CTD

What is CTD?

The Common Technical Document (CTD) is a set of specification for application dossier, for the registration of Medicines and designed to be used across Europe, Japan and the United States.Quality, Safety and Efficacy information is assembled in a common format through CTD .The CTD is maintained by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).


In simple words "CTD is the format for registration of medicines, generally used in EU region, USA and Japan."

Note : CTD format for submission of drug registration applications/dossiers is widely accepted by regulatory authorities of other countries too like Canada, Australia etc. 

The Common Technical Document is divided into five modules:

1. Administrative information and prescribing information

2. Common Technical Document summaries (Overview and summary of modules 3 to 5)

3. Quality 

4. Nonclinical Study Reports (toxicology studies)

5. Clinical Study Reports (clinical studies)

The  Common Technical Document is better understood with a CTD triangle which is  presented below-

Source: ich.org

The CTD is the mandatory format for new drug applications in the EU and Japan, and the strongly recommended format of choice for NDAs submitted to the FDA. Apart from EU region, USA and Japan, CTD format is widely accepted by many regulatory agencies across the world for registration of Medicines.

 What are the advantages due to the use of CTD?

• It has revolutionised the regulatory review processes

• It led to harmonised electronic submission which, in turn, enabled implementation of good review practices

• For industries, it has eliminated the need to reformat the information for submission to the different ICH regulatory authorities

All the ICH guidelines related to CTD (M4, M4Q, M4S, M4E) are presented below-

M4 Guideline of ICH-  This gives a complete information on the organisation of CTD




In the above guideline to get a complete idea on the sections under each module you need to focus on the content in the page- 5

M4Q Guideline of ICH- This  provides harmonised structure and format for presenting CMC (Chemistry, Manufacturing and Controls) information in a registration dossier.

M4S Guideline of ICH- This provides information on the non-clinical section of application

M4E Guideline of ICH- This provides information on the clinical section of application.



Keywords: CTD, CTD triangle, Quality, Safety , Efficacy,  M4, M4Q, M4S, M4E.

References: 
http://www.wikipedia.org/
http://ich.org/

ICH Guidelines

The guidelines of ICH may be broadly categorized into four types-

Quality Guidelines
Safety Guidelines
Efficacy Guidelines
Multidisciplinary Guidelines

Source: ich.org

Quality Guidelines : Harmonisation achievements in the Quality area include pivotal milestones such as the conduct of stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management.

Safety Guidelines : ICH has produced a comprehensive set of safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and reprotoxicity. A recent breakthrough has been a non-clinical testing strategy for assessing the QT interval prolongation liability: the single most important cause of drug withdrawals in recent years.

Efficacy Guidelines : The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials. It also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics/genomics techniques to produce better targeted medicines.

Multidisciplinary Guidelines : Those are the cross-cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology (MedDRA), the Common Technical Document (CTD) and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI).

Keywords: Quality Guidelines, Safety Guidelines, Efficacy Guidelines, Multidisciplinary Guidelines, CTD, ESTRI, MedDRA.

Reference : http://www.ich.org/

ICH

Source: ich.org

What is ICH?

• ICH is The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

• It is unique project that brings together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US to discuss scientific and technical aspects of drug registration.

• It was formed to achieve greater harmonisation in the interpretation and application of technical guidelines and requirements for pharmaceutical product registration in EU, Japan and USA

In Simple words " ICH was formed to have a common scientific and technical requirements for registration of pharmaceuticals in EU, Japan and USA to make the job easy for Regulatory agencies and Pharma companies". 

Benefits of Harmonisation/Benefits due to the formation of ICH-

Harmonisation is beneficial to both regulatory authorities and the pharmaceutical industry, ultimately having beneficial impact for the protection of public health. The benefits of harmonization are listed below-

• Preventing duplication of clinical trials in humans and minimising the use of animal testing without compromising safety and effectiveness.
• Harmonisation would lead to a more economical use of human, animal and material resources, and the elimination of unnecessary delay in the global development and availability of new medicines while maintaining safeguards on quality, safety, and efficacy, and regulatory obligations to protect public health
• Streamlining the regulatory assessment process for new drug applications; and reducing the development times and resources for drug development.
  
  

Origin Of ICH-

• Harmonisation of regulatory requirements was pioneered by the European Community (EC), in the 1980s, as the EC (now the European Union) moved towards the development of a single market for pharmaceuticals. The success achieved in Europe demonstrated that harmonisation was feasible.
• At the same time there were bilateral discussions between Europe, Japan and the US on possibilities for harmonisation. 
• It was, however, at the WHO Conference of Drug Regulatory Authorities (ICDRA), in Paris, in 1989, that specific plans for action began to materialize.
• Soon afterwards, the authorities approached IFPMA to discuss a joint regulatory-industry initiative on international harmonisation, and ICH was conceived.
• The birth of ICH took place at a meeting in April 1990, hosted by EFPIA in Brussels. Representatives of the regulatory agencies and industry associations of Europe, Japan and the US met, primarily, to plan an International Conference but the meeting also discussed the wider implications and terms of reference of ICH.
• At the first ICH Steering Committee (SC) meeting of ICH the Terms of Reference were agreed and it was decided that the Topics selected for harmonisation would be divided into Safety, Quality and Efficacy to reflect the three criteria which are the basis for approving and authorising new medicinal products.

ICH Secretariat-
ICH does not have "offices" as such, but ICH secretariat is based in Geneva, Switzerland. The biannual meetings and conferences of the ICH Steering Committee rotate between the EU, Japan, and the USA.

Members of ICH-

MHLW - Ministry of Health, Labour and Welfare

JPMA-    Japan Pharmaceutical Manufacturers Association

EU-          European Union 

EFPIA-    European Federation of Pharmaceutical Industries and Associations 

FDA-       Food and Drug Administration

PhRMA -Pharmaceutical Research and Manufacturers of America

MHLW and JPMA are from Japan
EU and EFPIA are from Europe
FDA and PhRMA are from USA

Non Voting Members of ICH-

WHO-World Health Organization

EFTA-European Free Trade Association

IFPMA- International Federation of Pharmaceutical Manufacturers & Associations

Organisation of ICH

Source: ich.org

Process of Harmonisation:

ICH harmonisation activities fall into 4 categories: Formal ICH Procedure, Q&A Procedure, Revision Procedure and Maintenance Procedure, depending on the activity to be undertaken (see below).

Formal ICH Procedure for new topic of harmonisation :

The Formal ICH Procedure is a step-wise procedure consisting of 5 steps .This procedure is followed for the harmonisation of all new ICH topics

ICH guidelines have been adopted as law in several countries, but are only used as guidance for the U.S. Food and Drug Administration

Finally, I would like to end with a beautiful quote by Henry ford  "Coming together is a beginning. Keeping together is progress. Working together is success"

P.S. 

1. Explanation of Abbreviations quoted in the above post-

(i)MedDRA or Medical Dictionary for Regulatory Activities is a clinically validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry throughout the entire regulatory process, from pre-marketing to post-marketing activities, and for data entry, retrieval, evaluation, and presentation.

(ii)

Q-Quality

S-Safety

E-Efficacy

M-Multidisciplinary

(iii)Q3C is - Impurities :Guideline for Residual Solvents

(iv) M2   is -Multi-disciplinary Group 2

2. In my next posts, I will be mainly focusing on the important ICH guidelines.

Keywords : ICH, MHLW , JPMA ,EU , EFPIA , FDA, PhRMA, WHO, EFTA, IFPMA.

References :
1.http://www.ich.org/
2.http://www.wikipedia.org/