Several factors need to be taken into consideration when planning a facility as outlined below:
- Cleanability, decontamination, and product changeover
- Controlling employee activity in the facility to minimize exposure potential
- Flexibility (i.e., does the design allow for easy reconfiguration?).
Operating an HPAPI facility
Operating an HPAPI facility means that a number of systems, policies, and standard operating procedures (SOPs) must be put
in place to protect staff. Additionally, manufacturers must ensure all employees handling HPAPIs be adequately trained. Senior
management must support the implementation of such systems, which includes providing the necessary funding for these systems.
There should be regular reviews of material safety data sheets, toxicological literature, and relevant occupational safety
and health literature for knowledge regarding the compounds used. These reviews should also include information on PPE and
To develop and monitor handling programs and training, it is recommended that a committee be established to take responsibility
for HPAPI-handling programs. Ideally, this committee would comprise a mixture of senior management, handling staff, experts,
occupational health professionals, and senior scientists. The committee should put together a general company policy and a
range of SOPs for potent-compound handling, including details of which staff members have access and are able to handle HPAPIs,
training-program requirements, development of SOPs, evaluation, categorization, and updating procedures and processes. For
each step, specific written instructions for equipment use and unit operations must be in force, though this could be applied
through the use of SOPs.
One of the primary concerns when handling potent compounds is employee exposure, which could potentially result in undesired
health effects and/or sensitization. It is vital to set up an appropriate employee medical surveillance and monitoring program.
An occupational physician should work closely with the committee, regulatory authorities, and any relevant health and safety
bodies. Another significant issue is the ability to clean contaminated surfaces to an established, acceptable and safe level
set out by GMP or industrial hygiene guidelines. Cleaning verification and validation procedures are critical and should include
a viable deactivation solution in the cleaning process whenever possible.
Response plans must also be in place to ensure employees react appropriately to an unplanned event. These plans should include
employee training for emergency response, communication plans, and an ongoing evaluation of the program. Involvement of local
authorities in the planning and training for emergency response is also important.
It is vital that HPAPI-handling systems and equipment are tested and verified to meet the necessary isolation requirements.
For example, isolation equipment may be expected to meet a containment capability of less than 1 μg/m3. The capability of equipment, systems, and procedures to contain and isolate materials under expected operating conditions
must be verified as a critical component of the overall HPAPI-handling program. This process typically requires the use of
both air and surface industrial hygiene sampling methods to confirm proper isolation following a detailed sampling plan. In
many cases, sampling and testing methods for products in early preclinical or clinical testing have not been developed. Therefore,
surrogate products such as lactose or naproxen sodium, are frequently used to complete the equipment testing.