DDReg Pharma

DDReg Pharma

Commitment to Biological Product and Patient Safety in India

Biological products are derived from living organisms or cells encompass a wide array of essential medical interventions, including vaccines, gene therapy products, and blood derivatives.  Thus, these products are relatively complex in nature which is why there is a need to maintain heightened vigilance and continuously monitor their safety and efficacy. It is crucial to ensure stringent oversight in order to safeguard against unforeseen risks while also enhancing confidence in their therapeutic benefits. In support of this, regulatory agencies across the globe are implementing guidance documents and notices. A recent example of this is the new draft guidance released by the Central Drugs Standard Control Organization (CDSCO) on post-approval changes for biological products that are subject to consultation. In this guidance, the CDSCO proposed adding new sections to address safety and efficacy changes.

Version 1.1 of Guidance on Post-Approval Changes to Biological Products

The journey towards revising the guidance began in 2013 when Indian officials formed a committee to update version 1.1 of the guidance on post-approval changes to biological products.

The objective of the guidance was:

  1. to assist with the classification of changes made to biological products approved by CDSCO for import/manufacturing and marketing in India, and
  2. to provide Marketing Authorization Holders (MA holders) with recommendations on the data to support a change which would be considered sufficient to allow a determination of the impact of the change on the quality of the approved products as it relates to safety, efficacy and/or effective use of the products.

Key Changes in Version 1.2

Version 1.2 of the guidance on post-approval changes to biological products introduces significant enhancements, including the proposal to add a new category of quality changes – Level IV. The changes will not require prior regulatory review if they are implemented by marketing authorization holders. Level IV changes are those that are not expected to adversely affect the identity, strength, quality, purity, or potency of the drug product. The aim of the revision is to ultimately ensure that the standards are aligned with international standards like the World Health Organization (WHO).

Classification of Changes

The draft guidance advises marketing authorization holders to categorize changes related to clinical use and product labeling into one of four categories based on their likely impact on safety and efficacy:

Level I– Supplements (Major Quality Changes) are changes that may potentially affect the identity, strength or potency of a product. Consequently, substantial documentation must be provided and CDSCO’s prior authorization is necessary before the amendments are implemented.

Level II – Notifiable Changes (Moderate Quality Changes) are intermediate modifications that have some impact on quality require notification to CDSCO before implementation.

Level III – Annual Notification (Minor Quality Changes) are minimal product quality impact type of changes which can be made without prior review by CDSCO but need annual submissions to this effect.

Level IV – Changes (Record of Changes) are modifications that cannot be accounted for in the first three categories and do not affect the quality of the drug. They may then be incorporated in MA holders’ documents.

Additional Updates

The draft guidance also proposes the inclusion of sections on administrative product labeling information changes, comparative studies, and quality by design. It is important that all stakeholders are involved such as healthcare providers, patients and civil society organizations in this process. CDSCO provided a window of 45 days for the public to give their responses regarding their guidance on the draft. 


CDSCO’s guidance on post-approval changes to biological products is a remarkable advance in improving regulatory procedures, and as a result ensuring that pharmaceutical products are safe and effective in India. The pilot by the CDSCO to refine the country’s regulatory framework for the advancement of public health and innovation in pharmaceutical industry through global integration is commendable. 

Reach out to DDReg for expert and end-to-end regulatory services to support first time-right drug and biological product submissions. Read more about biological products here: Standardizing Real World Data for Drug and Biological Product Submissions