Medicinal products dossier- CTD and eCTD

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Medicinal products dossier

• https//www.regulatory-affairs.pl/en/medicinal-pro
  ducts.html

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Documentation of human medicinal products

• The basic requirements are specified in Directive
  2001/83 (Annexes to the Directive), specific
  requirements are defind for particular issues in
  the guidelines for group of products
• CTD format (Common Technical Document) is
  required
• Details and requirements for each section vary
  depending on the nature of the product (e.g.
  synthetic products, herbal medicinal products,
  blood derrived products, biotechnology,
  antibiotics, etc.).

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Documentation of human medicinal products

• CTD documentation consists of sections called
  modules At the present moment we have 5 modules.
  The modules 2-5 has been agreed at the ICH (EU /
  US / JP). Module 1 is a specific module for the
  region THEIR

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Documentation of human medicinal products
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Documentation of human medicinal products
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Documentation of human medicinal products
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Documentation of human medicinal products
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Documentation of human medicinal products
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Electronic CTD dossiers

• In order to speed up the assessmend and handling
  of CTD dossier as well as for better traceability
  of the variations in the documents the electronic
  version of the CTD format called eCTD is created.
  eCTD format consists of pdf files reflecting the
  different sections of the modules organized as in
  CTD in a precisely defined structure. In
  addition, relationships and attributes of files,
  dossiers and its history are listed in the XML
  files. As with the CTD specification module 2-5,
  for eCTD ICH module 1 is described in the context
  of the specification EU or other countries of
  particular region (GCC, CH, USA, CA). Every
  supplement the documentation (e.g. to answer
  agency questions) take the form of so-called next
  sequence consisting of a group of documents
  changed with the appropriate XML files describing
  the file changes.

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Electronic CTD dossiers

• NeeS format (Non-eCTD electronic submission).
  This is a simplified version of the eCTD in the
  form of pdf files in a strictly defined CTD
  structure with hyperlinking in pdf table of
  contents. There is no corresponding XML files for
  document tracking changes.
• As of 2019 NeeS became obsolete in EU and eCTD is
  the only accepted format for human medicinal
  products.
• For veterinary products VNeeS is introduced in
  EU.
• Details and specifications of the EU eCTD format
  http//esubmission.ema.europa.eu/eumodule1/index.h
  tm

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Categories of applications

• There are two concepts legal basis and legal
  status.
• Legal basis is a category, which defines how
  safety and efficacy of the medicinal product is
  documented.
• Legal status is a category of availability on the
  market (OTC / Rx)

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Legal basis

• The main categories of applications in EU
• Full stand-alone application (Article 8 (3)
  Directive 2001/83 )- full clinical and
  preclinical dossier is required
• Generic applications - simplified applications
  referring to other products with full clinical
  dossier (so called reference products). You have
  to prove the equivalence vs. reference products
• Generic - the products that have the same
  strength, form, route of administration (oral
  form of immediate release are treated as
  equivalent, e.g., capsules, tablets) and the same
  indications as the reference product. Equivalence
  is proven by bioavailability (bioequivalence
  studies) or in special cases as a so-called
  biowaiver (exemption from bioequivalence studies-
  exclusively by the in vitro data, comparison of
  release profiles in the range of physiological pH
  (1,2-6,8 / 7.2)). Biowaiver is foreseen mainly
  for oral immediate release forms of the active
  substances of the classes I and III BCS, oral
  solutions, topical products in the form of
  solutions without the systemic action and
  parenteral solutions of identical / similar
  composition
• Hybrid generic like product which differs form
  the reference product in the field of the route
  of administration, indications, strenght or
  generics where due to the route of administration
  equivalence could not be demonstrated on the
  basis of the bioavailability studies and there is
  a need for testing therapeutic equivalence in
  conventional clinical equivalence /
  non-inferiority (inhalations).
• Biosimilar - application for generic products of
  biological origin

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Legal basis

• The main categories of applications
• Bibliographic applications (well established use
  WEU, article 10a of Directive 2001/83). This is a
  kind of full apllication (no reference product),
  the only difference is that all clinical and
  non-clinical topics are documented with studies
  published in literature. Formal requirement of
  presence of medicinal products for at least 10
  years in the EU in the same indication, route of
  administration.
• Fixed combination - the mixture of active
  substances used in medicinal products
  separately. The dossier not need to document
  efficacy and safety of single substances, but
  should be focused on the combination (e.g.
  interactions - pharmacokinetic, pharmacodynamic,
  the effect onthe safety, clinical benefit of
  combination etc.). The data for the combination
  should in principle be own data, but sometimes
  companies use this category to with bibliographic
  data for the combination to avoid documenting
  individual substances. It is also a full
  application dossier.

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Legal basis

• The main categories of applications
• Informed consent - another company grants all the
  right for documentation (modules 2-5) to another
  entity. The condition is that the first product
  must already be registered in the particular
  country. The assessment is then shortened and is
  based on checking how this dossier corresponds to
  the current requirements.
• Simplified applications for traditional herbal
  medicinal products (no evidence of efficacy with
  a proof of a minimum of 15 years in the EU), for
  homeopathy (without indications), pharmacopoeial
  products etc.
• Mixed application - a WEU application, which
  presents its own trials for certain topics, for
  example additional indications, other age groups
  etc. Such applications officially are classified
  as a full application according to article 8(3).