Additionally, companies should consider what items are appropriate for the manufacture. For example, the use of a certified laminar flow hood may be a better choice for manufacturing than a fume hood, because the former is designed to prevent contamination of the product, protect the operator, and the laboratory environment. In addition, with the appropriate cleaning, a laminar flow hood can more easily be used for multiple products. Small scale/manual equipment or procedures may be the best approach because the space is likely to be limited. With a small batch size, the use of small scale or manual equipment/procedures will minimize yield loss. Additional measures to be assessed include appropriate gowning and operator personal protection devices, area and operator monitoring for potent or radiolabeled drug exposure, and so forth.

Documentation of the facility preparation, product manufacture, and the return of the facility to the previous state, if needed, is recommended. This documentation should describe the rationale for the manufacture in the nondedicated area, risk assessment, preparation of the area, cleaning procedures, and list of responsible persons. This documentation can reference existing procedures or standard operating procedures (SOPs) along with documents associated with the meetings and preparation for the manufacture of the batch. Batch records and cleaning records should be part of the documentation and should follow the company's data-retention policy.

Preparation at the clinical site. On-site preparation of formulations, sometimes referred to as "extemporaneous preparation" or "compounding," is not considered manufacturing, but is an effective method to prepare early clinical supplies using the local laws governing the practice of pharmacy. The processes used for on-site preparation can be as simple as preparing and diluting solutions or filling capsules with API to more complicated processes such as blending and compression of tablets. An IQ working group addressing current practices in extemporaneous preparation has conducted a survey to be communicated at a later date, which confirms that only a few companies have adopted practices to take advantage of more advanced formulation approaches at the clinic site (8). This is a missed opportunity, because on-site preparation of formulations has the potential to dramatically speed industry's ability to answer critical questions related to pharmacokinetic parameters, absolute or relative bioavailability, feasibility of extended release and bioavailability enhancement approaches for difficult to deliver molecules. Currently, each company must develop its own best practices to assure product quality and patient safety; often, these practices are based on compendial or professional association publications (9–11). The authors believe this topic warrants further discussion between the industry and regulatory authorities to determine when dose preparation at the clinical site is appropriate and the level of quality controls required. The results of such a discussion could help to increase the utilization of on-site preparation of clinical trial materials to facilitate quick answers to critical questions in early drug development and ultimately bring the best possible products to patients in the shortest time.

The use of dedicated or disposable equipment or product contact parts may be preferable to following standard cleaning procedures to ensure equipment is clean and acceptable for use. However, not all equipment or equipment parts are disposable or may have a substantial cost that makes disposal prohibitive. In that case, the product contact parts could be dedicated to a specific drug substance for use in drug product manufacture. Dedicating product contact parts to a compound may be costly and may be avoided in some cases by carefully considering product changeover and effective cleaning methods when purchasing equipment.

Another item to consider with respect to equipment, is that the more complicated the equipment is to run or maintain, the less desirable it might be for early GMP batches. In most cases, simple equipment is adequate and will uses less material and consume less total time for preparation, operation, and cleaning activities.