Annexes 19, 21, 17 & 8 Flashcards
(30 cards)
How long do batch reference and retention samples need to be kept for?
Minimum one year after expiry date
How long do starting material reference and retention samples need to be kept for?
Two years after the release of the product (unless stability data is shorter)
How long do packaging reference and retention samples need to be kept for?
Shelf life of the product packed in them
Do you need to keep reference samples of each batch of veterinary medicinal products?
Not always – annex 4 recognises that impractical with premixes.
Always make sure you’ve got representative samples in containers of same material as marketed product.
Who has responsibility for reference and retention samples if MAH and site of batch release?
Responsibility for taking reference and retention samples should be in the Technical Agreement. QP needs to ensure samples are accessible and described in the Technical Agreement.
Where should retention samples be stored?
As they are representative of the packaging in EEA, Retention Samples are to be stored in the EEA.
They should be stored at the site of QP certification
Do you need to keep reference and retention samples of parallel imported products?
Where the secondary packaging is not opened, only the packaging material used needs to be retained, as there is no, or little, risk of product mix up
What do you need to keep if parallel imported packs are opened (eg for new leaflet)?
Why?
If the secondary pack is being opened then there’s a risk of mix up and you need to keep a full retention sample.
It is important to be able to identify quickly who is responsible in the event of a mix-up (original manufacturer or parallel import assembler), as it would affect the extent of any resulting recall.
What happens to reference and retention samples in the event of manufacturer closing down?
MAH is responsible for making sure the ref and ret samples are moved somewhere safe and convince the CA that it’s OK.
When can QP certification of an imported product take place
After it’s actually in the EU and has cleared customs
What must the QP certifying an imported batch ensure?
That it’s made to GMP equivalent to the EU
Products with an MA are tested (unless there’s MRA)
What impact is there to the PQR if you’re sampling in the third country
- The PQR needs to include an assessment of whether you can continue to rely on imported samples.
- Review of deviations relating to transportation up to point of certification.
- Analytical review of importation testing against the original manufacturer CofAs – any discrepancies or OOTs to be investigated.
How often is full batch documentation reviewed for imported batches?
At a frequency justified by risk assessment within the PQS.
What does the documentation available at the site for QP certification need to include for imported products?
- The site from whence it came (the origin of the product)
- The site of physical importation
- Shipping details including
transport route and temp details
customs docs like packing list, freight docs, customs import declaration
What does the QP certifying imported batches need to ensure?
The importing site has record retention policy equivalent to the EU.
The stability programme is in place and details such as protocols, results and reports are available for inspection at the site of certification
Ref and ret samples taken as per annex 19
Anything special about foreign batch documentation?
They should be in a format understood by the importer. It may be necessary to provide documents in more than one language to facilitate understanding
What’s needed for subdivided batches that are imported separately?
Documentation confirming reconciliation of the quantities should be made available at the site responsible for QP certification.
Any discrepancy should be investigated under the responsibility of the certifying QP
What are the minimum criteria to be established for parametric release?
(i) Parameters should be accurate predictors of the corresponding finished product attributes.
(ii) The acceptance criteria should be established with scientific evidence based on material, product and process knowledge.
(iii) The are enough measurements and other test data to provide a robust foundation for RTRT and the batch release decision.
RTRT vs end of batch testing – which takes precedent and can you switch?
RTRT should be used for batch release if approved.
Can’t substitute batch testing if there’s an adverse trend
What about attributes that are indirectly approved by RTRT?
Attributes such as dissolution / CU should still be quoted on the batch certificate stating “Complies if tested” with a footnote: “Controlled by approved Real Time Release Testing”.
What is Annex 21
Importation
What is Annex 19
Reference and Retention samples
What is Annex 17
Parametric Release
What is Annex 8
Sampling of starting and packing materials
