Pharma professionals who work in the GMP environment, encounter deviations on a daily basis. Unfortunately, most don’t know how to address them correctly and efficiently. This leads to compliance problems, warning letters, deficient processes, and time loss.
This article will help both newcomers and experts in the industry learn how to deal with deviations more efficiently and what the right framework for dealing with GMP deviations is.
What are GMP deviations?
‘Deviation’ is a broad term, including errors ranging from failures to follow a manufacturing process protocol to regulatory violations. Therefore, a deviation is any departure from an approved procedure, standard, or specification.
Standard operating procedures (SOPs) form the backbone of an efficient pharmaceutical manufacturing site. The quality department needs to implement SOPs across the organization and train their staff on each relevant SOP related to their activity. But inevitably, despite following SOPs, errors happen. Thus, a company must have robust processes in place to deal with these situations efficiently.
What are the most common GMP deviations?
Here are some of the most common deviations in the pharmaceutical industry:
– Equipment malfunctioning or failure
– Human error
– Issues with the starting materials
– Interruptions in the manufacturing process due to utility or service failure
What is the main cause of GMP deviations?
If you look at trend analysis, and conclusions for most the deviations in most companies, the result would probably be – Human Error. But is it really so?
Joanna Gallant investigated why human error appears to be the leading cause of GMP deviations in her article in Pharmaceutical Online. She concluded that people don’t conduct a thorough Root Cause Analysis.
For example, failure to follow a procedure is a common cause of deviations, but you must ask further questions.
Take a further look at your procedures and see if
- The procedures are hard to follow
- It is designed to prevent errors
- The user finds it hard to access the SOP
- Your company’s on-the-job training is appropriate
Updating procedures is another process that takes time and often proves to be difficult to achieve, therefore people are waiting for someone else to initiate the change process.
Try to ensure that human errors are always further investigated, as in most cases, it isn’t the root cause.
Type of GMP deviations
Alongside human error and its need to be further investigated, the incidents that could occur are unplanned and uncontrollable events of non-compliance. Such violations of the approved systems and procedures can hence be described as ‘unplanned deviations’.
You can classify unplanned deviations further as Critical, Major, or Minor. It depends on its impact on the product’s Critical Quality Attributes (CQA). Attributes such as quality, purity, and strength. CQAs are defined, measured, and monitored during the manufacturing process to ensure that the final product is within the predefined quality standards.
Here are some examples of Critical, Major, and minor deviations and how likely they are to impact the product’s CQAs.
|Type of deviation||Impact on CQA||Examples|
|Critical||Likely to have a significant impact on the product CQA||Using damaged/ expired raw materials batch contamination Printing wrong batch detailsSOPs not followed during product analysis|
|Major||Could or may have a significant impact on the product CQA||Using equipment that is out of calibration Process yield not in rangeCritical process parameters not monitored|
|Minor||Do not have a significant impact on the product CQA||Materials/solutions are not properly labelled|
On the other hand, you might also come across ‘planned deviations’ which are pre-approved deviations from an approved written instruction, covering a specific period or several batches. You should carry out a proper risk assessment and evaluation to ensure that the implemented change will not affect the product’s quality.
Risk assessments are systematic processes that organize information to support a risk decision within a risk management process. Therefore a planned deviation is classified as having a minor impact on the product’s CQA.
Regulators urge a change in terminology, as the pharma industry needs to treat planned deviations as temporary changes. You should evaluate these planned deviations under the change control procedures. Additionally, you should take requalification or revalidation into consideration.
Ultimately, it is the responsibility of the QA department to challenge and evaluate any planned deviations and, therefore, to urge for Deviations to remain unintentional, unplanned, and unexpected.
Immediate Corrective Actions
As soon as you have identified a deviation in your manufacturing process, you need to evaluate the impact it might have on your batch. Before anything else, you might need to implement an immediate corrective action. Consider the following examples:
– Products: quarantine/ isolate/ discard
– Equipment: remove from service/ replace
– Process: suspend manufacturing/ withhold testing
What caused the deviation in the first place?
You must document any deviation and explain it through a thorough investigation. The main question you might have at this point is if you can release the batch, but that is far from the purpose of the deviation investigation. Here are the main reasons you should perform a thorough analysis:
– Aim to determine the real root cause that lead to the deviation
– Identifying the real cause of your non-compliance will enable you to implement the correct and effective corrective actions
– An efficient investigation could lead you to discover a pattern and enable you to implement more preventative actions
During the investigation, collect data from a wide variety of staff, customers, and suppliers (if applicable) and take your time to review procedures and relevant records. Doing so will help you determine the root cause and develop an effective corrective action. Here are a few questions you should have in mind:
– What was discovered?
– Who was involved?
– When did the event occur?
– How was the deviation discovered?
– How frequently does the process occur?
Consider everything you find out and think about: work conditions, process flows, changes, and any previously reported facility problems.
Corrective and Preventive actions
The Corrective and Preventive actions (CAPA) is a deviation management program that will prevent the deviation from recurring in the future. After you have identified your root cause of the Deviation, you can develop the appropriate corrective actions. You are thus creating reactive measures to remediate the evet. Additionally, you could also create preventative actions as proactive measures meant to eliminate or reduce the recurrence of the issue.
Always ask yourself if what you implemented has had the desired effect after the implementation of the CAPAs. Think about the following points:
- Ensure you set an implementation date for all the measures you are proposing
- Verify that you and your staff implemented CAPAs correctly
- Set a timeline for evaluating the effectiveness of your implemented action.
- Ask yourself how soon you are going to be able to see an improvement.
- Know what you are looking for! Set your data source and follow the change for long enough so you have statistically significant results to evaluate
Qualistery’s short guide to handling deviations
Summing it all up, here is Qualistery’s short guide to GMP Deviations Management:
- Ensure that any deviation from current protocols and procedures is detectable and that your staff is adequately trained to recognize and report it. Staff training sits at the heart of an effective quality management system!
- Anytime a new issue occurs, you need to ensure that you record it properly in the relevant system (for example, in the masterbatch record, equipment/laboratory logbook). Make sure you have a full audit trail available.
- Report the deviation in real-time. Notify the QA within 24 hours.
- Remember – if you don’t document it, it didn’t happen! Think about how your staff could record the deviations more easily. For example, you could add a page in the production record to allow easy reporting of unexpected events or GMP deviations
- Think about the need to implement any immediate action.
- Ask yourself if this has happened before and look beyond your deviation history. Talk to the responsible staff, look out for patterns, and ensure you have an in-depth understanding of what happened!
- Carefully work your way through the investigation process, while performing the root cause analysis. Establishing the correct cause of the deviation is key to implementing the most efficient corrective action!
- Perform a time-sensitive and thorough investigation within 30 days.
- Evaluate the risk associated with the deviation and analyze the actions that you can implement to reduce the risk
- Look at both corrective and preventative actions that you could take. Make sure you follow the CAPA system!
- Implement the actions, while working closely with all departments involved.
- Always evaluate the actions you implement. Therefore, ask yourself if the actions effective? Can you improve these actions? If they aren’t working, did you have the right root cause in the first place?
Qualistery’s Top Tip
You should aim to streamline and standardize your issue management process.
Develop an efficient approach that can be easily applied to a range of situations from complaints to manufacturing and distribution issues. Look at the bigger picture, GMP deviations are just a part of this.
Found it interesting? If you want to master the essential elements for investigating GMP deviations, join our Deviations and Issue Management Systems Workshop starting this January!