Staying Ahead of the Curve in an Increasingly Complex Regulatory World as seen from Novo Nordisk A/S, a global pharmaceutical manufacturer

Søren Thuesen Pedersen, Novo Nordisk A/S

The External Requirement Process

Capture of new requirements

Pre-analysisCapture of

industry practice trends

Capture of regulator

expectations

AnalysisPlanning (of

implementation)Implementation &

Report

Influence

Formal HandoverTo Process

Organisation

25 Focus Groups Line of Business (Process Groups)

Process landscape

EudraLex Vol 4 EU - GMP

GMP Directive for MP(Directive 2017/1572, 15. Sept 2017)

Treaty of the EU and

European Community(2007/C 306/01)

Chapter 1-9ICH Q7

includes GDP for APIs(ICH Q9 principles added)

GMP for ExcipientsICH Q9, ICH Q10, SMF, Batch

certificate, API conf.

GDP for MP & API guidelines;Inspections: Compilation of

commutiy procedures

MP: Medicianl Product

red: medicinal product,

blue: API; brown: GDP

green: in consutat ion

Sec

onda

ry L

aw (‘

leve

l 1’)

Reg

ulat

ory

stat

utes

Community code Medicinal products for human use

(Directive 2001/83/EC)

Prim

ary

Law

Authorization: Art 40

GMP: Art 47

Saftey features: Art 54a(2)

GDP: Art 84

Art 168(4)(a)Art. 114

& 168(4c)

GDPAPI Excipients

Art 63(4) Inspections

Safety feature

Falsified Medicines Dir (Directive 2011/62/EC)

New EC gui (ex Annex 13; 24.11.15)

amending

Art. 95 &

152(4)(b)

Sec

onda

ry L

aw (‘

leve

l 2’)

Manufacturing of Med.Dev ISO13485, EC Mark (Directive 93/68/EEC),

‘Blue Guide’ ECnotice 2016/C 272/01

Medical Device Regulation (Regulation 2017/745, 05. April 2017)

(9) authorisation; (17) GMP; (21) IMP-GMP

Advanced Therapy MP(Regulation EC 1394/2007)

Art 5. GMP for ATMP

Specific APIs or therapies, specific conditions, supporting GMP processes, procedural gui, enablers

Part II

GMP Active Substances as starting material (incl. GDP)

Part I

GMP Medicinal Product(i.e. drug products)

Part III

GMP related

documents

Other Documents

Related to GMP(incl. e.g. Inspections, Certificat ion)

Stephan Rönninger, Amgen, 22.12.2017

Chapter 1-9

Regulation on safety features (Delegated regulation 2016/161, 02 Oct 15)

* Guidance exists; see ’Others’

(comp. of comm.procedures)

GMP for IMPs GMP for Active Substances (Regulation No 1252/2014)

Art 63(1) GMP IMP

Clinical Trials RegulationRegulation 536/2014

Pharmacovigilance(Regulation 520/2012)

amending

Art 93

also: Food law (Reg

EC No 178/2002) and

Cosmetics (Reg EC

No 1223/2009)

Authorisation of MP(Regulation 726/2004)

GMP Regulation for IMP(Delegated regulations 2017/1569, 23 May 17)

In vitro diagnostic MD reg

(Regulation 2017/746, 05. April 2017)

EC guidelines:GMP for IMPs

Annexes 1-13-17, 19, 21, 18 (ex ICH Q7), 20 (ex ICH Q9)

Existing gui

GMP for ATMPs (gui C(2017) 7694)

Part IV

GMP for ATMPs

documents

Example EU-GMPs: Legal System

New Requirements

• There are 48 pharmacopoeias

• 20 sets of GMP regulation

• EU-GMP; EudraLex

• 21CFR11

• ISO

• OECD

• EAEU

Regulator expectations

• Novo Nordisk 60 inspections/year and

• 90 internal audits

Industry Practice Trends

• 250 + External representation seats

What are Compliance Signals?

Into OneQualityManagement System

GMP Compliance Signals (2013-2019)

358

245

520469

424

522500

25

92 106 125

57 73 73

190

66 79 75

2013 2014 2015 2016 2017 2018 2019(Estimate)

Created Influenced Handed over

FDA Quality Metrics

Continuous Manufacturing

EU Medical Device Regulation

MRA EU - Japan (biologics)

EAEU

Chinese Pharmacopeia 2020

ICH Q12

EU Annex 1

Novo Nordisk Monographs

Brexit

Quality Focus Areas2018-2019

We will always advocate for harmonization of regulatory requirements

Monitor Active

• All external representation by Novo Nordisk is registered in TAR, the Trade Association Representation

• Create Synergy

• Training

External Representation

My Take Home messages:

• Gives a good overview and confidence !• Somewhat laborious. • Senior Mgt. buy-in is critical

Questions?