When developing a control strategy for a manufacturing process, two options are typically available to the license holder: a tightly controlled strategy based on the manufacturing process being repeated as closely as possible to the registered process, which is the strategy that has been widely and successfully used for the manufacture of biologics for many years. A drawback of this approach is limited flexibility to change the process.
The second option is to define a Quality by Design (QbD) control strategy based on product and process knowledge and understanding. This option typically requires development activities and registration of the manufacturing process that demonstrates an understanding of the impact of the different process steps, attributes, and parameters on product quality.
This latter approach has not been universally implemented by the biologics industry to date, as it is also perceived that it will increase the resources, materials, time, and costs associated with development activities. This is not always compatible with the finite resources of the industry and the accelerated timelines needed to meet patient demand as quickly as possible.
A benefit of the QbD approach is that changes to the manufacturing process have the potential to be more easily implementable – not from a technical point of view (the same technical justification to ensure the change does not impact product quality will be expected) but from a regulatory point of view.
Some BioPhorum member organizations have also successfully used the QbD tools to register the controls associated with manufacturing processes and have come together to summarize their best practices for initial submissions.
The team then added their best practices for post-approval changes that can be used throughout the product lifecycle, especially when the initial submission did not include QbD principles.
The paper Best regulatory practices for lifecycle management – registration of manufacturing controls is a collection of best and successful practices that can save time, resources, and costs, and simplify and continue the supply chain when faced with post-approval changes.
When implemented, these best practices will allow you to minimize the number of post-approval regulatory notifications to regulators and reduce the variation categories associated with product lifecycle changes.
Aiming for flexibility
Our paper summarizes the systematic approach industry uses for demonstrating product and process knowledge and defining the appropriate process controls that will allow future flexibility. The approach uses the regulatory tools available, especially the most recent ICH quality guidelines.
The desired state is to build regulatory flexibility into dossiers to reduce the burden of post-approval changes while enhancing the definition of product quality and promoting our industry’s agility and adaptability to meet patient needs.
The paper can be used by mature regulatory organizations as a reference to confirm that they are using all the regulatory tools available. Less regulatory-mature organizations and new regulatory professionals are encouraged to consult the paper to establish best practices based on industry successes.
BioPhorum members can add the paper to their toolbox of best practices and training materials. The team also plans to discuss implementing the guidance with the Drug Substance, Fill Finish, and Development Group Phorums.
This is the second paper of the BioPhorum series on regulatory best practices for the lifecycle management of biopharmaceutical products and follows The four steps for registering innovative and complex raw materials. The next paper in the series will look at the registration of analytical methods.
For more information, download the paper here and contact Isabelle Lequeux, Regulatory Lead, Program Manager and Global Change Facilitator, at email@example.com