BioPharmaceutical Quality Solutions



On-Site Tailored Courses 

Chemistry, Manufacturing & Control (CMC) regulatory compliance strategy encompasses all of those activities that are required/expected to be carried out by a regulatory authority to protect the patient from the manufactured drug product. Such activities involve Genetic Development (gene development, clonality), Process Development (design of the manufacturing process), Analytical Development (design of the test methods), Manufacturing (carrying out the production, drug substance, drug product), Quality Control (release/stability testing of the product), Quality Assurance (cGMP compliance oversight) and Regulatory Affairs (communication with the authorities).

John has worked with numerous biopharmaceutical companies, both large and small, both monoclonal antibody-based and gene therapy-based, to provide on-site training on CMC regulatory compliance. He can work with your company to tailor the course content to your specific interest/needs.  On-site courses are available for several hours (typically for senior management), and for 1-day or 2-day periods. Companies receive at the course end the tailored Powerpoint presentation used in the presentation, the course presentation in PDF format, and copies of all references used in the presentation. Video taping of the presentation is premitted.


A summary of a tailored 2-day presentation for gene and cellular therapies is provided as an example below: 

1. Overview of the ATMP/CGTP Landscape 

While the number of market-approved cellular and gene therapy medicines is still small (about 20), both the number and the diversity of these products are increasing. The two major regulatory authorities (FDA, EMA) are working hard to keep pace  and build a control system around the CMC patient safety concerns. These biologics are not regulated like the chemical drugs, and in several CMC areas are not regulated like the monoclonal antibodies. These differences are explored in this session, and why the differences are important from a patient safety perspective.  

2. Risk-Managed Advanced Therapy CMC Regulatory Compliance Strategy

One challenge for biologic manufacturers is what CMC regulatory requirements/expectations need to be met, and when during the clinical development process do they need to be in place/completed. Because the completion of the pivotal clinical trial can be so much sooner for cellular and gene therapy products, compared to that of chemical drugs and monoclonal antibodies, a 'minimum CMC regulatory compliance continuum' risk-managed approach is necessary (note, this phrase is more appropriate than the traditional 'phase-appropriate' approach due to the diversity of rapid clinical stages possible for these medicines). In addition, the evaluation of the risks for the cellular and gene therapy products is carried out according to the principles laid down by ICH Quality by Design (QbD) and ICH Quality Risk Management (QRM); which is the CMC language of the regulatory authorities, expected during clinical development, but required for market approval, in the CMC-content submissions to the authorities.

3. Applied Risk-Managed CMC Regulatory Compliance Strategy

In this session, the CMC regulatory compliance strategy will be applied to the develpment and manufacturing of the cellular and gene therapy products starting with the genetic development of the starting materials, onto the culturing/propagation upstream manufacturing process steps, into the downstream purification stages, continuing onto the formulation, and finally the assembly of the container-closure components and filling of the drug product, and last but not least the administration of the drug product to the patient. (Discussion can be broad to cover all cellular and gene therapy manufacturing platforms; or discussion can be fine-tuned covering some or all products such as viral vectors or non-viral vectors or genetically-modified patient cells or substantially-manipulated cellular therapies).

4. Challenge of Demonstrating Product Comparability After Process Changes

There are three (3) major risk-based concerns for the drug product that must be addressed when carrying out manufacturing process changes - these concerns apply to chemical drugs, monoclonal antibodies, and cellular and gene therapies. But the larger and the more complex the molecule, the greater the challenge in confirming that the drug product has not been impacted - and of course cellular and gene therapy products are the most challenging. Regulatory guidance is now available in navigating the steps to take to ascertain that the standard of 'highly similar' is achieved. However, due to the fast clinical development pace for cellular and gene therapy products, confirming this standard is challenging in the limited time frame available, which has led to major delays for several companies in obtaining market approval. 

5. Critical CMC-Focused Strategy Interactions with Regulatory Authorities 

While CMC regulatory compliance delays are rarely terminal either in initiating clinical studies or obtaining market approval, they can lead to significant delays in advancement. The regulatory authorities have provided opportunities to avoid these missteps. Discussion of the meeting opportunities available and what to expect from them will be discussed. The regulatory authority interactions both during the clinical development period and during the market application period will be discussed from both the FDA and EMA perspective. Resources available to assist companies in understanding the CMC regulatory compliance challenges that they will face will be presented.


 A similar pattern for a tailored 2-day CMC regulatory compliance course for recombinant proteins, monoclonal antibodies and biosimilars is also available.

Contact John Geigert    +1-760-525-5154