Dossier preparation and submission
- 1. DOSSIER PREPARATION AND SUBMISSION 1
- 2. DOSSIER PREPARATION AND SUBMISSION SUBMITTED BY: POOJA RATHEE DRA 2nd Semester MD UNIVERSITY ROHTAK SUBMITTED TO: PROF. SANJU NANDA PHARMACEUTICS 2
- 3. CONTENTS: • INTRODUCTION TO DOSSIER & REGISTRATION DOSSIER • CONTENTS OF DOSSIER • GOALS OF DOSSIER • COMMON DOSSIERS USED IN P’CEUTICAL INDUSTRY • DESCRIPTION OF VARIOUS FORMAT DOSSIERS • DOSSIER MANAGEMENT • COMPILATION AND REVIEW OF DOSSIER • REGULATORY SUBMISSIONS • PLANNING AND PREPARATION OF REGULATORY SUBMISSIONS • REVIEW ASPECTS FOR REGULATORY SUBMISSIONS • BINDERS IN PHARMACEUTICAL INDUSTRY 3
- 4. “Dossier” • BASICALLY Dossier is a collection or file of documents on the same subject, especially a file containing detailed information about a person or a topic. • In REGULATORY…. Dossiers are the vehicle in a country through which drug sponsors formally propose that the Regulatory Agencies approve a new pharmaceutical for sale and marketing. 4
- 5. “Registration Dossier” • “Registration Dossier” of the pharmaceutical product is a document that contains all the technical data (administrative, quality, nonclinical and clinical) of a pharmaceutical product to be approved / registered / marketed in a country. It is more commonly called as the New Drug Application (NDA) in the USA or Marketing Authorization Application (MAA) in the European Union (EU) and other countries, or simply Registration Dossier. 5
- 6. CONTENTS OF DOSSIER • Data proving that the drug has quality, efficacy and safety properties suitable for the intended use • Any Additional administrative documents • Samples of finished product • Related substances and reagents necessary to perform analyzes of finished product 6
- 7. Goals of the Dossiers • Is the drug safe and effective in its proposed use(s) when used as directed, and do the benefits of the drug outweigh the risks? • Is the drug’s proposed labeling (package insert) appropriate, and what it contain? • Are the methods used in manufacturing (Good Manufacturing Practice, GMP) the drug and the controls used to maintain the drug’s quality adequate to preserve the drug’s identity, strength, quality, and purity? 7
- 8. ATTENTION PLEASE………….. • Every country has its own regulatory authority, which is responsible to enforce the rules and regulations and issue the guidelines to regulate the marketing of the drugs. The single regulatory approach for marketing authorization application (MAA) of a new drug product applicable to various countries (on the basis of single dossier) is utmost difficult. • Therefore, the knowledge of exact and detailed regulatory requirements for MAA of each country should be known to establish a suitable regulatory strategy. Submission of applications, which do not comply with the prescribed requirements, may result in delays, queries or rejection of registration. 8
- 9. Common Pharmaceutical Dossier which is widely used in the Pharmaceutical Industry are: CTD Dossier ACTD Dossier eCTD Dossier Country Specific Registration Dossier 9
- 10. CTD Format Dossiers •This Format of Dossier is an Important & widely used Dossier format in most of the country, This format of any registration application for Marketing Authorization Dossier is submitted to Food and Drug Authority or Ministry of health or any other equivalent authority along with other required documents. •CTD Format Dossier is widely used in semi regulated & regulated market like CIS Countries, Middle East countries, European Union, USA , Australia, African Countries, Canada, Japan, etc 10
- 11. Common Technical Document Consists of the following Modules with the number of the required Documents. Module 1 – Administrative Information & Prescribing Information Module 2 - Common Technical Documents Summaries Module 3 –Quality Module 4 – Non Clinical Study Report Module 5 – Clinical Study Report 11
- 12. ACTD Format Dossiers • ASEAN CTD Dossier, ASEAN Common Technical Dossier (ACTD) provides a common format for the preparation of well-structured Common Technical Dossier applications for submission in ASEAN regulatory authorities for the registration of pharmaceuticals for human use. • ACTD format significantly reduce the time and resources needed to compile applications for registration. • Regulatory reviews and communication with the applicant is facilitated by a standard document of common elements. This guideline merely demonstrates an appropriate write-up format for acquired data. However, applicants can modify, if needed, to provide the best possible presentation of the technical information, in order to facilitate the understanding and evaluation of the results upon pharmaceutical registration. 12
- 13. Asian Common Technical Documents consists of following parts. Part I – Administrative Data and Product Information Part II – Quality Documents Part III – Non Clinical Documents Part IV – Clinical Documents. 13
- 14. • ACTD Format is Asian harmonization for Common technical Documents used in Brunei Darussalam, Cambodia, Indonesia, Laos, Myanmar, Malaysia, Philippines, Singapore, Thailand and Vietnam. 14
- 15. eCTD Format Dossier • This format of Registration Dossier is an electronic format for CTD Dossier, • Submission in eCTD format should be in accordance with the current ICH M2 EWG eCTD specification, • Electronic files should be in accordance with the Guidance for Industry on Providing Regulatory Information in Electronic Format. • The eCTD is an interface for the pharmaceutical industry to transfer regulatory information with various regulatory agencies. • The content is based on the Common Technical Document (CTD) format. • It was developed by the International Conference on Harmonisation (ICH) Multidisciplinary Group 2 Expert Working Group (ICH M2 EWG). 15
- 16. o The US FDA and Europe EMEA announced that the eCTD is the preferred format for electronic submission (eSubmisson) of Drug Dossiers. The drug manufacturer has to submit the drug dossier in eCTD format. 16
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- 19. NeeS format Dossier • Requirements for the submission of Non-eCTD electronic Submissions (NeeS). A separate EU guidance document covering eCTD submissions, which is regarded as the principal electronic submission format in EU. A NeeS format submission can normally be started with any initial, variation or renewal MA submission. 19
- 20. • Once the switch to this electronic format is made it is expected that further applications and responses relating to the particular medicinal product are submitted in NeeS format. Applicants can switch from NeeS to eCTD at the start of any new regulatory activity. Applicants should however not change from eCTD back to NeeS. There is no requirement to reformat the whole dossier into NeeS format when switching from paper to NeeS, but this could be done at the applicant’s discretion. 20
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- 23. Country Specific Format Dossier • This format of Registration Dossier is in accordance with the Specific Country Regulatory Guidelines. • Compile and write entire dossier of specified modules as per Guidelines provided by the Government Regulatory Authorities. 23
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- 25. 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. • 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. 25
- 26. 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 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. 26
- 27. Continued…… • 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. 27
- 28. Continued…… • 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".* *:not confirm in the year 2018 28
- 29. 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. 29
- 30. Regulatory Submissions • A regulatory submission for a healthcare product includes any documentation or information submitted to a regulatory agency for review, for notification or in response to a request for additional information related to a healthcare product. • The format can be paper or electronic, or both. 30
- 31. Types of regulatory submissions • Licensing applications for drug, biologics or devices • Clinical trial applications • Requests for orphan drug or fast-track designations • Requests for protocol assistance • Responses to agency questions that arise during the review; for example, clarifaxes, deficiency letter, requests for additional information • Post-approval studies or commitments • Amendment/variation applications or notification submissions 31
- 32. Planning and preparation of regulatory submission • Before preparing any regulatory submission, identify the relevant regulatory requirements so that you can ensure your submission will comply. Note that the requirements for drug and medical device submissions are quite different. 32
- 33. Continued…… • Who is the regulatory agency and what is the review division for healthcare product? • What are the regulatory requirements that govern submission? • What kind of information should be included? Is there a guidance document available that details the format and content requirements of the submission? • Where to send the submission? • How many copies should submit? • For hard-copy submissions, are there requirements regarding binding? 33
- 34. REVIEW ASPECTS FOR REGULATORY SUBMISSION: • As the submission should facilitate the regulatory review, organize the information so that it is easy to read and properly sectioned. Have it support navigation so the reviewer can quickly find what they need. Where applicable, consider using these elements: – Cover letter – Table of contents – Volume and page numbers – Clear headings and subheadings – Table and figure numbers, with accurate references to them from within the text – Tabs that aid quick finding of the submission sections – Reader-friendly font sizes, types and colours 34
- 35. • It is useful to always provide a concise summary at the start to “set the stage” for the submission. – Such information may highlight a very brief product description, the proposed indication, the intended patient population, the purpose of the submission (for example, a modification to an existing device design) or any key information that could assist the reviewer’s understanding prior to the review. • Ensure that content is clearly legible and that submissions are properly bound using binders acceptable to the regulatory agency • Lastly, if any source document is in another language, ensure you provide an appropriate translation 35
- 36. •BINDERS IN PHARMACEUTICAL INDUSTRY 36
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Editor's Notes
- moksh