The variance in fill count - also called process capability range - recurs. “Accurate fill limits should be based upon the control, understanding, and qualification of applicable equipment,” says Troy Fugate, vice president, Compliance Insight, Inc. “Process-
A stricter fill-count target does not mean that process controls would automatically become more efficient. A lax fill-control target would not be in accordance with the Current Good Manufacturing Practices (cGMPs) for pharmaceuticals as stipulated by the US Food and Drug Administration (FDA).
Though, the FDA has not issued any specific documents regarding fill-control targets because cGMP rules are not that specific. Fugate points out that we could infer the following from the applicable sections in the Code of Federal Regulations:
Equipment should be of proper design so that it can be used most efficiently for the purpose it is intended.
Equipment should be calibrated, and maintained for optimum performance.
These are general requirements but they imply that pharmaceutical manufacturers should automatically choose high-quality equipment that offers the least variance from fill-control targets. The packaging equipment must be maintained and operated in the most efficient manner.
Mechanical equipment would show some variation in results. But, the variations would also depend upon the kind of dosage form being packaged (e.g. - tablet, capsule), how well the equipment is maintained, and the operating set-up. These factors can be controlled to ensure minimal variation from fill-control targets. “However, some factors like product variables (e.g. - dust, static charge) are impossible to control. So, the most sophisticated equipment and vision systems cannot guarantee 100 percent accuracy in fill targets,” says Fugate.
All pharmaceutical companies are ethically bound to use the best equipment and ensure proper maintenance.
Key maintenance processes should include:
Preventive maintenance and calibration programs
Equipment capability evaluation through process studies or engineering
Ensuring the equipment meets industry standards
Monitoring regular processes and ensuring that fill-count targets are met on a regular basis.
No allowance should be made for any variance from the target fill at the outset though, it is understood, that some variance would occur. The intention should be to maintain 100 per cent fill-control targets to allow minimal variation. The manufacturers should also set a strict tolerance for extent of variation that is acceptable from the fill-count target.
Compliance Insight, Inc. specializes in Regulatory and Quality Assurance consulting and training for pharmaceutical, nutraceutical, medical device, chemical, and bio-technology companies in North America, Europe and Asia.