Freyr is a leading player in Centralized Chemistry, Manufacturing and Controls (CMC) and dossier life cycle management, offering services ranging from strategy consulting for CMC/legacy product life cycle management (LCM) delivery models (centralized), and operational outsourcing of CMC/life cycle activities. Freyr has an established Center of Excellence for Regulatory CMC and life cycle management – offering Regulatory support for hundreds of products of Top-20 Pharma/Consumer Healthcare companies.

Post-Approval Changes

After receiving the approval or during commercialization of the drug product, if manufacturers realize and propose any changes (administrative/quality) to the registered content (that is dossier), those shall be informed to Health Authority (HA) by filing supplements or variations or amendments, which are referred as post-approval changes. Based on the impact, these changes are categorized into:

  • Major Changes, which should be filed as prior approval supplement/Type II/Type C submission and require approval from HAs prior to distribution of the drug product made using the changes
  • Moderate Changes, which should be filed as Changes Being Effected (CBE) – 30/Changes Being Effected/ Type IB/Type IAIN/Type B submissions and require approval from HAs prior to distribution of the drug product made using the change
  • Minor Changes, which should be filed in Annual Report/Type IA/Type A submissions and these changes, in general, do not require prior approval from HAs for the implementation

Life Cycle Management

Apart from post-approval changes, marketing authorization holder is responsible for keeping the dossier updated periodically as per regional requirements for Pharma and Biological products' life cycle management. Based on the HA, they should file an Annual Report (AR) or Renewal on periodical basis.

Most of the HAs except few like, United States Food and Drug Administration (USFDA) and Health Canada, grant approval to a drug product for five years. To maintain the approval, the drug product’s dossier should be updated/renewed with renewal application before its validity period (6/9 months) comes to an end. On a keynote, the dossier content to be filed with renewal application varies from country to country.

Annual Reports/Biannual Reports​

The USFDA and Health Canada seek annual report submission to maintain the life cycle of the dossier. It should include all minor changes (which have very minimal or no impact on quality of the drug product) done to the registered content along with other amendment/supplements/commercialization/safety details. HA requires annual reports to be filed within the specified time frame (for example, before 60 days) from the anniversary date.

Either post-approval changes, or annual reports or renewals, HAs worldwide have different set of requirements for filing the submissions. In such scenarios, to get the approval/acceptance at the earliest, Regulatory strategy plays a significant role.

Freyr’s Regulatory Approach

Post Approval Changes

  • Evaluation of proposed change
  • Regulatory assessment of supporting documents
  • Preparation of Regulatory strategy for filing the changes i.e. submission category
  • Guidance to manufacturer on submission/approval and implementation timelines
  • Compilation and submission of post-approval change submissions
  • Follow-up with the HA for review/approval

Renewal filing for Marketing Authorization Application (MAA)

  • Due date tracking for renewal application
  • Send the renewal initiation documents request to manufacturer
  • Regulatory assessment of the supporting documents
  • Request for additional documents/justification
  • Compilation of renewal dossier and share with manufacturer for review
  • Finalization of renewal dossier and submission to HA before the due date

Annual Report filing for IND - Investigational New Drug/NDA - New Drug Application/ANDA - Abbreviated New Drug Application/NDS - New Drug Submission/ANDS - Abbreviated New Drug Submission

  • Due date tracking for annual report
  • Request for list of changes along with supporting documents implemented in the reporting period
  • Regulatory assessment of the supporting documents
  • Request for additional documents/justification
  • Compilation of annual report package and share with manufacturer for review
  • Finalization of annual report package and submission in electronic Common Technical Document (eCTD) format to HA before due date

Freyr Expertise

  • Change in manufacturing site, addition/deletion
  • Marketing Authorization Holder(MAH) transfers
  • Optimization of manufacturing process
  • Change in formulation
  • Batch size change
  • Addition of new supplier for active substance
  • Inclusion of additional source for starting material for drug substance
  • Change in route of synthesis
  • Certification of Suitability (CEP) updates/new CEP
  • Change in equipment/instruments
  • Monograph updates i.e. Compliance to Pharmacopoeia
  • Analytical method changes
  • Changes in container closure system
  • Change in primary packaging material supplier
  • Shelf life extension/reduction
  • eCTD/CTD dossier preparation
  • Pharma variations filing
  • Drug license renewal applications
  • Re-registration dossiers

Freyr Advantages

  • Experienced Regulatory professionals to provide the end-to-end Regulatory support from the development stage to registrations and approvals for drugs and other products
  • Expertise in handling pre-submission administrative activities
  • Regulatory submission strategies for product rollouts and expansions to other regions
  • Regulatory professionals with experience in compilation and submission
  • Accurate scientific justifications for HA query response