CMC Regulatory Compliance
Course Description -
This course will help the attendee to develop a CMC regulatory compliance strategy for biopharmaceuticals, biosimilars and other biologics, addressing the five core elements that comprise an effective strategy: (1) embracing the full spectrum of CMC activities, (2) addressing unique requirements for specific biologic manufacturing processes, (3) addressing unique requirements for specific biologic products, (4) aligning with the strategic ICH Q8/Q9/Q10 guidances, and (5) applying a risk-based approach. The critical importance of communicating CMC regulatory compliance strategy with the regulatory authorities at CMC-focused meetings will be stressed. In addition, this course will also help the attendee to better understand the CMC regulatory compliance requirements for Quality by Design applications.
Why This Course Matters
The Chemistry, Manufacturing & Controls (CMC) landscape of biologics is undergoing rapid development and constant change. In addition to commercial recombinant proteins and monoclonal antibodies, there are now biosimilars, antibody drug conjugates (ADCs), cellular therapy and gene therapy medicines. Vaccine manufacturing employing genetic engineering approaches has resurged due to the concerns of potentially pandemic mutated animal influenzas (e.g., COVID19). Strategic international regulatory guidances have been adopted that are driving the entire pharmaceutical industry, including biologics, to a higher standard of performance, including Quality by Design (QbD), Quality Risk Management (QRM) and Pharmaceutical Quality System (PQS).
Therefore, it is most important for a biologic company to have an effective CMC regulatory compliance strategy that can meet both FDA and EMA requirements and expectations. At each stage of drug development, from early stage clinical development through commercialization, the basic question needs to be addressed: ‘What is absolutely necessary from a CMC regulatory compliance perspective to be successful in moving our biopharmaceutical/biologic through clinical trials and into the market, but without impacting patient safety or creating delays in the program?' Deficiencies in the CMC regulatory compliance strategy have resulted in recent devastating clinical holds and market approval delays.
Who Should Attend
This three-day CMC regulatory compliance course is designed for senior management, directors, managers, supervisors, project planners and professional staff seeking to develop or implement a Chemistry, Manufacturing & Controls (CMC) regulatory compliant strategy for biopharmaceuticals, biosimilars or other biologics. Typical attendees include: Senior Management, Project Managers, Regulatory Affairs, Manufacturing, and Quality and Development personnel..
Course Agenda
Day One
CMC Regulatory Compliance is Challenging for Biologics
- Increasing diversity of biologicals: biologic, biopharmaceutical, biosimilar, advanced 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
- 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) 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, 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
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.