FDA Relaxes GMP Rules For Early-Stage Trials
3 CommentsBy Ed Silverman // July 24th, 2008 // 8:23 am
The impetus would be the different requirements for scaling up for clinical trials and commercial manufacturing, according to in-PharmaTechnologist, which adds that the FDA’s new regulatory guidance removes the requirement that candidate drugs are produced using a fully validated manufacturing process.
The ruling, which goes 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 regs that are applied to drugs produced on a commercial scale, the trade reports, according to in-Pharma.
Drugmakers must still comply with statutory current GMP guidelines and submit detailed info about production processes as part of an IND, or investigational new drug application, but the new guidance frees companies of some rules that are seen as relevant to commercial scale production, in-Pharma adds.
An agency spokesman tells in-Pharma that the: “FDA’s position is that the US GMP regulations were written primarily to address commercial manufacturing and do not consider the differences between early clinical supply manufacture and commercial manufacture.”
“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-Pharma speculates, and then adds that the change may provide drug developers with “considerable leeway in dealing with the variability that is common when production is scaled to create clinical trial inventories.”
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.
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. This approach will ensure that these investigational products can be developed as efficiently as possible with the highest level of patient protection.”
Anne
So in a time when parents are calling for safer vaccines, they’re relaxing the safety rules?
Nathan
Anne, this statement says it all: “US GMP regulations were written primarily to address commercial manufacturing and do not consider the differences between early clinical supply manufacture and commercial manufacture.”
There are big differences in the manufacture of a few kg of material for a phase I clinical trial vrs the manufacture of a few THOUSAND kg of material for commercial sale. The same regulations should NOT apply to both scenarios. Maybe someone on the GMP end of the business could elaborate on the specifics of these changes? CMC guy?
CMC guy
Nathan the inPharmaTechnologist post had another statement that also well summaries the meaning/motivation of “The new guidance liberates companies of some of the rules that are only really relevant to commercial scale production”. The early stages of development have long been a “gray area” in detailed application of the GMP regs since indeed those codes primary focus was on commercial manufacture (and mostly toward the Drug Product). IMO this only codifies what FDA has been saying in other ways (and largely practiced) for many years therefore provides more clarity and definition which is usually a good thing for industry. Also this makes more consistent with ICH and ROW regs.
I don’t see this as a lessening of Safety Rules (as implied by Anne) but allowing the required flexibility to operate in fluid status that still has high Quality Standards (i.e Safety). Helps confirm OK to be gathering info/data as you go rather than mandated certain tasks prior to production (i.e. process validation).
Maybe I am prejudiced (since is my area) but going from mg/g to kgs is usually more different/difficult than from a few kgs to 1000s kgs. The later is more engineering intensive, thus still different and needs correct expertise but not dramatic modifications. Bench to Pilot Plant is often tougher transition and typically is occurring during aggressive pre-IND and Phase I time constraints.