August 7, 2019 CMC

Regulatory CMC Changes for Pharmaceutical Products

All the biopharmaceutical companies must follow respective nation’s laws or regulations in order to develop, manufacture and sale their pharmaceutical products. Before any biopharmaceutical product goes in to market, it has to get marketing authorization from the relevant health authorities. Market authorization is issued on the basis of an assessment of submitted information that describes the quality, safety and efficacy of the product for a specified indication.

Applicants and manufacturers often implement changes in the product, production process, quality controls, equipment, facilities, responsible personnel, or labeling established in an approved application for licensed biological products for a variety of reasons. As a result of global regulatory requirements, many changes cannot be implemented until health authority reviews and approves them.

Health authorities often have several questions during their reviews for which a manufacturer needs to prepare for many rounds of responses. Multiple reviews of the same information can lead to high costs, a more complex supply chain, and a need for sophisticated systems to maintain regulatory compliance which in turn can lead to an increasing number of errors that affects regulatory compliance, complexity in cost management, and reduced resources as well as increase in the risk of an interrupted supply of drug products.


Changes are inevitable and necessary to ensure business continuity. Changes are certainly important for many reasons such as to improve process, reduce costs, improve efficiency, reduce potential failures, and meet state of art process or to improve compliance against regulations/ Good Manufacturing Process (GMP). However, making changes is highly complex and requires systematic planning, documentation and coordination to functional owners including quality and regulatory fronts.

The change management system should include the following as appropriate for the stage of the lifecycle:

  • Quality risk management (QRM- As per ICH Q9) should be utilized to evaluate proposed changes. The level of effort and formality of the evaluation should be commensurate with the level of risk.
  • Proposed changes should be evaluated relatively to the market authorization, including design space, where established, and/or current product and process understanding. There should be an assessment to determine whether a change to the regulatory filing is required under regional requirements. As stated in ICH Q8, working within the design space is not considered as a change (from a regulatory filing perspective). However, from a pharmaceutical quality system standpoint, all changes should be evaluated by a company’s change management system.
  • Proposed changes should be evaluated by expert teams having appropriate expertise and knowledge from relevant areas (e.g., Pharmaceutical Development, Manufacturing, Quality, Regulatory Affairs and Medical), to ensure the change is technically justified. Prospective evaluation criteria for a proposed change should be set.
  • After implementation, an evaluation of the change should be undertaken to confirm the change objectives were achieved and that there was no deleterious impact on product quality.


In conclusion, this document is useful to navigate widely accepted guidance to build overall change strategy, perform change evaluations in an industry. Any organization looking forward to handle changes more efficiently should certainly consider newer aspects while designing their requirements itself so that the Life Cycle Management becomes easier and requires a balanced resource planning in terms of supporting every change worldwide.

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