Test Your Knowledge on Raw Material Changes in the Pharmaceutical Industry

Regulatory Expectations and Challenges for Raw Material Changes in the Pharmaceutical Industry

• Shortages caused by single-sourced raw materials and increased demand forecasts can result in manufacturing delays or stoppages.
• Building sufficient inventory to ensure continuous product supply can mitigate the risk of shortages, but it increases production costs and the risk of scrapping raw material lots.
• Diversification and redundancy of raw material supplies through qualification of new sources ensure supply resiliency, but it can require approvals from multiple health authorities and delays implementation.
• The COVID-19 pandemic highlighted the challenges in the production of therapeutics and vaccines, and the pharmaceutical industry learned lessons that could be leveraged for future procedures and regulatory submission requirements.
• The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines contain information regarding regulatory requirements for raw materials.
• Raw materials should be evaluated, tested, and approved by quality upon receipt, and the specifications should include critical attributes, analytical procedures, and acceptance criteria.
• The Common Technical Document (CTD) for the Registration of Pharmaceuticals For Human Use: Quality—M4Q guidance covers the minimum requirements for submission of raw materials; however, certain regions have additional requirements.
• A change control system under the company’s pharmaceutical quality system (PQS) is required to evaluate all raw material changes, with established procedures for identification, documentation, review, and approval.
• A formal risk management system provides assurance to the health authorities that the applicant can ensure process consistency and product quality while continuously monitoring, verifying, and mitigating identified risks.
• The implementation of a global regulatory infrastructure that is harmonized, flexible, and predictable would provide drug manufacturers the agility to expedite raw material supplier qualifications to be better equipped to face raw material challenges while maintaining product quality and supply to patients.
• The identification of the critical raw material attributes and appropriate setting of specifications is a crucial first step.
• The adoption of the principles of ICH Q12 could result in fewer postapproval submissions and the ability to implement more changes prior to notification, providing more flexibility to implement changes and thus react more quickly to supply chain challenges.