I modelli decisionali in Europa

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I modelli decisionali in Europa

• X Congresso Nazionale CIPOMO

• Dr. Pasqualino Rossi
• Roma, 5 maggio 2006

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• EMEA'S ROLE IN HUMAN MEDICINES FIELD

• Evaluation of applications for marketing
  authorisation for Human medicinal products using
  the centralised procedure or referred by Member
  States
• Provision of Advice throughout the development
• Control of Safety of Centrally authorised
  products through a Pharmacovigilance Network
• Evaluation of applications for orphan designation
  in EU

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• EMEA'S ROLE IN HUMAN MEDICINES FIELD

Setting the standards Guidelines for industry
Safety monitoring pharmacovigilance,
post-authorisation applications and surveillance
Designation of Orphan Drugs Medicines for rare
diseases
R D
EMEA in the life cycle of a medicine
Medicines in use
Scientific Advice Support to sponsors during
research and development
Information for patients and health professionals
Pre-submission Support to companies before
submission of applications
Evaluation
EMEA Opinion Implemented through EU-wide
Commission authorisation
Evaluation Scientific assessment by CHMP and
additional high-level specialised expertise
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EMEA COMMITTEES ON HUMAN MEDICINES
CHMP (Committee for Medicinal Products for Human
Use ) Members Each of the 25 EU Member States
nominates one member and one alternate
Observers EEA-EFTA States (Iceland,
Liechtenstein and Norway) nominates 1 member and
1 alternate. The Committee has also co-opted an
additional 5 members with specific areas of
complementary expertise Chair Dr. Daniel
Brasseur COMP (Committee for Orphan Medicinal
Products) Members 1 per Member State 1
Management Board 2 CHMP 3 Patient
Organisation 1 Commission representatives Observ
ers ICE/NO/accession countries Chair Dr. J.
Torrent-Farnell
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EMEA
Working Party on Similar Biological (Biosimilar)
Medicinal Products
Paediatric Expert Group
Biologicals Working Party
CHMP Working Parties
Safety Working Party
Vaccine WP
Joint CHMP/CVMP Quality Working Party
Gene Therapy Working Party
Efficacy Working Party
Working Party on Cell-Based Products

• Scientific Advisory Groups (SAG)
• Infectious Agents (not HIV)
• Diagnostic Agents
• Oncology
• Future SAGS

Pharmacogenetics Working Party
Blood Products Working Party
Pharmacovigilance Working Party
Scientific Advice WP
Plus specific ad-hoc working groups or subgroup
meetings when needed
Ad-hoc Inspections Quality Review of
Documents Invented Names Review Group
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CENTRALISED PROCEDURE IS A RESERVED PROCESS

• It is not open to all products dedicated to
  innovative products
• It is not for old or established products in
  established indications, e.g. aspirin for
  headache
• it may be open to old products in new
  indications, or an old drug in a new delivery
  system, etc..e.g. aspirin for Alzheimer's
  disease
• Products eligible are defined in the legislation

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CENTRALISED PROCEDURE IS A RESERVED PROCESS

• Annex to Council Regulation (EEC) No 726/04
• recombinant DNA technology,
• controlled expression of genes coding for
  biologically active proteins in prokaryotes and
  eukaryotes including transformed mammalian cells,
• hybridoma and monoclonal antibody methods.
• Medicinal products for human use containing a new
  active substance which was not authorised in the
  Community, for which the therapeutic indication
  is the treatment of any of the following
  diseases
• acquired immune deficiency syndrome,
• cancer,
• neurodegenerative disorder,
• diabetes,
• and with effect from 20 May 2008
• auto-immune diseases and other immune
  dysfunctions,
• viral diseases.
• Medicinal products that are designated as orphan
  medicinal products pursuant to Regulation (EC) No
  141/2000.

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Rapporteur Appointment Process

• Objective Criteria ..best available
• (scientific) expertise
• Omission company preferences
• Omission statistical approach

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Presubmission contacts Rapporteurs/ EMEA

• Increasingly important in view of new CHMP policy
  on clock-stops
• Systematic in nature to guide applicant through
  key milestones of procedure
• Increased emphasis on scientific content of
  application time to availability

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• ACCESSING THE CENTRALISED PROCEDURE
• Optional scope

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Borderline between Mandatory Optional Scope

• Complications of the disease (e.g. diabetic
  neuropathy, diabetic retinopathy) unless the
  intervention is based on treatment of the
  underlying disease (e.g. treatment of oesophageal
  obstruction caused by a malignant tumour).
• Interventions that are intended for diagnosing,
  staging, or monitoring of the disease
• Treatment of adverse reactions caused by other
  treatments of the disease (e.g. nausea/
  anti-cancer drugs)
• Medicinal product intended for prevention of
  diseases

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Scope Legal Basis

• Article 3(2) of Regulation (EC) No 726/2004
• (a) the medicinal product contains a new active
  substance which, on the date of entry into force
  of this Regulation, was not authorised in the
  Community
• or
• (b) the applicant shows that the medicinal
  product constitutes a significant therapeutic,
  scientific or technical innovation or that the
  granting of authorisation in accordance with this
  Regulation is in the interests of patients or
  animal health at Community level.

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Optional Scope General Principles

• Two separate documents
• Guideline providing clarification on criteria of
  New active substance Innovation
• Reflection paper proposing notion and criteria
  for Interest of patients at Community level

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Optional Scope Guideline for New active
substance / Innovation principles

• Addressing the criteria of New Active Substance
  (NAS) not authorised in the Community
• Cut-off date 20/11/05
• NAS list of examples (not exhaustive!) Chapter 4
  NTA EMEA guideline on optional scope.

Marketing Authorisation in the EU EC Decision
for CP
NAS
20/11/05
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Optional Scope Guideline for New active
substance / Innovation principles

• Addressing criteria of significant Innovation
• Therapeutic e.g. New alternative to patients in
  treating, preventing or diagnosing a disease
• Scientific e.g. New scientific knowledge (for
  its development or is considered once approved
  as being a new scientific knowledge)
• Technical e.g. New technology or a new
  application of technology is used for the
  development or the manufacture of the medicinal
  product.

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Optional Scope Reflection Paper - notion and
criteria for Interest of patients at Community
level

• NOTION OF SPECIFIC HEALTH ISSUE
• Concerns the Community (in principle not limited
  number of Member States)
• Example of health issues
• Occurrence of an epidemic/pandemic disease or a
  particularly serious disease, or related to other
  emergency situations, including a bioterrorism/
  biochemical risk.
• Adequate safety measures must be applied at
  EU-wide level to prevent potential serious risk
  to public health

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Optional Scope Reflection Paper - notion and
criteria for Interest of patients at Community
level

• NOTION OF ACCESS TO MEDICINES
• Same (invented) name, presentation(s) and
  classification as defined in Article 70 of
  Directive 2001/83/EC (i.e. subject or not to
  medical prescription)
• If such product is not yet available.
• Non-prescription medicinal products
• Generics medicinal products
• Others

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Optional Scope Procedural consideration

• Eligibility Procedure - General Rule
• NEED to request EMEA/CHMP CONFIRMATION of
  ELIGIBILITY if MP falls under the scope of
  Article 3(2) of Regulation (EC) No 726/2004
• Request to be made to EMEA, up to 18 months in
  advance of submission date based on justification
  based on guideline/ reflection paper principles
• Justification will be assessed by
  EMEA/CHMP/relevant WP and EMEA will inform
  applicant accordingly.
• Timeline proposed 1 month Justified refusal

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SAGs Role and Mandate evaluation input

• Deliver independent recommendation to specific
  questions
• Related to
• Scientific /technical matters of products under
  evaluation (Pre - or Post- authorisation) or
• any other scientific issue relevant to the work
  of the Committee e.g. Scientific opinions (e.g.
  Commission, WHO) Scientific advice/protocol
  assistance, Referrals, and Guidelines

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SAGs Role and Mandate evaluation input

• Report to CHMP
• CHMP remains responsible for its final opinion ?
  evaluation input of the SAGs
• Meet on request from the CHMP

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SAGs Timing

• Scheduled meeting sequence vs Ad-hoc product
  requests
• Rapporteurs/CHMP members to identify need asap (
  also applies to involvement specialised expertise
  PhViG)
• Typically LoQ LooIs
• Company oral explanations ( may provision)

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SAGs Timing

• Re-examination presents particular challenge
• Ad-hoc meeting timing ( linked to submission
  timing)
• Chair-person presence within CHMP plenary

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Involvement Patients/ Consumer Organisations

• Better Info/ Communication matters common
  interest advisory basis
• Consultation agreed by CHMP define scope and
  questions tba
• Patients as representatives of their organisation
• Applicant informed /agreement re disclosure data
• Patients as experts
• Code DoI Confidentiality aspects

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New Decision Making Processes

• Before and After
• Reg 2309/93
• 30 days for the EMEA to transmit the Opinion to
  EC
• 30 days for the EC to prepare the draft Decision
• 30 days for the Standing Committee consultation
• 30 days for the EC to issue the final Decision
• 120 days
• Reg 726/2004
• 15 days EMEA to transmit the Opinion to the EC
• 15 days for the EC to prepare the draft Decision
• 22 days for the Standing Committee consultation
• 15 days for the EC to issue the final Decision
• 67 days

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New Decision Making Processes

• Post-opinion timelines
• Harmonised approach for
• New Applications Line Extensions
• Variations
• Renewals/Annual Re-assessment
• Referrals

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New applications L. Extensions

• Day 210 gt adoption of CHMP opinion
• Day 215 gt Co to submit Product Info
• Day 215-229 gt MS to review translations
• Day 229-232 gt Co to implement MS comments
• Day 232-237 gt EMEA final PIQ check
• Day 239-261 gt Standing Committee Cons.
• Day 277 gt Final Commission Decision
• !! Calendar Days!!

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Practical aspects

• Shorter checking deadlines gt quality of
  translations becomes very important
• Feedback on implementation of MS comments gt very
  important
• Poor quality gt not possible to meet shorter
  checking deadlines
• !!Return translation to applicant clock stop!!

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PIM

• Implementation date 20/11/2005
• PIM non-PIM submissions to follow the same
  timelines