#RegulatoryAffairsUpdate List- June 13th

My?#RegulatoryAffairsUpdate?List provides the?selection of interesting regulations updates of the last couple of weeks.

USA

New, Easy-to-Read Medication Guide for Patients, Patient Medication Information, 30-May-2023?

This press release highlights the FDA's commitment to providing accurate and timely information to ensure the safe and effective use of prescription medications. Currently, patients receive different types of written information depending on their prescribed medication. However, studies have revealed that the existing system for written information can be confusing, conflicting, incomplete, or repetitive. In response to this issue, the FDA proposes the introduction of a new Medication Guide called Patient Medication Information. This guide would be provided to patients along with their prescription drugs and certain biological products in outpatient settings. Additionally, the Patient Medication Information would be accessible online for the general public. The proposed rule represents a practical step towards improving public health.

https://www.fda.gov/news-events/press-announcements/fda-proposes-new-easy-read-medication-guide-patients-patient-medication-information

Draft Guidance for Industry: Drug Development Programs for Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS), Jun-2023

The Food and Drug Administration (FDA) has announced the release of a draft guidance titled "Interstitial Cystitis/Bladder Pain Syndrome: Establishing Drug Development Programs for Treatment." This draft guidance provides recommendations for drug development programs targeting the treatment of patients with interstitial cystitis/bladder pain syndrome (IC/BPS). It incorporates valuable insights gathered by the FDA during an advisory committee meeting in December 2017, which focused on patient selection criteria, trial design features, enrollment criteria, and acceptable efficacy endpoints for IC/BPS drugs. However, it's important to note that this guidance does not delve into the detailed design considerations for patient-reported outcome (PRO) instruments, as those issues are addressed in separate FDA guidance documents, such as "Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims" and the FDA Patient-Focused Drug Development (PFDD) guidance series.

The purpose of this draft guidance is to revise and replace the existing draft guidance titled "Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS): Establishing Effectiveness of Drugs for Treatment," which was issued on December 5, 2019.

Key changes introduced in the revised draft guidance include discussions on early drug development considerations, selection of patient outcomes for development, and clarification regarding the evaluation of Hunner's lesions. Additionally, editorial improvements have been made to enhance clarity, including updated references to current FDA guidances on patient-reported outcomes and updated clinical considerations.

https://www.fda.gov/media/169118/download

Draft Guidance: Migraine: Developing Drugs for Preventive Treatment, Jun-2023?

The purpose of this guidance is to provide assistance to sponsors involved in the clinical development of drugs intended for the preventive treatment of migraine. Migraine treatment approaches involve both abortive drugs to address individual migraine attacks (acute treatment) and drugs to reduce the frequency of migraine attacks (preventive treatment). This guidance specifically focuses on the FDA's current perspective on the development program and clinical trial designs necessary to support the approval of drugs for migraine prevention. It's important to note that this guidance does not cover the development of drugs intended for the acute treatment of migraines, as that topic has been addressed in a separate guidance document titled "Migraine: Developing Drugs for Acute Treatment".

Comments to be submitted by August 1, 2023.?

?https://www.fda.gov/media/168871/download

?FDA announcement on clinical trials

FDA announced the availability of a draft guidance with updated recommendations aimed at modernizing the design and conduct of clinical trials, making them more agile without compromising data integrity or participant protections.

https://www.fda.gov/news-events/press-announcements/fda-announces-additional-steps-modernize-clinical-trials

SWITZERLAND

Risk Mitigation Strategies for Transmissible Spongiform Encephalopathies (TSEs) (ZL000_00_035_WL), 23-May-2023

This guidance document outlines measures to minimize the risk of transmitting animal-origin transmissible spongiform encephalopathies (TSEs) through human and veterinary medicinal products. It applies to all human medicinal products subject to authorization that contain materials sourced from animals, particularly ruminants (cattle, sheep, and goats), or utilize such materials in their production processes.

By adhering to the guidelines outlined in this document, manufacturers and regulatory authorities can effectively evaluate and mitigate the risk of TSE transmission associated with medicinal products. It underscores the importance of assessing various factors related to the origin and processing of animal-derived materials to ensure the safety of medicinal products.

This guidance document serves as a valuable resource for industry professionals, offering comprehensive insights and recommendations to minimize the risk of TSE transmission in medicinal products.

https://www.swissmedic.ch/dam/swissmedic/en/dokumente/zulassung/zl_hmv_iv/zl000_00_035d_wl_betreffendminimierungdesrisikosderuebertragungtransmis.pdf.download.pdf/ZL000_00_035e_WL%20Anleitung%20betreffend%20Minimierung%20des%20Risikos%20der%20%C3%9Cbertragung%20transmissibler%20spongiformer%20Enzephalopathien%20tierischen%20Ursprungs%20durch%20Human.pdf

Guideline Amendments Clinical Trials (BW101_10_003_AA), 12-May-2023?

These instructions provide guidance on the following topics related to clinical trials:

1. Reporting amendments to the initial Clinical Trial Application submitted to Swissmedic.
2. Required reports throughout the course of a clinical trial.
3. Procedures to follow upon completion or premature interruption of the study.
4. Reports required after the completion or termination of a clinical trial.

It's important to note that these instructions specifically pertain to changes related to clinical trials of Category B and C. Any changes submitted in accordance with these instructions must receive approval from Swissmedic before implementation, except in cases of urgent safety measures.

When submitting the required documents, please ensure that the cover letter includes the Swissmedic reference number of the clinical trial, a description of the amendment, and the reason for it. Only complete and ready-to-process documents should be submitted, as incomplete dossiers will not be processed.

The revised version dated 12-May-2023 incorporates the following changes:

• Alignment with portal submission requirements.
• Clarification regarding the format of submitted documents.
• Clarification on the submission process for other administrative changes.

https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/clinical-trials/clinical-trials-on-medicinal-products/submission-of-changes-during-the-trial.html

Fast-Track Authorisation Procedure (ZL104_00_002_WL), 01-Jun-2023

This guideline outlines the necessary conditions for submitting a fast-track application and obtaining approval from Swissmedic. In contrast to the standard procedure, applicants must submit a request for a fast-track procedure in advance.

Section 5 of this guidance document outlines the prerequisites that must be fulfilled for approval of an application through the Fast-Track Authorisation Procedure (FTP). It also provides detailed information on the procedure for the applicant meeting (AAA) scheduled during the application processing. Section 6 specifies the formal and content requirements for a medicinal product authorisation application using the FTP, along with an overview of the review procedure itself.

The revised version dated 01-Jun-2023 incorporates following updates:

• Section 5.4: Clear explanation of the AAA procedure.
• Revised deadline for finalizing the decision minutes.

https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/information/anpassung-wl-bzv-befristete-zl-ham.html

Temporary Authorization for Human Medicinal Products (ZL109_00_001_WL), 01-Jun-2023

This guideline outlines the specific requirements for applying for a temporary authorization for human medicinal products. It is applicable only to the initial authorization of a human medicinal product containing a New Active Substance (NAS). It does not apply to additional indications or extensions of an existing authorization.

To apply for temporary authorization, a request for an Accelerated Application Hearing (AAA) must be submitted to Swissmedic. The AAA serves as a preliminary step to obtain approval for the temporary authorization procedure. Section 5 of this guidance document specifies the conditions that must be met before the authorization procedure for temporary authorization can be approved. It also provides detailed information on the procedure for the applicant meeting (AAA) scheduled during the application processing. Section 6 describes the formal and content requirements for an application seeking temporary authorization of a medicinal product, as well as the evaluation procedure itself.

The revised version dated 01-Jun-2023 incorporates following updates:

• Section 5.7: Clear explanation of the AAA procedure.
• Revised deadline for finalizing the decision minutes.

CHINA

NMPA Announcement No. 2023/68: Procedures for Adding Pediatric Medication Information to Package Insert for Marketed Drugs (Trial), 29-May-2023

With the aim of enhancing pediatric drug information in package inserts for marketed drugs and promoting the safe use of drugs among pediatric patients, this set of working procedures is established in accordance with the Drug Administration Law and Drug Registration Regulation.

These procedures apply to the relevant activities proposed by qualified pediatric-related medical institutions, societies, and industry associations for adding pediatric medication information to package inserts of marketed chemical drugs and therapeutic biological products (excluding cell gene therapy products and blood products).

The working procedures consist of the following steps:

1. Submission of suggestions: Qualified pediatric-related medical institutions, societies, and industry associations can submit written suggestions to the Center for Drug Evaluation, proposing the inclusion of pediatric medication information in package inserts of marketed drugs.
2. Research evaluation: The Center for Drug Evaluation conducts a technical review and organizes expert consultation meetings to evaluate the proposed drug varieties and revised package inserts.
3. Announcement and release: The Center for Drug Evaluation publishes the review results in batches, and once the public announcement is completed, it reports the findings to the National Medical Products Administration for release through an official announcement. If any objections arise during the public announcement period, the concerned drug varieties undergo further research, evaluation, and, if necessary, expert consultations.
4. Package insert revision: Upon the official release of the revised proposal for the package insert of a specific product, the drug marketing authorization holder can submit a supplementary application to add information on pediatric medication to the package insert of the marketed drug, based on the published information.

Please note that these procedures are currently in a trial phase and subject to further evaluation and potential revisions.

CDE Notification: Invitation for Public Comment on List of Reference Products for Generics (Draft), 02-Jun-2023

In accordance with NMPA Announcement No.2019/25: Release of Selection and Confirmation Procedures of Reference Preparations for Chemical Generics, 25-Mar-2019, CDE is currently issuing the draft list of reference products for generics. This list comprises essential information about the products, including their names, dosage forms, and marketing authorization (MA) holders.

The draft document encompasses the following sections:

1. List of reference products for generics that are yet to be released.
2. Supplementary list of reference products for generics that have already been released.
3. List of varieties that did not pass the review process

Please note that this document is in the draft stage, and CDE welcomes public comments and feedback on its contents.

SOUTH KOREA

MFDS Document for Public Comment No. 2023-264: Proposal for the Establishment of Good Manufacturing Practices (GMP) Regulation for Quasi-drugs (Draft), 30-May-2023

This document seeks public feedback on the implementation of the Regulation on Good Manufacturing Practices (GMP) for Quasi-drugs. The proposed regulation aims to establish comprehensive guidelines governing the manufacturing and quality control processes for Quasi-drugs that are not covered by the standards outlined in Article 38 of the Pharmaceutical Affairs Act and Article 48-2 of the Regulation on the Safety of Drugs.

The key elements outlined in the draft regulation are as follows:

• Purpose: Establishing manufacturing and quality control standards for Quasi-drugs, defining compliance subjects, application procedures, and data requirements (Article 1).
• Scope of application (Article 2).
• Approval criteria and requirements, along with the application procedure (Article 3 and 4).
• Approval process, requests for supplementary information, and issuance of compliance certificates (Article 5 to 7).
• Procedures for change approvals, extension of validity periods, and reissuance of compliance certificates (Article 8-10).
• Preferential measures and follow-up management, including corrective orders and increased inspections for non-compliant cases (Article 11-12).

MFDS Notification No. 2023-38: Introduction of Regulations for Approval of High-Risk Advanced Regenerative Medicine Medical Research Plans, 02-Jun-2023

The purpose of this regulation is to establish guidelines and procedures for the approval of medical research plans involving high-risk advanced regenerative medicine. It is in accordance with the Advanced Regenerative Medicine and Advanced Biopharmaceutical Safety and Support Act and its Enforcement Decree.

The key provisions of this regulation include:

1. Requirements and specifications for the data to be submitted when seeking approval for high-risk advanced regenerative medical research plans (Articles 3 to 4).
2. Procedures for the submission and reception of high-risk advanced regenerative medical research plans (Article 5).
3. Guidelines for requesting additional data, if necessary, and the process and timeframe for such requests (Article 6).
4. Criteria and essential details for making approval decisions on high-risk advanced regenerative medical research plans, as well as the method of notifying the results (Article 7).

Additionally, Appendix 1 provides information on the results of non-clinical trials required for the approval of high-risk clinical research plans, along with considerations based on the type of data. Appendix 2 offers methods for collecting, inspecting, processing, and storing human cells for high-risk advanced regenerative medicine clinical research, along with guidelines for document preparation to ensure validity.

This notification takes effect on 02-Jun-2023. However, the provisions related to expedited combined reviews outlined in Articles 5 and 7 will come into effect on 01-Jul-2023.

AUSTRALIA

Application Requirements for New Substances in Listed Medicines; Australian Regulatory Guidelines, Version 1.0, Feb-2023

This guideline is intended for applicants seeking the evaluation of a substance to be used as an ingredient in listed medicines. The guideline covers the following aspects:

• The application process for new substances.
• The regulatory framework followed by the Therapeutic Goods Administration (TGA) regarding market exclusivity of a new substance both before and after approval.
• The administrative, quality, and safety information requirements for submitting a substance application.
• A concise overview of the core information requirements specific to different types of substances.

https://www.tga.gov.au/sites/default/files/2023-02/application-requirements-for-new-substances-in-listed-medicines.pdf

JAPAN

PMDA Presentation: Support and Services for Venture Companies, Jun-2023

This presentation highlights the range of services and support provided by the Pharmaceuticals and Medical Devices Agency (PMDA) to venture companies in Japan. The document focuses on scientific reviews, inspections, and scientific advice, aiming to assist venture companies in navigating the regulatory landscape effectively.

PMDA's support encompasses several key areas, including internationally harmonized Japanese pharmaceutical regulations, fast review processes, various fast track systems, and a meticulous consultation system. The agency actively participates in international collaborations such as the International Coalition of Medicines Regulatory Authorities (ICMRA), the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and the Medical Device Single Audit Program (MDSAP). Through these collaborations, PMDA contributes to the development of new ICH topics and expedites the advancement of COVID-19-related product development.

The presentation provides insights into the different types of accelerated approval systems in Japan, along with their corresponding product features and applicable product types, such as drugs, medical devices, and regenerative medicinal products. By understanding the specific characteristics of each accelerated approval system, venture companies can navigate the regulatory pathway more efficiently.

Additionally, the document emphasizes the importance of regulatory science (RS) consultation in the research and development (R&D) strategy. PMDA offers RS consultations to facilitate the development of medical products by providing a reliable roadmap. These consultations also support the promotion of clinical trials led by academia and ensure the quality and non-clinical safety of regenerative medicinal products prior to clinical trial notification.

By availing themselves of the services and support outlined in this presentation, venture companies in Japan can benefit from PMDA's expertise and guidance throughout their product development journey. The agency's commitment to collaboration, regulatory excellence, and scientific advancements reflects its dedication to fostering innovation and ensuring the safety and efficacy of medical products in Japan.

https://www.pmda.go.jp/files/000252851.pdf

ARGENTINA

Regulation 4061/2023: Approval of the Stability Guideline, 05-Jun-2023

Regulation 4061/2023 has been enacted to approve the Guideline on stability studies in Argentina. The purpose of this guideline is to provide comprehensive instructions for conducting stability studies on both active pharmaceutical ingredients and medicinal products. These studies are essential components of applications for authorization and post-authorization variations.

The Guideline consists of two parts:

• Part A: Stability Studies for Active Pharmaceutical Ingredients
• Part B: Stability Studies for Medicinal Products

Each part addresses specific considerations and requirements related to stability studies for the respective category. Part A focuses on the stability studies for active pharmaceutical ingredients, while Part B covers stability studies for medicinal products.

It is important to note that the Guideline will come into effect 90 days after its publication in the Official Journal. During this transitional period, stakeholders in the pharmaceutical industry will have the opportunity to familiarize themselves with the new requirements and adjust their practices accordingly.

https://www.argentina.gob.ar/sites/default/files/infoleg/disp4061.pdf

EGYPT

Mechanisms for Second Brand Registration 2023, Version 2.0, 01-Jun-2023

The Egyptian Drug Authority (EDA), specifically the General Administration of Biological Product Registration Directorate, has released a guideline outlining the mechanisms for the registration of second brand biological products in Egypt.

This document serves as an updated version, incorporating revisions to the previous draft guideline titled "Procedure for the Registration of Second Brand Biological Products" published on 23-Mar-2023. The revised version aims to provide clarity and guidance on the registration process while emphasizing the importance of complying with EDA regulations.

Notable updates in this revised guideline include a reminder highlighting the necessity for applicants to adhere to the regulatory framework established by the EDA. Additionally, provisions in article 5 regarding variations without major changes have been rephrased to enhance clarity and understanding.

SAUDI ARABIA?

Guidance for Orphan Designation, Version 1 (DS-G-101-V01/230604), 04-Jun-2023

The Saudi Food and Drug Authority's (SFDA) Drug Sector has developed this guidance document to assist sponsors intending to apply for orphan drug designation (ODD) in Saudi Arabia. The guidance provides valuable information for sponsors at any stage of the development of a human medicinal product, prior to submitting a marketing authorization application.

This comprehensive guidance covers the following key areas:

1. Introduction: An overview of the guidance document and its purpose.
2. Orphan Drug Designation: An explanation of the concept of orphan drug designation and its significance in the context of rare diseases or conditions.
3. Orphan Indication Eligibility Criteria: Detailed criteria for determining whether a specific indication or orphan condition meets the requirements for orphan designation. This includes considerations such as seriously debilitating diseases, life-threatening conditions, prevalence of rare diseases or conditions, and lack of financial viability.
4. Under Development for Orphan Condition: Criteria for demonstrating that the medicinal product is being developed specifically for the orphan condition.
5. Comparison with Other Methods: Evaluation of the proposed medicinal product in comparison to other available methods for diagnosis, prevention, or treatment of the condition.
6. Incentives of Orphan Drug Designation: A description of the benefits and incentives associated with orphan drug designation, which may include market exclusivity, regulatory assistance, and fee reductions.
7. Timing of Submissions: Guidelines on when to submit an orphan designation application in relation to the development stages of the medicinal product.
8. Orphan Designation Procedure: A step-by-step explanation of the procedure for obtaining orphan drug designation, including the necessary documentation and submission requirements.
9. Post Designation: Information on post-designation obligations and reporting requirements for sponsors.
10. Electronic Submission of ODD Application: Guidance on the electronic submission process for orphan drug designation applications.

The guidance also includes an annex featuring the application form for orphan drug designation, providing sponsors with a structured format to submit their applications.

https://sfda.gov.sa/sites/default/files/2023-06/OrphanDrugDesignation.pdf

Braille Requirements for Labeling Information of Medicinal Products for Human Use, Version 1 (DS-G-100-V01 /230601), 01-Jun-2023

The Saudi Food and Drug Authority (SFDA) has issued a guideline addressing the braille requirements for labeling information on medicinal products. This guideline aims to ensure that drug information is accessible to individuals who are blind or visually impaired.

The guidance provides an interpretation of the requirements for including braille on the packaging of human medicinal products. It emphasizes the importance of making information available in formats suitable for blind and partially sighted individuals. However, it should be noted that the braille requirement does not apply to medicinal products intended solely for hospital use or those administered exclusively by healthcare professionals. For instance, vaccines are not required to have the product name in braille.

Regarding new medicinal products seeking marketing authorization, the final version of this document will become effective three years after the guideline's adoption date. After five years of publishing the final version, compliance with the guideline will be mandatory for all registered products. Nonetheless, companies are encouraged to submit a variation application to implement the guideline's requirements as soon as possible.

The document covers the following aspects:

1. Introduction

• Provides an overview of the guideline and its purpose.

1. Labeling Requirements

• Specifies the requirements for labeling medicinal products, including considerations for small volume packaging, braille printing position, language, and general considerations.

1. Braille Declaration

• Details the specific requirements for including braille on medicinal product packaging and labeling.

1. Appendix: Braille Declaration Form

• Provides a standardized form for declaring compliance with the braille requirements.

By implementing this guideline, Saudi Arabia aims to improve accessibility to vital information for individuals with visual impairments, ensuring equal access to medicinal product labeling.

https://sfda.gov.sa/sites/default/files/2023-06/BrailleLabelingREQs.pdf

SOUTH AFRICA?

Draft Guideline: Good Medicine Compounding Practice (GMCP), 05-Jun-2023

The South African Health Products Regulatory Authority (SAHPRA) has developed this draft guideline to provide comprehensive guidance on the requirements for Good Medicine Compounding Practice (GMCP). The purpose of this guideline is to ensure the safe and appropriate compounding of medicines intended for direct supply to specific individuals or animals. This includes compounding at the time of sale or administration, in anticipation of such events, or for sale in the retail trade.

Key features of this draft guideline include:

1. Scope and Application: A clear definition of the scope of the guideline and its application to the compounding of medicines.
2. Compounding Requirements: Detailed requirements and standards for the compounding of medicines, ensuring safety, quality, and efficacy.
3. Direct Supply to Individuals or Animals: Specific considerations for the compounding of medicines intended for direct supply to a particular person or animal.
4. Compounding for Sale in Retail Trade: Guidelines for the compounding of medicines intended for sale in the retail trade, addressing the unique requirements of this context.

SAHPRA welcomes stakeholder feedback and comments on this draft guideline. Interested parties can submit their comments to [email protected] using the "SAHPRA Form: Guideline Comments" by 08-Jun-2023.?

https://www.sahpra.org.za/documents-for-comments/