In the past decade, many guidance documents have been issued through collaboration of global orga... more In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts. At the 2014 American Association of Pharmaceutical Scientists (AAPS) annual meeting in San Diego, CA, Yan Wu (Merck) and Anita Freed (Pfizer) led a symposium entitled BBringing Drug Product Marketing Applications to Current Regulatory Standards: Trials and Tribulations.^This symposium was very timely as this topic is a growing industry concern, evidenced by over 300 attendees, and considering the new guidances (1-8) that have been established over the past decade. While most of these quality standards are applicable to new drug products, there is a risk that currently marketed products, known as legacy products, will not meet the new compliance standards during audits and inspections. Companies also need to continuously make process or method changes for in-line products as part of product life cycle management efforts or to meet different market needs. If legacy (or in-line) products undergo a change, the question is how much extra effort is needed to have these products meet current standards to support the associated submission. This symposium addressed these issues and offered modeling tools using existing data or other approaches and case studies to effectively manage post-approval changes. Presentations included the following: & Modeling historical data to support process and method stability changes & Food and Drug Administration (FDA) perspectives on application of International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q8 to legacy products
This chapter discusses International Conference of Harmonization (ICH) guidelines that are relate... more This chapter discusses International Conference of Harmonization (ICH) guidelines that are related to the Stability Sciences. It gives a brief history of how the Q1A was initiated. A summary of Q1A(R2) discusses thoroughly the current regulations that the industry supports and practices. While this handbook was being prepared, the FDA Stability Guidance was withdrawn; therefore, a brief discussion of the guidance status has been included. A discussion of mean kinetic temperature is included for a basis of understanding stability testing conditions.
An American Association of Pharmaceutical Scientists (AAPS) workshop on stability challenges for ... more An American Association of Pharmaceutical Scientists (AAPS) workshop on stability challenges for clinical supplies and commercial distribution of drug product that are not addressed in the International Conference on Harmonization (ICH) Quality documents was held from April 3rd-4th, 2017 in Rockville, MD. Seventeen subject matter experts (SME), from industry and the Food & Drug Administration (FDA) presented and facilitated the round-table discussions. A total of fifty-five participants that included experienced pharmaceutical scientists, both from small and large pharmaceutical companies and service providers, benefited from the opportunity to interact face-to-face with industry partners and regulatory agency SMEs. The two-day meeting was divided into five major sections to ensure face-to-face interactions and round-table discussions between participants and SMEs: 1) statistical approaches to stability, dissolution, and shelf life testing, 2) microbiological quality of drug products, 3) strategies to support distribution, unplanned excursions, and transportation of drug products, 4) regulatory considerations on stability testing of biologics, and 5) in-use stability during clinical and commercial phases. All in all, this interactive workshop focused on challenges and successes of addressing stability concerns that affect pharmaceutical development, manufacturing, distribution, and use of drug substances/products for which no or limited ICH guidance exists. The interactive meeting provided a unique opportunity to industrial scientists and regulatory agency liaisons to facilitate the discourse on how to address stability challenges that are not addressed in harmonized guidelines: this paper summarizes those discussions.
Brazil, the largest country in South America, has become the second largest pharmaceutical market... more Brazil, the largest country in South America, has become the second largest pharmaceutical market in the emerging world. The Brazillian Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria-ANVISA) was created in 1999 with the primary goal to protect and promote public health surveillance over products and services in Brazil. The governing body and structure of this new regulatory agency will be the aims of this paper, where the authors hope to share their understanding on the regulatory processes and its significant importance of this agency.
Abstract Qualification of analytical instruments has been a complex undertaking, not because the ... more Abstract Qualification of analytical instruments has been a complex undertaking, not because the process of qualifying instruments is complex, but because several opinions abound on how to perform a successful qualification. Recently, the United States Pharmacopeia issued General Chapter to provide guidance for Analytical Instrument Qualification (AIQ). The draft chapter has been published in Pharmacopeial Forum (latest in PF 32:6) and has gone through multiple cycles of public comments. The chapter is scheduled to become official in 2008 (USP 31). The purpose of this chapter is to provide general guidance for the qualification of analytical instrument establishing a common terminology and defining roles and responsibilities of those associated with an instrument’s qualification.
The Stability Community of the American Association of Pharmaceutical Scientists (AAPS) held a vi... more The Stability Community of the American Association of Pharmaceutical Scientists (AAPS) held a virtual workshop on "Vaccine Stability Considerations to Enable Rapid Development and Deployment", on March 24-25, 2021. The workshop included distinguished speakers and panelists from across the industry, academia, regulatory agencies, as well as health care leaders. This paper presents a review of the topics covered. Specifically the challenges in accelerating vaccine development and analytical characterization techniques to establish shelf-life were covered. Additionally, vaccine stability modeling using prior knowledge stability models and advanced kinetic analysis played a key in the EUA approaches discussed during the workshop. Finally, the role of stability studies in addressing the challenges of vaccine distribution and deployment during the pandemic were a focus of presentations and panel discussions. Although the workshop did not have any presentation topics directly dedicated to the mRNA vaccines, the techniques discussed are generally applicable. The mRNA vaccine developers were represented in the panel discussions, where experts involved in the EUA approval/deployment stages for this vaccine type could discuss the challenges as applied to their vaccines.
Combination products are therapeutic and diagnostic products that include two or more of the foll... more Combination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations (CFR) Part 4 was published to clarify the applicable GMP regulations when drugs, devices, or biological products are included. The FDA (U.S. Food and Drug Administration) released additional guidance in 2017 to streamline the regulatory framework and provide transparency about demonstrating GMP compliance when multiple regulatory standards overlap. This paper summarizes the Current Good Manufacturing Practice (CGMP) requirements for drug-device combination products (Biologic combinations are not discussed in this paper). Emphasis is placed on considerations for structuring a compliant drug-device stability program, including the use of bracketing and matrixing the test schedule to support the establishment of the product expiry date and how legacy products can be evaluated to meet current standards.
Combination products are therapeutic and diagnostic products that include two or more of the foll... more Combination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations (CFR) Part 4 was published to clarify the applicable GMP regulations when drugs, devices, or biological products are included. The FDA (U.S. Food and Drug Administration) released additional guidance in 2017 to streamline the regulatory framework and provide transparency about demonstrating GMP compliance when multiple regulatory standards overlap. This paper summarizes the Current Good Manufacturing Practice (CGMP) requirements for drug-device combination products (Biologic combinations are not discussed in this paper). Emphasis is placed on considerations for structuring a complian...
In the past decade, many guidance documents have been issued through collaboration of global orga... more In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts. At the 2014 American Association of Pharmaceutical Scientists (AAPS) annual meeting in San Diego, CA, Yan Wu (Merck) and Anita Freed (Pfizer) led a symposium entitled BBringing Drug Product Marketing Applications to Current Regulatory Standards: Trials and Tribulations.^This symposium was very timely as this topic is a growing industry concern, evidenced by over 300 attendees, and considering the new guidances (1-8) that have been established over the past decade. While most of these quality standards are applicable to new drug products, there is a risk that currently marketed products, known as legacy products, will not meet the new compliance standards during audits and inspections. Companies also need to continuously make process or method changes for in-line products as part of product life cycle management efforts or to meet different market needs. If legacy (or in-line) products undergo a change, the question is how much extra effort is needed to have these products meet current standards to support the associated submission. This symposium addressed these issues and offered modeling tools using existing data or other approaches and case studies to effectively manage post-approval changes. Presentations included the following: & Modeling historical data to support process and method stability changes & Food and Drug Administration (FDA) perspectives on application of International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q8 to legacy products
This chapter discusses International Conference of Harmonization (ICH) guidelines that are relate... more This chapter discusses International Conference of Harmonization (ICH) guidelines that are related to the Stability Sciences. It gives a brief history of how the Q1A was initiated. A summary of Q1A(R2) discusses thoroughly the current regulations that the industry supports and practices. While this handbook was being prepared, the FDA Stability Guidance was withdrawn; therefore, a brief discussion of the guidance status has been included. A discussion of mean kinetic temperature is included for a basis of understanding stability testing conditions.
An American Association of Pharmaceutical Scientists (AAPS) workshop on stability challenges for ... more An American Association of Pharmaceutical Scientists (AAPS) workshop on stability challenges for clinical supplies and commercial distribution of drug product that are not addressed in the International Conference on Harmonization (ICH) Quality documents was held from April 3rd-4th, 2017 in Rockville, MD. Seventeen subject matter experts (SME), from industry and the Food & Drug Administration (FDA) presented and facilitated the round-table discussions. A total of fifty-five participants that included experienced pharmaceutical scientists, both from small and large pharmaceutical companies and service providers, benefited from the opportunity to interact face-to-face with industry partners and regulatory agency SMEs. The two-day meeting was divided into five major sections to ensure face-to-face interactions and round-table discussions between participants and SMEs: 1) statistical approaches to stability, dissolution, and shelf life testing, 2) microbiological quality of drug products, 3) strategies to support distribution, unplanned excursions, and transportation of drug products, 4) regulatory considerations on stability testing of biologics, and 5) in-use stability during clinical and commercial phases. All in all, this interactive workshop focused on challenges and successes of addressing stability concerns that affect pharmaceutical development, manufacturing, distribution, and use of drug substances/products for which no or limited ICH guidance exists. The interactive meeting provided a unique opportunity to industrial scientists and regulatory agency liaisons to facilitate the discourse on how to address stability challenges that are not addressed in harmonized guidelines: this paper summarizes those discussions.
Brazil, the largest country in South America, has become the second largest pharmaceutical market... more Brazil, the largest country in South America, has become the second largest pharmaceutical market in the emerging world. The Brazillian Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria-ANVISA) was created in 1999 with the primary goal to protect and promote public health surveillance over products and services in Brazil. The governing body and structure of this new regulatory agency will be the aims of this paper, where the authors hope to share their understanding on the regulatory processes and its significant importance of this agency.
Abstract Qualification of analytical instruments has been a complex undertaking, not because the ... more Abstract Qualification of analytical instruments has been a complex undertaking, not because the process of qualifying instruments is complex, but because several opinions abound on how to perform a successful qualification. Recently, the United States Pharmacopeia issued General Chapter to provide guidance for Analytical Instrument Qualification (AIQ). The draft chapter has been published in Pharmacopeial Forum (latest in PF 32:6) and has gone through multiple cycles of public comments. The chapter is scheduled to become official in 2008 (USP 31). The purpose of this chapter is to provide general guidance for the qualification of analytical instrument establishing a common terminology and defining roles and responsibilities of those associated with an instrument’s qualification.
The Stability Community of the American Association of Pharmaceutical Scientists (AAPS) held a vi... more The Stability Community of the American Association of Pharmaceutical Scientists (AAPS) held a virtual workshop on "Vaccine Stability Considerations to Enable Rapid Development and Deployment", on March 24-25, 2021. The workshop included distinguished speakers and panelists from across the industry, academia, regulatory agencies, as well as health care leaders. This paper presents a review of the topics covered. Specifically the challenges in accelerating vaccine development and analytical characterization techniques to establish shelf-life were covered. Additionally, vaccine stability modeling using prior knowledge stability models and advanced kinetic analysis played a key in the EUA approaches discussed during the workshop. Finally, the role of stability studies in addressing the challenges of vaccine distribution and deployment during the pandemic were a focus of presentations and panel discussions. Although the workshop did not have any presentation topics directly dedicated to the mRNA vaccines, the techniques discussed are generally applicable. The mRNA vaccine developers were represented in the panel discussions, where experts involved in the EUA approval/deployment stages for this vaccine type could discuss the challenges as applied to their vaccines.
Combination products are therapeutic and diagnostic products that include two or more of the foll... more Combination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations (CFR) Part 4 was published to clarify the applicable GMP regulations when drugs, devices, or biological products are included. The FDA (U.S. Food and Drug Administration) released additional guidance in 2017 to streamline the regulatory framework and provide transparency about demonstrating GMP compliance when multiple regulatory standards overlap. This paper summarizes the Current Good Manufacturing Practice (CGMP) requirements for drug-device combination products (Biologic combinations are not discussed in this paper). Emphasis is placed on considerations for structuring a compliant drug-device stability program, including the use of bracketing and matrixing the test schedule to support the establishment of the product expiry date and how legacy products can be evaluated to meet current standards.
Combination products are therapeutic and diagnostic products that include two or more of the foll... more Combination products are therapeutic and diagnostic products that include two or more of the following: drug, biologic, and device. These products are needed for enhanced clinical outcomes and have more than one Mode of Action (MOA). Therefore, they require a more complex regulatory pathway and compliance with a minimum of two (2) sets of regulatory standards. In 2013, the 21 Code of Federal Regulations (CFR) Part 4 was published to clarify the applicable GMP regulations when drugs, devices, or biological products are included. The FDA (U.S. Food and Drug Administration) released additional guidance in 2017 to streamline the regulatory framework and provide transparency about demonstrating GMP compliance when multiple regulatory standards overlap. This paper summarizes the Current Good Manufacturing Practice (CGMP) requirements for drug-device combination products (Biologic combinations are not discussed in this paper). Emphasis is placed on considerations for structuring a complian...
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Papers by Kim Huynh-Ba