Compliance Risk Management Using a Top-Down Validation Approach 4

Identity addresses:

• Chemical structure
• API synthesis
• Bulk labeling
• Primary-container label
• Product name
• Dosage
• Lot number
• Expiration date
• Barcode
• Secondary-container labeling
• Product name
• Product insert.

Strength includes consideration of:

• Potency
• API synthesis
• Bulk-package integrity
• Final-package integrity
• Storage conditions
• Shipping conditions
• Stability
• Bulk material
• Presterilization
• Poststerilization
• Finished goods.

Other concerns
The previous lists include the primary concerns. Others considerations include:

• Stopper coreability
• Stopper and glass siliconization
• Stopper moisture content
• Intermediate-package cleaning
• Intermediate-package integrity
• API facility environmental conditions
• Fill-isolator integrity.

Analytical support to validation. To properly evaluate critical quality attributes, validated analytical methods are required. Validating a pharmaceutical process or product before the test methods used to evaluate it are validated severely limits the quality of the data and thus jeopardizes the entire effort. It is pointless to perform any analysis without being confident that the results can be considered reliable.
Sampling for microbial and foreign matter. Sampling methods can also play a major role in perceived and actual quality, especially as related to microbial and particulate (absence of foreign matter) quality. Taking a sample in these instances can harm the very property the sample is intended to evaluate. Sample procedures must be designed to avoid incidental contamination of the production materials and samples. Microbiological and foreign-matter test methods should incorporate appropriate controls to ensure the results are indicative of the material and not the test method itself.
System-performance qualifications. In addition to the product-quality attributes described above, the validation of other essential systems is necessary. The most important of these are water and environmental-control systems that have a significant albeit indirect effect on the product-quality attributes. Other systems with a less clear effect on end-product quality may be assessed in a less comprehensive manner. Utilities such as steam, compressed air, and jacket services, ordinarily do not have a direct effect on the key quality concerns and can be placed into service by commissioning rather than formal qualification. The American Society for Testing and Materials has developed an expanded analysis of risk-based qualification for pharmaceutical systems (7).