Effective Dossier Management in Regulatory Affairs


Importance of effective dossier management-

  • The registration dossier for medicines is an important document which is submitted for review to regulatory agencies by pharma companies for approval to market their medicines.
  •  Utmost care should be taken during its compilation and filing as it plays a direct role in earliest possible availability of medicines in the market which in turn translates into business for the company.
  • Of course, regulatory affairs professionals need to ensure the safety, quality and efficacy of  the medicines for which they are filing registration dossier.

Note : The dossiers could be anything among DMF, ASMF, ANDA, NDA or MAA.

From my experience I could possibly think of 3 important aspects which play an important role in effective dossier management-

  1. Planning aspects
  2. Formatting and compilation aspects
  3. Review aspects
  1. Planning aspects-
  • Deadline-It is important to know the deadline for filing the dossier and action plan should be prepared so as to meet the deadline.
  • Understanding the registration requirements of respective agencies- Although most of the regulatory agencies accept the CTD format for registration dossier,  the requirements for approving  marketing applications may vary for individual agencies. For example- USFDA requires Batch Manufacturing Records to be provided, while it is not necessary for approval by European regulatoryagencies. Hence it is necessary to completely read and understand the guidance document of each regulatory agency before going ahead with filing registration dossier with them.
  • Requirements Listing– Listing down all the requirements for preparing the registration dossier, for example in the preparation of section 3.2.S.1 of a DMF I need to have all the information on nomenclature, structure and general properties (like pH, Pka, solubility, partition coefficient, stereochemistry etc ) of drug substance. Similarly Listing down all the requirements for preparation of all the modules and their respective sections is an important aspect.
  • Sending the requirements list to respective departmentsPreparing an individual requirement list and sending them to each respective department. For example I need to have all the information regarding the general properties, synthetic scheme, manufacturing process development of drug from R & D department and finalised specification & test procedures, Batch manufacturing sheets from Quality assurance department.
  1. Formatting and Compilation Aspects-

       Format- As per the ICH’s M4 guideline the following are recommended-

  • The display of information should be unambiguous and transparent, in order to facilitate the review of the basic data and to help a reviewer become quickly oriented to the application contents.
  • Text and tables should be prepared using margins that allow the document to be printed on both A4 and 8.5 x 11” paper (For Europe and Japan regions A4 paper is recommended and 8.5 x 11” paper for USA).
  • Times New Roman, 12-point font is recommended for narrative text.
  • The left-hand margin should be sufficiently large that information is not obscured by the method of binding.
  • Font sizes for text and tables should be of a style and size that are large enough to be easily legible, even after photocopying.
  • Every page should be numbered, according to the granularity document (refer pages 6 to 14 of M4 guideline).
  • Acronyms and abbreviations should be defined the first time they are used in each module.
  • References should be cited in accordance with the current edition of the Uniform Requirements forManuscripts Submitted to Biomedical Journals, International Committee of Medical Journal Editors (ICMJE).
  • All pages of a document should include a unique header or footer that briefly identifies its subject matter.

      Note: For any person who is new/relatively new to the field of RA it is important to read and understand CTD       guidelines of ICH (M4, M4Q,M4S, M4E) before starting to compile any dossier. (Refer the post CTD in my           blog)


      The following compilation aspects are important-

  • The information should be specific, clear, precise and accurate.
  • Typographical and grammatical errors should be avoided.
  • The information should be arranged in a sequential order in computer. Each module could have a separate folder and in turn each section of a module could have a separate folder. This kind of orderly arrangement will help in easy access of information and help in taking printouts of finalized copy conveniently.
  • The line spacing should be preferably single.
  • All the documents received from other departments should be cross-checked so as to ensure that they are free from errors.
  • Ensuring the specifications & test procedures are designed in accordance with ICH guidelines Q3A, Q3B, Q3C, Q6A and Q6B. Stability Protocols are designed as per ICH guidelines Q1A through Q1E . Similarly ensuring that various documents are designed as per ICH guidelines. This can be ensured during drafting stages of preparation of various documents.
  • After the finalized soft copy is ready, printouts should be taken using a good quality printer and arranged sequentially in a module and section wise manner.
  • As per the note given in the website of  EMA-“All Microsoft Office documents submitted to the European Medicines Agency must be in a format compatible with MS Office 2003. Office 2007 and Office 2010 formats cannot currently be accepted”.

    3.Review Aspects

  • .Every human being is prone to make mistakes; hence it is important to re check the information in the dossier before filing it with regulatory agencies.
  • It is also important that a dossier meant to be filed with a regulatory agency should be cross verified by a person other than the one who has complied the dossier.
  • It is very useful to have a check list so as to ensure that all the required information is present in the dossier before submission to regulatory agency.
  • The USFDA has a check list which is very useful while filing an ANDA- ANDA checklist
  • The module 1 of CTD in most of the cases is completely different for various agencies hence care should be taken in compiling this section.

      Avoiding Deficiencies-

      You can learn without necessarily making mistakes. EDQM has compiled a list of top 10 deficiencies of CEP      dossier which will go a long way in preventing you from making the same mistakes.

    Key software skills for effective dossier management-

  • Proficiency in MS office (Yes, I know that most of you are proficient! ).
  • Proficiency in Adobe Acrobat tools. (Especially useful in preparing NeeS dossier and eCTD ).
  • Proficiency in ISIS draw or Chem sketch softwares, which are useful in drawing chemical structures.
  • Since we generally receive number of mails on a daily basis, we could sort the emails by using labels based on the sources. This will make your job easy while accessing mails.
  • ECTD is mandatory for the centralized procedures in Europe and it could be made mandatory for the other procedures as well in the future. Hence it is important to undergo training in the use of eCTD software.