Wednesday, 26 October 2011


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-

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 ICHThis 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.


Monday, 24 October 2011

ICH Guidelines

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

Quality Guidelines
Safety Guidelines
Efficacy Guidelines
Multidisciplinary Guidelines


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.


Thursday, 20 October 2011



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


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"

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.
(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.
References :

Friday, 14 October 2011

Drug Master Files (DMFs)

What is a Drug Master File (DMF) ?

A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

Important facts regarding DMFs
  • It is submitted to FDA to provide confidential information
  • Its submission is not required by law or regulations
  • It is neither approved nor disapproved
  • A DMF is NOT a substitute for an IND, NDA, ANDA, or Export Application.
  • It is filed with FDA to support NDA, IND, ANDA another DMF or amendments and supplements to any of these
  • It is provided for in the 21 CFR (Code of Federal Regulations) 314. 420
  • It is not required when applicant references its own information

Types of Drug Master Files-

Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel (No longer accepted by FDA)

Type II: Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product

Type III: Packaging Material

Type IV : Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation

Type V: FDA Accepted Reference Information  (FDA discourages its use)

Each DMF submission should contain -

1.Transmittal letter
2.Administrative information

1.Transmittal letter

For original submissions, transmittal letter should include-
 a.Identification of submission
 b.Identification of the applications
 c.Signature of the holder or the authorized representative.
 d.Typewritten name and title of the signer

For amendments, transmittal letter should include-
a Identification of submission
b A description of the purpose of submission
c Signature of the holder or the authorized representative
d Typewritten name and title of the signer

2.Administrative information

For original submissions, administrative information should include-
a. Names and addresses of the following:
(i) DMF holder.
(ii) Corporate headquarters.
(iii) Manufacturing/processing facility.
(iv) Contact for FDA correspondence.
(v) Agent(s), if any.
b. The specific responsibilities of each person listed in any of the categories in Section a.
c. Statement of commitment.
A signed statement by the holder certifying that the DMF is current and that the DMF holder will comply with the statements made in it.  

For amendments, administrative information should include-

a. Name of DMF holder.
b. DMF number.
c. Name and address for correspondence.
d. Affected section and/or page numbers of the DMF.
e. The name and address of each person whose IND, NDA, ANDA, DMF, or Export Application relies on the subject of the amendment for support.
f. The number of each IND, NDA, ANDA, DMF, and Export Application that relies on the subject of the amendment for support, if known.
g. Particular items within the IND, NDA, ANDA, DMF, and Export Application that are affected, if known.

Format, Assembly, and Delivery of DMF-
  • The DMF must be in the English language. Whenever a submission contains information in another  language, an accurate certified English translation must also be included.
  • Each page of each copy of the DMF should be dated and consecutively numbered. An updated table of contents should be included with each submission.
  • An original and duplicate are to be submitted for all DMF submissions.
  •    Each volume of a DMF should, in general, be no more than 2 inches thick. For multivolume submissions, number each volume. For example, for a 3 volume submission, the volumes would be numbered 1 of 3, 2 of 3, and 3 of 3.
  • Drug Master File holders and their agents/representatives should retain a complete reference copy that is identical to, and maintained in the same chronological order as, their submissions to FDA.
  • U.S. standard paper size (8-1/2 by 11 inches) is preferred.

 Drug Master File submissions and correspondence should be addressed as follows:
 Drug Master File Staff
 Food and Drug Administration
 5901-B Ammendale Rd.
 Beltsville, MD 20705-1266


Before FDA can review DMF information in support of an application, the DMF holder must submit in duplicate to the DMF a letter of authorization permitting FDA to reference the DMF

The letter of authorization (LOA) should include the following:

The date.
Name of DMF holder.
DMF number.
Name of person(s) authorized to incorporate information in the DMF by reference.
Specific product(s) covered by the DMF.
Submission date(s) of 5, above.
Section numbers and/or page numbers to be referenced.
Statement of commitment that the DMF is current and that the DMF holder will comply with the statements made in it.
Signature of authorizing official.
Typed name and title of official authorizing reference to the DMF.

The holder of DMF should send a copy of LOA to affected applicant, sponsor or other holder who is authorized to incorporate information contained in the DMF. The copy of LOA issued by DMF holder should be included in the application by applicant, sponsor or holder referencing the DMF.

Format and Content of DMF

DMFs may be submitted following the format recommended in the "Guidance for Industry  M4Q: The CTD - Quality".

Incomplete submission

If the submission is administratively incomplete or inadequate, it will be returned to the submitter with a letter of explanation from the Drug Master File Staff, and it will not be assigned a DMF number.

DMF review
  •  An original DMF submission will be examined on receipt to determine whether it meets minimum requirements for format and content. If the submission is administratively acceptable, FDA will acknowledge its receipt and assign it a DMF number.
  •  The agency will review information in a DMF only when an IND sponsor, an applicant for an NDA, ANDA, or Export Application, or another DMF holder incorporates material in the DMF by reference.                  
  •   If FDA reviewers find deficiencies in the information provided in a DMF, a letter describing the deficiencies is sent to the DMF holder and also the person who relies on the information in the deficient DMF (However, only general subject of deficiency is revealed to the applicant/person referring information in DMF)
  • When the holder submits the requested information to the DMF in response to the agency's deficiency letter, the holder should also send a copy of the accompanying transmittal letter to the affected persons relying on the DMF and to the FDA reviewing division that identified the deficiencies. The transmittal letter will provide notice that the deficiencies have been addressed.

Holder Obligations

Any change or addition, including a change in authorization related to specific customers, should be submitted in duplicate and adequately cross referenced to previous submission(s). The reference should include the date(s), volume(s), section(s), and/or page number(s) affected.

Notice Required for Changes to a Drug Master File

A holder must notify each affected applicant or sponsor who has referenced its DMF of any pertinent change in the DMF . Notice should be provided well before making the change in order to permit the sponsor/applicant to supplement or amend any affected application(s) as needed.

Listing of Persons Authorized To Refer to a Drug Master File
  • A DMF is required to contain a complete list of persons authorized to incorporate information in the DMF by reference. The holder should update the list in the annual report.
  • The updated list should contain the holder's name, DMF number, and the date of the update.
  • The update should identify by name (or code) the information that each person is authorized to incorporate and give the location of that information by date, volume, and page number.
  • Any person whose authorization has been withdrawn during the previous year should be identified under a suitable caption.

 Annual Report
  •  The holder should provide an annual report on the anniversary date of the original submission. This report should contain complete list of authorized persons persons referring the DMF and should also identify all changes and additional information incorporated into the DMF since the previous annual report on the subject matter of the DMF. If the subject matter of the DMF is unchanged, the DMF holder should provide a statement that the subject matter of the DMF is current.
  •  Failure to update or to assure FDA annually that previously submitted material and lists in the DMF remain current can cause delays in FDA review of a pending IND, NDA, ANDA, Export Application, or any amendment or supplement to such application; and FDA can initiate procedures for closure of the DMF.

 Appointment of an Agent

Domestic DMF holders do not need to appoint an agent or representative, although foreign DMF holders are encouraged to engage a U.S. agent.When an agent is appointed, the holder should submit a signed letter of appointment to the DMF giving the agent's name, address, and scope of responsibility (administrative and/or scientific). 

Transfer of Ownership

To transfer ownership of a DMF to another party, the holder should so notify FDA and authorized persons in writing. The letter should include the following:

Name of transferee
Address of transferee
Name of responsible official of transferee
Effective date of transfer
Signature of the transferring official
Typewritten name and title of the transferring official.

The new holder should submit a letter of acceptance of the transfer and an update of the information contained in the DMF, where appropriate. Any change relating to the new ownership (e.g., plant location and methods) should be included.


A holder who plans a major reorganization of a DMF is encouraged to submit a detailed plan of the proposed changes and request its review by the Drug Master File Staff. The staff should be given sufficient time to comment and provide suggestions before a major reorganization is undertaken.

  • A holder who wishes to close a DMF should submit a request to the Drug Master File Staff stating the reason for the closure. 
  • The request should include a statement that the holder's obligations  have been fulfilled.
  • The Agency may close a DMF that does not contain an annual update of persons authorized to incorporate information in the DMF by reference and a list of changes made since the previous annual report. The holder will be notified of FDA's intent to close the DMF.

Keywords- FDA, DMF, Types of DMF , CTD., LOA.

References from FDA's Website-

Monday, 10 October 2011

Universities offering Masters courses in Regulatory Affairs in USA

Here are the Universities in USA offering Master of Science (MS) in Pharmaceutical Regulatory Affairs and allied subjects -

1.Purdue University, College of Pharmacy, West Lafayette-IN
Master of Science in Regulatory Quality Compliance
Website Link-

2.University of Southern California, School of Pharmacy, Los Angeles-CA
Master of Science in Regulatory science 
3.North Eastern University, College of Professional studies, Boston-MA
Master of Science in Regulatory Affairs for Drugs, Biologics and Medical Devices 

4.Massachusetts College of Pharmacy and Health Sciences, Boston-MA
 Master of Science In Regulatory Affairs and Health Policy

5.Temple University, School of Pharmacy, Philadelphia-PA
Master of Science in QA/RA 

6.Arizona State University,College of Nursing and Health Innovation, Phoenix-AZ
Master of Science in Regulatory Science & Health Safety
Course developed in collaboration with USFDA
Website Link-

7.St. John's University,
College of Pharmacy and Allied Health Professions, Queens-NY
Master of Science in Pharmacy Administration (Specialization in Regulatory Affairs/Quality Assurance)
Website Link-

8.Long Island University,
Arnold  & Marie Schwartz college of Pharmacy and Health Sciences, Brooklyn-NY
Master of Science in Drug Regulatory Affairs
Website Link-

9. John Hopkins University, Centre for Biotechnology Education, Baltimore-MD.
Master of Science in Bioscience Regulatory Affairs (Mainly deals with Biotechnology Regulatory Affairs)
Website Link-

10. Regis college, Weston-MA

Master of Science in Regulatory and Clinical Research Management 
11.The University of Georgia, Gwinnett Campus, Lawrenceville-GA*
 Master of Science for Regulatory Affairs
Website Link-

12.San Diego State University, Centre for Distance Learning*
Master of Science in Regulatory Affairs
Website Link-

13. North Western University, School of Continuing Education, Chicago-IL*
Master of Science in Quality Assurance and Regulatory Science
Website Link-

14.University of Florida, Gainesville-FL*
Master of Science in Pharmacy-Drug Regulatory Affairs
Website Link-                                                                   
15. Tufts University, School of Medicine
Master of Science in Development and Regulation of Medicines and Devices

Other Related Course-
University of Florida, College of Pharmacy, Gainsville-FL
Master of Science in Pharmaceutical outcomes and Policy
Course is offered in collaboration with FDA Center for Drug evaluation and research.
The students enrolled for the course will have a guaranteed intership at the FDA or Industry.
Eligibility-Terminal Degree in Health Sciences such as PharmD
Website Link-

My preferred University-
 If I were to go for MS in RA,  Arizona State University would be my most preferred one for the following reasons-

1.The course is developed in collaboration with USFDA (the most respected Regulatory agency in the world) and the students will receive guest lectures from FDA personnel.
2. Chance for internship with FDA's CDER.
3.The fees and cost living will be much less than most of the  above universities.
4.The competition for admission will be probably less as the university is not much famous.

2. schools/pharmacy-rankings

1.Most of the Universities offer the courses through various modes such as Full time, Part time, online modes or combination of these modes. Hence the prospective students are advised to check with the university representatives whether the universities offer the courses in their mode of interest before applying.

2. The universities offering MS only through part time/online modes are indicated with "*" ..

Tuesday, 4 October 2011

Institutes offering Regulatory Affairs Courses in India

The colleges/ institutes offering Masters and Diploma courses in Pharmaceutical Regulatory Affairs in India -

 Masters Courses in Regulatory Affairs-

1.Birla Institute of Technology, Mesra, Ranchi
Approved by PCI and AICTE
M. Pharmacy (Quality Assurance and Regulatory Affairs )

2. JSS college of Pharmacy-Mysore
Approved by PCI and AICTE
M. Pharmacy (Pharmaceutical Regulatory Affairs )

3. JSS college of Pharmacy-Ooty
Approved by PCI and AICTE
M. Pharmacy (Pharmaceutical Regulatory Affairs )

4.Manipal University (Deemed University), Manipal, Karnataka*
Department of Advanced Pharmaceutical Sciences,
MSc Pharmaceutical Regulatory Affairs,

5.Lachoo Memorial College of Science and Technology (Pharmacy), Jodhpur
M. Pharm. (Pharmaceutical Management and Regulatory Affairs)
Approved by PCI and AICTE

6.Maharshi Dayanand University, Rohtak-Haryana
Department of Pharmaceutical Sciences
M.Pharma (Drug regulatory Affairs)
Approved by UGC and PCI

7. Alliance Institute of Advanced Pharmaceutical and Health sciences, Hyderabad*
Affiliated to JNTUH,
MS Drug Development and Regulatory Affairs

8. Brown's College of Pharmacy, Khammam, Andhra Pradesh
Affiliated to Kakatiya University & Approved by PCI.
M. Pharmacy (Drug Regulatory Affairs ) 

9. Sree Dattha Institute of Pharmacy, Ibrahimpatnam , R.R District. Andhra Pradesh
Approved by PCI and AICTE  
M. Pharmacy ( Pharmaceutical Management and Regulatory Affairs )

Institute offering Diploma Courses in Regulatory Affairs-

1.Jamia Hamdard University, New Delhi
Deemed University, Accredited by NAAC in 'A' grade
PG Diploma in Pharmaceutical Regulatory Affairs

2. Bioinformatics Institute of India (BII), Noida*
Industry Program in Pharma Regulatory Affairs

3. Institute of Pharmaceutical Education and Research (IPER), Pune*
 Diploma in Drug Regulatory Affairs
Website link-

4.Global Institute of Regulatory Affairs (GIRA), Pune *
Advanced PG Diploma in Regulatory Affairs (Full Time)
PG Diploma in Regulatory Affairs (Part Time)
Website Link-


1.The colleges/institutes with "*" mark are not recognised by any Government Councils, but I listed them because they are well recognised by Pharma companies for their courses.

2. I listed the Institutes in the decreasing order of my personal preferences based on the credibility of institutes/colleges, year of establishment, popularity etc.

3.Apart from the above colleges , I came across several other institutes/colleges offering courses in Pharmaceutical Regulatory Affairs but I didn't list them because I seriously doubt their authenticity and credibility.