US FDA
21 CFR Part 312 - Investigational New Drug Application
Plain-language explanation, inspection context and common violation patterns.
What it says
Part 312 establishes the Investigational New Drug Application framework required before a drug can be shipped for use in clinical trials, requiring submission of manufacturing information, preclinical data, and a clinical protocol, with FDA able to place a clinical hold if safety concerns arise, including manufacturing and control deficiencies.
Paraphrased for plain-language clarity. Always verify against the current published regulation text.
What it means in practice
- An IND is the regulatory gateway allowing clinical trial material to be legally shipped and administered to human subjects, functioning as the necessary precursor to the eventual New Drug Application pathway described under FD&C Act Section 505.
- Manufacturing information required at the IND stage is intentionally less extensive than what a full NDA eventually requires, reflecting a phased, risk-proportionate approach where manufacturing knowledge and control expectations increase as a product moves through clinical development toward approval.
- Clinical holds can be imposed specifically due to manufacturing and control deficiencies, not only clinical safety concerns, meaning inadequate chemistry, manufacturing and controls information can halt human trials entirely regardless of promising clinical data.
What FDA inspectors look for
- Whether manufacturing information submitted and maintained under the IND accurately reflects the actual process used to produce clinical trial material.
- Whether investigational product manufactured under an IND is being produced consistent with the more adapted GMP expectations described in EU GMP Annex 13, even though the specific regulatory vehicle, IND versus EU clinical trial authorisation, differs.
- Whether changes to manufacturing during clinical development are properly documented and, where significant, communicated to FDA as required.
Most common violation
Manufacturing changes made during clinical development, such as scaling up production between trial phases, implemented without adequately assessing and documenting whether the change affects the product characterisation and information on file with FDA under the IND.
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