Chemistry, manufacturing, and control (CMC) post-approval changes are part of the typical lifecycle of pharmaceutical products, and biologics are no different. These changes, however, need to ensure that there is no impact on the product quality, safety and efficacy of biologics. This requirement is essential to patients and is therefore reviewed by the national health agencies in which the products are marketed.
Yet, not all changes are equal: the most impactful may require a bridging clinical study to assess if there is any impact on product safety or efficacy. Minor changes may be documented in the license holder’s pharmaceutical quality management system, with little to no more information. But the first step is to document the change and assess it, i.e. what is its potential impact on product quality?
Answering this question led to BioPhorum co-authoring an article on a Risk-Based Approach for Analytical Comparability and Comparability Protocols.
The piece introduces comparability studies and analytical comparability as tools that can support biomanufacturers and health agencies when ensuring that patient safety, and product safety and efficacy, is maintained during proposed changes.
A risk-based review approach
The article recommends a scientific, risk-based review approach based on product and process knowledge, and the definition of acceptance criteria to ensure the product is ‘essentially similar’. What constitutes a holistic comparability study is also covered.
The approach allows the selection of relevant or applicable criteria to be investigated, depending on the nature and potential impact of the change. It also has the added benefits of positively influencing review timelines, enabling the effective use of resources and building efficiencies for agencies and industry.
Evaluating the impact of post-approval changes is also covered, as is the definition of comparability, the elements of analytical comparability and the considerations for a comparability exercise.
Published in the PDA Journal of Pharmaceutical Science and Technology, it includes two case studies for specific CMC changes that employed scientific, risk-based approaches for designing analytical comparability. One looks at changes to the manufacturing facility of a drug substance, and the other considers changes to the manufacturing process of a drug substance intermediate and manufacturing facility.
“When we first discussed with Anvisa [the Brazilian Health Regulatory Agency] about assessing a post-approval change in an effective and robust manner, we introduced the principles of analytical comparability and comparability protocols,” said Kavita Ramalingam Iyer, Director in BioPharm Regulatory CMC at GSK. “This led us to collaborate through BioPhorum to reflect on these principles and define the benefits in a simple guide to a risk-based approach to comparability with case studies. This paper is the result of our discussions and collaboration.”
Embracing a scientific, risk-based review approach is mutually beneficial to industry and health agencies and adds value to patient care. How do you assess the potential impact of CMC changes in your organization?