F-Value Reports for Child Resistant Packaging (CRP)

Child-resistant Packaging (CRP) is a type of packaging that is difficult for young children to open (or gain access to the contents) as opposed to adults. CRP reduces child mortality/adverse effects from the unintentional ingestion of oral prescription drugs. CRPs are usually designed and manufactured by changing the foil material, blister material, adhesives, the orientation of blister pockets, and using different wadding materials of the container closure systems.

The “F” value, also known as Failure Value, is defined as the number of individual dose units of a drug that can cause serious illness or injury in a 25lb (11.4kg) child. For highly toxic or harmful drugs, the “F” value is usually set at F1, indicating that the child’s access to a single unit is considered a failure. Less toxic or less harmful products have a higher “F” value (for example, F8). When a child acquires access to a 9th unit, a default restriction of F8 is typically adopted.

Regulatory Requirement:

For any drug packaging falling under the regulation of the Poison Prevention Packaging Act (PPPA), it is imperative to include the F value of the packaged substance. A comprehensive report, outlining evidence-based justification and the calculation of the F value, must be submitted to the US Consumer Product Safety Commission.

As per 16 CFR § 1700.20 on the testing procedure for special packaging, a test failure is considered when a child opens the special packaging or gains access to its contents. Similarly, in the case of unit packaging, a test failure is considered when a child opens or gains access to the number of individual units or accesses more than eight (08) distinct units within 10 minutes of testing whichever is lower.

“F” value Calculation:

Toxicologists by virtue of their knowledge and experience in toxicological risk assessment are the best professionals who can evaluate substance-specific hazards and assess the potential acute health effects, encompassing both systemic and local effects likely to occur in children.

The process involves systematic collection and analyses of acute and repeated dose toxicity data and adverse health effects in humans including any available overdosage information from published case studies involving both adults and children. In addition, clinical trial and post-marketing data in adults, pharmacokinetic (PK), and pharmacodynamics (PD) data are also useful and considered during analyses of data. In the absence of substance-specific information, a read-across strategy using information from structurally or functionally similar compounds is seldom used to fill up the data gaps. Based on an overall assessment, a scientifically appropriate Point of Departure (POD) in terms of a numerical value (for example, a maximum tolerated dose or accidental exposure dose) is selected for the calculation of the 'F' value which is then utilized for F value calculation for 11.4 Kg weighing child. The "F" value typically ranges between 1 to 8.

F-values are calculated for a substance with multiple types of packaging (ex: Blister, bottles, etc). Based on the derived F-value, the packaging is designed for the drug product.