Regulatory News

Overview of Changes

The new version of the "Guidance Notes on Registration of Pharmaceutical Products: Specific Requirements for New Drug Applications of Advanced Therapy Products via Abridged Evaluation or Verification Routes" (Version 4.0, effective 31 March 2026) introduces a consequential update due to the introduction of new application categorization and evaluation routes. It also includes cross-referencing to the new set of "<Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications>".

The "Guidance on Application of Certificate of Drug/Product Registration — Advanced Therapy Products" (Version 3.1) will remain applicable to applications accepted for evaluation prior to 31 March 2026 and will remain in effect for one year until 30 March 2027.

Key Changes

• Introduction of New Application Categorization and Evaluation Routes: The primary driver for the update to Version 4.0 is the establishment of new ways to categorize and evaluate applications for Advanced Therapy Products (ATPs). This implies a shift in how applications will be processed and assessed.
• Cross-referencing to New "Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications": Version 4.0 explicitly states that it cross-references to a new set of guidance notes titled "<Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications>". This suggests that applicants will need to consult these new notes in conjunction with the ATP-specific guidance.
• Transitional Provision for Older Guidance: The "Guidance on Application of Certificate of Drug/Product Registration — Advanced Therapy Products" (Version 3.1) is being phased out. It will continue to be valid for applications accepted before the effective date of Version 4.0 (31 March 2026) and for a subsequent transitional period of one year.

Suggestions for SOP Updates

• Update SOP Section on ATP Application Process: Review and revise the SOP section that details the process for applying for ATP registration. Ensure it reflects the new application categorization and evaluation routes introduced with Version 4.0.
• Incorporate Cross-References: Update the SOP to include explicit cross-references to the new "<Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications>" as required by Version 4.0.
• Clarify Transitional Period: The SOP should clearly outline the transitional arrangements for Version 3.1 of the "Guidance on Application of Certificate of Drug/Product Registration — Advanced Therapy Products," specifying its continued applicability for a limited period after the effective date of Version 4.0.
• Training on New Routes: Develop and implement training for relevant personnel on the new application categorization and evaluation routes. This should cover how to identify which route applies and the specific requirements for each.
• Document Control Update: Ensure that version control for the SOP accurately reflects the adoption of Version 4.0 of the guidance notes and the eventual retirement of Version 3.1.

Overview of Changes

The new version of the "Guidance Notes on Registration of Pharmaceutical Products: Specific Requirements for New Drug Applications of Advanced Therapy Products via Abridged Evaluation or Verification Routes" (Version 4.0, effective 31 March 2026) introduces a consequential update upon introducing new application categorization and evaluation routes, and cross-references to a new set of "Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications."

The "Guidance on Application of Certificate of Drug/Product Registration — Advanced Therapy Products" (Version 3.1) will remain applicable to applications accepted for evaluation prior to 31 March 2026 and will remain applicable for one year until 30 March 2027.

Key Changes

There are no substantive changes in the content of the "Guidance Notes on Registration of Pharmaceutical Products: Specific Requirements for New Drug Applications of Advanced Therapy Products via Abridged Evaluation or Verification Routes" between the old and new versions being compared. The primary change is the update to Version 4.0 and the cross-referencing to new application categorization and evaluation routes. The "Guidance on Application of Certificate of Drug/Product Registration — Advanced Therapy Products" is also noted to have a transitional period of applicability.

Suggestions for SOP Updates

• Update SOP references: Review all internal SOPs that reference the "Guidance Notes on Registration of Pharmaceutical Products: Specific Requirements for New Drug Applications of Advanced Therapy Products via Abridged Evaluation or Verification Routes." Update any version-specific references to reflect Version 4.0.
• Incorporate new guidelines: Ensure that any SOPs referencing the "Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications" are updated to reflect the new set of guidelines as indicated in the change history of Version 4.0.
• Address transitional period: If any SOPs are specific to the application process under Version 3.1 of the "Guidance on Application of Certificate of Drug/Product Registration — Advanced Therapy Products," ensure they are updated or that a clear process is defined for handling applications submitted before the transition date of 31 March 2026 and the extended applicability date of 30 March 2027.

Overview of Changes

The new version of the "General Requirements for Master Formula and Specifications for Non-Biological Products" introduces several clarifications and additions, particularly concerning the information required in the Master Formula and the guidelines for Specifications. Key changes include the explicit inclusion of references on quality standards in the Master Formula and a more detailed breakdown of general tests for product specifications, including a new Annex A with a comprehensive table.

Key Changes

• Master Formula - References on Quality Standards: The new version explicitly requires the inclusion of "references on quality standard(s) of the active ingredient(s) and excipient(s) (e.g. pharmacopoeial monographs or if no relevant pharmacopoeial monographs, manufacturer’s in-house specifications)" as part of the master formula. The old version mentioned that the certificate holder "may include the appropriate references".
• Master Formula - Overage of Active Ingredient: Question 3 in the Q&A section regarding overage of active ingredient remains largely the same but is renumbered.
• Master Formula - Change of Quality Standard: Question 5 in the old version regarding changes to quality standards has been significantly expanded in the new version (renumbered as Question 5). It now clarifies that approval is not required for changes from "in-house standard to pharmacopoeia standard, from one pharmacopoeia standard to another," but CORP application is still required when the quality standard is stated in the master formula.
• Master Formula - Change in Physical Form: Question 6 in the new version addresses changes in the "physical form of active ingredient (e.g. change to micronized form)" and specifies that supporting documents like "certificate of analysis of active substance, updated master formula and specifications (if applicable) together with stability reports" should be submitted.
• Master Formula - Change in Salt/Ester/Derivative: A new question (Question 7) has been added to the Master Formula Q&A concerning changes in the "salt/ester complex/derivative/isomer of active substance," stating that an "Application for new product registration is required."
• Specifications - Acceptance Criteria Reference: In section (c) of the Specifications, the new version requires "acceptance criteria with reference to a specified pharmacopoeia or ICH/WHO guidelines (See Annex A )". The old version stated "acceptance criteria".
• Specifications - General Tests: The Q&A on general tests in Specifications has been significantly expanded. It now provides a detailed list of pharmacopoeias and ICH/WHO guidelines that tests and acceptance criteria should be based on (e.g., "Pharmacopoeia of the People’s Republic of China", "British Pharmacopoeia", etc.).
• Specifications - Annex A: A new Annex A has been introduced, providing a comprehensive table detailing "general tests for reference" across different dosage forms (Oral, Cutaneous, Ear/Nasal, Eye, Parenteral, Solid, Liquid, Semi-Solid).

Suggestions for SOP Updates

• Master Formula - Section 2.1 (Content of Master Formula):
  • Update Requirement (e): Add a new sub-point to explicitly state that "References on quality standard(s) of active ingredients and excipients (e.g., pharmacopoeial monographs or manufacturer’s in-house specifications) must be included."
  • Update Q&A 5 (Change in Quality Standard): Revise the SOP section referencing this Q&A to reflect the clarification that changes from in-house to pharmacopoeial standards, or between pharmacopoeial standards, do not require CORP application, but must still be justified and comply with change control GMP.
  • Add New Q&A 6 (Change in Physical Form): Incorporate guidance on the supporting documentation required for changes in the physical form of an active ingredient.
  • Add New Q&A 7 (Change in Salt/Ester/Derivative): Add a statement that changes in the salt, ester, complex, derivative, or isomer of an active substance require a new product registration application.
• Specifications - Section 3.1 (Content of Specifications):
  • Update Requirement (c): Modify the wording to state that specifications must include "the relevant tests for final release of the drug product and their acceptance criteria with reference to a specified pharmacopoeia or ICH/WHO guidelines (See Annex A)."
• Specifications - Section 3.2 (Q&A - General Tests):
  • Revise Content: Update the SOP to detail the specific pharmacopoeias (e.g., PRC, BP, EP, IP, JP, USP) and ICH/WHO guidelines that should be referenced for general tests and acceptance criteria.
  • Incorporate Annex A: Integrate the information from the new Annex A into the SOP, possibly as an appendix, to provide a clear reference table for general tests based on dosage form.
• General Update: Ensure all references to "CORP application" are consistent with the updated definitions and requirements in the new version.
• Change Control: Reiterate the importance of adhering to "change control" GMP requirements when implementing changes to methods of analysis or specifications, as mentioned in the Q&A sections.

Overview of Changes

There are no substantive differences between the old and new versions of the "Guidance Notes on Registration of Pharmaceutical Products Containing a New Chemical or Biological Entity". The content, structure, and specific requirements remain identical.

Key Changes

None.

Suggestions for SOP Updates

No updates are required for the SOP as there are no changes in the provided guidance document.

Overview of Changes

The new version of the Guidance Notes on Registration of Medical Gases has been updated to reflect changes in referenced documents and their corresponding paragraph numbers.

Key Changes

• Paragraph 3.1.2(ii): The reference to the "Guidance Notes on Registration of Pharmaceutical Products/Substances" has been updated. It now directs applicants to paragraph 6.2.16 in the old version, and 9.7.2 in the new version for the countries listed.
• Paragraph 3.2: The referenced document for new medical gas applications has changed. It previously referred to “Guidance Notes on Registration of Pharmaceutical Products Containing a New Chemical or Biological Entity” and now refers to “Guidance Notes on Registration of Pharmaceutical Products : New Drug Applications ”.
• Paragraph 4.5: Similar to 3.1.2(ii), the reference to the "Guidance Notes on Registration of Pharmaceutical Products/Substances" has been updated from paragraph 6.2.16 in the old version to paragraph 9.7.2 in the new version.

Suggestions for SOP Updates

• Section [Insert Relevant Section Number/Title]: Update all references to "Guidance Notes on Registration of Pharmaceutical Products/Substances" paragraph 6.2.16 to 9.7.2.
• Section [Insert Relevant Section Number/Title]: Update the reference to the guidance for new medical gas applications from “Guidance Notes on Registration of Pharmaceutical Products Containing a New Chemical or Biological Entity” to “Guidance Notes on Registration of Pharmaceutical Products : New Drug Applications ”.

Overview of Changes

The new version of the guidance, titled "Guidance Notes on Registration of Pharmaceutical Products: Specific requirements for New Drug Applications of Advanced Therapy Products via Abridged Evaluation or Verification Routes," supersedes the previous version. The new document focuses on New Drug Applications (NDAs) for Advanced Therapy Products (ATPs) submitted through abridged evaluation or verification routes. It outlines specific requirements in addition to the general requirements for NDAs.

Key Changes

• Document Title and Scope: The title and scope have been significantly revised. The new document specifically addresses "New Drug Applications (NDAs) of ATPs via Abridged Evaluation or Verification Routes." The previous version was a general guidance on "Application of Certificate of Drug/Product Registration — Advanced Therapy Products."
• Introduction of Application Routes: The new version introduces the concept of "abridged evaluation or verification routes" for NDAs of ATPs. This implies a change in the application categorization and evaluation process.
• Additional Requirements for NDAs: Section 2 of the new version details "Additional requirements for NDAs of ATPs via the abridged evaluation or verification routes." These include:
  • Submission of site master file(s) or equivalent for ATPs manufactured outside Hong Kong.
  • Specific requirements for prototype sales packs, including labelling requirements for product code, unique donation identifier, and unique recipient identifier (for autologous products).
  • ICH CTD Modules 2 to 5 with specific requirements outlined in appendices.
  • A description of the traceability system.
  • Strategy to evaluate long-term efficacy.
  • Strategy for long-term follow-up of safety and efficacy, to be included in the RMP and/or REMS.
  • Information on specific expertise required for application, implantation, administration, or follow-up activities, and training plans for healthcare professionals.
• Renumbering and Restructuring: Section numbers and content have been reorganized. For example, the section on "Regulated Product under Human Organ Transplant Ordinance" is now Section 3 in the new version, and the appendices remain dedicated to CTD Modules 3, 4, and 5.
• Cross-referencing: The new version cross-references the new set of "Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications," indicating a broader framework for drug registration. The previous version had a cross-reference to "Guidance Notes on Registration of Pharmaceutical Products Containing a New Chemical or Biological Entity."
• Version Number and Date: The new version is 4.0, dated 31 March 2026, indicating a significant update from version 3.1, dated 1 November 2024.

Suggestions for SOP Updates

1. Update SOP Title and Introduction: Revise the SOP title to reflect the new guidance's focus on "New Drug Applications (NDAs) of Advanced Therapy Products (ATPs) via Abridged Evaluation or Verification Routes." Update the introduction to reflect this new scope and the introduction of different evaluation routes.
2. Incorporate New Section 2 - Additional Requirements: Integrate the specific additional requirements for NDAs detailed in Section 2 of the new guidance into the relevant sections of your SOP. This will involve creating new subsections or expanding existing ones to cover:
   • Site master file requirements.
   • Detailed labelling requirements for ATPs, especially regarding unique identifiers.
   • Explicit mention of ICH CTD Modules 2 to 5 with reference to the appendices for specific ATP requirements.
   • Requirements for detailing the traceability system.
   • Inclusion of strategies for long-term efficacy evaluation and safety/efficacy follow-up (RMP/REMS).
   • Provisions for expertise and training plans for healthcare professionals.
3. Review and Update Cross-References: Ensure all cross-references within the SOP are updated to align with the new guidance document, particularly the reference to the main "Guidance Notes on Registration of Pharmaceutical Products: New Drug Applications."
4. Revise Section on Regulated Products: While the core content regarding the Human Organ Transplant Ordinance (HOTO) appears similar, verify that the section numbers and any associated definitions or footnotes in the SOP accurately reflect the new document's structure.
5. Update Document Information: Update the SOP's "Document Information" or equivalent section to reflect the new version number (4.0), effective date (31 March 2026), and a concise description of the changes, referencing the new title and scope.
6. Reference Application Process: If the SOP details the application submission process, ensure it reflects any changes related to the new application categorization and evaluation routes mentioned in the new guidance.
7. Appendices Alignment: Confirm that the SOP's appendices, if they mirror the CTD module requirements, are consistent with the updated information in Appendices 1-3 of the new guidance.