent requirements provided in PE009-8 Annex 15§6. This clause introduces the terms CPP and CQA in line with ICH Q11

• terminology. While the terminology may be more prescriptive, the process
• f identifying critical steps (that directly influence the critical attributes of

the product) and acceptance criteria remain very similar to existing methods and expectations. (Note that these concepts already exist for API manufacturers)

• 6. A written protocol should be established that specifies how

qualification and validation will be conducted. The protocol should be reviewed and approved. The protocol should specify critical steps and acceptance criteria. Introduction of new terminology (CPP and CQA) into validation systems. Nil for some manufacturer s; minor for some.

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Adoption Plan – Examples

PIC/ S GM P Requirement Between 1 J anuary and 30 J une 2018 Between 1 J uly 2018 and 31 December 2018 From 1 J anuary 2019 Part I, Chapter 1 Clause 1.6 M anagement Reviews Approved policy Documented assessment of which data will be collated and reported. Commenced amending and drafting procedures Commenced training staff in M anagement Reviews Initial management review meetings held. M echanisms for resolving issues formalised and implemented Schedule for management reviews finalised. Full implementation Part I, Chapter 7 Outsourced activities M edium Risk Item Approved policy Commenced drafting procedures Risk assess/ Determine list of all service providers implicated. Develop priority list for evaluation and approval of providers. Approved procedures Commenced amending/ drafting new contracts Full implementation All outsourced activities approved and covered by an appropriate contract.

• Refer TGA website for guidance for deficiency reporting during the period

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MQB Adoption Timeline for PE009-13

November 2017

• 2nd notification for

industry

• Main changes table
• Adoption strategy
• Deficiency reporting

1 January 2018

• Adopt New GMP Guide
• Publish Q&A for GMP

31 June 2018 1 January 2019 Ongoing

Assess & establish Implement Full Compliance

12m Transition Period September 2017

• 1st notification for

industry

• APVMA notification

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Future Revisions of PE009

• 1 Jan 2017
• Chapter 1,

2, 6 & 7 (Part I)

PE009- 13

1 July 2018 Chapters 3, 5 & 8 Annex 17

PE009- 14

Future revisions Chapter 4 Annexes 1, 2, 11, 13, 16, 21

PE009- ??

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PE009-14 Chapter 3 – Premises and Equipment

• Additional guidance on Cross-contamination
• Quality Risk Management principles should be used to

assess and control the risks.

• Dedicated facilities are required when:

– the risk cannot be adequately controlled by operational and/ or technical measures, – scientific data from the toxicological evaluation does not support a controllable risk (e.g. allergenic potential from highly sensitising materials such as beta- lactams) or – relevant residue limits, derived from the toxicological evaluation, cannot be satisfactorily determined by a validated analytical method.

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PE009-14 Chapter 5 – Production – Cross Contamination (1)

• Quality Risk Management process… should be used to assess and

control the cross-contamination risks presented by the products manufactured.

• Technical Measures:

– Dedicated processes, equipment and facilities; – Use of closed systems, barrier, isolator, single-use technologies; – Dust extraction, air-locks, pressure cascades; – Clean-in-place, ease of cleaning considered in process/equipment design

• Organisational Measures:

– Campaign operation, campaign washing, cleaning verification; – Gown management, waste management, spill management; – Detailed cleaning records and instructions, continued oversight of compliance.

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PE009-14 Chapter 5 – Production – Starting Materials

• Selection, qualification, approval and maintenance of suppliers of starting

materials, together with their purchase and acceptance, should be documented as part of the pharmaceutical quality system.

• Staff involved in these activities should have a current knowledge of the

suppliers, the supply chain and the associated risks involved.

• Active Substances

– Supply chain traceability established and associated risks formally assessed and periodically verified. – Audits should be carried out at the manufacturers and distributors of active substances…audits should be of an appropriate duration and scope to ensure that a full and clear assessment of GMP is made. – The holder of the manufacturing authorisation shall verify such compliance either by himself/herself or through an entity acting on his/her behalf under a contract.

• Excipients

– formalised quality risk assessment (PI 045-1)

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PE009-14 Chapter 8 – Complaints & Product Recall

• Defined requirements for Personnel and

Organisation within the PQS

• Procedures for handling and investigating

complaints including possible quality defects

• Investigation and decision making
• Root cause analysis and CAPA
• Product Recalls and risk-reducing actions
• Reflects URPTG requirements

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PE009-14 Annex 17– RTRT & Parametric Release

• Real Time Release Testing (RTRT) (ICH Q8 Q&A)
• Control of critical parameters and relevant material attributes are

authorised as an alternative to routine end-product testing of active substances and/or finished products.

• RTRT may apply to any stage in the manufacturing process and to

any type of finished products or active substances, including their intermediates.

• Real time measurement of CPP(s) as a predictor of compliance with

CQA.

• Thorough understanding of critical material attributes.
• Well defined control strategy: QRM, validation, change control,

training, etc

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PE009-14 Annex 17– RTRT & Parametric Release

• Parametric Release – terminally sterilised products
• Updates to text providing clarification of existing requirements.
• Detailed guidance regarding the scope of the sterility assurance

program.

• Additional emphasis on Quality Risk Management.
• Guidance for pre-sterilisation bioburden testing and controls, and

consideration of heat-resistant organisms.

• Well defined control strategy: QRM, validation, change control,

training, etc

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Summary

• PE009-13 live from 1 January 2018

– Refer to TGA website for all updates (Ax 2, 3, 6, 7, 11, 13) – 12 month transition plan on TGA website – We encourage feedback and discussion (use Audit feedback form - interpretation of requirements) – Refer queries to gmp@tga.gov.au

• TGA has commenced reviews of PE009-14 and will continue to work with industry
• n adoption of future changes
• Get involved!

– EMA/EC Feedback – TGA/TIWGG Feedback

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