Application dossier

The content of the application is quite similar to EU requirements, although the structure and terminology is slightly different. The main headings are shown in Table 5.5. However, the FDA will now also accept IND application dossiers structured according to the CTD format (see Chapter 6 for the CTD format). 

The requirements for the contents of an application dossier are set out in Annex I of Directive 2001/82/EC. The dossier should be assembled in four parts, as outlined in Figure 7.6. The application form. Summary of Product Characteristics (SPC) and labelling, expert reports and quality sections are quite similar in content to human... 

Preparation of Marketing Authorization Application Dossier The application dossier is divided into four parts ... 

As well as GCP site inspections, an examination is imdertaken of the raw or source data and records of Chemistry Manufacturing and Control (CMC), non-clinical and clinical reports that are the basis of the application. This is to ensure that the application dossier accurately reflects the source data. The procedure issued by PMDA details that list of raw data and records must be provided. The applicant is required to bring the data and records to PMDA on the specified days and when the examination finishes they should be retrieved. Therefore, the raw data and records stored at overseas sites are usually categorised as documents not to be submitted and not subject to reliability review by PMDA. Instead, the MHLW may investigate the data from non-Japanese studies at the site of storage since submission of a photocopy of the data is not permitted. 

From 1975 onward, however, the EU has requested experimental validation studies for a manufacturing process to be included in the application dossier where a nonstandard method is being used or where it is critical for the product (Council Directive 75/319/EEC [36] as amended by 91/356/EEC [37]). This requirement is amplified in the Notice to Applicants [38]. 

For some time, the opinion has been divided in the EU regarding the assessment of such validation steps. In many cases it was held to be the remit of the GMP inspectorate while member states would expect to see varying degrees of validation studies presented in support of application for marketing authorization. The guideline Development Pharmaceutics and Process Validation [39] defined more clearly what the agency wants to see in the application dossier. 

It clearly expects to see a process validation protocol included in the submission. Validation data should be generated for all products. It is accepted, however, that the amount of data presented in the application dossier will to a certain extent depend on the nature and complexity of the drug substance, drug product, and manufacturing process. 

Decentralized Procedure (DCP) The decentralized procedure was established as an application route in late 2005. This procedure is essentially a combination of the national and the mutual recognition procedures. The applicant chooses a reference member state to undertake the initial assessment. On completion of the RMS assessment, the concerned member states can put forward additional questions to those raised by the reference member state. If the questions are answered by the applicant to the satisfaction of the reference member state and concerned member states, the drug can be authorized. The benefit of the decentralized procedure is that all concerned member states are provided with the application dossier from the start of the procedure. 

The application dossier shall be submitted in 4 separate volumes (administrative, chemical and pharmaceutical, pharmacological and toxicological and clinical parts). Its presentation and content should be compiled in full conformity with the respective EU requirements. English, Russian or Bulgarian versions are accepted. The dossier shall contain the data listed in Regulation No. 17 (as shown in Appendix 2). 

One copy of the application dossier should be submitted to the Licensing Secretariat of the NDI (Koom 420, Telephone +359 2 944 13 89, Fax +359 2 943 44 87). Upon submission of the registration dossier an application form (Annex 1 of Regulation No. 17) shall be filled out in 3 copies. 

The entire procedure should be completed within 12 months of submission of the application dossier. In the case of a negative statement of the Specialized Commission the MOH shall issue a reasoned refusal. The appeal against the rejection shall be made in court in confirmity with the Law of the Administrative Procedures. 

Review of foreign normative documents provided in the drug application dossiers. 

Submission of the full Application (dossier) PC (3 experts conduct the Examination of the dossier The session of PC decides to approve/not to approve the Dossier if positive, sent the applicant to SDQCI Sometimes the restricted CT are recommended after positive results from QCI 1 Month... 

A more rapid regulatory review may be anticipated for products of high medical value. This results from the medical need of society for the drug, the smaller application (dossier) compared to other drugs with substantially more data and the high priority of the application. In most circumstances, there will be a waiver of administrative fees charged (e.g. user fees) for orphan drugs to be reviewed. 

Figure 19.2 Review process at Evaluation Centre. The new drug application dossier is reviewed at the Pharmaceutical and Medical Devices Evaluation Centre. The Centre organises a review team with scientific support from external experts. The applicant has two opportunities to meet the team during the review process.

B deals with the presentation and content of the application dossier. 

The requirements for the content of the application dossier are stated in Directive 75/318/EEC as amended, i.e., the documents and data in support of the application for marketing authorization pursuant to Article 4 of Council Directive 65/65/EEC must be organized in a file in four parts, containing ... 

Under the centralized route, marketing authorization applications (dossiers) are submitted directly to the EMEA. Before evaluation begins, the EMEA staff first validate the application, by scanning through it to ensure that all necessary information is present and presented in the correct format. This procedure usually takes one to two working weeks to complete. Biotech-based dossiers are termed part A applications , whereas new chemical entities are termed part B applications . 

Common technical dossier (CTD) 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. It was developed by the European Medicines Agency (EMEA, Europe), the Food and Drug Administration (FDA, USA), and the Ministry of Flealth, Labour and Welfare (Japan). 

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