SubscribeA recent ICH guideline (ICH Q9) describes the use of risk management procedures as part of the quality management of pharmaceutical manufacturing and development.
The guideline accepts that no drug product can be completely risk free, but that manufacturers should have procedures to quantify and manage these risks.
Risk is defined as the combination of the probability of occurrence of harm and the severity of that harm. Risks can come from many areas:
- The drug substance may have serious side effects - it may be acceptable to have serious side effects in a treatment for a terminal condition such as cancer, but not in an OTC remedy for a common cold.
- The drug may have adverse effects on a particular subset of patients - this may not be observed until the product is marketed and large numbers of patients take it.
- The drug substance may degrade - the acceptability of this may depend on the toxicity of the degradation products.
- Manufacturing errors may cause product defects in parts of batches, which may not be identified by random testing.
- The properties of the drug substance may change over time as process improvements are introduced - particle size may affect drug absorption or a changed synthetic route may affect the impurity profile.
The guideline refers to a number of established risk management tools that may help companies to assess and manage the risks presented by their products. Essentially the process is:
- Identify the potential risk
- Estimate how often it is likely to occur
- Assess the effect
Risks can then be ranked in order of severity - a risk event that is serious but is very unlikely to occur may be less important than one which is less serious but could occur frequently. Companies should put resource behind reducing or removing the high-ranking risks first. This list must be reviewed periodically since, as specific risks are removed, others will rise to the top of the list. The review should also check that new risks have not been introduced as a result of the original risks being controlled.
The guideline proposes that companies should have systematic processes designed to coordinate, facilitate and improve science-based decision making with respect to risk. This should involve identifying a team leader with sufficient experience and resource to be able to carry out these risk assessments and propose risk reduction programmes. Senior management must also show commitment to this risk reduction process. This may need input from experienced consultants if the company does not have appropriate in-house staff.
Somerset House Consultants experts plan and carry out risk management programmes on behalf of their clients, in full compliance with the ICH Q9 guideline.