Pharmaceutical companies planning to market their products internationally must navigate a complex web of regulatory submission requirements. While many regions follow the ICH Common Technical Document (CTD) or its electronic version (eCTD), each regulatory authority has its own specifications, processes, and expectations. 

Understanding these differences is essential for regulatory affairs professionals to avoid delays, technical rejections, and compliance risks. 

1. USFDA (United States Food and Drug Administration)

The USFDA requires all prescription drug applications, including NDAs and ANDAs, to be submitted in eCTD format. 

Key points: 

• Format: eCTD is mandatory for all commercial submissions. 

• Submission Portal: FDA’s Electronic Submissions Gateway (ESG). 

• Module 1: Region-specific with detailed administrative information including FDA Form 356h, labeling, and patent information. 

• Lifecycle Management: The FDA places strong emphasis on tracking submission history through amendments, supplements, and annual reports. 

• Validation: FDA uses specific validation criteria for technical compliance before review begins. 

Important: Submissions not meeting technical specifications may be rejected before scientific review. 

2. Health Canada

Health Canada also uses the eCTD format but includes regional elements that differ from the US and EU. 

Key points: 

• Format: Mandatory eCTD for most drug classes, including biologics and generic drugs. 

• Submission Gateway: Uses the Common Electronic Submissions Gateway (CESG), shared with USFDA. 

• Module 1: Includes Health Canada-specific forms like HC-SC3011, Product Monograph, and risk management plans. 

• Language: English or French accepted. 

• Review Process: Submissions go through screening before review; rejections are possible at the screening stage for incomplete or incorrect documentation. 

Tip: Health Canada applies a structured premarket review and expects environmental assessments for certain applications. 

3. EMA (European Medicines Agency)

The EMA oversees centralized marketing authorization in the European Union, but decentralized (DCP) and mutual recognition procedures (MRP) are handled by national competent authorities. 

Key points: 

• Format: eCTD is the required format for most applications. 

• Submission Portals: eSubmission Gateway/Web Client for electronic delivery. 

• Module 1: Contains EU-specific content like the application form, Product Information in multiple EU languages, and the European Public Assessment Report (EPAR). 

• Procedures: Centralized Procedure (CP), Decentralized Procedure (DCP), and Mutual Recognition Procedure (MRP). 

• Language Requirements: Multilingual submission of key documents is required under CP and DCP. 

Note: Even with eCTD, national variations exist depending on the chosen procedure. 

4. PMDA (Japan’s Pharmaceuticals and Medical Devices Agency)

Japan follows the JP eCTD format, aligned structurally with ICH eCTD but with region-specific technical elements. 

Key points: 

• Format: eCTD mandatory for new drug applications. 

• Module 1: Includes extensive Japanese-language documentation. 

• Technical Requirements: More granular folder structure and metadata tagging. 

• Gateway: Uses its own secure portal for submission. 

Consideration: Documentation must be translated and aligned with Japanese regulatory expectations, often requiring more detailed justification. 

5. TGA (Therapeutic Goods Administration – Australia)

Australia is transitioning from CTD to eCTD for prescription medicine submissions. 

Key points: 

• Format: CTD still accepted, but eCTD is increasingly preferred. 

• Submission Portal: TGA eSub Portal. 

• Module 1: Australia-specific administrative and regional information. 

• Review Model: Rolling review not currently used; full submissions required at the start. 

Note: TGA maintains strong emphasis on GMP compliance and overseas inspection reports. 

6. NMPA (National Medical Products Administration – China)

China is in the process of adopting eCTD and aligning with ICH M4 and M8 standards. 

Key points: 

• Format: Transitioning to eCTD; some hybrid formats still accepted. 

• Language: All submissions must be in Chinese. 

• Module 1: Includes NMPA-specific forms and local clinical trial data requirements. 

• Localization: Heavy reliance on real-world evidence and Chinese patient data. 

Tip: Even global trial data may require local bridging studies for acceptance. 

Comparison Table: 

Regulatory Body	Format	Submission Gateway	Key Distinction
USFDA	eCTD	ESG	Lifecycle tracking, strict validation
Health Canada	eCTD	CESG	Unique Module 1, dual-language support
EMA	eCTD	eSubmission Gateway	Centralized and national procedures
PMDA (Japan)	eCTD	PMDA Portal	Detailed metadata, full Japanese translation
TGA (Australia)	CTD/eCTD	TGA eSub Portal	Flexible format, strong GMP focus
NMPA (China)	Hybrid/eCTD	Local Portal	Local data, Chinese language, evolving format

Although the eCTD format has brought global alignment to drug submissions, regional differences still demand a tailored approach. Regulatory affairs teams must understand and plan for country-specific requirements in Module 1, language, submission portals, and review expectations. 

Staying current with evolving standards, validation rules, and local expectations is critical to achieving timely approvals in global markets.