An Investigator Brochure containing a comprehensive summary of all non-clinical studies referenced in the IND may serve as a substitute for the 2.4 – Non-clinical Overview and 2.6 – Non-clinical Written and Tabulated summaries. Alternative approaches such as this may be considered on a case-by-case basis.
The overall goal of the non-clinical overview section is to provide the FDA with an integrated and critical assessment of the safety and efficacy of your product via pharmacologic and toxicologic evaluations. For more information on how to structure and key information to include in this section, check out the Module 2.4: Non-Clinical Overview template below and consider the pro-tips below while building yours. [2]
Pro tip: Ensure the document length is no more than 30 pages (maximum).
Some points you should consider highlighting in the non-clinical overview section include:
Relevant guidances on the conduct of studies and provide justification for any deviation made from the guidances
Discussion and justification of the non-clinical testing strategy
Good laboratory practice (GLP) status of the studies being submitted
Any association between non-clinical findings and the quality characteristics of the human pharmaceutical, clinical trials results, or effects seen with related analogues
Any literature which contains data or methods used to support the non-clinical information of the drug
You can cross-reference quality documents!
Can help justify proposed impurity in your drug substance and product
As AAV gene therapies are biotechnology-derived products, it is highly suggested that you:
Provide an assessment of the comparability of material you used in the non-clinical and clinical studies and one you are proposing to market
Provide relevant scientific literature and the properties of related products
For scientific literature used in place of studies conducted include justification around the design of the studies and deviations from available guidances
Provide information on the quality of batches for drug substance used in these referenced studies
If your drug product includes a novel excipient (i.e., an inactive substance that serves as the vehicle or medium for your AAV drug product, often to increase stability and thus shelf-life) then you should include excipient's safety information