Scenario Pavlov Flashcards
What are the initial Ringfence concerns with a cleaning failure?
What is the product?
What batches made before the contamination event?
Where are the batches?
Put batches on hold.
Put equipment on hold.
Are there any other similar processes that use the same CIP skid / undergo same clean that could be impacted
What are the Quality impact concerns from the cleaning failure?
How much residue in the batches
What contraindications of batch and contaminant
If batches out of your control then incident committee and medical advice
MACO
What to say about the cleaning investigation
Identify the failure mode – equipment clean failure or people
Does the failure mode implicate any other batches.
What additional ringfence concerns are there with a packaging complaint?
Packaging / component batches = huge compared to product
Thus there could be many batches implicated.
Thus ringfence and LIC and medical advice more important
What are you going to look at in the event of a customer complaint
What’s in my warehouse (component of finished pack)
Ref / ret samples
BD
location of stock if dreadful complaint
What picture thoughts on a confirmed stability failure?
What batch?
Where in the shelf life is the failure?
What were the other results at the time point?
What are the previous results (any trend)?
Why was it on stability?
Were there any other batches also on test?
What is the bracketing / matrixing representing?
What are the contents of a technical agreement?
The technical agreement details all responsibilities for GMP control of batches and required comms by CA and CG
ABCD FGHI MNOPQRSTU
Audits and self inspection
Batch control and certification
Communication and procedures for Change control, customer complaints, deviation, LIR, recall
Don’t outsource without consent
Finished pack QC and IMQC test results and procedures
GMP and Regulatory responsibilities, legal responsibilities
How long valid, who updates, signatures
IPCs – IPC expectations
MA variations and artwork
Nasty bugs killed – pest control
O – O, I forget what O was for.
PQS and PQR
Qualified inputs and approved suppliers
Reference, retention and batch sampling
Stability
Transport and distribution
UxD
What are you going to look for when there’s a sterile contamination event
Raise deviation and put on hold
ID
state the limit <1cfu
Investigate
Product impact? Organism type? What do you know about the organism.
What other samples would you expect to support your investigation
Stability OOT – what things to think about?
What is root cause from manufacturing investigation?
What is the trend at shelf life?
What is the product (medically critical or generic with lots of alternatives)
What is the market situation – SLIRB
Safety impact – degradants?
Recall committee to get medical advice and agree actions
Stability OOS – what things to think about?
Recall committee to get medical advice an agree actions
What is the product (medically critical or generic with lots of alternatives)
Inform CA
What did the manufacturing investigation identify the cause to be?
What is the scope – why was it on stability?
What is the stock location – can you reduce shelf life?
Recall, caution in use or do nothing?
Things to think about with complaints - rogue etc
Don’t forget packing! Different vision systems blister and bottle
Counterfeit?
Potentially test reference samples.
Recall?
Who would be on your recall committee?
Regulatory, Production, QA, legal, medical, logistics, phamacovigilance
Follow procedure!
Picture questions when receive complaint
What batch number
Pack type – bottle or blister?
Photos? Then sample
Product type – critical medicine?
Stock location – in my control or MMWs or pharmacy?
Shelf life
Supply Chain Scenario – what are the regulatory considerations
E T C Q B D W
Eudra
TSE
CEP
QP Dec
BD – template, actual
Docs – CofA, deviations, change controls, confirmation of manufacture to GMP, made to MA
Written Confirmation - white list
Supply Chain Scenario – what apply across all nodes
This question gives me ANGST
Audits in place
Named on the MA
GMP certs / site licences are in place
Supply Chain mapped out
Technical Agreements in place – all my company?
Supply Chain Scenario – what are the manufacturing considerations
On me ‘ED Son
Excipients manufactured to sufficient GMP – pharma grade / meet MA
Distribution – temp tales, DRA, validated routes, tamper evidence
Stability – Stability programme in place and supports certification
Supply Chain Scenario – what are the packing considerations
Shake your ASS
Artwork as per MA. Windsor labelling
Sampling – where ref and retention samples taken and stored?
Serialisation / Safety feature considerations
Supply Chain Scenario – what are the certification considerations
QP QO
QP named on the MIA
Product type / product named on MIA annex
QPPV understood
Outsourced companies on MIA (labs, warehouses, )
Supply Chain Scenario – what docs?
BD translation and BD
CofA
Deviations
change controls
confirmation of manufacture to GMP
made to MA – need access to MA
Why is maths and stats useful to a qp
What are the things you need to ask about in a Process Simulation failure? (Picture)
What did the vials look like (vial integrity OK?)
Why were you media filling?
What were the organisms recovered?
What likely cause if the organism is mould / yeast / general environmental contaminant
Airbourne which means HEPA or breach somewhere
If a breach then it will have been brought in on a person, materials or could be building fabric has got wet and had growth or air is getting in somewhere
What likely cause if the organism is GNR
Water bourne.
What are they using water for in the facility?
Cleaning / filtering failure = filter integrity tests OK?
What likely cause if the organism is GPC
This is from people. Ask to see the CCTV or the observer notes
Operator aseptic technique, gowning failure, hand spraying failure etc.
What are things to look at if you suspect autoclave to be the source of moisture / micro contamination?
Steam Quality
Wrapping
Load pattern
Any failures with the morning tests?
Water plant quality
Temperature probes / BI from the load.
What’s approved for import from MRA countries
Everything but…..
Switzerland – Everything covered
Australia – ATMP
NZ – ATMP
C – ATMP + Blood and plasma
US – ATMP, Blood and Plasma, Vaccines
Japan – ATMP, Blood and Plasma, Medicinal Gasses.
Isreal – ATMP, Blood and Plasma, Medicinal Gasses, homeopathic medicines,kk7
What is the pre-amble spiel for a deviation
Raise a deviation in my PQS
Identify impacted batches and place those under my control on hold
Assess impact with respect to product quality, patient safety, efficacy, identity and stability, regulatory, validation and compliance.
Assess the criticality
Investigate and identify root cause and then suitable CAPA
Implement the CAPA and then review to demonstrate that the CAPA is effective.
