Biologics

Module 1

Biologics Drug Life-Cycle

This presentation is designed to provide an introduction to biologics including: historical perspectives, current approaches to biotherapeutic product development, and an overview of the value chain of biologic drug development.  Learners will gain an understanding of how the operational elements of biotechnology development and the interdependency of specialty skills are synchronized to maximize the probability of success.

Goals of the Presentation

The primary objectives of this lecture are to provide an introduction the Biologics product development course; review the history of biologics; introduce the principles of biotherapeutic product development, including use of a Target Product Profile; and highlight the interdisciplinary approach required to achieve successful development of biologics.

Learning Objectives

Following completion of this session the learner will be able to:

• Recognize the operational elements of biotherapeutic product development
• Describe key disciplines required to successfully develop a variety of biotechnology products
• List the principles common to development of various biotechnology products
• Discuss the rapid scientific evolution of biologics

Instructor: Edmund J. Elder, Jr., PhD, RPh, Director, Zeeh Pharmaceutical Experiment Station, University of Wisconsin-Madison, School of Pharmacy

Module 2

Therapeutic Areas of Biologics

The Therapeutic Areas of Biologics will provide an overview of the biologics in research and development, a summary of the therapeutic targets and some examples of specific mechanisms of activity.   The talk will also provide general scope of the varied biologics from monoclonal antibodies, to proteins, to cells and living tissues.  The talk will touch on some of the challenges of drug discovery and development with biologics and discuss some of the current trends in biologic’s drug development.

Learning Objectives

Following this lecture, the learner will be able to:

• List common therapeutic targets and pathways for biologics
• Explain why certain therapeutic targets are better suited for biologics than others
• Describe various biological therapeutics and their basic mechanism of action
• Discuss the primary challenges of biologic drug development.

Instructor: Bryan Glaser, PhD
Vice President of Research, Invenra

Module 3

Bioanalysis of Biologics using Ligand Binding Assay (LBA) Methodology

Today immunoassay methods, known generically as ligand binding assays (LBAs), comprise the principal technology for regulated bioanalysis of biotherapeutics to support investigations of pharmacokinetics and pharmacodynamics.  Due to advancements in biotechnology and clinical successes there has been a dramatic increase in the numbers of new innovative biotherapeutics across the portfolios of traditional pharma and biotech companies.  Consequently, the demand for high quality and robust LBA methods has never been greater.  However, despite their conceptual simplicity, LBAs for regulated bioanalysis are deceptively complex.  Failure to realize the complexity of regulated LBAs, often leads to increased resource utilization, decreased efficiency and timeline delays.  This webinar will review LBA principals, discuss common interferences, strategies for avoiding pitfalls and review a recommended workflow for successful implementation involving method development, pre-study validation (method acceptance) and in-study validation (run acceptance).

Learning Objectives

Following this lecture, the learner will be able to:

• Have an understanding of LBA basic principles and recognize differences between competitive and noncompetitive assays
• Describe the differences in LBA performance that are needed to support exploratory research vs. regulated bioanalysis
• Have a basic understanding of factors that are important LBA design and development for support PK of biotherapeutics
• Recognize the common interferences in LBA methodology
• Explain the LBA workflow, from early phase development through In-study implementation

Instructor: Ron Bowsher, PhD, Partner & CSO at B2S Life Sciences

Module 4

Hybrid Immunoaffinity LC‐MS Technology in the Development of Protein Drugs

Small molecule bioanalysis is typically performed by LC-MS/MS, whereas, ELISA is the commonly used method for the quantification of protein biotherapeutics.  More recently, protein biotherapeutics are often structurally complex, with formats including fusion proteins, antibody-drug conjugates, bispecifics, antibody fragments and cyclic peptides. This has led to the development of new hybrid bioanalytical strategies involving affinity capture (IA) and LC-MS/MS as an alternative approach for protein bioanalysis. Key advantages of hybrid methods include high selectivity, minimal matrix effects, and multiplexing capabilities. This talk will present highlights of IA LC-MS/MS pharmacokinetic assay development and validation with a variety of nonclinical and clinical drug development case studies.

Learning Objectives

Following this lecture, the learner will be able to:

• Describe the structural characteristics of small and large molecules
• Discuss ligand binding, LC-MS/MS, and hybrid IA-LC-MS/MS technologies and their applications to the drug discovery process
• Explain the roles of bioanalysis in drug discovery and development
• Describe how to choose the appropriate assay platform based on project requirements

Instructor: Surinder Kaur, PhD, Director & Senior Scientist, Genentech

Module 5

Dose Selection for First in Human Dosing for Biologicals in Drug Development

This lecture focuses on the pharmacology, safety and preclinical PK of monoclonal antibodies and on how these data are integrated to propose a first dose in humans.  To that effect, a/ the salient points of relevant guidelines will be reviewed; b/ the type and use of preclinical pharmacology data will be discussed and c/ a strategy to integrate preclinical PK data (Species, Dose, Disposition, Target compartment) as well as preclinical pharmacology and safety data to select a first dose will be described.

Learning Objectives

Following this lecture, the learner will be able to:

• Describe relevant regulatory guidances for starting dose FIH clinical studies
• Discuss pharmacology data and its potential for use in dose selection
• Discuss calculation differences for the Maximum Recommended Safe Dose
• Explain calculations for scaling between monkeys and humans

Instructor: Douglas Leipold, Staff Scientific Researcher, Preclinical and Translational Pharmacokinetic and Pharmacodynamic Department, Genetech

Module 6

Clinical Pharmacology of Therapeutic Proteins

A complete clinical pharmacology dataset of biologics is a vital aspect of their development.  This lecture will describe the vital aspects, from the design of first-in-human (FIH) trials, PKPD analyses (including population analyses, running special population trials for biologics including drug-drug interaction studies and bioequivalence studies), and typical regulatory questions on clinical pharmacology for biologics encountered at EOP1, EOP2, and at registration. Finally, special cases where the norm is deviated (e.g. oncology) will be examined.

Learning Objectives

Following this lecture, the learner will be able to:

• Explain the importance of clinical pharmacology for therapeutic proteins
• Describe how FIH trials are designed with clinical pharmacology in mind
• List common PKPD analyses
• Recognize and prepare for common biologic clinical pharmacology regulatory questions.

Instructor: Balaji Agoram, PhD, Head of Clinical Pharmacology and DMPK, Forty-Seven, Inc.

Module 7

Drug Delivery Considerations for Biologics - a Focus on Protein Engineering

The delivery of biologic drugs represents a critical part in the overall drug development picture. Delivery considerations can have an impact on not only the pharmacokinetics, pharmacodynamics, and toxicity of a drug, but also on patient compliance, drug marketability, and the overall commercial success of the treatment. Within this lecture, a broad overview of drug delivery considerations for biologic drugs will be presented. In addition, several case studies for key areas will also be covered. Specific topics to be covered include routes of administration, challenges and opportunities in target/disease accessibility, and considerations for antibody-drug conjugate scaffolds.

Learning Objectives

Following this lecture, the learner will be able to:

• List major drug delivery options for biologics
• Explain importance of patient compliance and how it relates to drug delivery
• Describe how drug delivery modality can impact the pharmacokinetics and pharmacodynamics of therapeutics

Instructor: Frank Engler, PhD, Clinical Pharmacologist, Certara

Module 8

Regulatory Considerations of the Manufacture of Biologics

This lecture will provide a high-level overview of concepts and requirements which are important for manufacturing a wide range of biologics. Topics will include regulatory framework, quality systems, and considerations for the design and operation of facilities and processes.

Learning Objectives

Following this lecture, the learner will be able to:

•  Define the term “biologics” as used by FDA
•  Describe high-level regulation of biologics
• Locate key resources for manufacturing biologics
• Understand concepts and challenges of 21 CFR 210 and 211 pertaining to biologics
• Identify critical elements of Chemistry, Manufacturing, and Controls

Instructor: Carl Ross, MS, Managing Director-Waisman Biomanufacturing, UW-Madison

Module 9

Regulatory Approaches for Novel Biological Therapies

In recent years, the medical community has experienced a shift in health care practice. Rather than focusing solely on how to treat an overall disease type, medical innovators are now exploring how to tailor treatments that target unique characteristics of an individual’s disease, such as the genetic profile of a person's tumor. The FDA is modernizing multiple aspects of the drug development regulatory program and continues to clarify and expand on existing pathways that allows innovators to develop products based on the molecular markers that the drug targets, rather than the more traditional method, where new medicines were developed based on the disease phenotype. When drugs successfully target these “molecular mistakes” to reverse the effects of different diseases, we need a development pathway that allows the new drug to pursue approval in each of these novel settings on the basis of the molecular marker that the drug targets. In the setting of oncology, this is often referred to as tissue agnostic drug development. 

Historically, the clinical experts mostly drive the review process, while the product experts serve as consultants. Yet in these highly novel areas, it is the product-specific issues that create regulatory uncertainty. We will examine current FDA feedback on these novel therapies and address some of the challenges for drug developers in these areas. 

Learning Objectives

Following this lecture, the learner will be able to:

• Evaluate and identify appropriate accelerated approval pathways for biotech therapies
• Assess recent comments from the FDA regarding how biologics; including cell and gene therapy products, are being evaluated for approval including manufacturing and analytical challenges
• Interpret the 21^st Century Cures Act and how it relates to increased Agency interactions on large molecule development and approvals
• Describe Tissue-Agnostic Treatments and Basket Studies that are gaining FDA acceptance compared to tissue-specific treatments

Instructor: Michael Day, PhD, Director, Chemistry, Manufacturing, and Controls, Cardinal Health

Module 10

Biosimilars : Challenges and Possibilities

With a realization that US health care expenditures were approaching untenable levels for many health care consumers as well as the federal government, the Biologics Price Competition and Innovation Act was signed into law on 23 March 2010. This law allowed for an abbreviated pathway for biological products that were considered similar to biologic products already approved by the US FDA. The goal was to reduce the costs of product development, and by extension to reduce the costs to patients and third party payers, including government programs such as Medicare and Medicaid. Fast forward, eight years later and there are very few biosimilars approved, and even fewer launched. This course explores the challenges to biosimilar drug development, and discusses the prospects for the eventual uptake of these products in global healthcare markets.

Learning Objectives

Following this lecture, the learner will be able to:  

• Understand background of biosimilars in US and EU
• Understand the basic requirements of biosimilar drug development
• Understand the impediments to biosimilar uptake globally but particularly in the US

Instructor: Connie Cullen, PhD, Principal Consultant, Apollo Biologics