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TRANSCRIPT
GMP Updates
Dearbhla Cullen, GMP Inspector
QP Forum
25 April 2017
Content
MRA between the EU and the US
Safety features
Annex 17 revision
Draft Q&A on setting health based limits for manufacture of medicines in shared facilities
Reflection paper on Good Manufacturing Practice and Marketing Authorisation Holders
Annex 1 revision
78th Meeting of Pharmaceutical Committee for Human Medicines
24/04/2017 2
MRA between EU and US
• Annex to the EU-US Mutual Recognition Agreement (MRA)
which was signed in 1998 but not yet implemented.
• All human and veterinary API and finished product medicines
with the exception of veterinary immunological medicines.
What
• Teams from the European Commission, EU national competent
authorities, EMA and the US FDA have been auditing and
assessing the respective supervisory systems since May 2014. How
• November 1, 2017
• Initially, 8 EU member states
• Gradually extend to other member states When
24/04/2017 3
Safety feature requirements
4
Commission Delegated Regulation (EU) 2016/161 sets out detailed requirements
for unique identifiers, including the repository system where they will be stored
New requirements will apply to in-scope medicines released to the EU market from
9th February 2019
Batch document review: Print quality ok? Reconciliation ok? Tamper evidence ok?
Production order serial number data set uploaded to company database?
Data upload to EU Hub upon QP certification of batch
Confirmation of data upload to EU / national Hub
Visit EMVO website https://www.emvo-medicines.eu/
Annex 17 – Real time release testing
Parametric
release
Advances in
PAT, QbD &
QRM
Process
control,
continuous
monitoring,
verification
24/04/2017 5
Annex 17 – Real time release
Public
consultation
phase
complete
Working
group
progressing
through
comments
Planned for
publication
in 2017
07-02-17 6
Q&A on implementation of risk based
prevention of cross contamination in production
24/04/2017 7
‘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)
Public consultation started in Jan 2017.
Deadline for comments is 30 April 2017.
Health based exposure limits (HBELs) for highly hazardous
products are expected to be completed in full as per the
EMA guide (EMA/CHMP/CVMP/SWP/169430/2012)
Reflection paper on Good Manufacturing
Practice and Marketing Authorisation Holders
• Lack of clarity on the responsibilities of MAHs Why
• Concept Paper EMA/582064/2016 published 01 September
2016 (public consultation ended Dec 2016).
• Reflection paper to be prepared by drafting group Q3 2017. What
• Review of the reflection paper at the GMP/GDP Inspectors
Working Group: May 2017.
• Agreement of the reflection paper: June 2017. When
24/04/2017 8
Annex 1 - Rationale for Revision
Needed “Tidying up”
Introducing principles of Quality Risk Management
New technologies:
• Reinforcing the need of manufacturers to keep up with current technologies
• Single use closed systems
• Disposable systems
• Innovative technologies
• Some ambiguities
Micro data averages
9
Annex 1 – what’s changing?
24/04/2017 10
Additional guidance in each of the sections to
incorporate QRM and new technologies, in addition
to general clarifications e.g. Airlocks for personnel
and materials should typically be separate
Personnel: requirement for personnel to wear
goggles in grade A/B.
Premises: Requirement to measure 5.0µm particles
has been removed.
Annex 1 - revision timelines
Public Consultation phase – Estimated – Q3 2017
IWG & PICs review – Feb 2017
Container closure integrity & Pre-use post sterilisation integrity
Comments received back
Two rounds of review - circulated to PIC/S and IWG Mid 2016 & November 2016
Subgroups – tasked with drafting various sections
Joint working group between PIC/S and EMA
07/02/2017 11
78th meeting of the Pharmaceutical Committee
for Human Medicines, 27 March 2017
In March 2017, the European Parliament adopted some
recommendations on shortages of medicines. the Commission and
Council are to establish a mechanism whereby medicine shortages
across the EU can be reported upon on an annual basis
Proposal to examine Article 81 of the pharmaceutical legislation
which is difficult to implement and enforce.
Agenda and documents at
https://ec.europa.eu/health/documents/pharmaceutical-
committee/human-meeting_en
24/04/2017 12
Thank you
Additional information
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
07-02-17 15
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
07-02-17 16
Annex 21 – Importation of Medicinal Products
Concept paper & Draft developed
GMDP IWG review phase
Consideration for Definitions
•site for batch certification
•site for importation testing
•site of physical importation
Aspects of importation process
When is a product deemed to have been imported ?
07-02-17 17
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
07-02-17 18
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 2015.
Feedback from public consultation now published on the EU Commission website.
07-02-17 19
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
07-02-17 20
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 13th January 2017 – 10th February 2017
Commission better regulation portal
https://ec.europa.eu/info/law/better-
regulation/initiatives_en?field_brp_inve_resource_type=All&field_brp_inve_leadin
g_service=All&page=1
07-02-17 21
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
07-02-17 22
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
07-02-17 23