Risk assessment for quality issue

Any medicinal product, be it a device, drug, or combination, may have a quality issue that is also interconnected to pharmacovigilance. The quality issue itself may or may not lead to an adverse event (AE), and the ones associated with AE will be tracked in the global safety database, at the ICSR level. However, certain quality issues may require aggregate analysis and market actions that can impact patient safety and have a public health impact. These quality issues will require medical assessment on how serious the risk is, which is performed by a medical safety physician from pharmacovigilance.

These are typically non-product-specific and are deviations in manufacturing, packaging, or distribution of the product. These deviations or non-compliance with health authority specifications or internal marketing authorization (MAH) specifications are analyzed, evaluated, and then a recommendation is made by the pharmacovigilance team on the outcome of this deviation and its impact on patient and public health.

The following are the criteria /source of information used to perform the risk assessment of the deviation/quality issue/non-compliance. Although these are different terminologies and can mean different things as per the MAH internal process, for the sake of this blog, we will use them interchangeably. 

1. Global Safety database:

Using a search strategy that can retrieve all cases about that particular quality issue, all ICSRs should be analyzed and evaluated.  The time period is from the date of manufacturing of the product/ but ideally, from the date of market launch of the product until the quality issue was identified. If the dates are not available or complicated to retrieve, 3 years can be an ideal period retrospectively from the date of identification of the quality issue.

Most important is to choose the correct search strategy to retrieve the correct cases, the search strategy should be broad enough, but to avoid noise, narrow to exclude non-relevant cases. If the quality issue is contamination, retrieve cases of all reported contamination, color change issues reported.

2. Other sources:

Any literature articles published and available publicly about the reported quality issue. The search period is the same as explained above.

Any previous similar quality issues that occurred with similar risk assessment reports should be analyzed. 

Request toxicology reports, stability testing results, and investigation analysis done on the affected batches vs the non-issue batches. 

3. Risk assessment:

Once all the data is available, as a safety physician, an assessment needs to happen regarding the impact of the error on public health. While assessing, consider the type of adverse events that can occur or have occurred. The seriousness, severity, treatability, reversibility, and preventability of these adverse events. The patient population affected, e.g. comorbidities, age (geriatric or pediatric). 

4. Conclusion 

A conclusion should be provided regarding the mitigation of this risk, market recall being the most conservative for serious public health impact, sending a direct healthcare professional communication, change in the label, education material update etc.

Written by:

Dr.Shraddha Bhange.

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 References:

ICH guideline Q9 (R1) on quality risk management 

FDA – Recalls, Corrections, and Removals (21 CFR Part 7) 

Session 1- Complaints Investigation & Review- Jaidev Rajpal + Avinash Joshi