CMC Regulatory Compliance for Biopharmaceuticals & Biosimilars

Course Agenda

Day One

CMC Regulatory Compliance is Challenging for Biologics

• Increasing diversity of biologicals: biologic, biopharmaceutical, biosimilar, advanced therapy, gene therapy
• The regulatory authorities (FDA, EMA) involved and the changing regulatory review pathways (IND to BLA; IMPD to MAA) for biologics
• Four (4) CMC regulatory compliance differences between the two U.S. pharmaceutical laws (FD&C Act and PHS Act)
• Why biologics are not chemical drugs – the four (4) major differences in CMC regulatory compliance challenges presented by biologics

Risk-Managed Biologic CMC Regulatory Compliance Strategy

• Five (5) key design elements of an effective CMC regulatory compliant strategy
• Factoring in corporate culture (and the corporate risk acceptance level) into decisions
• Critical role of the strategic ICH guidances (Q8/Q9/Q10) on all biologics
• Effectively managing the ‘minimal CMC regulatory compliance continuum
• Impact of Clinical expediting on the CMC team

Day Two

Applied Risk-Managed Biologic CMC Regulatory Compliance Strategy

• Detailed roadmap for manufacture of a monoclonal antibody – from source material to final drug product
• General roadmap for manufacture of a genetically engineered virus medicine – from source material to final drug product
• Importance, and limitations, of small-scale studies for biologics
• 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., delamination)
• Extra challenge of Antibody Drug Conjugates (ADCs)

Demonstrating Biologic Comparability After Manufacturing Process Changes

• Three (3) key design elements of an effective comparability exercise
• Risk-based effort required due to the nature of the proposed manufacturing process change and the stage of clinical development
• Difference between a comparability exercise and a comparability contract
• Extreme comparability of biosimilars: limitations of CMC comparison, fingerprinting

Day Three

Critical CMC-Focused Strategic Interactions with Regulatory Authorities for Biologics

• Maximizing the value of CMC discussions with the regulatory authorities for your biologic
• Avoiding critical delays in clinical development (Clinical Holds) and market approval (Refusal to File, Complete Response Letters) due to an ineffective CMC regulatory compliance strategy
• Requesting CMC-focused meetings with FDA (PDUFA Type A-C meetings; BsUFA BPD 1-4 meetings) and EMA (Scientific Advice), and maximizing the opportunity for discussion
• How to word CMC questions to evoke a reactive response from the regulatory authority

Regulatory Review of Biologic Submissions for Market Approval

• Review procedures/timing for BLAs and MAAs
• Avoiding Refusal to File Letters, Complete Response Letters, and List of Questions due to CMC content (or lack thereof) in Module 3 for biologics
• Locating the FDA internal CMC review discussions for biologics on their website

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) for biopharmaceuticals, biosimilars and other biologics (cell and gene therapies), 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 and European Medicines Agency (EMA) 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
• Learn how to avoid major delays in clinical development or market approval due to an ineffective CMC regulatory compliance strategy for biologics

Testimonials

"This was an excellent course. Definitely one of the best I have ever attended. The material was useful, presented well and very interesting." Pascale J., Technical Manager, Genentech

"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 my 2nd course with this instructor. Great course and he is very knowledgeable." Dr. Pei M., Analytical Dev. QC Mgr, enGene

"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

"One of the best I have ever attended." Emmanuelle V. Quality Product Steward, Bayer

"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.