Transition to new GMP requirements for medicinal products

A notice about the implications of adopting PE009-13

21 November 2017

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Transition plan

The transition period from 1 January 2018 to 1 January 2019 serves to allow manufacturers to assess and plan for these changes and permit time for implementation.

For the most significant changes, we have produced transition plan tables, which summarise the minimum requirements to demonstrate compliance.

The approach that will be taken where these have not been met is outlined below.

Compliance with all other changes is expected from 1 January 2018 and transition arrangements do not apply.

Our expectation is that by 1 July 2018, manufacturers will have:

  • completed their assessment of the impact of the new manufacturing principles on their operations
  • completed, or be well advanced, towards updating quality systems documentation and implementing revised practices.

We recognise the complexity associated with these changes and have therefore provided appropriate timeframes for implementation, which reflect the complexity and significance of each change. Where the impact is minimal to the manufacturer, we would expect that adoption would be well progressed or implemented by July 2018, unless justified.

Transition plan diagram

diagram showing transition arrangements - for full description see text version below

1 January 2018 to 30 June 2018: Manufacturers assess impact of new manufacturing principles on their operations; Start updating quality systems documentation; Working towards implementing revised practices.

1 July 2018 to 31 December 2018: Completed assessment of impact; Approved quality systems documentation in place; Implementing revised practices quality policy/procedures; Staff awareness training complete; Commence trending critical parameters; Amending/drafting new contracts.

1 January 2019: Full implementation.

Reporting deficiencies in Post Inspection Letters (PIL)

We issue a PIL at the conclusion of an on-site inspection to communicate departures from GMP, with the purpose of assisting companies to restore compliance through root cause assessment and corrective actions.

During the transitional implementation period, we will be aiming to assist and encourage implementation of the new requirements. As a result, we will not cite a deficiency when companies demonstrate they are meeting the minimum expectations summarised below.

We will report a deficiency if the company has not undertaken an appropriate approach to implementing the new requirements or may not achieve compliance in a timely manner. This will usually be cited as an 'other' deficiency against the relevant part of the PIC/S Guide to GMP.

Major deficiencies will generally only be cited where a manufacturer has not commenced, or significantly progressed, action to implement the new PIC/S Guide to GMP requirements. A Major deficiency may also be cited where a manufacturer's implemented procedures and systems do not meet the requirements of the PIC/S Guide to GMP.

Transition plan tables

Part I, Chapter 1
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

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

Clause 1.7:

Quality Manual

  • Commence drafting of Quality Manual (ICH Q10)
  • Approved Quality Manual in place
Full implementation

Clause 1.10(i):

Review of supply chain traceability for APIs

  • Documented assessment of APIs utilised by the manufacturer
  • Commenced drafting procedures for the evaluation of API supply chains and schedule for completion
  • Drafting updates to existing Product Quality Review (PQR) procedures to incorporate new requirements
  • Commence evaluation of supply chains for APIs used by the site
Full implementation
Part I, Chapter 2
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

Clause 2.4:

Quality Policy

  • Senior management commence drafting of Quality Policy (ICH Q10)
  • Mechanism for continuous improvement defined and documented
  • Approved Quality Policy in place
  • Staff awareness training completed
  • Periodic reviews of Quality Policy scheduled
  • Full implementation
Full implementation
Part I, Chapter 6
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

Clause 6.16:

Trending of critical parameters

  • Documented assessment of which data will be collated and reported, including assessment of the extent of any retrospective trending
  • Commenced amending and drafting procedures
  • Commenced training staff in trending of critical parameters
  • Commence trending of critical parameters
Full implementation

Clauses 6.37-6.41:

Guidelines for method transfer

  • Documented assessment of existing procedures against new guidance
  • Defined timeline for any amendments required for existing procedures
  • Approved procedures in place for method transfer
  • Method transfer activities performed in accordance with new requirements
Full implementation
Part I, Chapter 7
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

Outsourced activities

  • 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

Part II, Chapter 2
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

Clause 2.2:

Application of Quality Risk Management (QRM) to the manufacture of Active Pharmaceutical Ingredients

  • Approved policy
  • Documented assessment where QRM will apply
  • Commenced amending and drafting procedures
  • Commenced training staff in QRM
  • QRM is built into the Quality System
  • Commenced using QRM in changes, investigations etc
Full implementation
Annex 2 Manufacture of biological medicinal substances and products for human use
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

Annex 2:

Manufacture of biological medicinal substances and products for human use

  • Documented assessment of Annex 2 changes and impact upon existing operations
  • Change controls initiated within Quality Management System (QMS)
  • Commence updates to Marketing Authorisations for affected products
  • Commence implementing changes
Full implementation

Application of Good Manufacturing Practice to additional elements of the supply chain, e.g. collection sites for animal/plant tissues

  • Documented assessment of Annex 2 changes and impact upon existing operations
  • Change controls initiated within QMS
  • Collate list of impacted manufacturing sites
  • Commence evaluation and supplier approval of additional manufacturing sites within the scope of Annex 2
Full implementation
Annex 3 Manufacture of Radiopharmaceuticals
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

Clause 18:

Requirement to have separate gowning facilities at entry of production area

  • Documented assessment of impact of change
  • Change controls and implementation plans initiated within QMS for any modifications identified
  • Commence any modification of facilities required
Full implementation

Clause 27:

Positioning of closed and automated systems

  • Documented assessment of impact of change
  • Change controls and implementation plans initiated within QMS for any modifications identified
  • Commence any modification of facilities where required
Full implementation

Clause 33:

Introduction of a fixed retention period for batch records

  • Documented assessment of impact of change
  • Commence drafting of procedures for document retention
  • Approved procedures in place for batch record retention
Full implementation
Annex 6 Manufacture of Medicinal Gases
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

General

  • Documented assessment of Annex 6 changes and impact upon existing operations
  • Change controls initiated within QMS
  • Commence implementing changes
Full implementation
Annex 7 Manufacture of Herbal medicinal products
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

General

  • Documented assessment of Annex 7 changes and impact upon existing operations
  • Change controls initiated within QMS
  • Commence implementing changes
Full implementation
Annex 11 Computerised Systems
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

General

  • Documented assessment of Annex 11 changes and impact upon existing operations
  • Change controls initiated within QMS
  • Commence implementing changes
Full implementation
Annex 13 Manufacture of Investigational Medicinal Products
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

Clauses 36 & 37:

Management of retention/reference samples

  • Documented assessment of Annex 13 changes and impact upon existing operations
  • Change controls initiated within QMS to address reference/retention sample requirements
  • Commence implementing changes
Full implementation
Annex 15 Qualification and Validation
PIC/S GMP Requirement Between 1 January and 30 June 2018 Between 1 July 2018 and 31 December 2018 From 1 January 2019

General

  • Documented assessment of Annex 15 changes and impact upon existing operations
  • Change controls initiated within QMS to address new requirements
  • Commence implementing changes
Full implementation

Removal of provision to perform retrospective process validation

  • Assessment of current products undergoing retrospective validation
  • Record plan for completion of process validation based on retrospective data
  • Update internal procedures to remove provisions for retrospective process validation
  • Prospective validation required prior to release for all new products
  • Full implementation from 1 July 2018
  • Only prospective or (in justified cases) concurrent process validation permitted from this date onwards
Full implementation

Clauses 5.8-5.32:

Introduction of ongoing process verification

  • Documented assessment of the impact of the new requirement
  • Commenced amending and drafting procedures
  • Commenced training staff
  • Commence collation of data for ongoing verification process
  • Commence reporting of outcomes from ongoing verification process
Full implementation

Clauses 6.1-6.4:

Verification of transportation

  • Approved policy
  • Commenced amending and drafting procedures including system for assessing transport routes
  • Identify key transportation methods and routes and define plan for assessment
  • Commenced training staff
  • Commence risk assessments for transportation methods and routes
  • Commence monitoring of transported products
Full implementation

Clause 10.6:

Cleaning validation - toxicological assessments

  • Approved policy
  • Commenced amending and drafting procedures for toxicological assessments
  • Identify actives and materials that require toxicological assessment and devise risk-based plan for systematic assessment
  • Commenced training staff
  • Commence performing and documenting toxicological assessment of actives and excipients used by the manufacturing facility
Full implementation

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