European Qualified Person Association - Publications/Question
and Answer Documents
Q: Manufacturing of tablets for a phase I and for a phase II study: is it possible to release and/or submit an IMPD or similar documentation without microbiological quality as a lot release parameters for tablets in phase I or IIa? (tablets do not contain any component that would have a high total viable aerobic count by origin).
A: Especially for IMPs manufactured the first time it should be proved that the microbial quality is satisfactory, since usually only limited experience and only little validation data are available.
Although the compounds are unlikely to be "contaminated", contamination may happen during manufacturing. Often the raw materials used for the manufacture are not tested for their MB status.
One approach could be to test at least the first 3 lots of a manufacturing sequence for MB status.
Independent of what is mentioned in the IMPD (and accepted by authorities), the QP keeps the final responsibility for the batch and should be able to justify her/his release decision.
If the QP decides to release without MB testing, we would strongly recommend to perform a risk analysis of the release decision.
Q: Is it true and do the health agencies/ inspectorates accept that a company can import medicine from outside the EU and use it as an IMP in a clinical trial inside the EU without performing reanalysis within the EU? Is there a reference in the respective legislation?
A: That is indeed correct, Clinical trial Material (CTM) imported from a non-EU country into the EU does not need to be reanalysed/retested in Europe.
This is covered in the Directive 2001/20/EC Article 13 (Manufacture and import of investigational medicinal products), at the end of paragraph 3:
“Insofar as the provisions laid down in (a), (b) or (c) are complied with, investigational medicinal products shall not have to undergo any further checks if they are imported into another Member State together with batch release certification signed by the qualified person”
In this article the QP certification act is described as well. In summary it mentions that the QP should certify that the CTM is compliant with:
- European (or equivalent ) GMPs
- The product specification file
- The IMPD (Investigational Medicinal Product Dossier)
-the IMP QP can always decide to reanalyse/ retest the imported CTM. Important to know is that this is not mandated by the EU HAs
Q: Should a QP audit CROs and investigators or can a QP rely on GCP-auditors of the own company?
A: The QP can rely on the information provided by the GCP auditors.
Q: When IMPs are imported from outside the EU; how could I set up a working relationship as a contract QP when it comes to liability and insurance?
A: As a contract QP you are a “normal” contracting party (i.e. just like any other service provider for the company but with the specific legal responsibilities and risks of a QP) and therefore no employee of the company. That means that you are not covered by any of the insurance programmes which companies usually provide for their employees (e.g. D&O insurance). As a result, you should mention that fact – and the related legal risks – during your contract negotiations with the company.
Ideally, there should be an indemnification clause in the service contract providing for that ‘the company indemnifies the contract QP from any and all third party claims related to the services which the contract QP may perform under the service contract’. If your current contract does not contain such provision, you should ask the company to sign an amendment with aforesaid clause.
You can also ask the company to get yourself explicitly included in its D&O insurance contract (some insurers may actually be ready to do so because of the specific situation of the contract QP).This inclusion could be the first part of the contractual provision, followed by the indemnification clause mentioned above.
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