Regulatory Update. Greg McGurk, GMP Manager (acting) GMP Conference. 7 February 2017 Dublin

Transcription

1 Regulatory Update Greg McGurk, GMP Manager (acting) GMP Conference 7 February 2017 Dublin

2 GMP Update Chapter 3 - Premises and Equipment (into operation since 1 March 2015) Chapter 5 - Production (into operation since 1 March 2015) Chapter 8 Complaints, Quality Defects and Product Recall (into operation since 1 March 2015) Annex 1 under revision Annex 2 Removal of References to ATMPs

3 GMP Update Annex 13 Investigational Medicinal Products Annex 15 (October 2015) Qualification & Validation Annex 17 Real Time Release Annex 21 GMP for Importers of Medicinal Products

4 Revisions to Legislation and other relevant changes Clinical Trials Regulation delegated acts / directives related to GMP for IMP Risk assessment of excipients Safety Features

5 Implementation of Chapters 3 & 5 Expectations for application of toxicological guidance Applicable for all new products (H+V) introduced from 1st June 2015 Applicable for legacy human medicines from 1st December 2015 (including assessment of vet products where vet and human medicines are manufactured in same facility) Applicable for legacy veterinary medicines from 1st June 2016 (manufacturers where only veterinary medicines are involved)

6 Implementation of Chapters 3 & 5 (continued) - Programme in place to deal with existing products - Risk based approach - Toxicological basis to justify approach taken - Select worst case products initially for tox evaluation Cleaning validation is only one aspect to be considered for cross contamination risk

7 Implementation of Toxicological Approach Questions and answers on implementation of risk based prevention of cross contamination in production and Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities EMA/CHMP/CVMP/SWP/169430/2012 Consultation deadline for comments April

8 Revision of Annex 1 Parallel session 1A Revision of Annex 2 Remove references to ATMP

9 Annex 15 revision Effective since October 2015 Take account of changes to other sections of the EudraLex, Volume 4, Part I, relationship to Part II, Annex 11, ICH Q8, Q9, Q10 and Q11 QWP guidance on process validation Changes in manufacturing technology

10 Annex 15 revision Traditional Process Validation Concept - Continuous Process Verification Hybrid approach Verification of Transportation Utilities Packaging Plenary session

11 Annex 17 Real time release testing Parametric release Real Time Release Testing Advances in the application of process analytical technology (PAT) Advances in the application of quality by design (QbD) Advances in the application of quality risk management (QRM) principles Combination of process controls, timely monitoring and verification of pre-established material attributes provides greater assurance of product quality than finished product testing alone

12 Annex 17 Real time release Public consultation phase complete Working group progressing through comments Planned for publication in

13 Annex 21 Importation of Medicinal Products Concept paper & Draft developed GMDP IWG review phase Consideration for Definitions Aspects of importation process site for batch certification site for importation testing site of physical importation When is a product deemed to have been imported?

14 ATMPs --New GMP Guidance ATMP Regulation, (EC) No 1394/2007, provides for development of GMP guidance for these products. Summary of feedback on consultation document published on EU Commission website along with details of the output from public consultation phase Intent of the document is to recognise that manufacture of ATMPs and ATIMPs is different to other products, (e.g. variable starting materials, small batches, short shelf life). Synopsises derogation from existing GMP guidance with some additional changes particularly for early stage development. Some cross reference to existing GMPs Applicable to Investigational and Commercial ATMPs Working group involving GMP inspectors and members of CAT

15 GMP for Investigational Medicinal Products Clinical Trials Regulation No. 536/2014 New Clinical Trials Regulation - Repeals Directive 2001/20/EC Published 16th April 2014 (effective 2018) Article 63 GMP for Manufacture and Import New GMP Guidance for Manufacture / Importation of IMPs issued for consultation from 28th August 2015 to 24th November Feedback from public consultation now published on the EU Commission website

16 New GMP Guidance for IMPs Commission Delegated Regulation on GMP for IMPs issued on 13th January 2017 deadline for comment 10th February 2017 Based largely on Directive 2003/94/EC (GMP Directive) Cross references to sections of the GMP Guide are included in the new guidance. Annex 13 to be deleted from the GMP Guide and some changes from current requirements

17 New GMP Guidance for Human Medicinal Products Commission Implementing Directive on GMP for Human Medicinal Products To replace existing Directive 2003/94/EC (GMP Directive) Feedback Period 13 th January th February 2017 Commission better regulation portal

18 Excipients Risk Assessment Guidelines for Risk Assessment for ascertaining appropriate GMP for Excipients for Human Medicines Published 19th March 2015 Excipient risk assessment to have been completed for authorised medicinal products by 21st March 2016 Principles of ICH Q9 Considerations: Source; Use of the excipient

19 Excipients Risk Assessment Identify relevant parts of Eudralex Vol IV which would be applicable based on the risk assessment Determine risk profile for the excipient manufacturer Confirmation of application of appropriate GMP in manufacture of the excipient Parallel session 1B

20 Safety Features Unique Identifier (2D Barcode) Harmonised EU format including: Product Code, Serialisation Number, National Reimbursement No (if applicable), batch number & Expiry Date Repository set up by stakeholders (supervision by CAs) Verification at Pharmacy Level Checks at Wholesale level based on risk Anti Tampering Device

21 Delegated Regulation on Safety Features Delegated Regulation (2016/161) published 9th Feb 2016 and mandatory implementation by 9th Feb 2019 New challenges for packaging of prescription products Interactions with Stakeholders in Ireland HPRA has written to stakeholders HPRA hosted workshops in Athlone, Cork and Dublin

22 Delegated Regulation on Safety Features Inspections: Will start asking about on-site plans for implementation of requirements for safety features Manufacturer s status regarding implementation of requirements will be documented in the inspection report as a Point to Note Controls and procedures for safety features to be reviewed in detail after implementation Parallel Session 2B

23 Thank you