Effective Dossier Management in Regulatory Affairs

Importance of effective dossier management

• The registration dossier for medicines is an important document that 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 the 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 that play an important role in effective dossier management-

1. Planning aspects
2. Formatting and compilation aspects
3. Review aspects

1. Planning aspect

Deadline

• It is important to know the deadline for filing the dossier and an 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 dossiers, 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 regulatory agencies. 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 the nomenclature, structure, and general properties (like pH, Pka, solubility, partition coefficient, stereochemistry etc.) of the 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 departments

• Preparing 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, and manufacturing process development of a drug from the R & D department and finalized specification & test procedures, and Batch manufacturing sheets from the Quality assurance department.

ALSO READ: New Drug Application (NDA) Process

2. 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.
• 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 for Manuscripts 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.

Compilation

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 the 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 copies 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 the drafting stages of the 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.

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 checklist so as to ensure that all the required information is present in the dossier before submission to the regulatory agency.
• The USFDA has a checklist that is very useful while filing an ANDA- ANDA checklist.
• Module 1 of CTD in most of 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 the top 10 deficiencies of the 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.
• Proficiency in Adobe Acrobat tools. (Especially useful in preparing NeeS dossier and eCTD ).
• Proficiency in ISIS draws or Chem sketch software, which is useful in drawing chemical structures.
• 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.

ALSO READ: Sample Product Dossier for WHO Prequalification