CMC Regulatory Compliance for Biopharmaceuticals & Biosimilars

Course Agenda

First Day

CMC Regulatory Challenges for Biologics are Different

• Understanding the terminology landscape: biologic, specified biologic, biopharmaceutical, biosimilar
• The regulatory authorities (FDA, EMA/NCA) and regulatory review pathways (IND/IMPD, NDA/BLA, MAA centralized procedure) for biologics
• Five (5) CMC regulatory compliance differences between the two U.S. pharmaceutical laws for biologics
• Biologics are not chemical drugs – four (4) unique CMC regulatory compliance challenges presented by biologics
• Biosimilars are not ‘bio-generics’’

How to Develop an Effective Corporate CMC Risk-Managed Regulatory Compliance Strategy for Biologics

• Two (2) major forces that shape the CMC regulatory compliance strategy of all biologics
• Five (5) essential elements of an effective CMC regulatory compliant strategy
• Impact of the strategic ICH guidances (Q8/Q9/Q10) on all biologics
• Potential benefits and limitations of Quality by Design (QbD) for biologics
• Necessity of a clinical phase-appropriate CMC regulatory compliance strategy

Applying the CMC Regulatory Compliance Risk-Managed Strategy to Control of Biologic Manufacturing Processes (Part 1)

• Critical importance of biologic starting materials
• Four (4) myths about cell banks
• Necessity of demonstrating appropriate clone selection

Second Day

Applying the CMC Regulatory Compliance Risk-Managed Strategy to Control of Biologic Manufacturing Processes (Part 2)

• Genetic stability determination
• Importance, and limitations, of small-scale studies for biologics
• Clinical phase-appropriate control of the biologic manufacturing process, including applying a Quality by Design approach
• Timing difference for process validation between biologics and chemical drug processes
• Formulation and container-closure challenges for biologics – impact of components on the biologic (e.g., aggregation) and impact of the biologic on components (e.g., glass flaking)
• Illustration of Quality by Design (QTPP, CQAs, CPPs, risk-ranking) in selecting the control system for host cell proteins (HCPs)

Challenge of Managing Manufacturing Process Changes and Demonstrating Biologic Product Comparability – Not an Easy Task

• Risk-based, sequential, clinical phase-appropriate comparability studies Demonstrating biologic product comparability – justifying CMC differences
• Difference between a comparability study and a comparability protocol
• Extreme comparability of biosimilars: limitations of CMC comparison, fingerprinting, which biologics currently are being considered for biosimilars
• EMA biosimilars – CMC biosimilarity successes and failures

Third Day

Critical CMC-Focused Strategic Interactions with Regulatory Authorities for Biologics

• Maximizing the value of CMC interactions with the regulatory authorities for your biologic
• Avoiding biologic market approval delays of months/years – clinical holds and refusals to file – due to an ineffective CMC regulatory compliance strategy
• FDA PDUFA CMC-focused strategic meetings (pre-IND, EOP2 and pre-submission)
• FDA BsUFA meetings for biosimilars (BIAM and BPDs)
• EMA strategic meetings (scientific advice and pre-submission)
• How to word CMC questions to evoke a reactive response from the regulatory authority

Preparing Module 3 (CMC) For Biologic Submissions

• Module 3 for biologics – clinical development and market submissions
• Location of biologic CMC information in Modules 1, 2.3 and 3
• Placement of QbD content (QTPP, CQA, CPP, etc.) into Modules 2.3 and 3
• Placement of the CMC biosimilarity study for biosimilars into Modules 1 and 3
• Similarities and differences between the FDA and EMA review of these submissions

Learning Objectives

At the end of the three-day course attendees will:

• Gain a solid understanding of the CMC regulatory compliance requirements and expectations (FDA, EMA, ICH, WHO) for biopharmaceuticals, biosimilars and other biologics, and understand why regulatory authorities treat biologics different than chemical drugs
• Have the tools and understanding to carry out an effective product comparability study after a change in a biologic manufacturing process, learning how to avoid the many pitfalls, and how to communicate and defend the study to a regulatory authority
• Understand the CMC challenges for biosimilars under the US FDA, European Medicines Agency (EMA) and World Health Organization (WHO) requirements, especially with the innovator's CMC development being blinded to the biosimilar manufacturer
• Understand the strengths and limitations of Quality by Design (QbD) - quality target product profile (QTPP), critical quality attributes (CQAs), critical process parameters (CPPs) and justification of the control strategy – for biologic manufacturing processes
• Be able to package the CMC information for biologics into the common technical document (CTD) format, including placement of the CMC biosimilarity study and QbD content
• Learn how to avoid major delays in clinical development or market approval due to an ineffective CMC regulatory compliance strategy for biologics

Testimonials

"Much, much better than courses I've taken with other providers. The instructor is obviously and expert in his field and has been "in the trenches". The best part of the course was his pragmatic advice based on experience gained over many years of service in many different scenarios." Stephanie D., Regulatory CMC Scientist, Cook Research

"This is one of the better courses I've taken. Course content was very relative to my daily job functions. The instructor was extremely knowledgeable and engaging and provided relevant case studies provided in a way that allowed for those with varying technical expertise to understand." Melanie K., Proposal Manager, Patheon

"Excellent, Top Tier! The course delivered new and useful information and clarified many of the unknown complexities of these CMC topics." Jim, T., Project Manager, Teva Pharmaceuticals

"Very good course for beginners to Biotech and Biosimilar topics." Asim A., Manager, Regulatory Affairs, Glenmark Pharmaceuticals

"The course exceeded all my expectations. Great balance between CMC regulatory requirements and the science and hands on experience necessary to establish the implementation plan. The instructor is very knowledgeable and shares his broad experience beyond the book "The Challenge of CMC Regulatory Compliance for Biopharmaceuticals and other Biologics". I am sure this course would be beneficial to anybody working with biopharmaceuticals. I would definitely recommend it and I'll certainly sign up for other CfPIE training courses tailored for the biopharmaceutical sector." Francisca G., Senior MSAT Specialist, 4 Tune Engineering Ltd.

"This is the most valuable course I have taken in many years. I will be applying what I learned to my current project immediately. The information could not have come at a better time for me. Every section was valuable!" Duane V., Program Director, Hoffmann-LaRoche

"Great course. Material was well thought out and presented in an efficient and understandable manner. John was a wonderful, knowledgeable proctor. Small classroom format provided ample format for specific questions and individual help." Seth K., Product Development Scientist, Cook MyoSite

"Course Director is really engaging and knowledgeable. The course provided you with a good overview of the topic for non-specialist" Francesca Z., Biotech Process Sciences, Merck Serono

"The course was really great, full of valuable information and interesting. The Course Director really keeps attention during whole three days of training. Explanations are clear, interesting, and full of real-life examples publicly available that can be more deeply explored. I reall enjoyed and would recommend to all CMC focused professionals from innovators and generic field." Suncana B., R&D RA Manager – CMC Documentation, Pliva Croatia Ltd, Member of TEVA Group

The training course was excellent and met all my expectations." Alexandre S., Director, Silva Regulatory Services Ltda

"Very useful to find a CMC course on biologics that explained the differences from chemical drugs in good detail and had fantastic examples." Lisa H., CMC Regulatory Director, Hazel CMC Regulatory Solutions Ltd

"I thought the Course Director did an outstanding job of giving a detailed overview of CMC issues. The course was rich with practical information and his examples made the information more interesting. Thanks!" Dana A., Consultant, The Vaccine Company

"This was the first course that totally deals with all CMC issues from Phase I through to BLA/NDA filing. I would recommend this course to any start-up biotechnology company on how to design your CMC strategy." Warren D., QA Manager, Progen Industries

"Small classroom format is very beneficial to learning. As a result classroom dynamics were excellent. Participants felt free to ask questions during the presentation and the ensuing discussions were beneficial to all attendees. Also, the course director was approachable and answered each question without dismissing seemingly obvious ones. He understood the diverse disciplines from which the attendees came." Maureen M., Manager, Regulatory Affairs, Merck Frosst Canada

"The Course Director was excellent and is extremely knowledgeable in regards to CMC for biopharmaceuticals/biologics. He presented various examples from his experience and answered all questions thoroughly." Nisha P., Associate Manager, QA Compliance, Centocor

"This course provided a thorough broad understanding of the CMC Regulatory process. I would highly recommend this course to any technical person who is involved in preparing CMC documents." Steven M., Senior Program Manager, Bristol-Myers Squibb

"The organization of the course material gave the proper foundation from topic to topic. Emphasis on critical development issues to avoid delays in the approval of the application were well discussed and rationalized. As someone with no prior Biologics regulatory background I found this a very good introduction to the complexity of the requirements for BLA/NDA submissions." David L., Director Regulatory Affairs, Forest Laboratories

"Good in-depth course covering all facets of CMC with biopharmaceutical focus - which is hard to find!" Greg S., QA Manager, GSK

"This course is a precise overview of current CMC regulatory requirements and approaches taken by industry to meet agency regulations. Instructors presentation of the topic under the theme of "CMC continuation" was excellent." Prakash S., Assoc. Director, Enzon Pharmaceuticals

"Excellent course! Everyone involved in CMC regulatory compliance related matters needs to attend." Richard S., Group Director – CMC, Hoffman La Roche

"This course was excellent. The amount of information is incredible and the content was laid out very well. Anyone who wants to learn about CMC Regulatory compliance for biopharma & biologics should take this course." Rodney C., Analytical Validation Specialist, BMS

"The course was very informative and helpful. The only CMC training program I have found that deals with Biologics and Biotech products." Anne G., CMC Associate, Intrexon

Frequently Asked Questions

Does the course cover both biopharmaceuticals and biologics in clinical development as well as market-approved?

The course covers the Chemistry, Manufacturing & Control (CMC) regulatory compliance requirements and expectations for biopharmaceuticals and biologics in clinical development (i.e., Phase 1 to Phase 3 studies) as well as those having market approval.

Does the course cover FDA and international concerns?

The course covers all aspects of CMC regulatory compliance requirements and guidance for biopharmaceuticals and biologics from the FDA, European Medicine Agency (EMA), and International Conference on Harmonisation (ICH).

How does this course differ from the course QA/QC Strategy for Biologics and Biopharmaceuticals™?

This course systematically covers all aspects of CMC regulatory compliance concerns, including areas of keen interest to regulatory affairs, manufacturing and development for biologics. On the other hand, the QA/QC Strategy course focuses on all aspects of keen interest to quality assurance and quality control, including control systems and setting of specifications and expiry dating of biologics.