Presentation at the Center for Professional Advancement (CFPA) Course on Generic Drug Approval, August 2013. New Brunswick, NJ., with a focus on how biosimilars are regulated
This document provides an overview of biosimilars and their regulatory framework. It begins with definitions of biologics and biosimilars. Biosimilars are highly similar versions of approved biologics whose patents have expired. The development of biosimilars is unique compared to small molecule generics due to the complex nature of biologics. The document then discusses issues with biosimilars including potential efficacy, safety and substitution concerns. Finally, it provides details on the regulatory frameworks and guidelines established by organizations like WHO, EU, US and India to help facilitate the development and approval of biosimilars.
Drug Types: Biosimilars, generics and more. December 2017 Webinar 12122017Fight Colorectal Cancer
This document provides information about an upcoming webinar on drug types including biosimilars and generics. It outlines details like the speaker, how to ask questions during the webinar, and instructions for accessing the webinar archive and following along on Twitter. It also provides brief bios of the speaker and gives technical instructions for participating in the webinar platform. Finally, it lists some resources and includes a standard disclaimer.
This document summarizes information about biosimilars and the regulatory pathways for their approval in the United States and European Union. It discusses how biosimilars differ from traditional small-molecule generics due to biological molecules' larger size, greater complexity, and manufacturing dependence. The U.S. passed the Biologics Price Competition and Innovation Act in 2010 to create an approval pathway for follow-on biologics, requiring biosimilarity demonstration and possible interchangeability labeling. Upcoming FDA hearings will provide information to guide biosimilar approval requirements regarding analytical and clinical data needs. The E.U. has approved several biosimilars under its regulatory framework established in 2005.
This document discusses biosimilars, which are biologic drugs developed after the patents expire on innovator biologics. It provides background on biologics and biosimilars, describing their complex structures and manufacturing processes. The document outlines global guidelines for biosimilars from organizations like the WHO and regulatory frameworks in regions like Europe. It also examines trends driving biosimilar growth and challenges in developing biosimilars, such as structural variability between products and potential immunogenicity.
Update on U.S. Regulation of BiosimilarsMichael Swit
This document summarizes key issues regarding U.S. regulation of biosimilars, including the filing of the first biosimilar applications, requirements for demonstrating interchangeability, state substitution laws, challenges around naming conventions, and arguments on both sides of the naming debate. Industry is pursuing clinical trial designs aimed at demonstrating interchangeability, while FDA guidance is pending and naming remains controversial with pros arguing it ensures traceability and cons arguing it reduces biosimilar uptake.
Biosimilars are biotherapeutic products that are similar to already approved reference biologics in terms of quality, safety and efficacy. They are developed to be highly similar but not identical to existing biologics. Regulatory agencies like EMA and FDA require extensive analytical, non-clinical and clinical studies including pharmacokinetic, immunogenicity and clinical efficacy trials to establish biosimilarity. While biosimilars could increase access and lower costs, issues related to efficacy, safety, substitution and labeling need to be addressed to ensure patient safety and appropriate use.
This document provides an overview of biosimilars and their regulatory framework. It begins with definitions of biologics and biosimilars. Biosimilars are highly similar versions of approved biologics whose patents have expired. The development of biosimilars is unique compared to small molecule generics due to the complex nature of biologics. The document then discusses issues with biosimilars including potential efficacy, safety and substitution concerns. Finally, it provides details on the regulatory frameworks and guidelines established by organizations like WHO, EU, US and India to help facilitate the development and approval of biosimilars.
Drug Types: Biosimilars, generics and more. December 2017 Webinar 12122017Fight Colorectal Cancer
This document provides information about an upcoming webinar on drug types including biosimilars and generics. It outlines details like the speaker, how to ask questions during the webinar, and instructions for accessing the webinar archive and following along on Twitter. It also provides brief bios of the speaker and gives technical instructions for participating in the webinar platform. Finally, it lists some resources and includes a standard disclaimer.
This document summarizes information about biosimilars and the regulatory pathways for their approval in the United States and European Union. It discusses how biosimilars differ from traditional small-molecule generics due to biological molecules' larger size, greater complexity, and manufacturing dependence. The U.S. passed the Biologics Price Competition and Innovation Act in 2010 to create an approval pathway for follow-on biologics, requiring biosimilarity demonstration and possible interchangeability labeling. Upcoming FDA hearings will provide information to guide biosimilar approval requirements regarding analytical and clinical data needs. The E.U. has approved several biosimilars under its regulatory framework established in 2005.
This document discusses biosimilars, which are biologic drugs developed after the patents expire on innovator biologics. It provides background on biologics and biosimilars, describing their complex structures and manufacturing processes. The document outlines global guidelines for biosimilars from organizations like the WHO and regulatory frameworks in regions like Europe. It also examines trends driving biosimilar growth and challenges in developing biosimilars, such as structural variability between products and potential immunogenicity.
Update on U.S. Regulation of BiosimilarsMichael Swit
This document summarizes key issues regarding U.S. regulation of biosimilars, including the filing of the first biosimilar applications, requirements for demonstrating interchangeability, state substitution laws, challenges around naming conventions, and arguments on both sides of the naming debate. Industry is pursuing clinical trial designs aimed at demonstrating interchangeability, while FDA guidance is pending and naming remains controversial with pros arguing it ensures traceability and cons arguing it reduces biosimilar uptake.
Biosimilars are biotherapeutic products that are similar to already approved reference biologics in terms of quality, safety and efficacy. They are developed to be highly similar but not identical to existing biologics. Regulatory agencies like EMA and FDA require extensive analytical, non-clinical and clinical studies including pharmacokinetic, immunogenicity and clinical efficacy trials to establish biosimilarity. While biosimilars could increase access and lower costs, issues related to efficacy, safety, substitution and labeling need to be addressed to ensure patient safety and appropriate use.
This document provides an overview of biosimilars including their advantages and disadvantages. It discusses regulatory guidelines for biosimilar approval in India, challenges in biosimilar development and production, and recently approved biosimilars. The conclusion recognizes biosimilars as an important part of the pharmaceutical ecosystem but one that faces barriers to adoption such as questions of interchangeability and not having approval for all reference product indications. It recommends overcoming challenges to biosimilar market access.
This document discusses biosimilars, which are biologic products that are highly similar to approved biologic reference products. It provides background on biosimilars, including their development process, advantages, limitations, and future outlook. The development process involves producing a cell line containing the gene for the desired protein, growing cells to produce the protein, purifying the protein, and preparing it for patient use. Biosimilars offer cost savings over biologics but have concerns around immunogenicity and long-term effects when switching between products. The global biosimilar market is expected to grow significantly as biologic patents expire and more companies develop biosimilar versions of treatments.
Biosimilars are protein drugs that are similar but not identical to existing biologic products whose patents have expired. They offer potential cost savings compared to innovator biologics but are more complex than traditional generics. Developing biosimilars requires extensive clinical testing to demonstrate similarity due to biologics' sensitivity to manufacturing processes. Regulatory approval pathways for biosimilars are more complex than for generics and involve demonstrating similarity rather than just bioequivalence.
This document summarizes the global regulatory landscape for biosimilars. It begins by defining biosimilars and biological drugs. It then discusses the guidelines established by various regulatory bodies including the EMA, FDA, WHO, and agencies in countries like Japan, Korea, Canada, China, and India. The guidelines generally require demonstrating biosimilarity to the reference product through comparative quality, nonclinical and clinical studies. The document also discusses business opportunities for biosimilars in emerging versus established markets and strategies used by originator companies to combat biosimilar competition. It concludes by noting concerns around interchangeability between biosimilars and reference products.
This document provides an overview of biosimilars including their definition, categories, development principles, and regulatory approval process. Biosimilars are biological products that are highly similar to an existing approved biologic reference product. They are developed through a stepwise comparative process to demonstrate similarity in terms of safety, purity and potency. Some key points covered include:
- Biosimilars are large protein therapeutics derived from living organisms unlike traditional small molecule drugs.
- They include categories like hormones, monoclonal antibodies, and recombinant proteins.
- Their development follows principles of extensive characterization studies comparing them to the reference product.
- In India, biosimilars require approval through the regulatory pathway overseen by authorities
This document discusses biologics and biosimilars. It begins by explaining that biologics are large protein molecules derived from living cells that are used to treat diseases. Examples include human growth hormone, insulin, and monoclonal antibodies. Biosimilars are similar but not generic versions of innovator biologic products. The document outlines key differences between biologics and small molecule drugs, challenges in developing biosimilar monoclonal antibodies, and regulatory guidelines for approving biosimilars from organizations like WHO. It also discusses benefits and concerns regarding the use of biosimilars.
Biosimilars are biopharmaceutical drugs that are similar to an existing approved biologic drug (the reference product). Biosimilars undergo a step-wise comparability exercise to demonstrate similarity in structure, function, safety and efficacy to the reference product. Regulatory agencies such as the FDA and EMA require extensive characterization, non-clinical and clinical studies to establish biosimilarity. Guidelines for approval of biosimilars have been established in regions such as Europe, US, Korea, Singapore and India to enable a pathway for approval of biosimilar versions of biologic drugs.
- Biosimilars are biologic medical products that are similar but not identical copies of original biologic drugs. They are developed when the patent expires on the original product.
- Regulatory agencies have stringent approval criteria for biosimilars to demonstrate similar quality, safety and efficacy as the reference product. Clinical trials must show comparable pharmacokinetics, pharmacodynamics and immunogenicity.
- While biosimilars increase access and lower costs, they are not generic copies and have unique safety profiles. Automatic substitution is not appropriate and unique nonproprietary names and labeling is required to facilitate pharmacovigilance.
This document discusses biosimilars and their regulation. It begins with a brief history of biotechnology and biopharmaceuticals. It then defines biosimilars as similar but not generic versions of biologic drugs whose patents have expired. The document outlines key differences between biosimilars and generic drugs, including their larger and more complex molecular structures. It also discusses concerns regarding biosimilar efficacy, safety, interchangeability, and pharmacovigilance. Finally, it provides an overview of regulatory frameworks for biosimilars in various regions like the EU, US, India, and WHO guidelines.
The document summarizes India's new guidelines for approval of biosimilar biologics. Some key points:
1) The guidelines define biosimilars as biological products claimed to be similar in safety, efficacy, and quality to an approved reference biologic.
2) Biosimilars are developed through analytical studies comparing properties to the reference product, which could reduce required clinical testing.
3) Clinical testing may include pharmacokinetic, pharmacodynamic, and safety/efficacy studies designed to establish comparability to the reference product. Post-market surveillance is also required.
4) The guidelines aim to balance regulatory standards with access to affordable biologics through a biosimilars pathway
This document discusses biosimilars and their regulation. It begins by defining biotechnology and biopharmaceuticals. Biosimilars are described as legally approved versions of biologic drugs that are similar but not identical to the original version. The document notes challenges in developing biosimilars due to the complex nature of biologics compared to traditional small molecule drugs. It also discusses concerns regarding efficacy, safety and interchangeability of biosimilars. Finally, it provides an overview of regulatory frameworks for biosimilars in the US, EU and India.
This document discusses the FDA's guidance on biosimilar interchangeability. It explains that a biosimilar designation means a product is highly similar to the reference product, while an interchangeable designation means a biosimilar can be substituted for the reference product without intervention from the healthcare provider who prescribed the reference product. To be deemed interchangeable, biosimilars must meet additional standards through dedicated switching studies. The document outlines expectations for such studies and notes that the FDA has not yet designated any biosimilars as interchangeable.
This document discusses biosimilars in India and the opportunities and challenges in the biosimilars industry in India. It defines biosimilars and provides an overview of the global and Indian biosimilars market and regulatory landscape. The key opportunities for India include providing affordable treatment options and commercial benefits from lower cost manufacturing. However, challenges include regulatory hurdles, concerns around quality and safety, high development costs, and physician reluctance to prescribe biosimilars.
Biogenerics – Evolving Risks and Opportunities_M Staples_Mar08m_a_staples
The document discusses the evolving risks and opportunities for biopharmaceutical, generic, and contract manufacturers related to biogenerics. A number of factors are converging to change the contribution of generics in the biological products segment, including high revenues potential for biogenerics, high costs of proprietary biologicals, expiration of patents on first biological products, clearer regulatory pathways for biosimilars, improved characterization of biologicals, and growing outsourcing to CROs and CMOs due to specialized manufacturing requirements. The regulatory pathways for approval of biogenerics in the US (505(b)(2) pathway) and EU (biosimilars pathway) are also covered.
Biosimilars are biologic medicines that are developed to be similar to existing approved biologic medicines known as reference medicines. Biosimilars must demonstrate similarity to the reference medicine in terms of quality, safety and efficacy through comprehensive testing and analysis. While biosimilars may provide reduced costs and increased access to biologic treatments, they are more complex than traditional small molecule drugs due to differences in size, structure, manufacturing processes, and potential for immunogenicity. Thorough evaluation and regulation is required to ensure biosimilars are interchangeable for the reference product without compromising patient safety.
Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings o...sstrumello
Inger Mollerup, Vice President of Novo Nordisk A/S, testified before the Government Oversight and Reform Committee about establishing a pathway for approval of follow-on biologics. She argued that any pathway must require clinical trials to demonstrate safety because even minor differences in biologics can have major health consequences, as shown through Novo Nordisk's experience. She also stated that traceability and unique names are important for pharmacovigilance, and that interchangeability is not supported by current science given potential immunogenicity differences between products.
This document discusses biosimilar medicines. It defines biosimilars as medicines similar to existing approved biopharmaceutical medicines. Biosimilars have similar quality, safety and efficacy profiles but are not identical. Their development and approval process is more complex than for generics due to the biological nature of biopharmaceuticals which are sensitive to manufacturing changes. Guidelines from the European Medicines Agency provide recommendations on demonstrating biosimilarity in terms of quality, non-clinical and clinical testing. Ensuring biosimilars are highly similar seeks to guarantee their safe substitution for biopharmaceuticals while increasing treatment access and lowering costs.
1) The document discusses the concept of biosimilars, including their definition as biological products that are similar but not identical to an approved biologic in terms of quality, safety and efficacy.
2) It provides an overview of the regulatory approval pathways for biosimilars in the European Union, United States, and India, which generally require demonstrating biosimilarity through comparative clinical and non-clinical studies.
3) The production of biologics is more complex than small molecule drugs due to biologics' larger size, more complex structures, instability, and potential microheterogeneity.
Presentation at the Biosimilars and Follow-On Biologics 2014 Americas Conference, sponsored by Paradigm Global Events, February 12, 2014. Presentation focused on:
•Interchangeability
•State Substitution Laws
•Naming
•Risk Evaluation & Mitigation Strategies (REMS) and Their Impact on Biosimilars
•Where FDA Stands on Biosimilars
FDA Regulatory Challenges for Biosimilars and CMOsMichael Swit
Presentation to webinar sponsored by FierceBiotech with a focus on:
* background behind creation of new law
* difference from chemical generic drug regulation
* details of new law
* challenges faced by new law
* interchangeability
Michael Swit presented at the RAPS Annual Conference in San Jose on October 25, 2010. He discussed the history of biologics regulation and the new pathway for biosimilars established by the Biologics Price Competition and Innovation Act of 2009. The new pathway allows for an abbreviated approval process for biosimilars but gives FDA flexibility in implementation. Biosimilars must show similarity to the reference product through analytical, animal, and clinical studies but may not need to repeat all studies. Interchangeability requires additional evidence and is not required for approval. FDA is seeking input on guidance and other implementation issues.
This document provides an overview of biosimilars including their advantages and disadvantages. It discusses regulatory guidelines for biosimilar approval in India, challenges in biosimilar development and production, and recently approved biosimilars. The conclusion recognizes biosimilars as an important part of the pharmaceutical ecosystem but one that faces barriers to adoption such as questions of interchangeability and not having approval for all reference product indications. It recommends overcoming challenges to biosimilar market access.
This document discusses biosimilars, which are biologic products that are highly similar to approved biologic reference products. It provides background on biosimilars, including their development process, advantages, limitations, and future outlook. The development process involves producing a cell line containing the gene for the desired protein, growing cells to produce the protein, purifying the protein, and preparing it for patient use. Biosimilars offer cost savings over biologics but have concerns around immunogenicity and long-term effects when switching between products. The global biosimilar market is expected to grow significantly as biologic patents expire and more companies develop biosimilar versions of treatments.
Biosimilars are protein drugs that are similar but not identical to existing biologic products whose patents have expired. They offer potential cost savings compared to innovator biologics but are more complex than traditional generics. Developing biosimilars requires extensive clinical testing to demonstrate similarity due to biologics' sensitivity to manufacturing processes. Regulatory approval pathways for biosimilars are more complex than for generics and involve demonstrating similarity rather than just bioequivalence.
This document summarizes the global regulatory landscape for biosimilars. It begins by defining biosimilars and biological drugs. It then discusses the guidelines established by various regulatory bodies including the EMA, FDA, WHO, and agencies in countries like Japan, Korea, Canada, China, and India. The guidelines generally require demonstrating biosimilarity to the reference product through comparative quality, nonclinical and clinical studies. The document also discusses business opportunities for biosimilars in emerging versus established markets and strategies used by originator companies to combat biosimilar competition. It concludes by noting concerns around interchangeability between biosimilars and reference products.
This document provides an overview of biosimilars including their definition, categories, development principles, and regulatory approval process. Biosimilars are biological products that are highly similar to an existing approved biologic reference product. They are developed through a stepwise comparative process to demonstrate similarity in terms of safety, purity and potency. Some key points covered include:
- Biosimilars are large protein therapeutics derived from living organisms unlike traditional small molecule drugs.
- They include categories like hormones, monoclonal antibodies, and recombinant proteins.
- Their development follows principles of extensive characterization studies comparing them to the reference product.
- In India, biosimilars require approval through the regulatory pathway overseen by authorities
This document discusses biologics and biosimilars. It begins by explaining that biologics are large protein molecules derived from living cells that are used to treat diseases. Examples include human growth hormone, insulin, and monoclonal antibodies. Biosimilars are similar but not generic versions of innovator biologic products. The document outlines key differences between biologics and small molecule drugs, challenges in developing biosimilar monoclonal antibodies, and regulatory guidelines for approving biosimilars from organizations like WHO. It also discusses benefits and concerns regarding the use of biosimilars.
Biosimilars are biopharmaceutical drugs that are similar to an existing approved biologic drug (the reference product). Biosimilars undergo a step-wise comparability exercise to demonstrate similarity in structure, function, safety and efficacy to the reference product. Regulatory agencies such as the FDA and EMA require extensive characterization, non-clinical and clinical studies to establish biosimilarity. Guidelines for approval of biosimilars have been established in regions such as Europe, US, Korea, Singapore and India to enable a pathway for approval of biosimilar versions of biologic drugs.
- Biosimilars are biologic medical products that are similar but not identical copies of original biologic drugs. They are developed when the patent expires on the original product.
- Regulatory agencies have stringent approval criteria for biosimilars to demonstrate similar quality, safety and efficacy as the reference product. Clinical trials must show comparable pharmacokinetics, pharmacodynamics and immunogenicity.
- While biosimilars increase access and lower costs, they are not generic copies and have unique safety profiles. Automatic substitution is not appropriate and unique nonproprietary names and labeling is required to facilitate pharmacovigilance.
This document discusses biosimilars and their regulation. It begins with a brief history of biotechnology and biopharmaceuticals. It then defines biosimilars as similar but not generic versions of biologic drugs whose patents have expired. The document outlines key differences between biosimilars and generic drugs, including their larger and more complex molecular structures. It also discusses concerns regarding biosimilar efficacy, safety, interchangeability, and pharmacovigilance. Finally, it provides an overview of regulatory frameworks for biosimilars in various regions like the EU, US, India, and WHO guidelines.
The document summarizes India's new guidelines for approval of biosimilar biologics. Some key points:
1) The guidelines define biosimilars as biological products claimed to be similar in safety, efficacy, and quality to an approved reference biologic.
2) Biosimilars are developed through analytical studies comparing properties to the reference product, which could reduce required clinical testing.
3) Clinical testing may include pharmacokinetic, pharmacodynamic, and safety/efficacy studies designed to establish comparability to the reference product. Post-market surveillance is also required.
4) The guidelines aim to balance regulatory standards with access to affordable biologics through a biosimilars pathway
This document discusses biosimilars and their regulation. It begins by defining biotechnology and biopharmaceuticals. Biosimilars are described as legally approved versions of biologic drugs that are similar but not identical to the original version. The document notes challenges in developing biosimilars due to the complex nature of biologics compared to traditional small molecule drugs. It also discusses concerns regarding efficacy, safety and interchangeability of biosimilars. Finally, it provides an overview of regulatory frameworks for biosimilars in the US, EU and India.
This document discusses the FDA's guidance on biosimilar interchangeability. It explains that a biosimilar designation means a product is highly similar to the reference product, while an interchangeable designation means a biosimilar can be substituted for the reference product without intervention from the healthcare provider who prescribed the reference product. To be deemed interchangeable, biosimilars must meet additional standards through dedicated switching studies. The document outlines expectations for such studies and notes that the FDA has not yet designated any biosimilars as interchangeable.
This document discusses biosimilars in India and the opportunities and challenges in the biosimilars industry in India. It defines biosimilars and provides an overview of the global and Indian biosimilars market and regulatory landscape. The key opportunities for India include providing affordable treatment options and commercial benefits from lower cost manufacturing. However, challenges include regulatory hurdles, concerns around quality and safety, high development costs, and physician reluctance to prescribe biosimilars.
Biogenerics – Evolving Risks and Opportunities_M Staples_Mar08m_a_staples
The document discusses the evolving risks and opportunities for biopharmaceutical, generic, and contract manufacturers related to biogenerics. A number of factors are converging to change the contribution of generics in the biological products segment, including high revenues potential for biogenerics, high costs of proprietary biologicals, expiration of patents on first biological products, clearer regulatory pathways for biosimilars, improved characterization of biologicals, and growing outsourcing to CROs and CMOs due to specialized manufacturing requirements. The regulatory pathways for approval of biogenerics in the US (505(b)(2) pathway) and EU (biosimilars pathway) are also covered.
Biosimilars are biologic medicines that are developed to be similar to existing approved biologic medicines known as reference medicines. Biosimilars must demonstrate similarity to the reference medicine in terms of quality, safety and efficacy through comprehensive testing and analysis. While biosimilars may provide reduced costs and increased access to biologic treatments, they are more complex than traditional small molecule drugs due to differences in size, structure, manufacturing processes, and potential for immunogenicity. Thorough evaluation and regulation is required to ensure biosimilars are interchangeable for the reference product without compromising patient safety.
Statement of Inger Mollerup, VP Novo Nordisk A/S for Congressional Hearings o...sstrumello
Inger Mollerup, Vice President of Novo Nordisk A/S, testified before the Government Oversight and Reform Committee about establishing a pathway for approval of follow-on biologics. She argued that any pathway must require clinical trials to demonstrate safety because even minor differences in biologics can have major health consequences, as shown through Novo Nordisk's experience. She also stated that traceability and unique names are important for pharmacovigilance, and that interchangeability is not supported by current science given potential immunogenicity differences between products.
This document discusses biosimilar medicines. It defines biosimilars as medicines similar to existing approved biopharmaceutical medicines. Biosimilars have similar quality, safety and efficacy profiles but are not identical. Their development and approval process is more complex than for generics due to the biological nature of biopharmaceuticals which are sensitive to manufacturing changes. Guidelines from the European Medicines Agency provide recommendations on demonstrating biosimilarity in terms of quality, non-clinical and clinical testing. Ensuring biosimilars are highly similar seeks to guarantee their safe substitution for biopharmaceuticals while increasing treatment access and lowering costs.
1) The document discusses the concept of biosimilars, including their definition as biological products that are similar but not identical to an approved biologic in terms of quality, safety and efficacy.
2) It provides an overview of the regulatory approval pathways for biosimilars in the European Union, United States, and India, which generally require demonstrating biosimilarity through comparative clinical and non-clinical studies.
3) The production of biologics is more complex than small molecule drugs due to biologics' larger size, more complex structures, instability, and potential microheterogeneity.
Presentation at the Biosimilars and Follow-On Biologics 2014 Americas Conference, sponsored by Paradigm Global Events, February 12, 2014. Presentation focused on:
•Interchangeability
•State Substitution Laws
•Naming
•Risk Evaluation & Mitigation Strategies (REMS) and Their Impact on Biosimilars
•Where FDA Stands on Biosimilars
FDA Regulatory Challenges for Biosimilars and CMOsMichael Swit
Presentation to webinar sponsored by FierceBiotech with a focus on:
* background behind creation of new law
* difference from chemical generic drug regulation
* details of new law
* challenges faced by new law
* interchangeability
Michael Swit presented at the RAPS Annual Conference in San Jose on October 25, 2010. He discussed the history of biologics regulation and the new pathway for biosimilars established by the Biologics Price Competition and Innovation Act of 2009. The new pathway allows for an abbreviated approval process for biosimilars but gives FDA flexibility in implementation. Biosimilars must show similarity to the reference product through analytical, animal, and clinical studies but may not need to repeat all studies. Interchangeability requires additional evidence and is not required for approval. FDA is seeking input on guidance and other implementation issues.
February 7, 2017
Many of today’s important medications are biological products made from living organisms, manufactured through biotechnology, derived from natural sources, or produced synthetically. Biosimilars are a type of biological product approved by FDA on the basis of being highly similar to an already approved biological reference product.
This panel of experts discussed the current state of biosimilars in the healthcare ecosystem and what comes next from a technical and legal perspective. Topics included how the next generation of biosimilars could improve patient access to standard-of-care therapies, the concept of “biobetters,” economic and intellectual property considerations, and policy approaches to support existing and future biosimilars.
Learn more on our website: http://petrieflom.law.harvard.edu/events/details/looking-forward
This document summarizes a presentation about FDA regulation of biosimilars. It discusses how biosimilars differ from traditional generics due to biologics being more complex molecules than small molecule drugs. It outlines the key provisions of the Biologics Price Competition and Innovation Act of 2009, including requirements for biosimilar applications such as analytical, animal and clinical studies demonstrating biosimilarity to the reference product. It also discusses requirements for interchangeability and other miscellaneous rules regarding biosimilar approval pathways.
ANDAs, OTCs, Orphans and Cosmetics – Key IssuesMichael Swit
August 7, 2013 lecture to RAC Test review course sponsored by San Diego Regulatory Affairs Network (SDRAN). Focused on:
♦ ANDAs and generic drug regulation
♦ OTC drug regulation
♦ Orphan drug regulation
♦ cosmetic regulation
ANDAs, OTCs, Orphans and Cosmetics – Key IssuesMichael Swit
June 24, 2015 lecture to RAC Test review course sponsored by San Diego Regulatory Affairs Network (SDRAN). Focus:
♦ ANDAs and generic drug regulation
♦ OTC drug regulation
♦ Orphan drug regulation
♦ Cosmetic Regulation
Us biosimilar guidance jim wei-june 2012 (3)Medpace
The document summarizes the key points of the FDA's 2012 guidance on biosimilars. It outlines the Biologics Price Competition and Innovation Act which created an approval pathway for biosimilar biological products. It describes the FDA's definitions and expectations for demonstrating biosimilarity through analytical, preclinical, and clinical studies comparing a proposed biosimilar to a reference product in a stepwise approach considering totality of evidence. The guidance addresses quality, scientific, and clinical considerations for biosimilar development and approval.
Biosimilars: Regulatory and Clinical ConsiderationsCovance
Other considerations for clinical studies are that the regulations are written with some flexibility, and although clinical studies have been required thus far, they are not mandated by the regulations. Perception from sponsors is that innovators make process changes all the time that impact structure and no clinical study is done because of good analytical characterization so why are biosimilars different? With solid analytical and functional data, we should continue to challenge regulators on the need for clinical studies.
FDA’s Draft Guidance on Biosimilar Product Development and Intellectual Prope...Patton Boggs LLP
The FDA released draft guidelines for biosimilar product development to help sponsors gain approval for biosimilar drugs under an abbreviated pathway. The guidelines recommend extensive data collection to demonstrate biosimilarity to the reference product using a totality of evidence approach. Sponsors should consider analytical factors like expression systems, properties, activities, and stability testing. Following these guidelines closely during development is important for positioning products for approval and reducing litigation risks with the reference product patent owner.
Regulatory & Quality Challenges of Combination ProductsMichael Swit
Overview of FDA regulation of combination products -- those featuring a drug and a device, a device and a biologic, or a biologic and a drug. Reviews key issues such as Primary Mode of Action, Requests for Designation, and how to handle GMPs and Adverse Event Reporting for combination products.
Biosimilar Drugs: Overview and Regulatory Issuesflasco_org
This document provides an overview of biosimilar drugs and regulatory issues from a presentation given by Phil Johnson. It defines biosimilars and the FDA approval pathways for biologics and biosimilars. The FDA process for demonstrating biosimilarity is described, focusing on analytical, functional, and clinical data requirements. Issues around naming, interchangeability, and state-level legislation regarding substitution are discussed. Finally, the potential financial impact of biosimilars on the healthcare system is noted given rising drug costs and the patent cliff facing many biologic drugs.
This document provides information on biosimilars and interchangeable biosimilars for health care providers. It defines key terms like reference product, biosimilar, and interchangeable. It describes the FDA approval pathways for biosimilars and generics. The FDA recommends a comparative analytical assessment and targeted clinical studies to demonstrate biosimilarity or interchangeability to a reference product. Clinical studies generally show biosimilars and interchangeable biosimilars are equivalent to their reference products in terms of safety, efficacy, and immunogenicity, including after switching. To date, the FDA has approved 4 interchangeable biosimilars.
“Principles of a Science-Based Regulatory Pathway for Biosimilar Products”
Provides an overview of the guiding principles for a science-based regulatory pathway for biosimilar products
The Future of BioSimilars, BioGenerics, Follow-On Biologics – A Rose by Any O...Michael Swit
The document discusses the future of biosimilars and how they differ from traditional generics. It notes that biosimilars are unlikely to achieve therapeutic equivalence due to structural complexity, making substitution and an abbreviated approval pathway difficult. Biosimilars will likely require clinical efficacy and safety trials like innovator drugs. Price discounts for biosimilars will likely be smaller than for generics, reducing incentives for utilization. Reimbursement and marketing will also present challenges without substitution. Overall, biosimilars represent a new business model compared to traditional generics.
Dialogue with Canada’s leading regulatory and assessment experts: Health Canada Bureau of Biologics and Genetic Therapies (BGTD) and Canadian Agency for Drugs and Technologies in Health (CADTH)
Date: June 29, 2016
Time: 1:00pm to 3:00pm EST
This document summarizes a presentation given by Michael Swit on FDA updates and trends. It discusses the impact of the 2012 election and upcoming FDASIA legislation. FDASIA makes changes to drug, device, and supply chain regulations. It aims to expedite drug development and approval for serious diseases. The presentation also covers FDA reorganizations and other regulatory trends.
Introduction to the Legal Basis for Generic Drug ApprovalsMichael Swit
Presentation at the Center for Professional Advancement (CFPA) Course on Generic Drug Approval, August 2013. New Brunswick, NJ., with a focus on how the 1984 Hatch-Waxman Act came to be enacted.
GMP Review -- Legal Letter from America Column -- How Data Integrity Issues S...Michael Swit
Article appearing in the October 2018 issue of GMP Review by Michael A. Swit explores how data integrity issues sunk a $4.3 billion acquisition of Akorn by Fresenius. Article stresses lessons not just for quality professionals, but also their top management.
FDA Regulation of Promotion & Advertising -- Part 8: Handling Promotional Com...Michael Swit
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Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices,
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Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 2, 2018, Boston.
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Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston
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Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston.
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Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston
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Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices,November 1-2, 2018, Boston
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Presentation to the Compliance Online 2-day course on Ensuring Compliance with FDA Requirements for the Promotion & Advertising of Drugs and Medical Devices, November 1-2, 2018, Boston.
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June 23, 2010 webinar sponsored by The Weinberg Group, with an emphasis on key issues to explore during due diligence in acquiring FDA-regulated products or companies.
Quality Considerations in Due Diligence for Pharmaceutical TransactionsMichael Swit
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2. www.duanemorris.com
What We Will Cover
• Contrasting the Past – How Small Molecule Generics
are Regulated and Early Attempts to Approve “Generic”
Biologics
• Biosimilars – Basic FDA Provisions of the Biologics
Price Competition & Innovation Act of 2009 (BPCIA)
– Patent provisions are not covered by today’s talk
• The Draft Guidances – What Hath FDA Wrought?
• Traps for the Unwary
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• Biologics approved under Public Health Services
Act – until 2010, no abbreviated pathway
– Precursor? -- Comparability Guidance, April 1996
• NDAs -- for few biologics (e.g., HGH, insulin) –
were approved
– No set criteria on appropriate data set to support approval
– Evaluated on a case-by-case basis
• Therapeutic Biologics – transferred from CBER to
CDER – June 2003
The Past
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Bioequivalence
• Lynchpin to traditional Waxman-Hatch generic
approval process – depends on:
– Pharmaceutical “equivalents” – active ingredient, dosage form,
strength, etc., must be SAME
– Highly unlikely with Biosimilars –
Characterization – still a challenge even for the innovators –
clinical trials may be needed to show comparability after process
changes
Chances of “equivalence” conclusions faint as even a single amino acid
can throw off conclusion (e.g., HGH)
Lovenox – only 70% characterized (but, is under an NDA and
approved under an ANDA in summer 2010)
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• Janet Woodcock, Director, Center for Drugs (before Congress,
March 2007):
– “there is general recognition that the idea of sameness, as the term
is used in the generic drug approval process under the Federal
Food, Drug, and Cosmetic (FD&C) Act and applied to small
molecules, will not usually be appropriate for more structurally
complex molecules of the type generally licensed as biological
products under the Public Health Service Act.”
Bioequivalence …
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Substitutability …
• Substitution -- core of classic Generic Industry Business
Model
– Depends on therapeutic equivalence
– Allows for minimal sales forces
– Drives pricing down -- multiple generics common – the generic
becomes a commodity
• Biosimilar world –
– Substitution – aka “interchangeability” -- may evolve, but on a very,
very limited basis
Woodcock – must be able to handle repeated brand/follow-in
switching without adverse events
Thus, business model will not be multiple generics & not a
commodity
– Without interchangeability, the Biosimilar IS a branded drug
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2006 – FDA Approves Omnitrope®
• A Biosimilar?
– approved as a 505(b)(2) NDA
– no interchangeability
– extensive data requirements – rumored to cost well into eight
figures, if not nine
• No floodgates because the NDA pathway was
limited to a handful of products
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• Biologics Price Competition & Innovation Act of 2009
(BPCIA)
– Creates an abbreviated pathway for “biosimilar” versions of
biologics, but gives FDA great flexibility/discretion in how it
implements statute
• Key features
– Abbreviated pathway created under the Public Health Service Act
(PHSA) by adding Subsection (k) to Section 351 of the PHSA
– Exclusivity – 12 years for new biologics
– Complex handling of patents
– FDA – flexibility granted in how it regulates biosimilars
What Hath Health Care Reform Spawned?
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• Must be biosimilar to Reference Product, by including:
– Analytical studies to show your product is Highly similar to the
Reference Product (RP) – i.e., the Biosimilar has no clinically
meaningful differences from the RP in terms of safety, purity and
potency, notwithstanding minor differences in clinically inactive
components; and
– Animal Studies – including toxicity studies; and
– “A clinical study or studies” -- including assessment of
immunogenicity and pharmacokinetics or pharmacodynamics
to show safe, pure and potent
in 1 (one) or more appropriate conditions of use for which the RP is
licensed and intended to be used
• FDA – can decide any of the above are unnecessary
What’s Required for a Biosimilar
Application?
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• Must use same mechanism(s) of action – if the MOA is
known for the RP
• Conditions of use in labeling -- have to be previously
approved for the RP
• Must match RP as to:
– Route of administration
– Dosage form
– Strength
• Facility in which manufactured, processed, packed or
held – must meet standards designed to assure the biosimilar
continues to be: Safe. Pure. Potent.
Required for a Biosimilar Application …
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• Not required – 351(k)(2)(B)
• To prove interchangeability – 351(k)(4)
– Drug must be biosimilar to RP
– BP “can be expected to produce the same clinical result” as the
RP “in any given patient”
– If BP is administered more than once to patient, the risk in
terms of safety or diminished efficacy of switching between the
BP and the RP is “not greater than the risk of using the RP”
without switching
How to study – multiple switch study
Interchangeability
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• Only One RP per BP application – 351(k)(5)(A)
• Reviewing division – same as handled the RP – 351(k)(5)(B)
• REMS authority under FDAAA -- applies to Biosimilars –
351(k)(5)(C)
• Biologics approved under Section 505 of Federal Food, Drug,
and Cosmetic Act as New Drug Applications (NDAs)
– Can still be filed as NDAs (indeed, must be until an “innovator” BLA is
approved)
– However, if there is a BLA-licensed biologic that you want to use as the
RP, the biosimilar application must be filed as a BLA
– Ten years after enactment – all NDAs for biologics are deemed approved
under Section 351 of PHSA
Miscellaneous Rules
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• Guidances
– Not required prior to approval of a biosimilar application
No biosimilar application yet approved; draft guidances published on
Thursday, February 9, 2012
– Regulations – also not mandated
– Product Class Specific Guidances
Can be issued
FDA – can issue one saying that the science is not sufficient to allow a
biosimilar application
Later can be reversed
Absence of such a guidance does not mandate that a biosimilar application
can be approved
• Pediatrics – all the rules and benefits under 2007 FDAAA for
both doing studies and pediatric exclusivity apply to biologics
Miscellaneous …
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• How will FDA implement BPCIA?
– Teva – announced it was pursuing full BLAs as of now –
– Leah Christl, Ph.D. – Acting Director in CDER for Biosimilars
• FDA – Public Meeting on Biosimilars
– Oct. 5, 2010 Federal Register – 75 Fed. Reg. 61497
– Nov. 2 & 3, 2010 in Maryland (were webcast)
Uncertainty … Was Rampant
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• Scientific and technical information on how to
implement the statute
• “Extra-statutory Issues”
– Pharmacovigilance
– Common or usual names
– Safeguards on unsafe substitution
– Bridging data needed when comparing a BP to an RP after
prior studies done on BP vs. a non-U.S. biologic (e.g., in EU)
The result ?? … the February 9, 2012 Draft Guidances …??
Input FDA Sought at Hearing
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Three Draft Guidances
• Biosimilars: Questions and Answers Regarding
Implementation of the Biologics Price Competition and
Innovation Act of 2009 -- “Q&A Guidance” or “Q&AG”
– http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM273001.pdf
• Scientific Considerations in Demonstrating Biosimilarity to a
Reference (Protein) Product – “Scientific Guidance” or “SG”
– http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM291128.pdf
• Quality Considerations in Demonstrating Biosimilarity to a
Reference Protein Product – “Quality Guidance” or “QG”
– http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM291134.pdf
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What Did FDA Clarify?
• Protein products – direct subject of new guidances, but
guidance does provide general advice for other biologics
subject to BPCIA
• Three Key Messages:
– Development process towards demonstrating biosimilarity -- should
be “stepwise”
– FDA’s evaluation will be on the “totality of the evidence”
– The more you can analytically compare the BP to the RP and the
closer the two products are in all key respects, the less you may need
to do to (a) show biosimilarity, and (b) secure approval.
“The more comprehensive and robust the comparative structural and
functional characteristics are, the stronger the scientific justification
for a selective and targeted approach to animal or clinical testing.”
See SG at 9.
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What Did FDA Clarify … ?
• Early interaction with FDA –
– expected – but don’t do so until you :
can provide a plan for development;
have manufacturing process information – including planned
methodology and assay validation; and
have preliminary comparative analytical data with the RP
– may need to be frequent due to the stepwise approach to
development contemplated
but no guidance on how often FDA will meet with you
• Biosimilarity – type and amount of data, analyses,
testing, etc., required will be determined on a product-
specific basis.
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The “Stepwise” Approach
1 – Extensive Structural and functional characterization
of RP and BP, including:
– Mechanism of Action (MOA)
– clinical relevance of any observed structural differences
– clinical knowledge of RP and its class shows overall safety risk
is low
– availability of clinically relevant PD measure
More you understand these, less you may need to do later
2 – Role of animal data in assessing toxicity, including
immunogenicity assessment.
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Stepwise Approach …
3 – Comparative human PK and PD studies (if a
clinically relevant PD measure exists)
4 – Comparative clinical immunogenicity studies
5 – Comparative clinical safety and effectiveness
studies
FDA – can waive certain requirements if “unnecessary in an
application” under 351(k)
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Clinical Studies
• Legal standard – “no clinically meaningful differences” between
the BP and RP “in terms of safety, purity and potency …” –
351(i)(2)(B) of PHSA; 21 USC 262(i)(2)(B)
• SG, at 12:
– In general, the clinical program for a 351(k) application must include a
clinical study or studies (including an assessment of immunogenicity and
PK or PD) sufficient to demonstrate safety, purity, and potency in one or
more appropriate conditions of use for which the reference product is
licensed and intended to be used and for which licensure is sought for the
biological product, as set forth in the PHS Act.
– The scope and magnitude of clinical studies will depend on the extent of
residual uncertainty about the biosimilarity of the two products after
conducting structural and functional characterization and possible animal
studies.
– The frequency and severity of safety risks and other safety and
effectiveness concerns for the reference product may also affect the design
of the clinical program.
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Clinical Studies …
• SG, at 16:
– As a scientific matter, comparative safety and effectiveness
data will be necessary to support a demonstration of
biosimilarity if there are residual uncertainties about the
biosimilarity of the two products based on structural and
functional characterization, animal testing, human PK and PD
data, and clinical immunogenicity assessment.
– A sponsor may provide a scientific justification if it believes
that some or all of these comparisons on clinical safety and
effectiveness are not necessary.
• Endpoints – can be different from sponsor’s own
clinicals if “scientifically justified” – SG at 18.
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CMC Considerations
• Quality Guidance – aimed at CMC considerations
• Key attributes to analyze to show similarity:
– Molecular weight
– Complexity of protein, including higher order structure and
post-translational modifications
– Degree of heterogeneity
– Functional properties
– Impurity profiles
– Degradation profiles denoting stability
• Different excipients – possible, but need tox data
(existing or new) to support use in formulation
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What Else Did FDA Clarify … ?
• Do not have to secure approval of all
“presentations” of the innovator’s product
• Foreign comparative data on non-U.S. licensed
innovator product – can be used:
– “bridging” data will be needed – likely a clinical PK and/or PD
study
– could allow you to use data from an EU approval where the
RP was “different from” the U.S. RP (e.g., different facility not
covered by U.S. BLA approval)
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What Else Did FDA Clarify … ?
• Interchangeability – not addressed in guidances in any
detail, except that FDA states that “it would be difficult”
to establish interchangeability in the initial 351(k)
application “given the statutory standard for
interchangeability and the sequential nature of that
assessment.” See Q&AG, at 11.
– Why? – not stated, but likely because the interchangeability
standard under 351(k)(4)(A)(ii) is that the BP “can be expected
to produce the same clinical result” as the RP “in any given
patient…”
but, FDA may not allow extrapolation of data to all indications
in first 351(k) application
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Traps for the Unwary
• Development Plans – highly variable and will require
considerable “stepwise” FDA input –
– licensing payments – may be difficult to structure or should be
tied to more interim milestones
– time lines – still unpredictable as path has not been used
Omnitrope® – took at least 7 years (after initial FDA filing)
• DMFs not allowed (QG) – sponsor must be able to
control manufacturing either directly or consistent with a
an arrangement contemplated by FDA’s 2008 guidance -
- Cooperative Manufacturing Arrangements for Licensed Biologics
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Traps for the Unwary …
• Biosimilar products – trigger pediatric study
requirements under PREA – Pediatric Research Equity
Act – regarded as a new active ingredient unless found to
be interchangeable
• Multiple indications under a single 351(k)
application – allowed, but will need to be justified
scientifically.
– SG did not clarify under what circumstances this might be
allowed, but did list key factors to address (see SG at 19-20)
– Key here – may be to select an indication that is most able to
be extrapolated across multiple indications
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Traps for the Unwary …
• Exclusivity – is retroactive, but there’s no “Orange
Book” to look up when it expires
– Can be extended via Pediatric Exclusivity
• Patent Process –
– very detailed; not same as Waxman-Hatch
– “opening the kimono”
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Uncertainty … Continues Still
• Abbott Citizen Petition – filed in April 2012 – argues
that retroactive application of BPCIA to already-approved
biologics is unconstitutional
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Small vs. Large Molecule Realities
• Small Molecule
– Therapeutically equivalent
Same molecule
– Substitutable
– Multiple generics of same
innovator are common
– Multiple generics drive price
down
– Insurance coverage follows
ANDA approval
– Marketing – cost sells; little need
for sales & marketing staff
– Legal Pathway – clear under
Waxman-Hatch Act – 505(j)
• Biosimilar
– Not therapeutically equivalent
Not same molecule
– Substitutable only if interchangeable
– Multiple biosimilars for same
innovator less likely
– Price difference to brand likely
smaller
– Separate coverage likely needed for
the Biosimilar
– Requires sales and marketing staffs
to drive utilization vs. “Brand”
– Legal Pathway – clear(er)
BPCIA – new Biosimilar App.
But can go full BLA
505(b)(2) – case-by-case -- for 10
yrs. under BPCIA
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