1. New legislation impacting IMP
Brenda Van Assche – 16 Dec 2016

2. Definitions GMP related documents: ICH, PDA, ISO, PIC/S, WHO, ...
Regulation:
Binding legislative act.
It must be applied in its entirety across the EU.
Directive:
Sets out a goal that all EU countries must achieve.
Up to the individual countries to devise their own laws on how to reach these goals.
Guideline:
Translates all regulations and directives into best practices.
The GMP guide will be regularly revised in order to reflect continual improvement of best practices in the field of Quality.
a special category of law in addition to EU directives and regulations, has supremacy over national laws and national constitutions.
Delegated Act:
Delegated act = non-legislative acts of general application to supplement or amend certain non-essential elements of a legislative act.
Parliament and Council can delegate to the commission the power to adopt “non legislative” acts of general application to supplement or amend certain non essential elements of a legislative act. Advantage is that a delegated act does not need to go via Parliament and Council and therefore should be a faster update process.
The Lisbon Treaty makes a distinction between two sets of Commission acts – delegated acts, and implementing acts. Delegated acts are dealt with by Article They are defined as non-legislative acts of general application to supplement or amend certain non-essential elements of a legislative act. Implementing acts are dealt with by Article These are to be used where uniform conditions for implementing legally binding Union acts are required.
GMP related documents:
ICH, PDA, ISO, PIC/S, WHO, ...

3. New and upcoming legislation impacting IMPs
OPPORTUNITY TO INFLUENCE
Delegated act GMP for IMPs
(Comments due 24Nov2015) c
Guideline GMP for IMPs
(Comments due 24Nov2015)
Guideline GMP for ATMPs
2° consultation paper: (Comments due 26Sep2016)
Delegated act on definition of IMPs
and use of AMPs
(Comments due 31Aug2016)
Eudralex Vol 4
Annex 1
(3-4Q2016 ?)
CT Regulation 536/2014
(Oct2018 at the latest)
Eudralex Vol 4 Annex 21
(Sep 2016 ?)
EU MD Regulation
(Effective date unknown)
Eudralex Vol 4 Annex 16
(15Apr2016)
IMPD Guideline
(Comments due 12Oct2016)
Eudralex Vol 4 Annex 17
(Comments due 11Dec2015)
Guideline on continuous mfg
ISO MD
(28Feb2019)
Data Integrity (WHO)
Upcoming
Draft
Final, not effective
Effective

4. New and upcoming legislation impacting IMPs
OPPORTUNITY TO INFLUENCE
Delegated act GMP for IMPs
(Comments due 24Nov2015) c
Guideline GMP for IMPs
(Comments due 24Nov2015)
Guideline GMP for ATMPs
2° consultation paper: (Comments due 26Sep2016)
Delegated act on definition of IMPs
and use of AMPs
(Comments due 31Aug2016)
Eudralex Vol 4
Annex 1
(3-4Q2016 ?)
CT Regulation 536/2014
(Oct2018 at the latest)
Eudralex Vol 4 Annex 21
(Sep 2016 ?)
EU MD Regulation
(Effective date unknown)
Eudralex Vol 4 Annex 16
(15Apr2016)
IMPD Guideline
(Comments due 12Oct2016)
Eudralex Vol 4 Annex 17
(Comments due 11Dec2015)
Guideline on continuous mfg
ISO MD
(28Feb2019)
Data Integrity (WHO)
Upcoming
Draft
Final, not effective
Effective

5. Eudralex Vol 4 Annex 16: Final, Effective
“Certification by a Qualified Person and Batch release”
Effective since 15 April 2016
The principles apply to IMP for human use
Reasons for changes: to reflect the globalisation of the pharmaceutical supply chains and the introduction of new quality control strategies
Highlights:
Supply Chain Map
Continous QP training
Deviation Handling
Quality Management System
QP to QP agreement
EMA Q&A pending release

6. New and upcoming legislation impacting IMPs
OPPORTUNITY TO INFLUENCE
Delegated act GMP for IMPs
(Comments due 24Nov2015) c
Guideline GMP for IMPs
(Comments due 24Nov2015)
Guideline GMP for ATMPs
2° consultation paper: (Comments due 26Sep2016)
Delegated act on definition of IMPs
and use of AMPs
(Comments due 31Aug2016)
Eudralex Vol 4
Annex 1
(3-4Q2016 ?)
CT Regulation 536/2014
(Oct2018 at the latest)
Eudralex Vol 4 Annex 21
(Sep 2016 ?)
EU MD Regulation
(Effective date unknown)
Eudralex Vol 4 Annex 16
(15Apr2016)
IMPD Guideline
(Comments due 12Oct2016)
Eudralex Vol 4 Annex 17
(Comments due 11Dec2015)
Guideline on continuous mfg
ISO MD
(28Feb2019)
Data Integrity (WHO)
Upcoming
Draft
Final, not effective
Effective

7. Data Integrity Data Integrity = The Topic of the Year
Attributable
Legible
Contemporaneous
Original
Accurate
Current regulatory framework:
WHO guideline = current “State of the Art”
FDA
PIC/S
EU regulations:
EMA Q&A
MHRA: consultation paper (v3)
EU Inspections versus Chapter 4 “Documentation” and Annex 11 “Computerised systems”
Christina => to comment on current legal framework in EU to conduct inspections

8. New and upcoming legislation impacting IMPs
OPPORTUNITY TO INFLUENCE
Delegated act GMP for IMPs
(Comments due 24Nov2015) c
Guideline GMP for IMPs
(Comments due 24Nov2015)
Guideline GMP for ATMPs
2° consultation paper: (Comments due 26Sep2016)
Delegated act on definition of IMPs
and use of AMPs
(Comments due 31Aug2016)
Eudralex Vol 4
Annex 1
(3-4Q2016 ?)
CT Regulation 536/2014
(Oct2018 at the latest)
Eudralex Vol 4 Annex 21
(Sep 2016 ?)
EU MD Regulation
(Effective date unknown)
Eudralex Vol 4 Annex 16
(15Apr2016)
IMPD Guideline
(Comments due 12Oct2016)
Eudralex Vol 4 Annex 17
(Comments due 11Dec2015)
Guideline on continuous mfg
ISO MD
(28Feb2019)
Data Integrity (WHO)
Upcoming
Draft
Final, not effective
Effective

9. Final, not effective Clinical Trial Regulation 536/2014
Effective as from Oct 2018, at the latest Expect more communication from EMA EO 2016
EU Medical Device Regulation
Effective date unknown yet
ISO Medical device
Effective as from 28 Feb 2019

10. New and upcoming legislation impacting IMPs
OPPORTUNITY TO INFLUENCE
Delegated act GMP for IMPs
(Comments due 24Nov2015) c
Guideline GMP for IMPs
(Comments due 24Nov2015)
Guideline GMP for ATMPs
2° consultation paper: (Comments due 26Sep2016)
Delegated act on definition of IMPs
and use of AMPs
(Comments due 31Aug2016)
Eudralex Vol 4
Annex 1
(3-4Q2016 ?)
CT Regulation 536/2014
(Oct2018 at the latest)
Eudralex Vol 4 Annex 21
(Sep 2016 ?)
EU MD Regulation
(Effective date unknown)
Eudralex Vol 4 Annex 16
(15Apr2016)
IMPD Guideline
(Comments due 12Oct2016)
Eudralex Vol 4 Annex 17
(Comments due 11Dec2015)
Guideline on continuous mfg
ISO MD
(28Feb2019)
Data Integrity (WHO)
Upcoming
Draft
Final, not effective
Effective

11. Draft
“Commission Delegated Act on Principles and guidelines on GMP for IMPs for human use and inspection procedures”
and
“Detailed Commission guidelines on GMP for IMPs for human use”
Comments have been submitted by 24 Nov 2015, pending revisions. Comments focused on clear delineation between IMP vs commercial MP.
Directive 2003/94/EC is split into 2 new documents: one for IMP (= Delegated Act) and one for commercial MPs
Annex 13 will become obsolete when the guideline becomes operational
New structure in IMP legislation

12. Draft Guideline on GMP for ATMPs
ATMPs = Advanced Therapy Medicinal Products
What is an ATMP?
Defined in Directive 2001/83/EC, as amended.
An ATMP is a medicinal product, which is either:
a gene therapy medicinal product as defined in Part IV of Annex 1 to Directive 2001/83/EC
a somatic cell therapy medicinal product as defined in Part IV of Annex 1 to Directive 2001/83/EC
a tissue engineered product as defined in Article 21 (b) of the ATMP Regulation 1394/2007
What about new structure for ATMP legislation ?

13. Draft Guideline on GMP for ATMPs
Stand-alone guideline document pursuant to Article 5 of Regulation 1394/2007, hence independent from EU GMP guidelines Part I & II and Annexes. One standard to reduce burden and allow flexibility for manufacturers to apply measures best suited to the specific product.
In-Scope: ATMPs for commercial as well as clinical use
Out-of-Scope: Manufacturing of ATMPs under the hospital exemption

14. Draft Guideline on GMP for ATMPs – Current status
Current draft is developed from Annex 2 repetition of much of Volume (personnel, premises, equipment, documentation, etc.), however key components from Volume 4 are missing (key elements of pharmaceutical quality management system e.g. Change Control, QRM = reflected in risk based approach, no link to ICHQ10)
Possible ways to go:
Include into Volume 4 as a new annex,
Stand-alone document with cross-references to relevant Volume 4 chapters and annexes,
Stand-alone document with potential repetition of GMP requirements from relevant Volume 4 chapters and annexes

15. New and upcoming legislation impacting IMPs
OPPORTUNITY TO INFLUENCE
Delegated act GMP for IMPs
(Comments due 24Nov2015) c
Guideline GMP for IMPs
(Comments due 24Nov2015)
ATMPs
2° consultation paper: (Comments due 26Sep2016)
Delegated act on definition of IMPs
and use of AMPs
(Comments due 31Aug2016)
Eudralex Vol 4
Annex 1
(3-4Q2016 ?)
CT Regulation 536/2014
(Oct2018 at the latest)
Eudralex Vol 4 Annex 21
(Sep 2016 ?)
EU MD Regulation
(Effective date unknown)
Eudralex Vol 4 Annex 16
(15Apr2016)
IMPD Guideline
(Comments due 12Oct2016)
Annex 2: technical revision ongoing, ATMP removed and being moved to ATMP guideline. ATMP guideline expected to be final 2017
Eudralex Vol 4 Annex 17
(Comments due 11Dec2015)
Guideline on continuous mfg
ISO MD
(28Feb2019)
Data Integrity (WHO)
Upcoming
Draft
Final, not effective
Effective

16. Thank You !
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