ABSTRACT
The manufacture and control of oral solutions and oral suspensions presents some unusual problems not common to other dosage forms. Although bioequivalency concerns are minimal (except for products in which dissolution is a ratelimiting or absorption-determining step, as in phenytoin suspension), other issues have frequently led to recalls of liquid products. These include microbiological, potency, and stability problems. In addition, because the population using these oral dosage forms includes newborns, pediatrics, and geriatrics, who may not be able to take oral solid dosage forms and who may have compromised drug metabolic or other clearance function, defective dosage forms can pose a greater risk if the absorption profiles are significantly altered from the profiles used in the development of drug safety profiles.
The designs of the facilities are largely dependent on the type of products manufactured and the potential for crosscontamination and microbiological contamination. For example, the facilities used for the manufacture of over-thecounter oral products might not require the isolation that a steroid or sulfa product would require. However, the concern for contamination remains, and it is important to isolate processes that generate dust (such as those processes occurring before the addition of solvents). The HVAC (heating, ventilation, and air-conditioning) system should be validated just as required for processing of potent drugs. Should a manufacturer rely mainly on recirculation rather than filtration or fresh air intake, efficiency of air filtration must be validated by surface and air sampling. It is advisable not to take any shortcuts in the design of HVAC systems, as it is often very difficult to properly validate a system that is prone to breakdown; in such instances a fully validated protocol would need stress testing-something that may be more expensive than establishing proper HVAC systems in the first place. However, it is also unnecessary to overdo it in designing the facilities, as once the drug is present in a solution form, crosscontamination to other products becomes a lesser problem. It is, nevertheless, important to protect the drug from other powder sources (such as by maintaining appropriate pressure differentials in various cubicles).
