Annual submissions are critical in regulatory
submission processes to maintain a product’s quality, safety, and efficacy over its duration in the market. These submissions are part of post-marketing activities for the product and are an essential part of the product’s lifecycle. While the product is marketed to end users, the product must remain consistent even after getting approval from regulatory agencies. 

This also applies to manufacturing and other processes such as Quality Control (QC), labeling, packaging, and similar processes that can impact product quality and safety. Therefore, regulatory agencies require sponsors to provide documentation periodically that indicates if there are any changes to the processes impacting the product or to the product itself.  

Changes to the processes or products are classified as critical or major, moderate, and minor, based on the impact of the changes on the product quality, safety and efficacy, and end-user health.

1. Critical or Major changes: A major change is a change that has a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of a drug product, as these factors may relate to the safety or effectiveness of the drug product. A major change requires the submission of a supplement and approval by the FDA before the distribution of the drug product is made using the difference. This type of supplement is called and should be clearly labeled a Prior Approval Supplement.CC

2. Moderate changes: A moderate change is a change that has a moderate potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product, as these factors may relate to the safety or effectiveness of the drug product. One type of moderate change requires the submission of a supplement to the FDA at least 30 days before the distribution of the drug product made using the change. This type of supplement is called, and should be clearly labeled, a Supplement – effective changes being in 30 Days. The drug product made using a moderate change cannot be distributed if FDA informs the applicant within 30 days of receipt of the supplement that a prior approval supplement is required. FDA may identify specific moderate changes for which distribution can occur when FDA receives the supplement. Therefore, this type of supplement is called and should be clearly labeled a supplement – effective changes. More details regarding this type of change can be found here.

3. Minor changes: A minor change is a change that has minimal potential to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product, as these factors may relate to the safety or effectiveness of the drug product. The applicant must describe minor changes in its subsequent annual report filing.  
There are several annual submissions that pharmaceutical companies may be required to make to regulatory agencies. These changes are considered changes to the original NDA. These include:

4. Annual Product Quality Review (APQR):  This report provides an overview of the quality of a product over the past year, including any issues, change controls, market complaints, or deviations that occurred. An annual product review is an effective product quality improvement tool conducted annually to assess the quality standard of each drug product, verify the consistency of the existing manufacturing process, and check the appropriateness of current specifications. This evaluation report can also highlight trends to determine the need to change drug product specifications, manufacturing processes, or control procedures. Companies must have an SOP for this process.

5. Annual Safety Report (ASR)/ Periodic Safety Update Report (PSUR):  This report must be provided by IND application sponsors. Additionally, IND application sponsors are required to notify FDA in a written safety report of: 

  • Any adverse experience associated with the use of the drug that is both serious and unexpected or 
  • Any findings from laboratory animal tests suggest a significant risk for human subjects, including reports of mutagenicity, teratogenicity, and carcinogenicity.  

The submission must be identified as: 

  • “IND submission of the safety report” for 15-day reports, or 
  • “7-day IND safety report” for unexpected fatal or life-threatening suspected adverse reaction reports, or 
  • “Follow-up IND safety report” for follow-up information.

More information on Annual Safety reports can be found here.

Similar to the annual Safety report for the US, the Periodic Safety Report (PSUR) is required to submit to the EMA (Europe). This report provides an overview of a company’s financial performance, including revenue, expenses, and profits. The objective of the PSUR is to present a comprehensive and critical analysis of the product’s risk-benefit balance, considering new or emerging safety information in the context of cumulative data on risk and benefits. This evaluation should ascertain whether further investigations need to be carried out and whether changes should be made to the product information or marketing authorization.

1. Annual Report (AR):  The Annual Report is a brief report that needs to be submitted to the USFDA within 60 days that an IND/ NDA/ANDA application going into effect. This report provides a summary of significant sections of the main application over the past year of the product being studied or marketed, such as: 

  • Information obtained during previous years’ clinical and non-clinical investigations, any adverse events, a summary of all IND safety reports. 
  • Any significant manufacturing or microbiological changes (CMC), deviations, complaints, and investigations made during the past year. 
  • A description of the general investigational plan for clinical studies for the next year. 
  • Any significant foreign marketing developments such as marketing approval in another country, withdrawal or suspensions from any market. 
  • Any change in labeling that can impact the end user.

2. Annual Regulatory Compliance Report: This report summarizes the company’s compliance with the regulatory requirement of the country they operate in. Regulatory compliance reporting is essential to document your compliance with regulations and protect your business from serious issues. 

3. Annual Report on Post-Marketing Surveillance: This report provides an overview of the company’s post-marketing surveillance activities, including reported adverse events and changes to the product’s labeling or packaging. This report also indicates any market withdrawals or suspension of products from any market, complaints, and corresponding investigations into the product. 

Annual submissions are significant and a way to ensure that the product remains compliant with the standards set by the agencies and maintain the product quality, strength, potency, and safety throughout the product’s lifecycle.

When it comes to authoring or maintaining any regulatory submission, generation of post-marketing approval documents and annual submission documents, and supporting product maintenance throughout the lifecycle, PSC Biotech provides expertise in all such regulatory authoring or compliance activities. PSC can help you develop an effective strategy to generate and maintain post-approval products and help you understand critical regulations and guidelines to help your product stay compliant as long as it is marketed. PSC also has the expertise that can help you navigate the regulatory process right to the end and gain marketing approval for your product.  

Contact PSC Biotech to help ensure your company stays compliant with all regulatory standards! 


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