Dispensing Trial Drugs for Home Use
CPSC outlines child-resistant packaging guidelines for manufacturers.
The U.S. Consumer Product Safety Commission (CPSC) administers the Poison Prevention Packaging Act (PPPA) and its regulations. Congress enacted this law in 1970 to address the rising numbers of deaths and serious injuries to young children from the handling or ingestion of hazardous household substances and drugs.
In 1974, a child-resistant packaging regulation for certain prescription drugs went into effect. That regulation, 16 CFR section 1700.14(a)(10), requires that all prescription drugs intended for oral administration in humans comply with the child-resistant packaging requirements unless specifically exempted. The regulation applies to drugs dispensed for home use, but does not cover those drugs dispensed for use in hospitals or similar institutions. Clinical trial drugs in a dosage form intended for oral administration in humans are subject to these requirements when they are dispensed on an outpatient basis for use in the home. Additionally, OTC drugs used in clinical trials that are dispensed for outpatient use must comply with the child-resistant packaging requirements if they are subject to one or more of the other regulations issued under the PPPA.
Over the past few years, conducting clinical trials on an outpatient basis has increased. We recently learned that child-resistant packaging has not always been used for oral prescription drugs dispensed in clinical trials for household use. We have had several meetings with industry to discuss this issue.
Industry expressed concern that the development of a unit-dose package for use in each clinical trial that is both child resistant and effective in accomplishing the objectives of the protocol could be difficult. They also noted that the varying amounts and types of drugs used during crossover and titration studies could significantly affect the costs of such packaging and the time necessary to acquire it. Industry requested the Commission consider a two-year phase-in period during which firms would develop and implement an immediate child-resistant package for use with clinical trial drugs.
The CPSC staff appreciates the need to ensure patient compliance during clinical trials. However, we are concerned that allowing clinical trial drugs to enter homes in non-child-resistant packages could expose young children to serious injury if the children ingest those products. On May 23, 2000, we issued a statement that strikes a balance between these competing concerns. The statement, an exercise of our enforcement discretion, permits manufacturers of drugs dispensed for household use in clinical trials to use the following alternatives to strict compliance with the requirements of the PPPA.
Non-child-resistant packaging may be used if the amount of drug that is dispensed into the home will not cause serious injury or illness to a young child. Firms packaging clinical trial drugs who wish to take advantage of this option must maintain data that demonstrate that that amount, if ingested, would not be expected to cause serious injury to children. This data must be made available to CPSC upon request.
Clinical trial drugs with sufficient toxicity to cause serious injury or illness to a young child must be packaged with a child-resistant feature. This can be achieved in one of two ways. First, the units can be made with any of the features described in ASTM D-3475, provided that the packaging has at least one recognized child-resistant feature. This option alleviates the need to test the packaging of each different drug that is to be used in clinical trials. We generally expect manufacturers who choose this option to procure packaging from firms that can demonstrate that the package designs to be used with clinical trial drugs have been tested and meet the requirements for child resistance. The clinical trial package itself, however, would not require testing.
Alternatively, subject to the time limitations discussed below, non-child-resistant unit-dose packages can be placed in an outer container that meets the standards for child resistance (16 CFR section 1700.15). This will allow firms to comply by using child-resistant outer containers until they are able to use child-resistant unit packaging.
These two options may be used in Phase IV clinical trials only when it is not possible to use a commercially available child-resistant package or when the use of such a commercial package configuration would be detrimental to the study. If neither of the preceding conditions exists, commercially available child-resistant packaging must be used during Phase IV trials.
Child-resistant outer packages are currently available and can be used without the need to change the immediate package of a clinical trial drug. Accordingly, all drugs used in Phase II, III, or IV clinical trials initiated after 6 months from our May 23, 2000, statement must be packaged in accordance with the guidance above. (Initiated is defined as the date a firm submits its protocol to conduct a clinical trial to FDA.) We encourage all firms currently conducting clinical trials and firms who initiate clinical trials within 6 months of the date of this statement to use child-resistant packaging when available, feasible, practicable, and appropriate for the clinical application.
Finally, the immediate packages of all toxic oral drugs intended for human use that are dispensed for household use in Phase II, III, or IV clinical trials initiated after 24 months from our May 23, 2000, statement, must be child resistant. This means that, after May 23, 2002, a firm conducting a new clinical trial, regardless of the phase, can no longer use a child-resistant outer container to satisfy the child-resistant requirements. Based on our familiarity with the packaging industry, we believe that this is a reasonable time frame. Firms may continue to use non-child-resistant packaging for drugs that are not toxic under the conditions outlined above.
In summary, the CPSC staff is exercising its enforcement discretion to permit makers to use non-child-resistant packaging for clinical trial drugs dispensed for household use that are currently being used during clinical trial studies (Phase II, III, or IV), or that will be used during clinical trial studies (Phase II, III, or IV) that are initiated before November 23, 2000 (6 months from our May 23, 2000, statement). The following should provide further clarification:
Example 1. If a Phase II trial is initiated in June 2000, which is less than 6 months after May 23, 2000, the packages do not have to be child resistant and no overpackage is required. If the Phase III trial of this study is initiated in January 2001, more than 6 months after May 23, 2000, then the drugs used in this phase must, at a minimum, be in a child-resistant overpackage. If the Phase IV trial of this study is initiated in June 2002, after the two-year period that began May 23, 2000, these drugs must be dispensed in child-resistant immediate packaging.
Example 2. If a Phase II trial is initiated in January 2001, more than 6 months after May 23, 2000, then the drugs dispensed during this phase must, at a minimum, be in a child-resistant overpackage. If the Phase III trial of this study is initiated in March 2002 (more than 6 months after May 23, 2000, but still within the two-year time period that began May 23, 2000), the drugs in this phase must, at a minimum, be in a child-resistant overpackage. However, if the Phase III trial is instead initiated in June 2002 (more than 2 years after May 23, 2000), these drugs must be dispensed in child-resistant immediate packaging.
Example 3. If a Phase II trial is initiated 2 years after May 23, 2000, then all drugs used in Phase II, III, and IV trials of this study must be in child-resistant immediate packaging.
These options are not normally available under the PPPA. However, we are exercising our enforcement discretion with regard to Phase II, Phase III, and Phase IV clinical trials as described above. These determinations are based solely on the information currently available to the staff and the enforcement posture the CPSC currently has in effect. They could be changed if the facts change, and they could be superseded by the Commission.