CRED SMPC 2024

CRED An Overview of Regulatory Product Information 2 5 September 202 4

©The Organisation for Professionals in Regulatory Affairs 202 4 Presentations are supplied to delegates for their personal reference and are the copyright of the speaker and The Organisation for Professionals in Regulatory Affairs. The presentations must not be copied, stored in a retrieval system or transmitted in any form without prior permission from TOPRA. Agreement must be reached with TOPRA before any part of this material is reproduced, abstracted, stored in a retrieval system or transmitted in any form by any means – that is, electronic, mechanical, photocopying, recording or otherwise.

CRED Development of Regulatory Product Information in Europe 25 September 2024

Course Chair: Petrina Pearce, Advanz Pharma

Time

Session

Presenter

08:45 Registration and Coffee

09:00 Welcome from TOPRA

Petrina Pearce Advanz Pharma

Welcome from Chairman • Overview of the day

09:05

09:10 The Company Core Data Sheet •

Gabriela Fok Ipsen

Origins of the CCDS and its purpose • Preparation and implementation of the CCDS • Implications of regional differences for the CCDS and global labelling management

09:50

SmPC: Regulator’s perspective • The role of the SmPC •

Ronan Donelan HPRA

Overview of SmPC legislation/guidelines and template • Current SmPC issues and developments

10:50

Break

11:05 Strategy for the Development of the Optimal SmPC • Definition of an optimal SmPC • Contributing factors to an optimal SmPC • Key Stakeholders in an optimal SmPC •

Khristy Horsley and Lucy Paterson ICON plc

Common Pitfalls in the development of an optimal SmPC • Influence of the optimal SmPC on the development programme • Competitor analysis

Thomas Liebers ICON plc

12:05 Case Study and feedback - SmPCs

Gabriela Fok Ipsen

12:45 Panel Discussion

13:00 Lunch

Julia Coombes MHRA

13:45

Labels and Leaflets: Regulator’s perspective • Current legislation including recent changes • Label and leaflet requirements, including guidelines • Packaging with patient safety in mind • Good quality patient information & user testing • Future focus for patient information

Time

Session

Presenter

14:45 Preparation of the Label and Leaflet: Industry perspective Practical issues encountered when preparing proposed label and leaflet text for an MAA, including: • Specific requirements for Mutual Recognition, • Decentralised and Centralised procedures • Readability • Translations • Timings 15:30 Implementation of Labels and Leaflets: Industry perspective Practical issues encountered when implementing MA approved text into the marketplace, including: • Cross functional collaboration with stake holders • Safety issues • Commercial aspects • Production and logistical issues • Timelines 15:15 Break

Robert Hetherington Kyowa Kirin

Betti Mozes Stoddart Jazz Pharmaceuticals

Thomas Liebers ICON plc

16:15 Case Study – Labels and Leaflets

Gabriela Fok Ipsen

Petrina Pearce Advanz Pharma

16:55

Chairman’s Review of the Day & Final Discussion Session

17:10 Close of Workshop

Delegates will be encouraged to ask questions throughout the day so as to ensure the meeting is as interactive as possible.

Speaker Biographies

Petrina Pearce Petrina Pearce is a Senior Manager Regulatory Affairs New Products at Advanz Pharma, where she assumes overall responsibility for the registration and successful delivery of new product pipeline products from product identification up to commercial launch. Petrina has over 30 years’ experience in the pharmaceutical industry, from analytical testing through to the licencing of Medicinal Products and Medical Devices. Prior to joining Advanz, Petrina was employed as Regulatory Affairs Manager at Diamond BioPharm where she predominantly provided support to clients for licensing and post licensing activities for National, MRP/DCP and Centralised Procedures. Prior to that, she worked in Regulatory Affairs for Forest Laboratories, where she gained broad experience in regulatory strategy, regulatory CMC and regulatory compliance and built a solid knowledge base of regulatory procedures and guidelines. Before moving into Regulatory Affairs, Petrina spent many years in Quality Assurance at GSK. During this time she was responsible for a variety of activities, such as the release of batches of active pharmaceutical ingredients, inspection readiness, GMP compliance and regulatory conformance, implementation/maintenance of the validation lifecycle for nominated processes and also the investigation of problems (including the implementation of corrective and preventative actions). Petrina possesses an honours degree in Chemistry and is a member of the Organisation for Professionals in Regulatory Affairs (TOPRA). Gabriela Fok Gabriela "Gaby" Fok (mTOPRA) has been in the pharma industry for over 10 years with global and local regulatory affairs experience in a broad range of countries and regions. Gabriela holds a BSc in Biochemistry and an MSc in Forensic Science. Since 2010, Gaby has been working in regulatory affairs, with a significant portion of her career dedicated to life-cycle management of Prescription Only Medicines (POM), Pharmacy Medicines (P), Over-the-Counter (OTC) products, and General Sales List (GSL) items, with a particular emphasis on safety and product labelling in medicinal products. Gaby has experience in consultancy as well, and in recent years, her focus has shifted towards new active substances. Since 2023, Gabriela has been recognised as a Chartered Scientist through TOPRA since December 2023. Gaby currently leads a team in Ipsen as a senior Regulatory Affairs Manager, providing life-cycle management as well as strategic regulatory input, for the UK and Ireland business, focusing on oncology and rare diseases. She is also an advocate for workplace well-being and is a trained first-aider for the office. Gaby has previously also implemented document management systems for regulatory affairs, and collaborated on process optimization projects, as well as interacting with several European health authorities. Gaby is fluent in English, Cantonese and Mandarin, currently learning Japanese and is currently completing her Chartered Scientist Application.

Ronan Donelan Dr Ronan Donelan, HPRA Policy and Stakeholder Lead, has over 25 year’s experience in drug development and regulatory affairs. His career positions have included: EU Head of Regulatory Affairs for a Global CRO, Global Head of Regulatory Affairs for a global mid-size Pharma company, Head of Regulatory Affairs and PV in a start-up Pharma. He has experience in a broad range of therapeutic indication approvals. He has supported several TOPRA workshops during the past 20 years. He holds amMSc in Pharmaceutical Medicine, from Trinity College Dublin and a PhD from Cardiff School of Pharmacy. Khristy Horsley Khristy is an experienced Regulatory Labeling Professional with over 15 years of experience in Regulatory Affairs, Global Labeling Strategy and EU Labeling Operations. Khristy is currently a Associate Director Regulatory Labeling at ICON overseeing a small team of labeling professionals and supporting Labeling Strategy across several pharmaceutical companies. Khristy leads cross-functional teams in the development and lifecycle maintenance of company core datasheet (CCDS), based on signals or new data in alignment with client processes and regulatory guidance. She coordinates and leads cross-functional teams in the review and management of local labeling, content deviations and impact assessments. Khristy has extensive experience updating EU Product information (both Centralized and Mutual Recognition/Decentralized procedures) and supporting Local Affiliates worldwide in the implementation of CCDS updates. Additionally, Khristy has experience in labeling audits, development of end-to-end labeling process, SOPs and continuous improvement activities. Lucy Paterson Lucy is a Regulatory Labeling Professional with 4 years of experience. Lucy is responsible for development and lifecycle maintenance of Company Core Datasheet (CCDS), based on signals or new data in alignment with client processes and regulatory guidance. Lucy also provides support for worldwide labelling submissions to implement CCDS variations and support responses to health authority requests in markets such as the EU, US, Canada, Australia, Switzerland, Japan and China. She coordinates and leads cross-functional teams in the review and management of local labeling deviations. Additionally, Lucy has experience in reviewing and updating EU Product information, supporting the development of client end-to-end labelling processes, including authoring updates to labelling work instructions. She also provides support for client's audits, including researching auditor questions, filling document requests, and presenting on labeling systems.

Thomas Liebers Regulatory leader with over 15 years of expertise in the healthcare sector and pharmaceutical industry. My diverse background encompasses clinical nursing practice, experience at the European Medicines Agency, and successful leadership of an international team delivering regulatory services to the pharmaceutical and biotech industries. Central to my approach is a commitment to cultivating thriving client partnerships that offer flexible and cost-effective solutions. Adapting to evolving client requirements, I demonstrate strong management and oversight skills, ensuring the consistent delivery of top-tier regulatory services. These efforts have directly contributed to several successful initial authorizations of groundbreaking and innovative treatments. Overall, my track record reflects a steadfast dedication to excellence, innovation, and driving positive outcomes in the dynamic field of healthcare regulations. Julia Coombes I completed my BSc in Physiology and PhD at the University of Edinburgh. Following this, I took up two post-doctoral research positions at the National Institute for Medical Research (NIMR) and St Mary’s Hospital, Paddington. In July 1995 I joined the MHRA (MCA at the time) as a scientific assessor with the Product Information Quality Unit. I am now the Unit Manager, managing a team of three assessors. The team is responsible for the assessment of labels and leaflets for licensed medicines, in line with current legislative requirements. My work also involves investigation of complaints regarding medicines packaging, parliamentary work such as private office and treat official cases and projects to improve the quality of patient information. Robert Hetherington Rob has over ten years of regulatory labelling experience. For over six years, Rob has managed CCDSs for a number of innovator products across a range of therapeutic areas, coordinating and leading cross functional teams to ensure safety and efficacy concepts were introduced effectively into worldwide labelling. Rob has contributed to the creation of local Product Information for worldwide territories such as Brazil, China, Russia (EAEU) and Japan, ensuring compliance with CCDSs, accurately recording deviations and requesting approval from Labelling Oversight Committees when required. Rob has been involved in the development of labelling processes and actively contributed to the successful integration of processes. Rob also has experience within a generic pharmaceutical setting where he supported the creation and maintenance of product information for EEA (EU) Marketing Authorisations during applications and throughout the product lifecycle.

Betti Mozes Stoddart Betti Mozes-Stoddart is a regulatory labelling professional with 17 years of experience gained at the European Medicines Agency, ICON plc and Jazz Pharmaceuticals, with specific expertise in the EU centralised procedure including regulatory requirements, management of the product information translations and the EMA linguistic review, artworks, blue box requirements and labelling exemptions. In her current role as Labelling Operations Lead for neurology and oncology products in the EU and international markets, she is responsible for ensuring timely and compliant implementation of printed labelling materials.

17/09/2024

CRED Development of Regulatory Product Information in Europe

25 September 2024

Introduction

Petrina Pearce, Senior Manager Regulatory Affairs New Products,

Advanz Pharma

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Learning Outcomes for Today

⚫ The Company Core Data Sheet, including origins and purpose

⚫ The role of the SmPC and how to produce the optimal SmPC

⚫ Current SmPC issues and developments including common pitfalls

⚫ Overview of SmPC and labelling legislation, guidelines and QRD template

⚫ Practical advice on compliance with the legislation

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Morning Agenda

⚫ The Company Core Data Sheet, Gabriela Fok, Ipsen

⚫ SmPC : Regulator’s perspective, Ronan Donelan, Health Products Regulatory Authority

⚫ Break

⚫ Strategy for the development of the optimal SmPC, Khristy Horsley and Lucy Paterson, ICON plc

⚫ Case Study- SmPCs

⚫ Panel Discussion

⚫ Lunch

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Before we start- a question :

What does “Labelling” mean to you?

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CRED Regulatory Product Information

The Company Core Data Sheet (CCDS)

25 September 2024

Gabriela Fok Senior Regulatory Affairs Manager (UK&IE), Ipsen

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Learning Outcomes

What is a Company Core Data Sheet (CCDS) and what is its purpose?

Origins of the CCDS

Preparation and implementation of the CCDS

Implications of regional differences for the CCDS and global labelling management

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What is a CCDS and what is its purpose?

Company internal reference document – Summarises the company position on the safety and efficacy of a product – Basis for all Product Information globally – Mechanism for driving consistency across labelling globally – Vehicle for communicating company-driven labelling changes to affiliates and partners – Dynamic document: updated as new information becomes available – Reference Information* for PSUR/PBRER

*GVP Module VII (Rev 1)

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Origins of the CCDS

CIOMS: Council for International Organizations of Medical Sciences est. 1949 – Guidelines for Preparing Core Clinical Safety Information on Drugs Second Edition CIOMS III and V (1999): Working Group focused on international harmonisation of practical aspects of defining, creating and updating safety information in labels “A document prepared by the pharmaceutical manufacturer, containing (among other things) all relevant safety information , such as adverse drug reactions, which the manufacturer requires to be listed for the drug in all countries where the drug is marketed . It is the reference document by which ‘labelled’ and ‘unlabelled’ are determined for the purpose of international ADR reporting”.

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ICH E2C* Definition

CCDS: “A document prepared by the Marketing Authorisation Holder containing, in addition to safety information, material relating to indications, dosing, pharmacology and other information concerning the product”. Company Core Safety Information (CCSI): “All relevant safety information contained in the CCDS prepared by the MAH and which the MAH requires to be listed in all countries where the company markets the drug, except when the local regulatory authority specifically requires a modification. It is the reference information by which listed and unlisted adverse drug reactions are determined for the purposes of periodic reporting for marketed products, but not by which expected and unexpected ADRs are determined for expedited reporting.”

*Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs

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Definition retained in ICH E2C (R2) - Periodic benefit-risk evaluation report (PBRER)

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The need for a CCDS

● Product licensed in > 1 country – Local PI may not be suitable reference, since may differ between countries ● Only licensed in 1 country, local PI can be the reference doc ● Innovator company vs. Generic company approach

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Basic principle of a CCDS

CCDS contains critical information concerning the safe and effective use of the product. The CCSI portion of the CCDS must be included in the prescribing information in all countries where the drug is marketed except at the direct request of a local regulatory authority.

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Structure and Format of CCDS

● One CCDS for each active ingredient – Consider >1 CCDS for different pharmaceutical forms if the labelling content is very different – Consider approaches for products with more than 1 active ingredient ● CIOMS recommends an SmPC type format using SmPC headings – But not mandated; other formats can be used – Write content with other label formats in mind ● Level of information depends on stage of development and lifecycle of product ● May also choose to have core patient information to complement the prescribing information

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Classification of CCDS Information

● In some companies all information in CCDS is considered mandatory – Text: Incorporation verbatim – Concepts: Text should be consistent with CCDS ● Other companies have different classification levels of information in CCDS

– Mandatory: Text/Concepts – Optional: Text/Concepts

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● Historically a reactive, retrospective region-specific process ● Generally now a more proactive, prospective, global process – Focus on target label throughout development – Design the development programme to support desired labelling claims and the optimum product labelling – Developed with multiple countries in mind – CCDS developed ahead of or in parallel with major markets – CCDS should be agreed before first country submission - establishes the company position – CCDS evolves as new data become available – continues to be the reference for all labels globally Company Preparation of Labelling

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CCDS Process

● Need a defined process within the company for the preparation, review, approval, maintenance and implementation of CCDSs – SOP controlled process ● All appropriate staff should be trained on the process.

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CCDS Process Overview

Multi-Disciplinary Team Evaluates Safety & Efficacy Data and Develops Company Position

Proposes Revisions to CCDS

Formal Approval of CCDS

Communicate to stakeholders

Implementation of CCDS Revisions into National Labels

Monitoring of Compliance with CCDS

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CCDS Process Considerations

● Establish multi-disciplinary teams (usually per product) to evaluate new information & propose revisions to CCDS

● Regular company review of safety information (and benefit-risk) – Consider timelines, especially for safety changes – Clock starts from the ‘safety decision’ ● Consider a minimum review period if no triggers, e.g. annual review

● Formal procedure for internal approval of CCDSs

● Robust document management system – Version control ● Communication: Ensure dispatch to all that need

– Communicate submission deadlines where relevant (e.g. safety changes) ● Ensure documentation captured to demonstrate SOP has been followed

● Monitoring system for compliance of national labels with the CCDS – timing and content

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CCDS references/support documentation

● The CCDS is a data-driven document ● Each CCDS data-driven statement should have references to support it ● Consider what documentation you will provide to support implementation of the CCDS into national labels e.g. clinical overview addendum

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Implementation Monitoring

● Company approaches will differ ● May be a central/HQ review of affiliate labels before submission

● Provide guidance on submission timing, taking into consideration labelling dependencies/other local regulatory considerations. Particularly key for safety-related changes ● Responses to regulatory authority labelling issues; management of deviations from the CCDS ● Track implementation – Formal tracking systems/spreadsheets – increasing trend for end-to-end ● Audits: product or process/system – may also include partner companies (if relevant).

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Differences in Regional Labelling Requirements

● Common themes, but structure/format and level of detail may differ ● Some country/region-specific requirements - consider whether/how these will be addressed in the CCDS – e.g. Region-specific population data

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Implications of Regional Differences for CCDS and Global Labelling Management

● For CCDS sections where labelling requirements differ, what should be included in CCDS? ● Company evaluates data and makes a decision – May include some optional sections or appendices ● CCDS reflects company position on safety & efficacy information ● Important to provide guidance on how to implement CCDS into regional/local labelling

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Implications of when Country Labelling Deviates from CCDS

● Recommend there is a process to manage this ● Provide guidance on what is considered a ‘deviation’ ● Evaluate country-specific label statements – Rationale for statements e.g. health authority request ● Develop a company position on the country- specific label statements – Accept or not – Consider CCDS impact – If appropriate, based on company position, statements may be included in CCDS and implemented globally ● Document the deviation: important part of the labelling history

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Learning Outcomes: Recap

What is a CCDS and what is its purpose?

Origins of the CCDS

Preparation and implementation of the CCDS

Implications of regional differences for the CCDS and global labelling management

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23/09/2024

The SmPC: Regulator’s Perspective

CRED SmPC, Patient Information Leaflet and Labelling

Dr Ronan Donelan

HPRA

The Organisation for Professionals in Regulatory Affairs The Organisation for

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➢ The role of the SmPC ➢ Overview of SmPC legislation/guidelines and template ➢ Regulators perspective ➢ Current issues and developments

Special thanks to Dr Doreen Fagan, HPRA

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Introduction

Crucial role in the regulatory framework for medicinal products:

• (SmPC) The Summary of medical Product Characteristics

• Intrinsic and integral part of the MA

• Describing the properties and officially approved conditions

• Summary – not all information; aims to provide important and relevant information clearly.

• Updated throughout the lifecycle of a medicine as new data emerge

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The Role of the SmPC

• Legal mandatory document agreed and approved as part of the marketing authorisation of each medicinal product • The SmPC is based on facts and provides primary source information for healthcare professionals on how to use the medicinal product safely and effectively

• Essential tool in HCP clinical decision-making

• Basis for patient information leaflet and labels

• Sets the limits for MAH marketing and promotion

• SmPCs are dynamic and updated throughout the life-cycle of the product in line with current scientific knowledge via variations.

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The Role of the SmPC

• Ensures Regulatory Compliance

• Standardised format

• Common basis for communication in EU

• Consistency - presentation of scientific data presented according to a predefined structure • The scientific assessment should evaluate how the SmPC will optimise the benefits and manage the risks • SmPCs can be found on competent authority websites and on the EMA website (centralised products)

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SmPC – what information does it contain?

• Legal

• Pharmaceutical

• Clinical…. Efficacy

• Clinical…..Safety

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EU SmPC legislation – brief history

Directive 65/65 EEC

CHAPTER II: Authorisation to place medicinal products on the market

Article 4a states:

The summary of the product characteristics referred to in point 9 of the second paragraph of Article 4 shall contain the following information …

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QRD – established June 1996

● Practical advice on how to draw up the SmPC is provided to the applicant in the form of templates developed by the Quality Review of Documents (QRD) group, for centralised, decentralised and mutual recognition procedures. ● Composition:

– EMA (chair & secretariat) – MSs (1 Human + 1 Vet) – European Commission – NO + IS (as observers) – Translation Centre

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QRD mandate

● To ensure clarity, consistency and accuracy of the PI and of its translations. ● To verify terminology. ● To review and update templates ● To promote legibility of patient information. ● To contribute to the development of common understanding on the implementation of legislation and guidelines

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QRD tools

● Legislation, Guidelines, Notes for Guidance

● Product Information Templates

● QRD Reference Documents

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EU SmPC legislation - history

Directive 83/570/EEC…

It is necessary from the point of view of public health and free movement of medicinal products for the competent authorities to have at their disposal all useful information on authorised medicinal products based in particular on summaries, adopted in other member states, of the characteristics of products.

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EU SmPC legislation

Directive 2001/83/EC as amended

This directive lays down the community code relating to medicinal products for human use. It specifies the requirements for the SMPC including its structure and content and

TITLE III: PLACING ON THE MARKET

CHAPTER 1: Marketing authorisation

Article 11 states: The summary of the product characteristics shall contain, in the order indicated below, the following information: Sections 1-12 are outlined

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EC SmPC Guidelines

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SmPC Guidelines – EC 2009

The SmPC guideline advises on the principles of presenting information in the SmPC

• Clear and concise language

• Consistent terminology

• Product specific information for use in the population for whom the medicine is indicated followed – where necessary – by information for any relevant special population

(Public Assessment Report provides more detailed information)

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SmPC Content

1. Trade name of the medicinal product

2.Qualitative and quantitative composition

3.Pharmaceutical form

4.Clinical particulars

5.Pharmacological properties

6.Pharmaceutical particulars

7.Marketing authorisation holder

8.Marketing authorisation number

9.Date of first authorisation

10. Date of (partial) revision

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SmPC: Pharmaceutical information 2. Qualitative and quantitative composition 2. Qualitative and quantitative composition

– Active ingredient and the quantity found in the product.

– Excipients and its compositions found in the product.

(Full list of excipients in the product detailed under “Section 6.1 List of excipients”)

ingredient and the quantity found in the product.

Excipients and its compositions found in the product.

(Full list of excipients in the product detailed under “Section 6.1 List of excipients”)

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SmPC: Pharmaceutical information 2. Qualitative and quantitative composition 3. Pharmaceutical form

– Description of dosage form (film coated tablet, oral solution, solution for injection

– Organoleptic properties (colour, shape, size, pH) of the dosage form .

Excipients and its compositions found in the product.

(Full list of excipients in the product detailed under “Section 6.1 List of excipients”)

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Clinical information

4.1 Therapeutic indications

● Detail on the treatment is for symptomatic, curative or preventive purposes

● Any restrictions that may apply to certain patient populations, such as patients with renal failure

4.2 Posology and method of administration

● Based on indication, age, and comorbidities, the maximum recommended single, daily or total dose, and the normal duration of use with any restrictions on duration is described

4.3 Contraindications

● Situations where the medicinal product must not be given for safety reasons

4.4 Special warnings and precautions for use

● Risks requiring a precaution for use prior or during treatment

● Special patient groups that are at increased risk

4.5 Interaction with other medicinal products and other forms of interaction

4.6 Fertility, pregnancy and lactation

4.7 Effects on ability to drive and use machines

4.8 Undesirable effects

4.9 Overdose

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SmPC guideline

4.1: Therapeutic indications

Defines the target disease and the population where a positive benefit-risk has been demonstrated, specifying age group(s) as appropriate

4.2: Posology and method of administration

Recommended dose(s) in general population and special populations.

Also informs on the method of administration.

4.3: Contra-indications

Situations where the medicinal product must not be given for safety reasons

4.4: Special warnings and precautions for use

• Risks requiring a precaution for use prior or during treatment

• Special patient groups that are at increased risk

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SmPC Guideline

4.5: Interaction with other medicinal products and other forms of interaction

Emphasis on the interactions which result in a recommendation

4.6 Fertility, pregnancy and lactation

Reasons for the recommendations should be provided

4.7 Effects on ability to drive and use machines

On the basis of pharmacodynamics/pharmacokinetic/reported adverse reactions and/or specific studies.

4.8: Undesirable effects

All adverse reactions at least possibly causally related.

Data to be presented in a standard structure in order to provide clear and readily accessible information

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SmPC Guideline

4.9

Overdose

Symptoms, signs and potential sequelae. Describe management taking into account all relevant evidence. Additional information on special populations.

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SmPC Guideline

5.1: Pharmacodynamic properties:

Mechanism of action; Main results of the clinical trials supporting the marketing authorization; Statistically compelling and clinically relevant results; Information on clinically relevant populations studied e.g. paediatric

5.2: Pharmacokinetic properties:

Absorption, distribution, biotransformation (including results from in vitro interaction studies), elimination, linearity/non linearity, special populations

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SmPC Guideline

5.3: Preclinical safety data

Information of relevance for the prescriber in recognising the safety profile of the medicinal product.

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Section 6.3: Pharmaceutical Particulars

6.1 List of Excipients excipients

A) Tablet core: Mannitol, Cellulose microcrystalline, Crospovidone, Sodium carbonate, Povidone, Methionine, Magnesium stearate b) Coating: Hypromellose 6 cP, Macrogol 6000, Titanium dioxide (E 171), Talc

6.2 Incompatibilities

Information on physical and chemical incompatibilities with other medicinal products.

6.3 Shelf life

Information on the finished product shelf life and on the in-use stability after 1 st opening and/or reconstitution/dilution.

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6. Pharmaceutical particulars

6.4 Special precautions for storage

Description of the product if sensitive to light moisture or any particular temperature

6.5 Nature and contents of container

Information on the pack size and material of the container such as glass vials PVC dash aluminium blister

6.6 Special Precautions for disposal and other handling

Information on product needs to be disposed of in accordance with local requirements.

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SmPC Postion

● Legal document ● Document addressed to HCPs

leaflet Labelling SmPC

• Distillation of >10 years R&D

NC Overvi ew NC Summ ary

Clinical Overview

EPAR

Clinical Summary

• MAH asset

• Interface with RAs

Module 5 Clinical

Module 3 Quality

Module 4 Non-clinical

• HCP communication

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SmPC evolution of guidance updates

• 2017, Jan: EMA Scientific Guidelines with SmPC recommendations

• 2019, Oct, EMA guidance document: Wording of therapeutic indication A Guide for Assessors of Centralised Applications

• 2019 Nov update: European Commission Excipient guidelines

• CMDh – product information recommendations

• 2024, Jan: Scientific guidelines

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Why SmPC Guidance Revision?

● To ensure reflection of latest scientific knowledge, regulatory requirements and safety information ● Changes in legislation and guidance – Paediatric Regulation (2007) – Risk Management Plans – Pharmacovigilance – Pharmacogenomic data

● Medical progress and new therapies

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Regulation (EC) No 1901/2006

The Paediatric Regulation came into force in the EU on 26 th January, 2007

Article 17: “ To provide healthcare professionals and patients with information on the safe and effective use of medicinal products in the paediatric population , and as a transparency measure, information on the results of studies as well as on the status of the paediatric plans, waivers and deferrals, should be included in the product information”.

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EC Paediatric Regulation Objectives

● To ensure high quality research into the development of medicines for children.

● To ensure, over time, that the majority of medicines used by children are specifically authorised for such use.

● To ensure the availability of high-quality information about medicines used by children;

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SmPC Guidance Revision

● Guidance for Paediatric Information in many SmPC sections

Sections: 4.1; 4.2; 4.4; 4.5; 4.8; 4.9; 5.1; 5.2.

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SmPC and Risk Management Plan (RMP)

Section 4.4 For example; “Liver function should be monitored before initiation of treatment and monthly thereafter”, “Patients should be advised to immediately report any symptoms of depression and/or suicidal ideation”, “ Women of childbearing potential should use contraception”, …)

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SmPC Guidance Revision

Section 4.2

• In case of restricted medical prescription, this section should be started by specifying the conditions.

• In case of specific safety or monitoring need, any recommended restriction to a particular type of clinical unit should also be stated.

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Black symbol and additional monitoring

The summary of product characteristics and the package leaflet shall include the statement “This medicinal product is subject to additional monitoring”. That statement shall be preceded by a black symbol which shall be selected by the Commission following a recommendation of the Pharmacovigilance Risk Assessment Committee by 2 July 2013*, and shall be followed by an appropriate standardised explanatory sentence (Art. 11 and 59 of Directive 2001/83/EC and Art. 23(5) of Regulation (EC) No 726/2004).

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Location and wording of the statements for additional monitoring

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Reporting suspected adverse reactions (ADRs)

For all medicinal products for human use:

A standard text shall be included in the summary of product characteristics expressly asking healthcare professionals to report any suspected adverse reaction in accordance with the national spontaneous reporting system referred to in Article 107a(1) (Art. 11 of Directive 2001/83/EC). A standardised text shall be included in the package leaflet, expressly asking patients to communicate any suspected adverse reaction to his/her doctor, pharmacist, healthcare professional or directly to the national spontaneous reporting system referred to in Article 107a (1), and specifying the different ways of reporting available (electronic reporting, postal address and/or others) (Art. 59 of Directive 2001/83/EC).

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Location and wording to encourage ADR reporting

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SmPC Advisory Group

Established March 2010 to promote and facilitate the application of the SmPC guideline. The SmPC guideline and other information including training material to help reviewing of SmPCs are available on the EMA website.

How to prepare and review a summary of product characteristics

Best practice approach

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Regulation on advanced therapy

Dir 2001/83/EC Article 11

medicinal products

Paediatric Regulation 1901/2006

SmPC Guideline

MA Application

SmPC

EMEA Q, S&E Guidelines

“Core SmPC”

HCP’s needs

Disease concerned

QRD Templates

link_header_fp2_r2_c5

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● Tailored prescription ● Paediatric data ● Subpopulation data, elderly ● Benefit risk information ● Interactions

● Clear ● Concise ● Informative

● Pharmacogenetics ● Origin of product

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Retour vers l

Agencies websites

SmPC

e Prescribing

Medical Sales representatives

Package Leaflet

image002

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The Role of the SmPC

• Regulatory Authority MA and LCM assessment • Communication tool for appropriate delivery of concise relevant information to HCPs • Source document to facilitate clinical decision-making

• Adaptable to legal and scientific changes • A “living” constantly changing document

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SmPC: Queries

• SmPC content (or lack of) is a main query received from HCPs • Tool to facilitate clinical decision-making • Posology and administration • Interactions / Con-meds • PK • AE’s • Shelf-life • MAH Medical Information contact

Patients: …….

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References and useful links

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Useful links – European Commission

European Commission “A Guideline on Summary of Product Characteristics. Ref: https://ec.europa.eu/health/sites/health/files/files/eudral ex/vol-2/c/smpc_guideline_rev2_en.pdf

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Useful links - CMDh

The Co-ordination group for Mutual Recognition and Decentralised Procedures – Human (CMDh) website https://www.hma.eu/cmdh.html for:

• Any previously recommended Pharmacovigilance working party recommendations and sometimes class effects wording*

• Any CMDh recommendations or advice from CMDh for SmPC wording for a particular active substance

• Some agreed core SmPCs

• The MRI Product index which often gives agreed product information from MR/DCP procedures • Paediatric Regulation: Any published Article 45 or Article 46 which may have recommendation for SmPCs with regard to use in the paediatric population

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Useful links – European Medicines Agency (EMA)

Human Regulatory/Marketing authorisation/Product-information requirements

https://www.ema.europa.eu/en/human-regulatory/marketing authorisation/product-information-requirements

• Product information templates - QRD

• How to prepare and review a SmPC

• Product information : Reference documents and guidelines

Wording of therapeutic indication A Guide for Assessors of Centralised Applications – October 2019 https://www.ema.europa.eu/en/human-regulatory/marketing authorisation/product-information/how-prepare-review-summary-product characteristics

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Useful links – EMA

Article 30 or Article 31 referrals agreed wording

https://www.ema.europa.eu/en/medicines/ema_group_types/ema_referral

Periodic safety update single assessment (PSUSA) reports: ref

https://www.ema.europa.eu/en/search/search/field_ema_web_categories%25 3Aname_field/Human/ema_group_types/ema_document psusa?search_api_views_fulltext=periodic%20safety%20update%20report%2 0single%20assessment

Latest excipient guidelines (section 4.4 of SmPC) Ref:

https://www.ema.europa.eu/en/documents/scientific-guideline/annex european-commission-guideline-excipients-labelling-package-leaflet medicinal-products-human_en.pdf

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Thank you

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CRED Regulatory Product Information

Strategy for the Development of the Optimal Summary of Product Characteristics (SmPC)

25 th September 2024

Khristy Horsley and Lucy Paterson Global Labelling Strategists

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

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Learning outcomes

• Definition of an optimal SmPC and its purpose (the “what” and the “why”) • Developing the SmPC within the development programme (The “when”) • Key Stakeholders in developing an SmPC (The “who”)

• How do you develop a good SmPC ? (The “how”)

• … and the “where” …

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Mentimeter exercise

⚫ Who are the users of our Summaries of Product Characteristics (SmPCs?) [free text]

⚫ What is the purpose of the SmPC? [free text]

Go on – www.menti.com

Access code:

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The Basic Elements

What

Where

Why

SmPC

How

When

Who

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The SmPC is an integral part of the marketing authorisation

What

m1-3-1-spc-label-pl SmPC is the ultimate summary of the Common Technical Document (CTD)

Module 1 Regional Administrative Information

2.1 CTD table of contents 2.2 CTD Introduction

2.5 Clinical overview

2.4 Non-clinical overview

2.3 Quality overall summary

2.6 Non-clinical written & tabulated summaries

2.7 Clinical summary

Module 3 Quality

Module 4 Non-clinical study reports

Module 5 Clinical study reports

A GUIDELINE ON SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) September 2009 https://health.ec.europa.eu/system/files/2016-11/smpc_guideline_rev2_en_0.pdf

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What

The SmPC sets out the agreed position of the medicinal product as distilled during the course of the assessment process between the Company and the Health Authority

A GUIDELINE ON SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) September 2009 https://health.ec.europa.eu/system/files/2016-11/smpc_guideline_rev2_en_0.pdf

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Informs prescribers and patients

What

• The primary purpose of the SmPC is to inform prescribers how to use the product safely and effectively ▪ Updated through the life of a product as new data emerge • Reference document for preparation of the Patient Information Leaflet • Important that the sections are clear, consistent and concise……

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The SmPC sets boundaries for promotion and is key for market access and reimbursement

Why

ABPI Code of Practice for the Pharmaceutical Industry (2021):

Clause 11.2 “The promotion of a medicine must be in accordance with the terms of its marketing authorization and must not be inconsistent with the particulars listed in its summary of product characteristics……

EFPIA Code of Practice:

Section 1.02 “Promotion must be consistent with the particulars listed in the summary of product characteristics of the relevant Medicinal Product.”

Final labelling has to be commercially viable

● A medical need exists for the indication

● Different from and improves upon competitors

● Generates revenue to justify development

● Fits within corporate pipeline

The Organisation for Professionals in Regulatory Affairs

2021-abpi-code-of-practice.pdf (pmcpa.org.uk)

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