Overview

After a marketing authorization application (MAA) is granted approval in European Union (EU), in view of commercialization of a product (minimize costs, time or other reasons), the manufacturer may consider making necessary changes. Such changes must be notified to the Health Authorities (HAs) by proposing a Post-approval change submission.

As per the guidance, any changes proposed to the registered content in MAA shall be informed to HAs by filing Variations. Based on the impact of changes on quality of the medicinal product, they are categorised as:

  • Major Changes: Have substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product / drug substance as these factors may relate to the safety and / or effectiveness of the medicinal product.
  • Moderate Changes: Have moderate potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product/drug substance as these factors may relate to the safety and/or effectiveness of the medicinal product.
  • Minor Changes: Have minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product/drug substance as these factors may relate to the safety or effectiveness of the medicinal product.

Along with proposed changes, it is mandatory to submit impacted Common Technical Document (CTD) sections with supporting documents / data as variations with scientific justification. They play a significant role in maintaining the Regulatory compliance of the MAA against the procedures followed at manufacturing site. Approval / acceptance of the submitted variations is mandatory for the moderate and major changes before implementation.

Having the appropriate strategy is very important for variation submission based on the complexity of the proposed changes. Any error in variation submission strategy leads to rejection and subsequent delays in the approval of proposed changes.

Freyr is adept at handling Post-approval changes of MAA for EU member states to maintain the Regulatory compliance in a timely manner. With multi-functional capability, Freyr also supports in streamlining the changes in formulation, batch size, synthesis route and other important Post-approval activities.

 

Freyr Expertise

  • Marketing authorization holder transfers
  • Change in manufacturing site, addition/deletion
  • Optimization of manufacturing process
  • Change in formulation
  • Batch-size change
  • Monograph updates i.e., compliance to European pharmacopoeia
  • Analytical method changes
  • Changes in container closure system
  • Change in primary packaging material supplier
  • Shelf life extension/reduction
  • Addition of new supplier for active substance
  • Inclusion of additional source for starting material for drug substance
  • Change in route of synthesis
  • CEP updates / New CEP
 

Freyr Approach

  • Tracking of Post-approval changes for timely submission of variations
  • Evaluation of proposed changes
  • Preparation of Regulatory submission strategy for filing the changes i.e. variation submission strategy (Type II/Type IB/Type IAIN/Type IA)
  • Gap analysis / Regulatory assessment of supporting documents for their adequacy for variation submission
  • Guidance to manufacturer on generation of additional/pending data to fulfil the variation submission requirements
  • Guidance to manufacturer on submission / approval and implementation timelines
  • Compilation and submission of post-approval changes i.e. variation submissions
  • Follow-up with HA for review / approval
  • Preparation of Regulatory strategy for response to HA queries
  • Preparation of response to HA queries with scientific justification