FDA relaxes GMP rules for Ph I candidates

July 25, 2008

The US Food and Drug Administration (FDA) has relaxed the regulatory good manufacturing practice (GMP) rules for drugs in early-stage clinical trials in recognition of the different requirements of trial scale and industrial scale manufacture.

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.

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.”

Analyzing Risk in Medical Devices is that required

July 17, 2008

Why should we perform risk analysis?

1. Risk analysis is now required by law (Revised GMP, see below)
2. Identification of device design problems prior to distribution eliminates costs associated with recalls.
3. It offers a measure of protection from product liability damage awards.
4. Regulatory submissions checklists (PMA and 510k) used by the FDA now call for inclusion of risk analysis.
5. It is the right thing to do.


“Pre-production Quality Assurance Planning Recommendations For Medical Device Manufacturers” identifies three tools for risk analysis: 1. Failure mode effects analysis (FMEA),
2. Fault tree analysis (FTA), and Failure mode effects criticality analysis (FMECA)
3. Failure Mode Effects Analysis (FMEA) and Failure Mode Effects Criticality Analysis (FMECA)

Failure mode effects analysis (FMEA) is a “bottom up” approach which assumes a basic defect at the component level, assesses the effect, and identifies potential solutions. It should be conducted at the beginning of the design effort and as part of each design review to identify potential design weaknesses. Failure mode effects criticality analysis (FMECA) adds probability of occurrence and severity of failure to the FMEA process.

The steps of the FMEA process:

• Define the function of the unit being analyzed.
• Identify all potential failures.
• Determine the causes of each failure types.
• Determine the effects of potential failures.
• Assign a risk index to each of the failure types.
• Determine the most appropriate corrective/preventive actions.
• Monitor the implementation of the corrective/preventive to ensure that it is having the desired effect.

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