In the pharmaceutical, chemical, cosmetic and biotech industries, deviation management is a major issue for the continuous improvement of the Quality Management System (QMS).
Good Manufacturing Practices
One of the fundamental guidelines of the pharmaceutical industry is « Good Manufacturing Practices » or GMP. This is a set of rules, established by the drug safety or health safety agencies, which guarantee a high level of quality for medicines and ensure their safety for users and consumers.
These rules impose, in particular, a monitoring of products and processes. Any deviation from expectations, any malfunction, will be declared as a « deviation ». Deviations will be investigated and corrective actions or preventive actions will be taken to avoid the recurrence of deviations.
This principle of corrective and preventive action, whose objective is to make products and processes more reliable, is commonly used under the term CAPA (Corrective Action & Preventive Action, see chapters 1.4 and 1.8 of the ANSM GMP).
In addition to these principles, the GMPs require traceability of deviations and related CAPAs, ensuring that products placed on the market have passed through an effective quality process. Thus, a product can only be released if the process in which it has passed has not been deviated from, or if the impact of the deviation has been assessed, CAPAs have been implemented and the deviation has been closed.
If GMP formally requires the identification of deviations, and calls for investigations to be carried out in order to find the root cause, assess the impact on the product and implement corrective actions, it leaves it up to the manufacturer to decide on the method of doing so.
Compliance with the requirements produces a drug of the expected quality: pure, effective and safe. The process of managing deviations and their associated CAPAs is an integral part of an effective quality system. This process, through a risk analysis, aims at assessing, as soon as the deviation is detected, the potential consequences on the product. The systematic search for causes must be based on specific quality tools and a structured investigation methodology. The objective of this structuring is not only to simplify and organize the root cause search process and the implementation of effective CAPAs, but above all to control the deviation management process, and consequently to control the quality risk.
According to the Lean Management culture, deviations can be considered as an obstacle and a hindrance to the continuous improvement process, a source of costs and waste without added value to the quality of products and/or systems. But if the process of managing deviations and their associated CAPAs is properly managed, it can bring areas of failure to light and deal with them before they have recurrence or greater consequences, which can reduce non-quality costs. But effective deviation handling also requires time and investment, and that’s the challenge.
What to do when something unexpected happens?
The unexpected happens…, you did not respect the procedures, your product is not conform, you have a contamination, you deviate from a protocol… What to do and how to do it ?
These unforeseen events must be treated in 11 steps:
1. Description / Declaration of the event (QQOQCCP): describe the event in a precise and factual way in order to differentiate between a deviation and an incident.
2. Description of the deviation: describe precisely the deviation in relation to the procedure or reference system concerned and if possible illustrate with photos.
3. Immediate actions: Describe the actions taken to stop the propagation of the event and to control all the products/materials potentially concerned (e.g. blocking the product, segregation)
4. Risk Assessment / Deviation Classification (Minor, Major, Critical) :
Severity:
○ Patient Risk : Specifically describe the risk to the patient ( incomplete dose, loss of product sterility, product not usable by the patient…………).
○ Regulatory risk: Country of destination not registered, parameter not in compliance with registration file, unauthorized operation…..
○ Market impact: accurately describe the risk of disruption.
○ Brand Image: Risk of customer complaints.
Occurrence:
○ State the occurrence of deviation and the proportion of defects.
○ Make this assessment using a risk assessment grid (ICH Q9).
5. Investigation – Search for root cause:
7M = Examination of the event from 7 different angles:
○ Material = materials, materials used, process inputs
○ Equipment = equipment, machines, means…
○ Method = Operating mode, procedure, process
○ Manpower = human interventions
○ Environment = environment
○ Measurement = parameters, indicators
○ Management = union of the 4 management styles = human at the center
Timeline:
○ Indicate on a timeline the date of detection of the event / the date of occurrence of the event / the manufacturing dates of the potentially impacted batches,
○ In the case of microbiological contamination, trace the path of contamination using a BIA plan.
Gemba:
○ Go to the field, observe, measure, record (diagrams, sketches, photos)
○ Question (interview)
○ Validate understanding
5. Why:
○ Focus on causes, not symptoms, and dig until root cause is identified.
6. Conduct a more thorough Quality Impact Analysis:
Accurately list all potentially impacted Systems/Products/Batches:
- Lot number
- Batch size:
- Date of manufacture (filling/packaging)
- Status (released with release date, semi-finished product and manufacturing stage)
- Destination
- System status (validated/qualified/ requalified…)
7. Implement Remediation Actions:
Describe the actions defined to eliminate/correct the nonconformance.
8. Root cause:
Indicate the confirmed/potential root cause(s) and the status of the investigation.
9. CAPA:
Indicate the proposed CAPAs and the date of implementation.
NB: No root causes identified = No CAPA to be implemented
10. Product Quality Impact Assessment :
Final verdict = Proposal to accept/refuse impacted lots.
11. Closure:
Any deviation must be closed within 30 days.
Benefits of the approach:
Have a robust, streamlined system that continuously measures deviation management and closes them on time to avoid the deviation backlog.
Control the risks related to product manufacturing.
Guarantee the expected quality and release products that are pure, effective and safe for the patient.
To avoid having a product that can generate :
1- A danger for the patient
2- A delay in delivery
3- A stock shortage
4- A claim
5- A batch recall
In conclusion
To better deal with deviations within 30 days, it is necessary to efficiently conduct a complete investigation to find the root causes and implement corrective actions to avoid recurrences and document everything.
Performing an effective investigation following a deviation has become a key step in risk management and quality improvement (GxP, ICH, ISO). This investigation is an essential point examined during audits or inspections.
Nadjim Mhoma