The FDA’s new regulatory guidance, which was detailed in a recent edition of the US Federal Register, removes the requirement that candidate drugs are produced using a fully validated manufacturing process.
The ruling, which comes into effect on September 15 and will apply to most candidate biologics, small molecules and vaccines, also removes some of the stock rotation requirements and labelling regulations that are applied to drugs produced on a commercial scale.
Drugmakers must still comply with statutory current good manufacturing practice (cGMP) guidelines and submit detailed information about their production processes as part of the investigational new drug (IND) application. The new guidance liberates companies of some of the rules that are only really relevant to commercial scale production.
The move could encourage innovation in the drug discovery sector as it considerably lowers the cost of moving candidates from the laboratory to the clinic. In addition, it provides developers with considerable leeway in dealing with the variability that is common when production is scaled to create clinical trial inventories.
An agency spokesman explained that the: “FDA’s position is that the United States’ [GMP] regulations were written primarily to address commercial manufacturing and do not consider the differences between early clinical supply manufacture and commercial manufacture.”
Companion guidance document
The FDA first proposed making candidate drugs exempt from Phase I GMP requirements in 2006 only to withdraw its ruling later that year following several adverse comments from industry players.
The new exemption does not apply to investigational drugs that are also in Phase II or III examination, or those that are already commercially available but are being assessed at Phase I for alternate indications.
The agency has also issued the companion guidance document, cGMP for Phase I Investigational Drugs, to help drugmakers comply with the cGMP statutory rules.
These include standards for facilities and equipment, control of components, testing, stability, packaging, labelling, distribution, and recordkeeping that are all still absolute requirements.
US Health and Human Services Deputy Secretary Tevi Troy said: “We are tailoring the cGMP requirements to make them appropriate to the earliest stages of drug development.”
Troy added that: “This approach will ensure that these investigational products can be developed as efficiently as possible with the highest level of patient protection.”