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Regulatory Roadmap for the development of human medicinal Products
(Europe focus)

Welcome to the Regulatory Roadmap. This roadmap will help to identify the applicable Regulations and Guidance* for each phase of the development of Human Medicinal Products. It represents a time-based path through the entire lifecycle of a drug, from initial inception through to distribution and pharmacovigilance of the marketed product.

Just click on the various stages below to reveal the information.

Idea Expand  

  • 'Non GxP' Research

Description

Formulation of an idea or thesis to investigate a particular disease area. For pharmaceutical development purposes this should be linked to potential means of treating disease / curing disease / reducing symptoms / maintaining quality of life associated with producing a medicinal treatment.

Inputs

None

Processes

"Non GxP" Research

Outputs

Target Drug / Hypothesis

Discovery Research Expand  

  • 'Non GxP' Research

Description

Scientific investigation of a disease model and potential active candidates to establish possible marketable products.
No formal regulatory requirements exist for scientific research of this type and it must be understood that information gathered at this stage is inadmissible in regulatory filings.

Discovery Research covers the period from target identification to nomination and may be used when clinical studies yield results that require further investigation to:

  • Identify potential candidate drugs (CDs)
  • Perform preliminary safety & formulation tests
  • Confirm pharmacological mode of action (potency & selectivity)
  • Identify potential biomarkers
  • Perform preliminary PK
  • Demonstrate activity in in-vivo and/or in-vitro models

The aim is to select one or more CDs for each target for pre-clinical safety evaluation.

Inputs

Target drug / Hypothesis
Current medical knowledge

Processes

“Non GxP” Research

Outputs

Identification of Test Articles
Scientific Evidence to support hypothesis
Target identified

Pre- Clinical Testing Expand  

  • 'Non GxP' Research
  • GLP : Pre-Clinical Research

Pre-Clinical Testing

Description

Research designed to fulfill the requirements of the non-clinical safety section of the common technical document (ICH M4S). Safety evaluation of candidate Investigational Products (New chemical entities and Biologics), known as test articles, governed by Good Laboratory Practice (GLP).

Pre-clinical testing is performed to GLP and covers pivotal toxicology & safety pharmacology studies. This phase continues once clinical trials have commenced to establish the long term safety of new chemical entities.
Non-clinical evaluation of drug safety usually consists of standard animal toxicology studies. These studies usually include assessment of drug exposure, primarily parent drug plasma concentration. Generally, drug plasma concentration and systemic exposure in the non-clinical studies are compared with systemic exposure in humans to assess the potential risks suggested by non-clinical findings and guide monitoring in clinical trials.

Pre-clinical testing is done to evaluate the properties of a test article to either determine its characteristics or to evaluate the effect that it has upon a test system. This involves both in-vitro and in-vivo testing.

Inputs

Test Articles

Processes

“Non GxP” Research
GLP : Pre-Clinical research

Outputs

Test Article Safety Reports

RQA Courses / Seminars / eLearning

First in man/ clinical trials Expand  

  • GLP : Pre-Clinical Research
  • GMP : Test Article
  • GMP : IMP Manufacturing
  • GMP & GCP : Trial Supplies
  • GCP : Clinical Research (Phases I,II,IIa)
  • GCP & GPVP : Pharmacovigilance

First in Man/Clinical Trials

Description

Phase I or First in Man/Clinical Trials - when an investigational medicinal product (IMP) developed and assessed through in-vitro or animal testing, is tested on human subjects for the first time.

Marketed products may fall under the same Regulations if the product is used as part of an interventional trial. (The product must meet the definition of an IMP).

Inputs

Test Article Safety Reports (GMP)
Pre- clinical Data (GLP)

Processes

GCP : Clinical Research (Phases 1)
GCP & GPVP: Pharmacovigilance
GMP : IMP Manufacturing

Regulations

Outputs

  • Clinical Study Reports (CSR)
  • Data to support the creation of the Common Technical Document for submission for marketing application
  • Trial Master File (TMP)

RQA Courses / Seminars / eLearning

Pre- Licensing Activities Expand  

  • GLP : Pre-Clinical Research
  • GMP : Test Article
  • GMP : IMP Manufacturing
  • GMP & GCP : Trial Supplies
  • GCP : Clinical Research (Phases I,II,IIa)
  • GCP & GPVP : Pharmacovigilance

Pre Licensing Activities

Description

  • Phase II-IIIa research covers subsequent clinical trials conducted prior to a marketing licence application and is designed to gather further data in relation to safety and efficacy to be used as part of the submission. Marketed products may fall under the same Regulations if the product is used as part of an interventional trial. (The product must meet the definition of an investigational medicinal product -IMP.)
  • Company Core Safety Information finalised and benefit-risk confirmed.
  • Prepare marketing authorisation application (MAA)/new drug application(NDA) dossier.
  • The process for gathering data contained in the clinical safety and efficacy section of the common technical document (ICH M4E) and establishing the Processes which formulate the Quality and Chemistry and Manufacturing Controls section of the common technical document (ICH M4Q).

Inputs

Clinical Study Reports
Trial Master File
Data to support the Dossier (Chemistry Manufacturing Control (CMC))
Test Article Safety Reports

Processes

GCP : Clinical Research (Phases II-IIIa)
GCP & GPVP : Pharmacovigilance
GMP : IMP Manufacturing
GMP : Test Article Manufacturing

Regulations

Outputs

Common Technical Document (CTD)
Prepare MAA/NDA dossier
Licensed/Compliant Manufacturing Facility
Finalise Company Core re Safety information, prepare regions prescribing information
Propose Clinical Phase IIIb and IV plans
Develop Life Cycle Management plans
Benefit-risk confirmed
Patient Risk Management Plan implemented 

BARQA Courses / Seminars / eLearning

Licence Granted Expand  

  • GMP : IMP Manufacturing
  • GMP & GCP : Trial Supplies
  • GCP : Clinical Research (Phases I,II,IIa)
  • GCP & GPVP : Pharmacovigilance
  • GMP : Product Manufacturing
  • GMP : Distribution
  • GCP, GMP & GPVP : Post Marketing Studies

Licence Granted

Description

Manufacturing Authorisation(s) and product licence granted for the medicinal product.
Commencement of post marketing surveillance requirements for the product and commencement/continuation of clinical trials required for line extension or new indications.

Inputs

Common Technical Document (CTD) Dossier
Licensed/Compliant Manufacturing Facility

Processes

GMP : IMP Manufacturing
GMP & GCO : Trial Supplies
GCP : Clinical Research (Phases I-IIIa)
GCP & GPVP : Pharmacovigilance

Regulations

Pharmacovigilance

The reporting obligations under the provisions on pharmacovigilance for authorised medicinal products are set out in Directive 2001/83/EC and Regulation EC No. 726/2004

Clinical Research

Investigational medicinal product (IMP) Manufacturing

  • Directive 2003/94/EC laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use

Outputs

Product Licence
Label and regulatory approval finalised
Sustain and maximise sales by introducing Life Cycle Management (LCM) line extensions
PRMP implemented, strategy for post launch surveillance defined 

RQA Courses / Seminars / eLearning

Variations to a Licence Expand  

  • GCP & GPVP : Pharmacovigilance
  • GMP : Product Manufacturing
  • GMP : Distribution
  • GCP, GMP & GPVP : Post Marketing Studies

Variations to Licence

Description

Maximised potential/contribution of compound
New indications
Patent extensions
Paediatric studies
Orphan drug status

Inputs

Product Licence
Submission of change request
Life cycle management
Ongoing surveillance
Signal detection
Updates to Company Core Safety Information

Processes

GMP : Product Manufacturing
GMP : Distribution
GCP, GMP & GPVP : Post Marketing Studies
GCP & GPVP : Pharmacovigilance

Outputs

Updated product licence
Change process(es)
Maintain support to health authorities, routine compliance activities
Maximised potential/contribution of compund

RQA Courses / Seminars / eLearning

Licence Renewal Expand  

  • GCP & GPVP : Pharmacovigilance
  • GMP : Product Manufacturing
  • GMP : Distribution
  • GCP, GMP & GPVP : Post Marketing Studies

Licence Renewal

Description

Under the medicines legislation which was implemented on 30 October 2005, marketing authorisations (MAs) will be valid for five years and then may be renewed on the basis of a re-evaluation of the risk-benefit balance. Once renewed, the marketing authorisation will be valid for an unlimited period unless there are justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal. In addition, the five-yearly cycle of Periodic Safety Update Reports (PSURs) with renewal has been replaced by a three-year cycle.

Inputs

Periodic Safety Update Reports (PSURs)
PSUR Assessment reports
Post-marketing studies
PRMP

Processes

GMP : Product Manufacturing
GMP : Distribution
GCP, GMP & GPVP : Post Marketing Studies
GCP & GPVP : Pharmacovigilance

Outputs

Renewed Product Licence

RQA Courses / Seminars / eLearning

Terminate Licence Expand  

  • GCP & GPVP : Pharmacovigilance
  • GMP : Product Manufacturing
  • GMP : Distribution
  • GCP, GMP & GPVP : Post Marketing Studies

Terminate Licence

Description

The voluntary, or otherwise, termination of the licence to manufacture and market a particular product;

At the end of the product life-cycle, i.e. when the product is off-patent and generic competition has eroded product revenue, the product may be removed from sale following withdrawal of the product from the supply chain and termination of all existing product licences.

Alternatively, the product may be divested and the product licences transferred to the new owner of the product.

Inputs

Product Licence
Submission for Termination / Transfer Request
Product Divestment

Processes

GMP : Product Manufacturing
GMP : Distribution
GCP, GMP & GPVP : Post Marketing Studies
GCP & GPVP : Pharmacovigilance

Outputs

Confirmation of Cancellation of Licence
Or
Agreement of Licence Transfer 

RQA Courses / Seminars / eLearning


*Covers Regulations, legislation and Guidance within the European Economic Area level, not including national legislation except for the UK.

The Roadmap is an overview generated by the RQA Regulatory Roadmap Working Party and is for Guidance only.
Users should ensure that its content is suitable for their particular use.

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