Procedure for Filing New Drug Applications (NDA) in Different Markets Globally

The detailed procedure for filing New Drug Applications (NDA) in key global markets, including the FDA, EMA, PMDA, and more. Understand the regulatory requirements, submission processes, and timelines for NDA approval in different countries. Filing a New Drug Application (NDA) is an essential process for pharmaceutical companies aiming to introduce new drugs into various global markets. Each regulatory authority has its own set of guidelines and procedures to ensure the safety, efficacy, and quality of the drug. Below is an overview of the procedure for filing NDAs in key global markets, along with their respective websites and important details.Procedure for Filing New Drug Applications (NDA)


SOP for the Procedure for Filing New Drug Applications (NDA):

Purpose

The purpose of this SOP is to outline the standardized procedure for the preparation, submission, and follow-up of a New Drug Application (NDA) to regulatory authorities globally. This ensures compliance with regulatory requirements, efficient submission, and effective management of NDAs to facilitate approval and market authorization.


Scope

This SOP applies to all departments involved in the process of submitting an NDA, including but not limited to Regulatory Affairs, Clinical Development, Quality Assurance, and Manufacturing. It covers the NDA submission procedures for major regulatory bodies, including the FDA (USA), EMA (EU), PMDA (Japan), NMPA (China), Health Canada, CDSCO (India), and TGA (Australia).


Responsibilities
  • Regulatory Affairs Department: Responsible for coordinating the entire NDA process, preparing submission documents, and liaising with regulatory authorities.
  • Clinical Development Department: Responsible for providing clinical study data, including safety and efficacy results.
  • Quality Assurance (QA) Department: Responsible for ensuring all documents are compliant with regulatory standards and maintaining documentation integrity.
  • Manufacturing Department: Provides detailed manufacturing process information and quality control data.

Procedure
1. Pre-NDA Preparation

1.1 Pre-submission Meetings/Consultations:

  • Schedule pre-submission meetings with the respective regulatory authorities (FDA, EMA, PMDA, etc.) to seek guidance on the application.
  • Identify potential regulatory hurdles and confirm the submission strategy.

1.2 Clinical Trial Application (CTA):

  • Before initiating clinical trials, ensure that the Clinical Trial Application (CTA) is approved by the relevant authority.
  • Gather all necessary clinical trial data, including preclinical toxicology and pharmacokinetic (PK) studies.

1.3 Compilation of Required Documentation:

  • Module 1 (Administrative Information): Include cover letter, application form, and financial disclosure.
  • Module 2 (Summary of Reports): Provide clinical summaries, non-clinical overviews, and quality summaries.
  • Module 3 (Quality Data): Include drug substance and drug product details, manufacturing information, and quality control.
  • Module 4 (Non-Clinical Study Reports): Provide toxicological studies, pharmacology, and safety pharmacology data.
  • Module 5 (Clinical Study Reports): Provide data on clinical trials, efficacy, and safety studies.

1.4 Document Format and Language:

  • Ensure that all documents are prepared in the format required by the regulatory body (eCTD format for FDA, EMA, and others).
  • Ensure that documents are written in the appropriate language (e.g., English for FDA, EMA; Japanese for PMDA).

2. NDA Submission Process

2.1 Review of Final Documents:

  • Review all submission documents for accuracy, completeness, and compliance with regulatory guidelines.
  • Perform internal audits by the QA department to ensure document integrity.

2.2 Submission Portal:

  • For FDA: Submit via the FDA Electronic Submission Gateway (ESG).
  • For EMA: Submit via the eSubmission Gateway or Web Client.
  • For PMDA (Japan): Submit via the Medical Products Review Portal (MP-Review).
  • For NMPA (China): Submit via the China Drug Electronic Application System (CDE).
  • For Health Canada: Submit through the Common Electronic Submission Gateway (CESG).
  • For CDSCO (India): Submit via the Sugam portal.
  • For TGA (Australia): Submit via the TGA Business Services portal.

2.3 Acknowledgement of Submission:

  • Ensure acknowledgment of receipt from the regulatory authority, including submission ID, tracking number, and estimated review timeline.

3. Review and Follow-Up

3.1 Regulatory Authority Review Process:

  • Follow the regulatory authority’s review timeline (FDA: 6-10 months, EMA: 210 days, etc.).
  • Respond promptly to any queries or requests for additional data from the authority.

3.2 Communicate with Authorities:

  • Liaise with regulatory authorities during the review process to ensure the smooth progression of the NDA.
  • Provide clarifications or submit additional data if required by the regulatory body.

3.3 Final Review and Decision:

  • Upon completion of the review, receive the regulatory authority’s decision (approval, conditional approval, or rejection).
  • If approved, proceed to the market authorization phase. If rejected, assess the reasons and determine the next steps.

4. Post-Approval Activities

4.1 Post-Marketing Surveillance:

  • Implement post-marketing surveillance (Phase IV studies) as required to monitor the safety and efficacy of the drug after market approval.

4.2 Submission of Periodic Reports:

  • Submit periodic safety update reports (PSURs) and pharmacovigilance data as per regulatory requirements.

4.3 Labeling and Advertising Compliance:

  • Ensure that the labeling, packaging, and advertising materials comply with the approved NDA and regulatory requirements.

Documentation and Record Keeping
  • Maintain all submission-related documents and correspondence with regulatory authorities for a minimum of 10 years or as specified by local regulations.
  • Ensure that all electronic records are stored securely in the company’s document management system.

Training

All personnel involved in the NDA process must undergo periodic training to stay updated with the latest regulatory guidelines and changes in submission procedures. The Regulatory Affairs department is responsible for organizing and documenting training sessions.


References
  • FDA’s Code of Federal Regulations (21 CFR Part 314)
  • EMA’s EudraLex Volume 2
  • PMDA’s Pharmaceutical Affairs Law
  • NMPA’s Drug Administration Law
  • Health Canada’s Food and Drugs Act
  • CDSCO’s Drugs and Cosmetics Act
  • TGA’s Therapeutic Goods Act
Change Control

Any updates or changes to this SOP must be reviewed and approved by the Regulatory Affairs and Quality Assurance departments. All revisions should be documented and communicated to relevant departments.

1. United States (FDA – Food and Drug Administration)

Regulatory Body: U.S. Food and Drug Administration (FDA)
Procedure:
  • Pre-NDA Meeting: Companies often meet with the FDA to discuss their data and NDA preparation before filing.
  • IND (Investigational New Drug) Application: Submit an IND before initiating clinical trials.
  • Filing NDA: Submit the NDA electronically through the FDA’s Electronic Submission Gateway (ESG). The submission must include preclinical, clinical, safety, efficacy, labeling, and manufacturing data.
  • Review Process: The FDA reviews the NDA, assigns it a standard or priority review, and takes up to 6-10 months for approval.

Key Documents:

  • Preclinical and clinical data
  • Drug formulation and manufacturing process
  • Proposed labeling
  • Toxicological data
  • Risk-benefit analysis

Relevant NDA Guidelines:

  • FDA’s Code of Federal Regulations (21 CFR Part 314) provides guidelines for submitting an NDA.
  • Additional guidance can be found on FDA’s Drug Applications website.

2. European Union (EMA – European Medicines Agency)

Regulatory Body: European Medicines Agency (EMA)

Procedure:

  • Pre-submission Meeting: Companies may request scientific advice from EMA regarding their submission.
  • Clinical Trial Application (CTA): Prior to an NDA, a CTA must be filed for clinical trials in the EU.
  • Centralized Procedure: For most innovative drugs, the Centralized Procedure must be followed, submitting the Marketing Authorization Application (MAA), which is equivalent to the NDA.
  • Submission Portal: The application is submitted via the eSubmission Gateway or eSubmission Web Client.
  • Review Timeline: The EMA takes about 210 days to review the application, followed by an opinion from the Committee for Medicinal Products for Human Use (CHMP).

Key Documents:

  • Non-clinical and clinical data
  • Quality and manufacturing information
  • Risk management plan
  • Proposed packaging and labeling

Relevant NDA Guidelines:

  • EMA’s EudraLex Volume 2 outlines guidelines for marketing authorization.
  • Guidance on filing can be found on the EMA website under the Marketing Authorization section.

3. Japan (PMDA – Pharmaceuticals and Medical Devices Agency)

Regulatory Body: Pharmaceuticals and Medical Devices Agency (PMDA)
Procedure:
  • Pre-NDA Consultation: The PMDA encourages sponsors to consult with them early in the process.
  • Clinical Trial Notification (CTN): Submit a CTN before initiating clinical trials.
  • Filing NDA: The NDA submission to PMDA must include clinical, non-clinical, and manufacturing data, similar to the FDA process.
  • Submission Portal: NDA submissions can be made through the Medical Products Review Portal (MP-Review).
  • Review Timeline: PMDA typically completes its review within 12 months.

Key Documents:

  • Clinical and non-clinical study results
  • Manufacturing details and quality assurance
  • Proposed labeling and risk analysis

Relevant NDA Guidelines:


4. Canada (Health Canada – HPFB)

Regulatory Body: Health Canada – Health Products and Food Branch (HPFB)
Procedure:
  • Pre-submission Meeting: Health Canada recommends a pre-submission meeting to ensure all aspects are well-prepared.
  • Clinical Trial Application (CTA): Required for clinical trials in Canada.
  • Filing NDA (New Drug Submission – NDS): The New Drug Submission (NDS) is equivalent to the NDA and is filed with detailed clinical trial data, safety, efficacy, and manufacturing information.
  • Submission Portal: Submissions are done through the Common Electronic Submission Gateway (CESG).
  • Review Timeline: The typical review period is between 300 and 365 days, depending on the priority status.

Key Documents:

  • Clinical and toxicology data
  • Proposed labeling and patient information
  • Manufacturing details

Relevant NDA Guidelines:


5. China (NMPA – National Medical Products Administration)

Regulatory Body: National Medical Products Administration (NMPA)
Procedure:
  • Pre-NDA Communication: The NMPA encourages consultation meetings prior to NDA submission.
  • Clinical Trial Application (CTA): A CTA must be approved by the NMPA before starting trials.
  • Filing NDA: Known as a New Drug Registration Application (NDRA) in China, the NDA submission must include comprehensive clinical trial data, manufacturing details, and safety assessments.
  • Submission Portal: Submissions are made via the China Drug Electronic Application System (CDE).
  • Review Timeline: The typical review period is around 12 months.

Key Documents:

  • Clinical trial results
  • Manufacturing process data
  • Toxicological and safety data

Relevant NDA Guidelines:


6. India (CDSCO – Central Drugs Standard Control Organization)

Regulatory Body: Central Drugs Standard Control Organization (CDSCO)

Procedure:

  • Pre-submission Meeting: CDSCO recommends a pre-NDA meeting for regulatory clarity.
  • Clinical Trial Application (CTA): A CTA is needed for clinical trials in India.
  • Filing NDA: Known as a New Drug Approval in India, the NDA submission must include clinical and preclinical data, labeling, and manufacturing details.
  • Submission Portal: Submissions are made through the Sugam portal.
  • Review Timeline: The review process takes around 12 to 18 months.

Key Documents:

  • Clinical trial and bioequivalence data
  • Manufacturing process details
  • Proposed labeling

Relevant NDA Guidelines:

  • CDSCO follows India’s Drugs and Cosmetics Act.
  • Guidance for NDA filing can be found on the CDSCO website.

7. Australia (TGA – Therapeutic Goods Administration)

Regulatory Body: Therapeutic Goods Administration (TGA)
Procedure:
  • Pre-submission Consultation: The TGA encourages early discussions about the application.
  • Clinical Trial Notification (CTN): Required for clinical trials.
  • Filing NDA (Marketing Authorization): The NDA, or Marketing Authorization, is filed with data supporting the drug’s safety, efficacy, and quality.
  • Submission Portal: Applications are submitted through the TGA Business Services portal.
  • Review Timeline: The typical review process takes about 255 days.

Key Documents:

  • Clinical and non-clinical data
  • Manufacturing details
  • Risk-benefit assessment

Relevant NDA Guidelines:


Conclusion

The NDA submission process varies by region, but all global markets share a commitment to ensuring the safety, efficacy, and quality of pharmaceuticals before allowing them on the market. Each regulatory body offers specific guidelines, submission portals,

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