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CDSCO issues draft revised guidance on quality & safety documents for post approval changes in biological products

Gireesh Babu, New Delhi
Monday, March 4, 2024, 08:00 Hrs  [IST]

The Central Drugs Standard Control Organisation (CDSCO) has come out with a draft of revised guidance document for the industry related to the quality, safety and efficacy documents for Post Approval Changes (PACs) in biological products in order to align the standards with the international guidelines including that of World Health Organisation (WHO) and current international practices by various regulatory agencies.

The guidance document is expected to emphasise on applying a science-based and risk-based approach to the quality, safety and efficacy assessment of the biological products, it said.

The CDSCO, while releasing the draft document, solicited suggestions, comments and objections from the stakeholders within 45 days from the date of issuance of the notice, by email for consideration before finalising the guidance.

The guidance document would apply to the marketing authorisation (MA) holders intending to make changes to biological products that have received an approval to market the products, and it is expected to assist the MA holders with the classification of changes made to biological products approved by the CDSCO for import or manufacturing and marketing in India.

It will provide 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 effective use of the products.

According to the guidance document, the regulator has classified the PACs into four levels, with the first level being supplement changes, which are major quality changes that have a substantial potential to have an adverse effect on the identity, strength, quality, purity, or potency of the biological product as these factors may relate to the safety and efficacy of the product.

A change that is supported by extensive documentation and/or requiring extensive assessment of the supporting documentation, such as a change supported by in-vivo studies, would be considered a Level I - Supplement(Major Quality Change).

This is to allow CDSCO the opportunity to apply the principles of risk management by having the necessary time for an appropriate assessment of the documentation. This assessment will take into consideration any potential impact upon market availability as well as the adverse effects on the identity, strength, quality, purity, or potency of the biological product.

Level II are notifiable changes, which are moderate quality changes that have a moderate potential to have an adverse effect on the identity, strength, quality, purity or potency of the biological product.

The Level III is annual notification or minor quality changes that have minimal potential to have an adverse effect on the identity, strength, quality, purity or potency of the product. While the first two levels of changes were not to be implemented for commercial purpose without approval from the CDSCO, the Level III may be implemented by the MA holder without prior review by the regulator, except for cases of change in shelf life.

The Fourth level of 'quality only' changes are those which are not the other three levels of changes and are not expected to have an adverse effect on the strength, quality or other factors of the drug products. The changes included in this reporting category may be implemented by the MA holders without prior review by CDSCO. The changes should be retained as part of the drug product’s record by MA holders and should comply with the requirements of ‘Good Manufacturing Practices’.

The guidance further elaborates on the documentation requirements related to each of the levels of changes. All data recommended to support the change should be provided with the submission. Where applicable, these data should be provided in the format defined by CDSCO or in the format of Common Technical Documents (CTD), it said.

Annual notifications shall be submitted to CDSCO by the first quarter of every calendar year. Any data for the calendar year (January to December) that may have been generated by the MA holders in support of a Level III change should not be submitted with annual notification, however, should be available to CDSCO within thirty (30) calendar days, if requested.

Administrative product labelling information changes are changes that are not expected to affect the safe and efficacious use of the biological product. The review and approval timeline for an administrative product labelling information change shall be around 30 days from the date of submission.

The document also mentions the Post-approval change management protocol (PACMP), which establishes a framework for a well defined plan for the future implementation of a quality change, including the tests to be done and acceptable limits to be achieved to demonstrate the lack of negative effect of specific manufacturing changes on the quality, safety or efficacy of a biological product. A comparability protocol is a highly specific plan for the future implementation of a quality change.

It added that expedited review/Reliance pathway can be considered in Biological products for priority diseases to treat serious or life-threatening illness with unmet medical needs, in public health emergencies or during shortages, and also for orphan products.

Following approval, a Similar Biotherapeutic Product (SBP) or similar biologics, is considered to be independent from the reference product and has its own life-cycle. The manufacturer is not required to re-establish similarity to the reference product when comparability exercises are conducted. A major change in clinical use for an SBP that relies on the previously demonstrated similarity provided in the original approval of the SBP may be considered by CDSCO on a case-by-case basis.

However, when new safety information on the reference product is added after the original approval of the SBP, the labelling information changes of the SBP should follow the changes made for the reference product unless it can be demonstrated that the new information on the reference product is not relevant to the SBP, it said.


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