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. They are usually manufactured by changing the foil material, blister material, adhesive, the orientation of blister pockets, and using different wadding materials in container closures.

Background

The Consumer Product Safety Commission (CPSC) declared the Poison Prevention Packaging Act in 1970 to establish standards for the special packaging of any household substances to protect children from serious personal injuries, or serious illnesses resulting from the handling, using, or ingesting such substances. In 2001, the CPSC extended the CRP requirements to oral drugs approved by the United States Food and Drug Administration (USFDA) for sale as Over-the-Counter (OTC) drugs.

CRP testing is required to demonstrate that the packaging is safe. Formal tests are usually conducted to demonstrate that children cannot open the package, but adults/elderly can do so. However, there is no formal guidance available for this assessment. Limited guidance/support documents from the CPSC or the industry provide some basis for this assessment. Therefore, this evaluation is generally performed based on the scientific principles of risk assessment.

‘F-Value’

“F” value, aka 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 in the US, a default restriction of F8 is typically adopted. The "F" value is typically calculated from F1 to F8.

‘Fail Test or Test Failure’

As per 16 CFR § 1700.20 on the testing procedure for special packaging, a test failure shall be any child who opens the special packaging or gains access to its contents. In the case of unit packaging, a test failure shall be any child who opens or gains access to the number of individual units, or for the complete ten (10) minutes of testing, accesses more than eight (08) distinct units, whichever is lower.

Role of a Toxicologist in ‘Child Resistant Packing’

Toxicologists can characterize substance-specific hazards (Carcinogenic, Mutagenic, and Reprotoxic (CMR)) and possible acute health effects (both systemic and local effects) in children.

Based on the acute data, repeated dose non-clinical toxicity data, acute human data, overdosage information, and various case studies (both adults and children), the Maximum Tolerated Dose (MTD) is identified and based on the allometric scaling, a Point of Departure (POD) needs to be determined for F-Value calculation after which the ‘F’ value is calculated.

Data Used for Determining the ‘F-value’

Overdose data in children and MTD in humans, clinical trial and post-marketing data in adults, Pharmacokinetic (PK) and Pharmacodynamics (PD) data, acute and repeat-dose toxicity data in animals, read across approach using surrogate molecules if needed, etc., is the main data used to determine the ‘F-value.’

Conclusion

Determination of the ‘F-value’ guides the requirement of CRP for a final formulation. If the ‘F-value’ is near one, it indicates that it requires special CRP, and if it is near eight, it indicates that the final formulation does not possess any significant safety concerns for children.

Therefore, it is of utmost importance that manufacturers consider the determination of the F-value to make the packaging child-resistant. A team of experienced toxicologists can support in determining the correct F-value, making it simple and compliant for the manufacturers. At Freyr, our expert toxicologists can help you with all your drug packaging needs. Consult Freyr for compliance.

Author:

Bakul Datta
Manager, MPR Medical writing.

 

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