Scenario - Lump in the sugar.

Production operatives are dispensing a powdered excipient and discover a small black lump.  They bag this up and drop into the QA office after the batch has been made.  They used material from the same lot to continue manufacture except the bag they found the lump in.  Any concerns?

                                                           

First thought

  • Orientate - need to understand what the lump is, what the excipient is and what product it is used in.

  • Extent - how much material is in this lot from the supplier? How much has been used?

Follow up detail

The examiners offer the following

  • Material of lump found to be Polypropylene upon analysis.  Approx. 1.5mm x 1mm x 3mm

  • Excipient is mannitol - fairly common sugar alcohol used as a sweetener

  • Same container / lot of material has been used on six batches before this is noted. 4 are on market. No complaints/ AEs.

  • Product is oral liquid suspension.

  • Administered to paediatric patients, administration using a small syringe.

And the heart of this scenario comes into view… what are you going to do about those batches out on the market….

How would you handle this?

So lets start with the process. The key QMS process would be a deviation to:

  • Document the visible contamination of the material, record batches of except and fished good that may be impacted

  • Investigate root cause. How many times and where/how do we broach the container during use? As a basic level if its a black lump of plastic we will be checking the dispensary for sources of black lumps of plastic…

  • Link to either a suppler complaint or notification record if we think the supplier needs to complete their won root cause and analysis and risk assessment. Bear in mind this may need to go through a third party or two if the supply chain is complex enough.

  • Document any CAPAs that arise.

A key aspect here is asking a follow up to the information above. Who is the patient population and how/when is this product used? Are there any controls in the manufacturing process like a filter or sieve?

So in this case the product is something like Calpol. It is administrated using a small 10ml syringe. No controls exist downstream to remove any plastic lumps during manufacture or fill.

At this point you need to articulate who you will call on for advice. Two spring to mind

  • QPPV / Clinical team - I would ask them to articulate the risk to patients if a lump like this made it into the product.

  • A tame chemist or formulation scientist - check the other ingredients to see if they will react in a detrimental manner with the plastic.

You receive feedback from the clinical team that the risk is negligible - most lumps this size would not even make it through the dosing syringe and if ingested the clinical impact on a child will be small. Formulations don’t believe any chemical impact on the product is foreseen.

What do you do?

Let me put down an approach - it is not the only answer.

The batch made when the lump was discovered:

Reject. Same for the remaining mannitol lot.

Batches using the same lot of mannitol on the market:

Baring no further information, complaints, PhV instances etc I am proposing (with informed agreement of the QPPV and leadership) to leave them on the market. This is on the basis that the potential for clinical harm is very low.

Competent authority:

Defect notification as required by the territory where it is marketed. Outlining why no market action is proposed at this time.

But management point out that the batch you are rejecting is worth a lot of money…. Can we not inspect it?

Liquid suspensions in general are opaque or cloudy in appearance - a 100% inspection is not feasible. For a widely used OTC medicine market exhaustion is not usually a concern.

Supplier Quality Assurance

If there is evidence to point to the supplier as a source of the contamination I would recommend reassessment of their risk ranking in your supplier listing and potentially pulling an audit forward.

Final thoughts?

As with all scenarios this changes radically for different product types and patient populations. You can rehearse with variations - what would need to be the circumstances for you to release the impacted lot? What might make you start a recall of everything impacted?

Disclaimer

This document is not a legal document not should it be interpreted in any fashion as a guide. This is a set of notes compiled as part of a personal training program.  It is not complete or authoritative. I hope it gives you some value.

This is a personal effort and is not affiliated with my current role or employer.

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. If you use it to train someone else, fantastic, but give the QP Notebook a plug. Thanks