How to Reduce Variance in Solid Oral Dosage Form Fill Counts

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					How to Reduce Variance in Solid Oral
Dosage Form Fill Counts
Surveys taken over the last 25 years demonstrate that 100 percent fill counts for solid oral
dosage form are achievable. Pharmaceuticals that maintain their equipment to appropriate
levels can reach their objective in normal operations. Nonetheless, variations are a reality
despite companies aiming to have their fill count match their label claim.

It is not abnormal for variance in fill counts, also referred to as process capability range, to
occur. To limit fluctuations, Troy Fugate, vice president, Compliance Insight, Inc. recommends
process-based statistical sampling. Fugate urges, “companies ought to focus on the control,
understanding, and qualification of manufacturing equipment to help achieve their goal.”

The Current Good Manufacturing Practices (cGMPs) for pharmaceuticals promotes guidelines
for fill-count targets as set by the US Food and Drug Administration (FDA). But it is not
sufficient merely to set a better fill-count target and simply hope it translated to better process
controls that produce better outcomes.

There is no FDA document that specifically addresses fill-count targets due to the fact that the
cGMP rules are not specific. However Fugate recommends these actions after a review of
applicable sections in the Code of Federal Regulations:
    Choose equipment that focuses on delivering high efficiency for a specific purpose

      High performance equipment requires regular calibration and maintenance

The two messages from above are clear if pharmaceutical manufacturers are serious about
reducing variance in fill-counts: (1) choose excellent equipment; (2) set clear operational and
maintenance policies.

Variation in results can reasonably be expected from mechanical equipment. Other contributing
factors to variations include how the operations are setup, the focus on equipment
maintenance, and the kind of dosage form being packaged. These things can be controlled with
enough focus but there are other factors that cannot. “Product variables, which include things
such as dust and static charge,” remarks Fugate, “can defeat even the best equipment.”

Part of the ethical code of conduct for pharmaceutical companies includes purchasing excellent
equipment that is well maintained.

Proper maintenance includes:
    Calibrate and maintain equipment proactively

      Determine equipment competence utilizing engineering or process studies
      Demand industry standards as minimum equipment performance

      Review process and fill-count results regularly to meet your objectives

While it is reasonable to expect some variance in fill-counts, the best approach is to begin with
an objective to produce 100 per cent fill-control targets. It is also important to not to accept
lenient variation results for the fill-counts.
Author: Beth James

Pharmaceutical compliance resource website:

This article is free for republishing provided no modifications are made and writer`s name and
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Description: How Accurate are Fill Counts for Solid Oral Dosage Forms? This is an important question facing pharmaceutical manufacturers. This article proposes to address this challenge.