CDER International Program

Contents:

• CDER International Program
• International Regulatory Harmonization
• International Agreements & Information Sharing
• Partnerships and Collaborations
• Resources for Foreign Pharmaceutical Regulatory Authorities

 

 

Mission and Purpose

The Center for Drug Evaluation and Research (CDER) has a mission to ensure the availability of safe and effective medicines to improve public health in the United States. Recognizing that pharmaceutical development, manufacturing, and marketing are a global enterprise, with a number of CDER-regulated products manufactured abroad. International harmonization of regulatory standards and convergence of practice have become essential. The CDER International Program facilitates engagement with pharmaceutical regulatory counterparts, global pharmaceutical companies, and other organizations, often through multilateral efforts, to achieve the mission. The CDER International Program represents FDA in international forums and leads and coordinates bilateral and multilateral collaborations.

Regulatory Harmonization

CDER works with international regulatory and industry counterparts to harmonize scientific and technical standards, and regulatory requirements across different global regions. This work is primarily conducted through the International Council on Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). This regulatory harmonization improves efficiency in drug development and manufacturing, minimizes unnecessary animal studies, and reduces duplication in clinical studies needed to meet regulatory requirements for marketing in different regions of the world. Regulatory harmonization is also advanced through the regulators-only information sharing and project work conducted by the International Pharmaceutical Regulators Programme (IPRP), and the strategic information sharing in emerging areas, and collaboration and convergence efforts advanced through the International Coalition of Medicines Regulatory Authorities (ICMRA).

Information Sharing

CDER also engages closely with foreign regulatory counterparts to share information on regulatory best practices, scientific advances, and emerging public health threats. This work is accomplished through CDER’s engagement in various international venues, including ICMRA, ICH, and IPRP, and through bilateral and other multilateral engagements coordinated by the CDER International Program.

Program Structure

CDER’s International Program is led by the Associate Director for Strategic Initiatives, with staff in CDER’s Office of the Center Director.

Contact Information:

• Theresa Mullin, PhD
  Associate Director for Strategic Initiatives
• William Lewallen, BA, FAC-P/PM 
  International Program Analyst
• Brooke Dal Santo, MSPH 
  Public Health Analyst/ICH Coordinator
• Tisha Washington 
  Project Specialist

For more information contact: CDERINTLEXEC@fda.hhs.gov

International Regulatory Harmonization

Regulatory harmonization is the process where regulatory authorities align technical requirements for the development and marketing of pharmaceutical products. Harmonization of regulatory requirements has many benefits such as ensuring favorable marketing conditions to accelerate patient access to new medicines, promoting market competition and drug development efficiency, and reducing unnecessary duplication of clinical testing.

FDA engages with international stakeholders to address the increasingly complex and global nature of pharmaceutical operations and regulatory oversight. This work is accomplished through FDA’s involvement in several international organizations including the International Council for Harmonisation (ICH), International Coalition of Medicines Regulatory Authorities (ICMRA), International Pharmaceutical Regulators Programme (IPRP), the Pharmaceutical Inspection Co-operation Scheme (PIC/S), and Asia-Pacific Economic Cooperation (APEC).

International Council for Harmonisation

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an international nonprofit association that brings regulatory authorities and pharmaceutical industry together to harmonize scientific and technical aspects of drug registration. ICH's mission is to achieve greater harmonization to ensure that safe, effective, and high-quality medicines are developed and registered in the most resource-efficient manner. This work is accomplished through the development of internationally harmonized guidelines in the areas of Safety,Efficacy, Quality, and Multidisciplinary topics. International harmonization contributes to:

• streamlining regulatory review processes,
• accelerating patient access to new medicines,
• reducing patient burden by preventing the unnecessary duplication of clinical trials and post market clinical evaluations,
• reducing unnecessary animal testing without compromising safety and effectiveness.

FDA has participated in ICH as a Founding Member since 1990 and implements all ICH Guidelines as FDA Guidance. FDA encourages implementation of ICH Guidelines by pharmaceutical regulatory authorities globally.

International Coalition of Medicine Regulatory Authorities (ICMRA)

ICMRA is an executive-level forum of medicines regulatory authorities that works to:

• Provide strategic coordination, advocacy, and leadership
• Address current and emerging human medicine regulatory and safety challenges globally
• Provide direction for areas and activities common to many regulatory authorities' missions
• Identify areas for potential synergies

CDER participates in ICMRA and supports its strategic initiatives including on pharmaceutical quality knowledge management (PQKM), reducing animal testing, pharmacovigilance, supply chain integrity, innovation, crisis management, and regulatory communication and information sharing.

International Pharmaceutical Regulators Programme (IPRP)

The International Pharmaceutical Regulators Programme (IPRP) was established on January 1st, 2018 as a result of the consolidation of the International Pharmaceutical Regulators Forum (IPRF) and the International Generic Drug Regulators Programme (IGDRP). The membership of IPRP is comprised of representatives from pharmaceutical regulatory authorities and organizations. IPRP establishes a forum for its members and observers to exchange information on issues related to regulation of pharmaceutical medicinal products for human use and to promote regulatory convergence. IPRP provides a multilateral forum for FDA to engage with other pharmaceutical regulatory authorities to:

• address the increasingly complex global nature of pharmaceutical regulation,
• advance regulatory harmonization projects,
• promote regulatory best practices,
• better understand opportunities that may exist for international harmonization under other venues such as ICH.

Pharmaceutical Inspection Co-operation Scheme (PIC/S)

The Pharmaceutical Inspection Co-operation Scheme (PIC/S) is a non-binding, informal co-operative arrangement between regulatory authorities in the field of Good Manufacturing Practice (GMP) of medicinal products for human or veterinary use. It is open to any authority having a comparable GMP inspection system. PIC/S aims at harmonizing inspection procedures worldwide by developing common standards in the field of GMP and by providing training opportunities to inspectors.

PIC/S also aims at facilitating co-operation and networking between competent authorities, regional and international organizations, thus increasing mutual confidence. This is reflected in PIC/S’ mission which is to lead the international development, implementation, and maintenance of harmonized GMP standards and quality systems of inspectorates in the field of medicinal products. This is to be achieved by developing and promoting harmonized GMP standards and guidance documents; training competent authorities, in particular inspectors; assessing (and reassessing) inspectorates and facilitating the co-operation and networking for competent authorities and international organizations.

FDA became a Member of PIC/S in 2011, serves on the PIC/S Steering Committee and provides leadership and technical contributions in many of the PIC/S Work Groups and Expert Circles.

Asia-Pacific Economic Cooperation (APEC)

APEC is a regional economic forum established in 1989 to leverage the growing interdependence of the Asia-Pacific region. APEC's 21 member economies aim to create greater prosperity for the people of the region by promoting balanced, inclusive, sustainable, innovative and secure growth and by accelerating regional economic integration.

FDA participates in the Regulatory Harmonization Steering Committee (RHSC) under the auspices of APEC’s Life Sciences Innovation Forum (LSIF). The RHSC focuses on developing tools and delivering training on drug regulatory best practices and internationally harmonized guidelines such those developed by ICH and the World Health Organization (WHO). The RHSC's objective is to enable regulatory authorities in the APEC regions and beyond to implement regulatory best practices and increase regulatory harmonization, improving drug product safety and quality globally.

The APEC RHSC currently conducts work in six priority areas including:

• Multi Regional Clinical Trails and Good Clinical Practices Inspections
• Pharmacovigilance & Medical Device Vigilance
• Biotechnological Products
• Cellular Therapies
• Good Registration Management
• Global Supply Chain Integrity

In addition, the RHSC has established APEC Training Centers of Excellence for Regulatory Science (COEs) to promote regulatory convergence, capacity, and cooperation in topic areas relevant to medical product regulation. The COEs are located in various APEC regions and develop and provide training programs based on internationally harmonized standards where the RHSC provides input on core content and training objectives. The COE model is intended to be self-sustaining.

International Agreements & Information Sharing

The Food and Drug Administration (FDA) fosters partnerships with counterpart foreign government agencies and international organizations. The tools that FDA uses to set up and memorialize these partnerships include two categories of onal Arrangements: Cooperative Arrangements (which include Memoranda of Understanding and similar documents) and Confidentiality Commitments.

A Cooperative Arrangement is a written understanding that FDA can establish with one or more foreign governments or international partners that describes the willingness and good-faith intentions of FDA and its counterpart(s) to engage in activities. Even with a Cooperative Arrangement in place, the FDA cannot share non-public information unless a Confidentiality Commitment exists. Cooperative Arrangements allow for FDA to engage with foreign regulators on various emerging regulatory topics to advance public health interests.

A Confidentiality Commitment (CC) is a document that establishes a legal framework for FDA to share certain kinds of non-public information with FDA counterparts in foreign countries and international organizations as part of cooperative law enforcement or regulatory activities. A CC must be in place before FDA can share non-public information with a counterpart, but a CC never requires FDA (or its counterpart) to share information. The ability to share certain types of information with foreign pharmaceutical regulatory authorities, allows CDER to collaborate in addressing potential public health concerns, offer better regulatory guidance in its review activities, and improves the Agency’s ability to perform its role in providing regulatory oversight. CDER shares non-public information with foreign counterparts in reliance of confidentiality commitment through many mechanisms including through clusters, and working groups, in response to counterpart requests or CDER’s own proactive information sharing with foreign counterparts and other channels for information sharing.

All “non-public” information must be shared following procedures outlined in Staff Manual Guide 2830.3 and in compliance with CDER-specific procedures. Please contact: William.Lewallen@fda.hhs.gov and CDERINTLEXEC@fda.hhs.gov for international regulatory inquiries.

Clusters

FDA engages with foreign pharmaceutical regulatory authorities on a bilateral and multi-lateral basis to work together on special topics and therapeutic areas identified as requiring an intensified exchange of information and collaboration through its clusters. A list of current ongoing clusters in which FDA participates is provided in the following table.

Center for Drug Evaluation and Research Ongoing Clusters
Type of cluster	Cluster Objective	Regulatory Participants
Advanced-therapy medicinal products (ATMP)	This cluster develops a common understanding of each agency's regulatory approaches for advanced-therapy medicinal products, including gene therapies, cell therapies, and tissue-engineered products. Documents exchanged include scientific advice, ATMP classification reports, and assessment reports of marketing-authorization applications from EMA, as well as Investigational New Drug (IND), pre-IND, and pre-biologics-license-application meeting minutes from FDA. Both agencies share draft and finalized guidelines to promote regulatory alignment and scientific consistency in ATMP evaluation.	EMA FDA Health Canada PMDA/MHLW Swissmedic
Anti-infectives	This cluster shares scientific evaluation approaches and regulatory strategies for antibacterial and antifungal drug development to enhance understanding and coordination across global regulatory bodies. The forum addresses dose selection methodologies, trial endpoint selection, patient population identification, and opportunities for regulatory flexibility including approval pathways supported by alternative study designs and novel endpoints. The cluster provides confidential exchange of draft documents, policies in development, and detailed scientific rationale supporting regulatory decisions, with product-specific discussions focusing on challenging development programs, including programs for the treatment or prevention of infections due to antimicrobial resistant pathogens.	EMA FDA HC PMDA/MHLW
Antivirals	This cluster facilitates the sharing of information and best practices on the application of artificial intelligence technologies in pharmacovigilance activities. The forum enables exchange of policy approaches, tool implementation strategies, ongoing research projects, and communications from regulated industry regarding AI applications in drug safety monitoring. Discussions include machine learning algorithms for signal detection, natural language processing for adverse event reporting, and automated data analysis tools for safety surveillance.	EMA FDA
Artificial Intelligence (AI) in Pharmacovigilance	This cluster facilitates the sharing of information and best practices on the application of artificial intelligence technologies in pharmacovigilance activities. The forum enables exchange of policy approaches, tool implementation strategies, ongoing research projects, and communications from regulated industry regarding AI applications in drug safety monitoring. Discussions include machine learning algorithms for signal detection, natural language processing for adverse event reporting, and automated data analysis tools for safety surveillance.	EMA FDA HC (Observer) PMDA/MHLW (Observer)
Bioequivalence Collaboration	This cluster streamlines information sharing on bioequivalence study inspections and enhances collaborative oversight of new and generic drug applications. The forum coordinates sharing of inspection information for bioequivalence studies conducted and planned for new and generic drug applications, covering both clinical and analytical facilities. Activities include site, study and product-specific discussions, collaborative work-sharing arrangements, and harmonization of inspection standards and practices.	EMA FDA HC MHRA
Biosimilars	This cluster achieves common understanding of scientific and regulatory approaches to biosimilar development and promotes alignment in data expectations. The forum provides discussion of general and product/class-related scientific review issues based on internal policies, guidance documents, and regulations and research activities. The confidential forum enables exchange of draft documents, policies in development, and detailed scientific rationale supporting regulatory decisions, with discussions focusing on analytical comparability, clinical development strategies, and other biosimilar-related topics.	EMA FDA HC PMDA/MHLW
Biostatistics	This cluster shares statistical methodologies and approaches for drug development and safety evaluation to enhance regulatory decision-making. The forum exchanges information on statistical methods for clinical trial design, data analysis approaches, and safety signal detection. Topics include adaptive trial designs, Bayesian methods, real-world evidence analysis, and statistical considerations for rare diseases and pediatric populations.	EMA FDA PMDA/MHLW
Cardiovascular	This cluster shares scientific evaluation approaches for cardiovascular drug development to inform regulatory decision-making. The forum addresses various aspects of cardiovascular drug development including trial design, endpoint selection, safety evaluation, and post-marketing surveillance. Discussions cover both product-specific evaluations and broader policy considerations for cardiovascular risk assessment and management strategies.	EMA FDA Swissmedic
Drug Shortages	The Drug Shortages Global Regulatory Working Group is an international forum of medicine regulators and the World Health Organization, established to share information about medicines' shortages with a global impact and the actions taken by each jurisdiction to prevent, mitigate, and monitor the impact of these shortages. In addition, relevant policy measures and best practices to address shortages are discussed.	EMA FDA HC MHLW MHRA/DHSC TGA WHO (observ
Generic Drug Cluster	This cluster establishes global regulatory coordination for generic drug development with emphasis on complex generic products and international harmonization. The forum serves as the primary venue for international regulators to address generic drug development globally, focusing on complex generic drug products and sharing current thinking through guidance documents. The cluster facilitates discussion of general and product/class-related scientific review issues while fostering alignment in evaluation approaches, and addresses long-term safety issues through confidential sharing of safety reports to ensure a comprehensive global safety network.	EMA FDA Health Canada Israel Ministry of Health MHRA SwissMedic TGA
Good Clinical Practice (GCP) Initiative	This cluster enhances global coordination of GCP oversight through information exchange and collaborative inspection activities. The forum conducts periodic information exchanges on GCP-related matters, coordinates collaborative GCP inspections, and shares interpretations of GCP requirements. Activities include work-sharing arrangements, harmonization of inspection practices, and development of common approaches to GCP compliance assessment.	EMA FDA PMDA/MHLW
Kidney Disease	This cluster shares regulatory and scientific information regarding drug development, evaluation, and monitoring for kidney disease treatments. The forum exchanges information on clinical trial design for nephrology products, endpoint selection, patient population considerations, and post-marketing surveillance strategies.	EMA FDA
Non-clinical Oncology	This cluster examines nonclinical topics related to review of oncology products for regulatory submissions with the goal of understanding divergent recommendations related to certain safety signals, and bringing consistency across regions, as appropriate. The forum discusses respective agency's guideline recommendations in oncology and exchanges data and publications of common interest. Activities include sharing non-clinical evaluation approaches for oncology products, harmonizing safety assessment methodologies, and coordinating regulatory guidance development to ensure consistent scientific standards across agencies for nonclinical development of anticancer products.	EMA FDA
Oncology-hematology medicinal products	This cluster shares clinical review information and coordinates scientific evaluation of cancer treatments with a focus on clinical and statistical considerations. The forum addresses marketing-authorization applications under review and pre-submission activities, with emphasis on clinical trial design, endpoints, statistical methodologies, and safety evaluation. Discussions could also include identification of safety issues in clinical development, confirmatory trial requirements, and post-marketing surveillance strategies for oncology products.	EMA FDA HC PMDA/MHLW Swissmedic TGA
Pharmacometrics / Modelling and simulation	This cluster exchanges information and perspectives on pharmacometrics approaches to support drug development and regulatory decision-making. The forum shares guidelines, workshop outcomes, publications, and experiences with products under parallel assessment. Discussions include population pharmacokinetic/pharmacodynamic modeling, model-informed drug development, quantitative systems pharmacology, and regulatory applications of modeling and simulation across therapeutic areas.	EMA FDA HC PMDA/MHLW TGA
Pharmacovigilance	Share information on drug safety issues, providing advance notice of anticipated regulatory action, public information and communication prior to decision-making and publication. Focuses on product-related risk assessments especially emerging safety concerns, policies, guidance documents and regulations are typically exchanged during the cluster meetings.	EMA FDA HC PMDA/MHLW
Pregnancy & Lactation	This cluster fosters consistent global approaches to ensure evidence-based safe and effective use of medicines and vaccines during pregnancy and lactation. The forum addresses product-specific safety considerations, regulatory alignment on pregnancy and lactation labeling, and development of evidence generation strategies. Discussions include clinical trial design considerations, post-marketing surveillance approaches, and risk communication strategies for healthcare providers and patients.	EMA FDA MHRA
Rare Diseases	This cluster exchanges information on development and scientific evaluation of medicines for rare diseases, addressing unique methodological and regulatory challenges. Key discussion areas include clinical trial design for small populations, evidence generation strategies, risk management for long-term safety monitoring, and post-marketing study approaches. The cluster emphasizes regulatory flexibility, innovative trial designs, and evidence standards tailored to rare disease contexts.	EMA FDA HC
Real-World Evidence (RWE)	The primary goal of the cluster on Real World Data (RWD) is to support regulatory decision-making through information sharing and the development of new approaches for the assessment of evidence derived from RWD or other big data sources. The collaboration seeks to foster a consistency of approach across regulatory jurisdictions, aim to resolve common challenges, leverage data, network and expertise resources available to the organizations and facilitate advances in regulatory science.	EMA FDA HC

Partnerships and Collaborations

President’s Emergency Plan for AIDS Relief (PEPFAR)

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) is the U.S. Government’s response to save the lives of those suffering from HIV/AIDS around the world. PEPFAR partially reimburses FDA’s Center for Drug Evaluation and Research (CDER) to review marketing applications for antiretrovirals (ARVs) to treat and prevent HIV/AIDS that are intended to be marketed outside of the United States. The Program has had a tremendous positive impact on the quality of life and life expectancy of people living with HIV/AIDS in the developing world by increasing the availability of quality assured ARVs to combat HIV/AIDS globally. FDA’s Tentative Approval/Approval Program along with the expedited review process has either tentatively approved or approved over 250 new and abbreviated drug applications (containing ARV products) for procurement by PEPFAR and the Global Fund to Fight AIDS, Tuberculosis, and Malaria (the Global Fund).

>PEPFAR only procures ARVs that have been granted tentative approval or approval by FDA/CDER to be distributed outside the United States.

>The CDER International Program is the point of contact for CDER and coordinates with FDA’s Office of Global Policy and Strategy (OGPS), HHS, and the US Department of State on PEPFAR efforts and outreach activities.

• FDA PEPFAR Database

Resources for Foreign Pharmaceutical Regulatory Authorities

FDA Overview

• Overview of FDA Review Process for Investigational New Drugs
• Overview of FDA’s Regulatory Review and Research Activities

FDA Review Processes

• Good Review Management Principles and Practices for New Drug Applications and Biologics License Applications
• Biosimilar Biological Products
• Abbreviated New Drugs

Technical Standards

• Electronic Common Technical Document
• Electronic Transmission of Individual Case Safety Reports Implementation Guide (E2B(R3))

Searchable database for FDA Guidance documents:

• Search for FDA Guidance Documents

External Resources

• Training for ICH Guidelines

For more information contact: CDERINTLEXEC@fda.hhs.gov