Investigation tools used in Pharmaceuticals

Step-1 Brain Storming:
What is Brain Storming :
Brainstorming is a situation where a group of people meet to generate new ideas and solutions to find a conclusion for a specific problem. In this session people are able to think more freely and they suggest as many spontaneous new ideas as possible. The term was popularized by  Alex Faickney Osborn  in the 1953.
 To be performed immediately upon receipt of complaint/ deviation
 Questions for Brain storming
What happened? Describe actual problem. Provide Details of the defect. What has happened to the product? What patient is trying to say? Convert it to technical language.
When did it happen? When was the defect discovered? What was the condition of the patient?
Where did it happen? What were the situation/ location?
What is the impact? What is the impact over the product? What is the impact over patient? What could be impact over the batch/ other batches in market?
What could be the probable causes that have lead to this defect/deviation? Describe briefly (in short) the probable causes for deviation/ defect. It must be just bullet points (atleast 10 in numbers).
 Additional Questions:
Whether similar nature of defect reported in past?
Whether similar nature of observation was noted during manufacturing in-process checks or in quality control?
Was any breakdown observed in the equipment or instrument during the manufacturing?
Was any deviation reported during manufacturing?
Has any in-process check failed during manufacturing?
 Based upon the brain storming session, Fish bone diagram is to be derived.

Affinity Diagram or Affinity Chart or Affinity Mapping :

The affinity diagram organizes a large number of ideas into their natural relationships. It is the organized output from a Brain storming session.It can be used to generate, organize, and consolidate information related to a product, process, complex issue, or problem. After generating ideas, group them according to their affinity, or similarity. It was created in the 1960s by Japanese anthropologist Jiro Kawakita.

The affinity diagram organizes ideas with following steps:

  • Record each idea on cards or notes.
  • Look for ideas that seem to be related.
  • Sort cards into groups until all cards have been used.
  • Once the cards have been sorted into groups the team may sort large clusters into subgroups for easier management and analysis.

Step-2 Fish Bone Diagram or Ishikawa diagram (Cause and effect diagram)

Ishikawa diagrams were popularized in the 1960s by Kaoru Ishikawa, who pioneered quality management processes in the Kawasaki shipyards, and in the process became one of the founding fathers of modern management.

The defect is shown as the fish’s head, facing to the right, with the causes extending to the left as fish bones the ribs branch off the backbone for major causes, with sub-branches for root-causes, to as many levels as required.

Analysis of Fish Bone diagram:

  1. Man:
  • Educational Qualification
  • Experience
  • Association with Company
  • Workload

2. Machine:

  • Qualification
  • Preventive Maintenance
  • Breakdown
  • Calibrations

3. Measurement:

  • Inprocess checks
  • Release testing
  • Control sample testing
  • Stability testing

4. Material:

  • Raw material (API& Excipients)
  • Packing materials
  • Semi finished Goods

5. Method:

  • Dispensing
  • Sifting
  • Granulation ( Dry & Wet Granulation)
  • Blending
  • Capsule Filling
  • Compression
  • Coating
  • Visual Inspection
  • Packing ( Blistering, Bottle packing & Dry Syrup Filling etc)

6. Environment:

Details of Temperature, RH and DP during the process & storage

Summary of Fish Bone Analysis:

Provide the probable root causes from above fish bone details.

Step -3 Root cause:

Based upon the probable root cause, conduct a 5 Why?  Analysis to reach to root cause. For example but not limited to

5 Why ?

Step -4 Review of complaint history:

Include details of any similar defect/ deviation reported in past.

What was the root cause of that defect?

What were the CAPA derived?

What is the status of those CAPA? What is the difference between current scenario and the past scenario?

Step-5 Medical Opinion:

What will be the impact of the defect to the patient?

Is any risk involved, if patient has consumed the defective product or patient continues to take the medicine?

What is the recommendation to the patient- Whether to stop taking the medicine or continue?

Step-6 Impact assessment:

Include the impact of this defect over other batches.

Were the batches manufactured in campaign?

Whether the defective RM/ PM used in this batch was used in other batches?

What is the recommendation for those batches?

Include the details of the impacted batches’- batch no. mfg. expiry, customer etc.

Whether any action is required to be initiated for the impacted batches.

Step-7 Conclusion :

Include the actual root causes.

Include the review of complaint history.

Include what is recommended to the patient/ user.

Include details of impact assessment.

Conclusion :

  • All the Investigation tools mentioned above shall be used in case of any Market complaint, Product complaint and in case of any deviation to find out the root cause but not limited to. Other tools also can be used to find out the root cause for any problem. Based upon the root cause Appropriate CAPA shall be taken.
  • Mistakes can be happens by knowingly or unknowingly by the person but it should be reported immediately to take proper action and the person should not hide the problem.
  • Failures are unavoidable in any organization however, it is important that organization shall performed a detailed investigation to identify the root cause for the reported non-compliance or failure in order to take an appropriate corrective action to avoid recurrence.
  • Proactive organizations do not wait for the failure to be reported but take preventive action to improve the system.
  • Proactive organization not only save money by avoiding these batch failures but also avoid potential questions / observations during regulatory audits.
  • Investigation team shall be cross functional team comprising of members from following functions like Initiating department, Quality Assurance, Quality Control, Manufacturing, Engineering, Formulation & Development and Warehouse etc.
  • The investigation team shall list down all the documents which need to be reviewed as part of the investigation like Batch manufacturing record and packing record, Control sample, Analytical data of Raw material, packing materials, In process & Finished products,Instrument / Equipment calibration /qualification status, Personnel training record,Interview of involved personnel & stability data etc.

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