Non-sterile hazardous preparation

In the past 10 years, the use of oral anticancer agents for the treatment of various type of cancer has been increasing. Of all the cancer therapy under clinical development, 20 to 25% are expected to be oral. The common situations that require to crush or break the oral dosage form are in the pediatric population. But in adult oncology, patients with gastric or head and neck cancer, as well as the elderly, often experience swallowing problem or dysphagia. These patients may have difficulty with oral ingesting solid form of drugs, for example, tablets and capsules. Some of these patients may require feeding tube to help them maintain normal nutrition.

In nursing home or long-term care setting, a common practice for nurses is to crush pills and mix them in a liquid or other food for ease of administration for elderly patients with swallowing difficulties. The crushing of tablets and the mixing of powders goes hand in hand with the generation of airborne particle of the product used, and is to be avoided whenever possible. The crushing of cytotoxic tablets or the opening of capsules in an open mortar should be avoided. For mixtures, many tablets may be dispersed in pre-calibrated bottle. Single dose mixture are recommended. Staff are vulnerable to contamination by either direct contact or by the inhalation of these potentially toxic products.

The hierarchic order in prevention is also applicable to this kind of activity. As replacement or the use of a contained system is unlikely, reliance is on ventilation and use of personal protective equipment. Oncology pharmacists face challenge of dealing with oral anticancer drugs that are not available in liquid dosage forms, and extemporaneous preparation of oral liquid formulations is required. Data on dose uniformity and stability of extemporaneous oral liquid formulations of oral anticancer drugs are scarce. Few study have evaluated the bioequivalence and safety of administering extemporaneous prepared oral anticancer agents, either mixed with fluids or flushed through a feeding tube.

When extemporaneously compounding oral chemotherapeutic agents with a narrow therapeutic index that are not properly prepared, one may also raise a concern of an increased risk of over- or underdosing, leading to increased adverse events or decreased effectiveness, respectively. In the community and home setting, oral chemotherapy agents are often dispensed or administered without proper safeguards. Patients or caregivers without adequate counseling and education on how to safely handle these agents may also be at an increased risk of exposure to these hazardous drugs. As a general rule, the opening of capsules, crushing tablet, and dissolving powder should not be done outside of the pharmacy. The extemporaneous preparation of cytotoxic drugs should be performed under the same condition as for parenteral cytotoxic drugs.

This operation should be carried out in a separate room specifically dedicated to this purpose. Tablets and capsules must be handled in a manner that avoids skin contact, liberation of drug into the air, and chemical cross contamination with other drugs. All equipment used in the dispensing of cytotoxic solid dosage form must be dedicated to this purpose and clearly labelled as such. Cytotoxic tablets or capsules should not be counted using a counting machine. Containers with damaged contents should be discarded. All activities likely to result in particle generation, for example, weighing, crushing, mixing or filling capsules, should be performed in a Class I Biological Safety Cabinet.

A Class I cabinet extracts the air from behind the operator, flowing over the arms, hands and the product itself before being exhausted via the top of the cabinet. A Class II B2 could also be used, but this cabinet should not be used for a mixed activity of sterile and non-sterile preparation. This is because of the liberation of powders and other particulate contamination into the clean room. The risk of this type of contamination is high. Possibly some disposable system would be a better option. For example, bag fitted with gloves for containment in laboratory. In addition, a negative air pressure Biological Safety Cabinets Type III is an alternative to a dedicated Type II B2 Biological Safety Cabinets.

Normally, a HEPA filter is located within the cabinet exhaust. An additional filter such as an active carbon filter may also be installed. As for the cabinets used for the sterile preparation, these cabinets should also be validated, preferably every 6 months. Personal protective equipment must be used by the personnel. This consists of gowning, the use of non-sterile gloves and masks. The mask could be P2 to P3 in European and Australian system, or N95 in North America. In the case of cleaning activity inside the class 1 cabinet or in the event of spills or other incidents. All equipment used in the extemporaneous preparation of cytotoxics must be dedicated to this purpose and clearly labelled as such.

This equipment should be cleaned immediately after use with a strongly alkaline solution. In summary, hazardous including most of the anticancer agents, including traditional cytotoxics, hormones, many new target agents, and also other agents. The preparation of these agents require protection of handling personnel and in the sterile product preparation, final drug products. The protection requires primary engineer controls and personal protective equipment. All these devices require the appropriate selection, maintenance, and use. Pharmacists are at the center of the safety in the hazardous drug use. All other health care professionals rely on your special knowledge and skills in preventing and managing the hazardous drugs in your institution. Thanks for your attention!

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