CRED 8 Presentations

03/07/2024

CRED European Regulatory Procedures (ERP)

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CRED Navigating European Regulatory Procedures - 9-10 July 2024

Case Studies

Matthew Sardo, Regulatory Affairs Director, Sardo Trading Limited matthew@sardotradinglimited.com

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

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Background

• We introduce the Case Studies as the first order of business so you can consider them whilst listening to the presentations • Important part of the course; enables you to apply what you’re learning; discuss different options • Please take note of what you hear in the presentations as there are some key clues and answers (if you’ve not read them, please read them before the lunch break) • Not necessarily always one right answer • Suggested Points for Consideration will be shared at the end of Day 2 • Case Studies have been developed over a number of years and in some cases are based upon real-life scenarios that you might actually encounter and are directly applicable to the course • In your career you’ll need to interact with and present different information to different audiences; in this case as Director to Executive Board and then to your regulatory team; the Case Studies attempt to reflect this

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Task

• Day 1 (all Case Study groups) 45 mins : • Develop an EU strategy for presentation to company governance board for Case Study 1 • Put yourself in the position of a Regulatory Affairs Director presenting your proposed strategy to the board of directors • Day 2 (all Case Study groups) 1 hour 30 mins : • Describe practical implementation to your regulatory affairs team as part of a company EU Regulatory Affairs department for Case Study 1 • Put yourself in the position of a Regulatory Affairs Director explaining to your departmental team how you want the agreed strategy implemented • Develop an EU strategy for Case Study 2 for presentation to company governance board for and its practical implementation to your regulatory affairs team

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Learning Outcomes

• Strategy • Focus on developing: Regulatory Strategy • Consider strategic options – advantages/disadvantages • Filing route/Legal Basis • Incentives: Orphan Drug Designation

• Commercial needs • HTA considerations • Data considerations

• Scientific Advice • Justify decisions • Implications of each decision • Presentation to company board (governance)

• Practical implementation* • Executing a company agreed EU filing strategy • Key points to consider when leading an EU Regulatory filing • Practical considerations when compiling the dossier

*Practical implementation for Case Study 1 will be done on Day 2 after hearing relevant presentation

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Presentation

• Nominate a team speaker • Work as a team to discuss and agree a strategy and its practical implementation (practical implementation piece is Day 2 only) • Prepare presentation (5 minutes maximum) • Focus on key points • Respond to questions from the floor

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CRED Navigating European Regulatory Procedures – 9-10 July 2024 Overview of the European Regulations

Kora Doorduyn-van der Stoep; EU-representative at the MEB Medicines Evaluation Board / NL

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Learning Outcomes

 A brief outline of the Centralised and Mutual Recognition /Decentralised procedures  The role of the regulatory bodies, i.e. EMA, CHMP, COMP, PDCO, SAGs, EU Commission, CMDh, National Authorities, ATMP, PRAC, EMA-re-structure (new tasks)  Update to ongoing pharmaceutical legislation  Orphan Drug Regulations  Paediatric Regulations  PRIME and similar initiatives  Considerations for SMEs  The role of patients

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 A brief outline of the Centralised and Mutual Recognition /Decentralised procedures (see also pre-read documentation)

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Marketing authorisation routes Legislative governance

The EU governance of new marketing authorisation applicationsis laid down in  Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (MRP/DCP and purely national applications)  Regulation 726/2004/EC: laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (applications via centralise procedure) NB: Draft proposal for revision of Directive and Regulation published in April 2023!

See also pre-read documents and next 4 slides for more information 4

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Marketing authorisation routes in EU

 Centralised procedure (CP): one marketing authorisation (MA) granted by European Commission for Europe  Other (than CP) marketing authorisation application (MAA) procedures  Purely national procedure: MA in one Member State (MS)  Mutual recognition procedure (MRP): MA in more than one Member State  Decentralised procedure: MA in more than one Member State

These 3 procedures concern all national MAAs resulting in national MAs but procedure differs and for MRP/DCP result is harmonised!

See also pre-read documents

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Legal provisions Centralised Procedure (CP)

 Regulation 726/2004/EC: laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency

 One new marketing authorisation application submissionto EMA

 Assessment by Rapporteur/co Rapporteur

 Assessment Risk Management Plan by PRAC

 Scientific discussion and final opinion by CHMP

 One EU MA for EU issuedby European Commission

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Legal provisions MRP/DCP (1/2)

National applications for the same medicinal product, resulting in national MAs in more than one MS, but European harmonised assessment and outcome!

Legal provisions in Article 28 of Directive 2001/83/EC, only difference in initial phase Both the mutual recognition procedure and the decentralised procedure aim at facilitating access to the market by relying upon the principle of mutual recognition. Not applicable for products falling under the mandatoryscope of centralised procedures

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Legal provisions MRP/DCP (2/2)

 Mutual recognition procedure (MRP) where the medicinal product has already received in a MS a MA at the time of application (Articles 28.2 and 28.4) or

 Decentralised procedure (DCP) where the medicinal product has not received a MA in a MS at the time of application (Articles 28.1 ; 28.3 and 28.4)

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 Regulatory bodies: EMA and European Commission

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European Commission (1/2) • Proposes EU legislation in the pharmaceutical field (EU Parliament and Council of the EU adopt legislation via so-called “Co-decision procedure”)

• Coordinates EU policy in the field

• Develops guidelines and coordinates Notice to Applicants (NtA) WG group (drafting/updating chapters of Volume 2A of NtA)

• Organizes pharmaceutical committee and expert groups

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European Commission (2/2) • Adopts decision on granting: •

Marketing authorisations in the centralised procedure

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Orphan designations

• Certain referrals and other procedures affecting NAPs

International cooperation

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The Organisation for Professionals in Regulatory Affairs NB: Recently the EC has published a proposal for revision of Pharma legislation: New Directive and new Regulation plus Council Recommendation on AMR These proposals have been drafted also based on input from EMA/EU NCAs and other stakeholders 11

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EU legislation- which EU institutions involved?

 the European Parliament, which represents the EU’s citizens and is directly elected by them; has legislative, supervisory, and budgetary responsibilities  the Council of the European Union, which represents the governments of the individual member countries (“voice” of EU member governments, adopting EU laws and coordinating EU policies). The Presidency of the Council is shared by the member states on a rotating basis (current Presidency = Hungary).  the European Commission (a team or 'College' of Commissioners, 1 from each EU country), which represents the interests of the Union as a whole and promotes the general interest of the EU by proposing and enforcing legislation as well as by implementing policies and the EU budget

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EU legislative process

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EU legislative process

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European Medicines Agency (EMA)

• EU decentralised agency responsible for scientific evaluation, supervision and safety monitoring of medicines in the EU

• Founded in 1995

• Located (since 2019) in Amsterdam

• Reg. (EC) No 726/2004

[previously Reg. (EEC) No 2309/93/EC]

• Scientific secretariat responsible for coordinating the existing scientific resources put at its disposal by Member States for the evaluation, supervision and pharmacovigilance of medicinal products *

• * Art. 55 of Reg. (EC) No 726/2004 15

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EMA – new tasks as of 1 March 2022 (and later)

• REGULATION (EU) 2022/123 of the European Parliament and of the Council of 25 January 2022 on a

reinforced role for the European Medicines Agency in crisis preparedness and management for medicinal products

and medical devices published on 31 January 2022 has come into force 1 March 2022 except for:

 Medical devices shortages : 2 February 2023  the European Shortages Monitoring Platform (ESMP): 2 February 2025

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EMA – new tasks as of 1 March 2022 (and later)

• New tasks (during crisis management) as included in the Regulation concern:

 monitoring and mitigating the risk of shortages of critical medicines and medical devices;  providing scientific advice on medicines that may have the potential to treat, prevent or diagnose the diseases causing those crises;  coordinating studies to monitor the effectiveness and safety of medicinal products intended to treat, prevent or diagnose diseases related to the public health crisis;  coordinating clinical trials for medicinal products intended to treat, prevent or diagnose diseases related to the public health crisis;  transferring of the EU Expert Panels for clinical evaluation of certain high-risk medical devices and invitro diagnostics of the Medical Device Regulation to the Agency. 17

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EMA – new tasks as of 1 March 2022 (and later)

• To perform these tasks new groups are being established/formalised

 The role of the current EU Executive Steering Group on Shortages Caused by Major Events will be formalized

(MSSG). Additionally, the Regulation provides a legal basis for involving ECDC (European Centre for Disease

Prevention) to obtain epidemiological data to help forecast medicines needs and to request specific data from

Member States and supply-chain stakeholders

 A Medical Devices Executive Steering Group on shortages and safety of Medical devices (MDSSG) will be established

 Current Emergency Task force will be formalised responsible for leading the scientific response to a declared public

health emergency (e.g. accelerated scientific advices, advice on clinical trials, undertake reviews of medicines to be

used in the public-health emergency and provide recommendations on compassionate use of medicines and on use

and distribution of unauthorized medicines)

 The Regulation provides a legal basis for the establishment of the vaccines monitoring platform and for DARWIN

(Data Analysis Real World Interrogation Network). 18

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Structure of the EMA

• Supervised by an independent Management Board • Day-to-day operations are carried out by the EMA staff overseen by EMA's Executive Director • Scientific Committees • European experts • Working parties (currently being restructured in domains)

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EMA and EU regulatory network

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Experts and Committees Experts: members of committees, working parties, assessment teams, expert group General principles composition Committees: - 1 member + 1 alternate nominated by each of the 27 EU MSs - 1 member + 1 alternate from NO and IS (observers) - Co-opted members for specific expertise on

scientific or technical matters - Elected Chair and Vice-Chair - 3 years renewable mandate

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Scientific Committees  CHMP Committee for Human Medicinal Products  PRAC Pharmacovigilance Risk Assessment Committee  CAT Committee for Advanced Therapies  COMP Committee for Orphan Medicinal Products  PDCO Paediatric Committee  CVMP Committee for Veterinary Medicinal Products  HMPC Committee for Herbal Medicinal Products Agendas, minutes and meeting highlights are published on EMA website

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Main tasks of the CHMP • Conducting initial assessment of EU-wide MAAs • Assessing modifications ( variations ) to an existing EU-MA • Deliver opinions to European Commission:  - on new medicinal products/variations/renewals/line extensions - on arbitration/referral procedures • Providing scientific advice and protocol assistance to companies

• Preparing scientific guidelines & regulatory guidance • Establish Working Parties, SAGs & Expert Groups • Interaction with regulators (e.g. ICH process) • Deliver Scientific opinions to WHO

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Main tasks of the PRAC  Responsible for all aspects of the risk management of medicines • Detection, assessment, minimisation & communication on risk related to medicinal products • PSURs and signal assessment (for CAPs and NAPs) • Design and evaluation of post-authorisation safety studies • Assessments of Urgent/ non-Urgent Union Procedure triggered due to safety concerns (safety referral procedures) • Regulatory oversight of RMP and assessment of outcome of risk minimisation measures in RMP for CAPs (for NAPs only in case of MS request for PRAC advice) • Advice to CHMP on selected post-authorisation procedures

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Main tasks of the CAT

• Prepare a draft opinion on each advanced therapy medicinal product (ATMP) application before the CHMP adopts a final opinion • Upon request, opinion on any scientific matter relating to ATMPs • Participate in procedures for ATMP classification and certification • Contribute to other procedures and activities as needed (e.g. scientific advice for ATMPs)

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Main tasks of COMP

• Delivering opinions on orphan drug designation applications

• Providing advice to EU Commission on policy on orphan medicines and assists in drafting detailed guidelines

• Assisting in international co-operation

• Link with patients’ associations

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Main tasks of the PDCO

• Assessing content of paediatric investigation plans (PIPs) and applications for full or partial waivers and deferrals;

• Assessing data generated in accordance with agreed PIPs;

• Adopting opinions on Q/S/E of a medicine for use in the paediatric population at request of CHMP or NCA;

• Advising MS on content and format of data to be collected through surveys on the uses of medicines in children;

• Advising and supporting the development of the European Network of Paediatric Research at the EMA;

• Providing advice on questions on paediatric medicines

• Establishing and updating an inventory of paediatric medicine needs

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Involvement of Scientific committees

T-36/48 MO

T-36/12 MO

T-24/12 MO

T-12 MO T 0

CHMP PRAC COMP PDCO SAGs WPs

CHMP PRAC SAWP

CHMP SAWP

CHMP PDCO

COMP PDCO

In addition, CAT involved in all steps for ATMPs

Launch

Pre-Submission phase

Post MA

Evaluation

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 Regulatory bodies: CMDh and National Competent Authorities  (will be further explained in other presentations)

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CMDh (article 27 of Directive 2001/83/EC (1/2)

• The Co-ordination group for Mutual recognition and Decentralised procedures – human (CMDh) is set up for examination of any question relating to MA of a medicinal product in two or more MSs in accordance with the MRP or DCP. In particular, tasks include: ● Examination of any question relating to MRP/ DCP, esp. solving disagree ments on grounds of ‘potential serious risk to public health’ between MS ● Examination of questions related to the pharmacovigilance of medicinal products authorised by the Member States, in accordance with Articles 107c, 107e, 107g, 107k and 107q ● CMDh takes binding decisions on PRAC recommendations for article 107i and 31 safety referrals ● Examination of questions related to variations

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CMDh (article 27 of Directive 2001/83/EC (2/2)

……. ● Harmonisation of MAs in the Union – annual lists for SmPC harmonisation ● Ensure consistency of standards and good quality decision making across EU

• One representative per EU MS (+IS, NO, LI), MS may appoint an alternate

• CMDh is not a working group of HMA nor an EMA committee

• No systematic discussion on all ongoing MRP/DCP applications!

• CMDh advice: see CMDh website under Q&As and Advice from CMDh

• CMDh minutes/agenda’s and monthly press release published on CMDh website

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National EU-Competent Authorities

Products

Activities

MRP/ DCP/ purely national

• Assessment of applications and authorisation

All

• Authorisation and supervision of clinical trials • Conduct of Inspections (GMP, GLP, GCP, PhV) • Manufacturing authorisations • Supervision of distribution • Testing of samples • Supervision of advertising and promotion • Etc.

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 Update to ongoing Pharmaceutical legislation

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New proposal Pharma Legislation EC

 On 26 April 2023 the EC has published a proposal for revision of Pharma legislation: • New Directive (= revision Directive 2001/83/EC • New Regulation (Revision and combining current regulations on Centralised procedures/EMA Governance/Paediatric and Orphan Regulation) • Council Recommendation on AMR (antimicrobial resistance)  These proposals have been drafted also based on input from EMA/EU NCAs and other stakeholders

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New proposal Pharma Legislation EC

New Regulation (Reg) • Specific rules for the most innovative medicines such as orphans, antimicrobials • Rules on shortages • EMA governance

New Directive (Dir) • Placing on the market of all medicines • Authorisation and labelling requirements • Strong incentives for access

Several operational aspects will be later drafted via so called Implementing and Delegated acts after adoption of the Regulation and Directive

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Some aspects of the new Directive/Regulation

Digitalisation

Vouchers

Timetables (from 210 days to 180 days)

Restructuring Committees

Bio-hybrid

Shortage management plan

Additional Monitoring disappears

Environmental Risk Assesment

ASMF

No standard 5y renewal, unless…

No RMP for off-patent product, unless…

Borderline products

Priority antimicrobials

Rawdata

Temporary Emergency MA

Regulatory Sandbox

Phased reviews (=Rolling review)

ePI

Scientific advice

Inspections

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Proposal incentives

+2 year possible if medicine launched in all 27 MS within 2 years from EU authorisation and continuously supplied

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 Orphan Regulations

Reg. (EC) No 141/2000 Reg. (EC) No 847/2000

NB: Revision of orphan regulation ongoing

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Orphan designation

At time of MAA

Before MAA submission

• Assessment by COMP; EC decision for designation (Orphan register) • To be granted at any stage before MAA submission • To be confirmed before the granting of the MAA

2 nd hurdle: maintenance of OD

1 st hurdle - OD

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Orphan designation criteria (cumulative)

•Rare condition affecting less than 5 per 10.000 persons in the EU, or •[exceptionally] it is unlikely that the medicine would generate sufficient returns to justify the investment

Prevalence

Seriousness of condition

•Life threatening and/or chronically debilitating condition

Comparison to available treatments

•No satisfactory methods exist, or •Significant benefit vs. existing methods

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..what about significant benefit?

• “A clinically relevant advantage or a major contribution to patient care” • Based on assumptions at the time of orphan designation • Significant benefit over authorised products • COMP to assess whether or not sign benefit assumptions are supported by available data/evidence • Significant benefit to be confirmed prior to marketing authorisation to maintain orphan status

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Incentives for orphan medicines • 10 year market exclusivity* (protection from similar medicines in same indication) • + 2 years of market exclusivity for completion of the paediatric investigation plan (PIP) • Protocol assistance throughout development • Access to centralised procedure • Fee reduction / exemption

Impact of authorised orphan medicines Other medicines (orphan or not) for the same or overlapping indication must: • Demonstrate that the medicine is not similar, or Justify a derogation if: • Consent from MAH of orphan product • MAH of orphan product unable to supply sufficient quantities •

• It’s established that the second product is clinically superior (e.g. safer or more effective)

* Can be reduced to 6 years post-authorisation if criteria no longer met

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 Paediatric Regulation

Reg. (EC) No 1901/2006

NB: revision of Paediatric regulation ongoing

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EU Paediatric Regulation  EU Regulation 1901/2006 , as amended  Three groups of medicinal products:  - Products in development/ not yet authorised in the Community ( Art. 7 )  - Authorised products still covered by patents ( Art. 8 ) - Authorised products no longer covered by patents ( PUMA )  Articles 7 and 8 do not apply to applications based on  - Article 10 of Directive 2001/83 (generics, hybrids, WEU, biosimilars)

 - Article 13 and 16 – homeopathic medicinal products  - Article 16a to 16i – traditional herbal medicinal products NB: but Article 46 does apply!

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Objectives of EU Paediatric Regulation

 Improve the health of children ● Increase high quality, ethical research into medicines for children ● Increase availability of authorised medicines for children ● Increase information on medicines

 Achieve the above ● Without unnecessary studies in children ● Without delaying authorisation for adults

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Obligations of EU Paediatric Regulation

 Paediatric development is now mandatory in the EU • Unless a product-specific waiver (for all indications/conditions, in all paediatric subsets) or a class waiver is granted (only for specific conditions and dosage forms) • Deferrals can also be granted (studies in children can be initiated and/or completed after applying for marketing authorisation in adults)  NB: deferral is for completing the studies/measures, not for describing the PIP!

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Main pillars Paediatric Regulation

• An expert committee: the Paediatric Committee ( PDCO ) • An agreed (evolving) paediatric development: the Paediatric Investigation Plan ( PIP ) • A system of obligations and rewards (e.g. ‘patent’ extension, free scientific advise)

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Paediatric Investigation Plan (1/2)

 Paediatric investigation plan (PIP) – a development plan aimed at ensuring that the necessary data are obtained to support the authorisation for children of new medicines or new indication, pharmaceutical form or route of administration

- Should be submitted around end of Phase I studies - Outlines timing and measures to be undertaken - Deferral or waiver possible, if applicable - Modifications possible

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Paediatric Investigation Plan (2/2)

 Submission of results of studies on authorised medicines conducted in children to EMA/NCAs  In case of compliance with agreed PIP, information in SmPC and if a MA is granted in all Member States: 6-month extension of the patent protection (= Supplementary Protection Certificate = SPC)

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Paediatric Use Marketing Authorisation (PUMA)

 Introduced by the Paediatric Regulation for medicines that are: - Already authorised; - No longer covered by a supplementary protection certificate (SPC) or a patent that qualifies as a SPC; - To be exclusively developed for use in children.  The development of a PUMA must follow a paediatric investigation plan (PIP), to be agreed by the Paediatric Committee (PDCO).

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PIP related obligations vs. incentives

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Conditions for paediatric rewards

• Development is compliant with the agreed PIP • Results of studies included in Product information • Product is authorised in all MSs (except for PUMA) • Compliance statement included in the MA

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 PRIME (PRIority MEdicines) and similar initiatives

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Accelerated assessment

• For products of major interest from the point of view of public health and in particular from the view point of therapeutic innovation − What are the unmet needs? − How the product will address these? − What evidence supports? • Request to be submitted and agreed in advance of submitting the MA application • In accelerated assessment maximum ‘active’ time reduced from 210 to 150 days  > May revert back to standard timetable at any time during assessment!

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Goal and scope of PRIME

To foster the development of medicines with high public health potential .

Building on existing framework, eligibility according to existing Accelerated Assessment criteria.

Reinforce scientific and regulatory advice  Foster and facilitate early interaction  Raise awareness of requirements earlier in development Optimise development for robust data generation  Focus efficient development  Promote robust data generation Enable accelerated assessment  Promote generation of high quality data  Facilitated by knowledge gained throughout development

?

!

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Justification for eligibility to PRIME

 Unmet medical need  Epidemiological data about the disease

 Description of available diagnostic, prevention and treatment options/standard of care (SOC), their effect and how medical need is not fulfilled  Potential to significantly address the unmet medical need  Description of observed and predicted effects, clinical relevance, added value and impact  If applicable, expected improvement over existing treatments  Data required at different stages of development

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EMA report on 5 year PRIME in 2022

• EMA published on 3 March 20202 a report evaluating 5 year PRIME from March 2016 (Start PRIME) – June 2021 • 18 medicines that had PRIME support were approved in the European Union (EU) of which 10 received a conditional MA • 7 were ATMP, 16 concern rare diseases • Positive conclusion (PRIME enables earlier availability of life changing medicines) plus recommendations for improvement NB: In December 2021 PRIME elegibility granted to the first academia-led development!

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• During the pandemic in 2020 and 2021: rolling reviews were introduced for e.g. assessment Covid-19 vaccines • Evaluation of advantages and disadvantages ongoing Rolling review (e.g. Covid vaccins)

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 Considerations for SMEs

Reg. (EC) No 2049/2005

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Assignment of SME status • Registration with EMA SME Office • For enterprises/applicants within EU/EEA • SME criteria defined in Recommendation 2003/361/EC:  Headcount <250 and annual turnover not more than € 50 mil or balance sheet not more than € 43 mil. • Partner enterprises and linked enterprises affect te calculation • Submit information to show compliance with criteria • Limited validity, renewable

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Incentives for SMEs

• Administrative and procedural assistance from EMA SME office

• Fee reductions for procedures in the pre- and post-authorisation phases, fee exemptions for certain administrative services of EMA

• Deferral of the MAA and MAA related inspection fees

• Conditional fee exemption if scientific advice is followed but MAA outcome is negative

• Assistance with translations of the Annexes to MA, including product information (EU languages only) • For micro- or small-sized enterprises, also waiver of the MedDRA licensing fee when registering with EudraVigilance

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 Patient involvement

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Patient involvement at EMA

Key milestones of EMA interactions with patients/consumers:

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Patient involvement at EMA

 In 2006 Patients' and Consumers' Working Party (PCWP) established: provides recommendations to EMA and its human scientific committees on all matters of interest in relation to medicines.  Objectives: • supporting the Agency to access experiences of diseases, their management and information on current use of medicines • contributing to more efficient and targeted communication to patients and consumers; • enhancing understanding of the role of the EU medicines regulatory network.

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Patient involvement at EMA

 Activities:  Patients and consumers are involved in a wide range of activities:

• as members of the Management Board

• as members of scientific committees (COMP, PDCO, PRAC)

as members in MSSG

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• participation in SA meetings / being consulted on disease-specific requests by the scientific committees and working parties

• Taking part in discussions on the development and authorisation of medicines

• Reviewing written information on medicines (package leaflets, EPAR summaries)

• Involvement in the preparation of guidelines

• Taking part in the Agency’s conferences and workshops e.g. on shortages

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 Recap

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Learning Outcomes: Recap

 A brief outline of the Centralised and Mutual Recognition /Decentralised procedures  The role of the regulatory bodies, i.e. EMA, CHMP, COMP, PDCO, SAGs, EU Commission, CMDh, National Authorities, ATMP, PRAC, EMA-re-structure (new tasks)  Update to ongoing pharmaceutical legislation  Orphan Drug Regulations  Paediatric Regulations  PRIME and similar initiatives  Considerations for SMEs  The role of patients

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Any Questions?

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Back-up slide

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Types of marketing authorisations

“normal” MA

Conditional MA

MA under exceptional circumstances

Comprehensive data impossible

Comprehensive data at the time of authorisation

Comprehensive data after authorisation

‘full’ MA

To later switch to ‘full’ MA

To remain such indefinitely

Valid for 5 years (renewable)

Valid for 1 year only (renewable)

Valid for 5 years (renewable), but annual re-assessment procedure

Standard situation in all registration procedures

Possible in centralised procedure only

Possible in all registration procedures

May have conditions (e.g. PASS, PAES)

Specific Obligations + may have conditions

Specific obligations + may have conditions

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Developing Your Global Filing Strategy

Bob Clay Consultant, Highbury Regulatory Science Limited bob@bobclay.eu

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Agenda – Developing Your Regulatory Strategy

Regulatory strategy – what, why, when?

Influencing factors, e.g. product type, strength of data, internal & external initiatives

Scientific advice – where and how to obtain it

Utilising internal and external expertise

Integrating filing strategy with commercial objectives

Final remarks

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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01/07/2024

Global Regulatory Strategies – What, Why, When?

Access to new medicines is dependent on successful approval

Ensure the development plan is focused on product approval in a diverse regulatory environment with commercially viable labelling

Begin at the beginning...follow through

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Elements of a Global Regulatory Strategy

Strategic input during stages of development • discovery and early development • Phase III and filing • registration and life-cycle Consider an alternative/modern approach:

• Breakthrough Designation/PRIME • Early dialogue/Innovative Pathways

Eichler, H. et al. 2015. From adaptive licensing to adaptive pathways: Delivering a flexible life ‐ span approach to bring new drugs to patients. Clinical Pharmacology & Therapeutics . (2015).

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Labelling Drives Development and Supports Promotion

Differentiation must be reflected in the label • therapeutic • commercial • regulatory Strategies for success • target profile • label development • regulatory intelligence • define what is essential or negotiable

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Target Product Profile

Global Submission Strategy

Regulatory Pathways

Supporting Documentation

Scientific & Technical Data

Elements of a Regulatory Strategy

Market Exclusivity

Regulatory Risks and Mitigations

Patient Engagement

Approval Options

Scientific Advice and Regulatory Interactions

Development Plan

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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01/07/2024

Agenda

Regulatory strategy – what, why, when? Influencing factors, e.g. product type, strength of data, internal & external initiatives Scientific advice – where and how to obtain it Utilising internal and external expertise Integrating filing strategy with commercial objectives Final remarks

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Influencing Factors

Patients & medical need

Product type

Strength of data

Internal & external initiatives

• Development programme is focussed on achievement of the target profile • Adapting to the results of your development programme • Understanding weaknesses in your data • Impact of competitors or regulatory decisions

• Demographics • Disease prevalence • Seriousness & severity • Differentiation • Precedent

•New Chemical Entities • Line Extensions • Biologics • Generics • Orphan Products • Advanced Therapeutics • Therapeutic Area • Devices and Diagnostics • Integrated Solutions

• Company Portfolio • Interactions with

Regulatory Authorities

• Emerging

Regulatory Environment • Market Access Strategies

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Influencing Factors: Internal & External Initiatives

Interactions with Regulatory Authorities • Range of advice that may be expected • Building on solid foundations •Understanding of regulators expectations • Importance of transparency • Appropriate level of interaction • Potential for HTA interactions, including parallel or joint advice

Emerging Regulatory Environment

Market Access Strategies

Company Portfolio

• Patient

• Regulatory science • Early access to medicines • Therapeutic developments • Opportunities for global trials • Regional trends • Emerging guidelines • Competitor products • Emerging safety concerns • Political dimensions

• Experience • Skills base • Positioning • Priority • Life cycle • Investor objectives

engagement • Payer Landscape • Key opinion leaders • Value messages • Health Technology Assessment (HTA) • Access & Reimbursement

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Agenda

Regulatory strategy – what, why, when? Influencing factors, e.g. product type, strength of data, internal & external initiatives Scientific advice – where and how to obtain it Utilising internal and external expertise Integrating filing strategy with commercial objectives Final remarks

The Organisation for Professionals in Regulatory Affairs

09/07/2024

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Scientific Advice – Where and How to Obtain It

Advice is an integral part of the drug development process

• Agencies participating in ICH generally provide opportunity to gain “advice” • Key role of regulators is the protection of public health which includes support for innovation • HTA advice from multiple archetypes, opportunities for joint or parallel advice

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Scientific Advice From a Sponsor’s Perspective

New medicines are usually intended for a global market • The US remains the largest single market • Impact on global trials • Long development times are associated with significant commercial risk Diverse sources of advice are available and are often not consistent • National agencies • US, Japan, European, China, Other Agencies • EU Scientific Advice • Health technology assessment

• Parallel/joint advice –MHRA/NICE, HTA/EMA, HTA networks Consider diagnostic co-development and HTA input

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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01/07/2024

Agenda

Regulatory strategy – what, why, when? Influencing factors, e.g. product type, strength of data, internal & external initiatives Scientific advice – where and how to obtain it Utilising internal and external expertise Integrating filing strategy with commercial objectives Final remarks

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Internal and External Expertise

Existing products and therapeutic areas On-going development projects Competitor activity Investigators and academic experts Conferences, scientific societies and expert groups Regulatory consultants Regulatory agencies Health technology assessment Personalised medicine/diagnostic requirements

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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01/07/2024

Agenda

Regulatory strategy – what, why, when? Influencing factors, e.g. product type, strength of data, internal & external initiatives Scientific advice – where and how to obtain it Utilising internal and external expertise Integrating filing strategy with commercial objectives Final remarks

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Filing Strategy and Commercial Objectives

Understanding value • new therapeutic approach • therapeutic improvement or differentiation • time • commercially acceptable launch label • access & health technology assessment strategy • intellectual property and data exclusivity • synergy within your portfolio

Drivers for submission strategy

• economic drivers • development drivers • competitive environment • approval times • HTA strategy • diagnostic requirements • early market entry opportunities

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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01/07/2024

Agenda

Regulatory strategy – what, why, when? Influencing factors, e.g. product type, strength of data, internal & external initiatives Scientific advice – where and how to obtain it Utilising internal and external expertise Integrating filing strategy with commercial objectives Final remarks

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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Final Remarks

Drug development is an increasingly complex activity

Approval times are converging with greater interdependence of the outcomes

HTA interactions should be integrated into development

Significant resources need to be applied effectively by applicant and regulators

Labelling drives development, the data should drive the labelling and the label supports access

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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A cknowledgements

While the views expressed are my own I am grateful for the input of many colleagues in the development of this presentation

The Organisation for Professionals in Regulatory Affairs

09/07/2024

Developing your Global Filing Strategy – July 2024

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03/07/2024

CRED Navigating European Regulatory Procedures

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CRED Navigating European Regulatory Procedures – 11-12 July 2024 Developing Strategy for Non-NCEs

12-13 th March 2020

Eesha Vyas, Oncology Regulatory Lead, GSK

ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION

The Organisation for Professionals in Regulatory Affairs

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Learning Outcomes

This session is intended to give the delegates an overview of developing their strategy for non-NCEs, in Europe

Key points to be covered:

● Understand the legal basis, and the complexities involved when considering the Regulatory Strategy for:

• Bibliographic/ Well Established Use • Line extensions/generics/hybrids • Biosimilars • Borderline and Combination Products • Herbals

The Organisation for Professionals in Regulatory Affairs

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03/07/2024

Agenda

• Fundamentals • Abridged applications

• Well established Use • Fixed Combination • Informed Consent • Generic • Line Extension/Hybrid • Biosimilars

• Data Protection • Strategic Considerations • Borderline Products • Combination Products • Herbals

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Fundamentals…

• No medicinal product may be placed on the markets unless a marketing authorisation has been issued by a competent authority. • NCE - A chemical active substance that is not previously authorised in a medicinal product for human use in the European Union • From a chemical structure point of view not related to any other authorised substances • Considered to be new in itself as the structure of the therapeutic moiety is different from any other authorised so far as a medicinal product for human use. • If the chemical active substance is structurally related (salt, ester, ether, isomer, mixture of isomers, complex or derivative) of an already approved active substance, assess whether it shares the same therapeutic moiety at the site of the biological activity as the already approved active substance AND whether it differs significantly in properties with regard to safety and/or efficacy.

https://www.ema.europa.eu/en/documents/scientific-guideline/draft-reflection-paper-chemical-structure-properties-criteria-be-considered-evaluation-new active_en.pdf

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