The primary focus of risk assessment for the use of excipients in any drug product is patient safety. According to the International
Conference on Harmonization (ICH) Q9 guideline on quality risk management, "Quality risk management is a process that supports
science based and practical decisions when integrated into quality systems" (1).
Twenty years ago, excipient manufacturers, distributors, and users established the International Pharmaceutical Excipients
Council of the Americas (IPEC–Americas) to apply the concept of science-based and practical decision-making to the evaluation,
qualification, and control of excipients. Since its inception, IPEC has developed and promoted the implementation of appropriate
and scientifically valid, voluntary industry guidance documents for the excipient industry.
IPEC's mission has been and continues to be to ensure that excipients meet the highest appropriate standards for quality,
safety, and functionality throughout their manufacturing process and supply chain. The use of risk-management principles furthers
The need for risk assessment
In a recent article, J. Orloff aptly noted "the potential for quality risk-management to degenerate into a non-value added
exercise of identifying noncritical, improbable, low-risk scenarios indefinitely" (2). Equally detrimental to effective application
of risk-management principles is the blinding self-deception emerging from group-think or tunnel vision that reasons away
all possibility of risk. Effective risk assessment should identify the proper balance of risk for which control is necessary
to ensure the quality, safety, and functionality of excipients. Focusing too much on controls aimed at low-risk hazards only
diverts resources and attention from high risk hazards, and can ultimately lead to an unsustainable control system and unrecognized
At the other extreme, failing to acknowledge vital risk can lead to unknowingly accepting failure. Orloff explained that "risk
assessment and control fundamentally rely on hypothesis, judgment, and expert opinion." He clarified that this judgment call
is "to be made by experts backed with an in-depth understanding of the underlying science and a common covenant to work on
what is vital."
Manufacturers typically produce a material that is sold into diverse markets (e.g., excipients, food, cosmetics, and industrial)
and their knowledge base tends to tilt toward their primary market. However, the risk assessment for excipients is unique
because of their use in drug products. Risk assessment for use in food or chemical applications do not properly account for
the risk unique to drug-product components.
Many industry manufacturers and users of excipients rely on good manufacturing practices (GMPs) coupled with hazard analysis
critical control point (HACCP) plans for food-ingredient manufacturers or failure mode effect analysis (FMEA) for chemical
manufacturers. These tools may provide adequate controls to ensure that food is safe for human consumption or that an ingredient
quality is sufficient for household products. Implementing these tools for excipients used in drug products, however, may
not be adequate to ensure patient safety.
Excipients share some similar hazards to food, but they also have a risk associated with their function in drug-product formulations
and manufacturing. The act of a physician prescribing a medicine for a patient is the result of a risk assessment that concluded
the benefit of taking this medication is greater than the consequence from lack of treatment. Under these conditions, a patient
suffers harm when the drug product does not function as intended or is not available in the market. A patient may be harmed
not only as a result of the excipient's composition, but also by potential variation in an excipient's characteristics. This
variation can result in erratic performance in the drug-product formulation.