Scenario - Peanut Oil runs low.

Your factory uses a continuous process that uses peanut oil. The approved supplier cannot meet the next delivery date. To keep the process going the production department want to source from an unapproved supplier who can deliver on time.

As the QP what are your concerns and actions?

First thoughts

• If the change is implemented can I certify the resultant product? Does the work required to ensure I can certify the resultant product outweigh the benefits of continued production? What are the impacts to patients if we decided not to put the change into effect?

How would you handle this?

The key QMS record is a change management record. You mention this before anything else. (You assume they know, you know, that this is a change management process. The assessors aren’t allowed to assume.)

In the most literal sense the question “What needs to happen to implement the change and permit you to certify product?”. In other words “Ensure everything in Annex 16 section 1.7 remains in place”

For each of the 21 duties laid out in the legal duties in Annex 16 we need to lay out what they mean for this scenario

Now we already have a way to remember these:

1)      The marketing authorisation (the MA or CTA)

o   Sites comply with MA - OK

o   Processes comply with MA - OK (unless the change in material necessitates a process change)

o   Materials comply with MA (Site and Spec) / Supplier QMS in place - THIS is likely the rate limiting step. Variation required.

o   Batch in Specification to MA - OK

o   TSE compliant if in MA - Would need to examine supply chain

2)      Site licensing (think MIA, ManA)

o   All sites (Manufacture/Test/AS) audited and reports available - OK

o   Self inspection is active and current - OK

o   All processes in validated state and personnel are trained. - Need to understand nature of current validation - what limits have been validated - has the validation been done with differing oils?

o   Supply chain available to QP - Needs updated

o   Required technical agreements are in place - Needs updated

3)      The falsified medicines directive

o   AS complaint to GMP and GDP - OK

o   AS imported has written confirmation of GMP (if not on whitelist) - OK

o   Safety feature in place - OK

o   Agreement for dist and shipment in place - OK

o   Excipients compliant to GMP - Need to establish

4)      The batch documentation pack – what the QP will see at the time of release

o   Manufacturing and testing are in accordance with GMP - OK

o   All records complete and IP checks complete - OK

o   Post marketing commitments met, stability data supports investigation - How robust is the formulation to oil changes? Would stability remain valid?

o   Any changes assessed and any needed checks completed - Big change needs managed

o   All investigations complete to a sufficient level - OK

o   Nothing open that stops certification (complaint/recall etc) - OK (Setting aside what’s covered already)

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

• A tame chemist or formulation scientist - how comparable are the oils. Even if they are both BP/EP/USP grade they may have different colouring or compositions. Would this impact the functionality, safety, purity or look of the end product?

• Supplier qualification / QC - Can the team do the technical legwork to incorporate the new material into your approved materials list? They will need typically to test multiple lots. What info do they need and when? There is quite a lot of things that could “trip up” this process when done in a hurry. How quickly can we onboard the supplier and complete an audit? Are they an existing supplier for other materials or is this a supplier we haven’t worked with before?

• Purchasing - can the supplier management team support the process and ensure the supplier is supportive? Its one thing to sell oils to a pharma company, its a different matter to support a Pharma graded product in use.

• Regulatory team. From the Annex 16 assessment above you will need to understand the process for updating the product licence (manufacturign authorisation) as you have altered. Remember the full wording of the first sentence of Annex 16 1.7.6 is “The source and specifications of starting materials and packaging materials used in the batch are compliant with the MA”

At this point it may seem like a dead in the water idea but its important to remember that skilled cross functional teams can pull off changes like this compliantly. If your supply team is forecasting demand and supply in an effective manner you should have some warning of a change this momentous and be able to act accordingly. At the same time the competent authorities can be incredibly supporting if you have critical medicines to supply and a force majeure requires a late notice change.

A good follow on thought exercise is what information would you prepare if you had to present this change to your competent authority and plead for accelerated approval of the variations required. How would you communicate with the competent authority if you had to seek specific approval release product where not all of the Annex 16 Section 1.7 requirements could be met?