Any sponsor company planning clinical studies in Europe needs to be prepared for the QP process. Our first blog post outlining the QP processes proved to be one of our most popular blog posts to date. That and the tremendous response we got to our QP expert panel at our summer seminar last month showed us that there are a lot of questions surrounding the QP process - so welcome to the first of our three part blog series focused entirely on the QP process! Check back next Thursday September 14th for the next installment.
Under what circumstances can a sponsor company provide a QP with an audit from a different client, different drug product. Does it really have to be a de novo audit for each individual QP process?
Audits can be overdone, however there are a few things that need to be considered. First of all, the audit needs to cover the specific production process used, and the scope has to be identical. For example, if a solid oral drug is being produced, and the audit report covers the production of a liquid injectable drug, this audit report would not be relevant. Second of all, the scope needs to be European GMP. Many sponsor companies say they have audit reports, and they do - but it’s cGMP, not European GMP. It has to be European GMP or else it is not valid. Finally, the CV of the auditor comes into play, and permission from the other company to use their audit report is also needed. For example, if company A audited a CMO and company B wants to have access to the audit report, company A needs to agree to it. If company A gives their blessing, then yes - the audit report can be used.
IN A SITUATION WHERE A SPONSOR DIDN’T KNOW THEY WOULD BE GOING TO EUROPE – THEY’RE IN EARLY CLINICAL TRIALS, THE MATERIALS HAVE BEEN MANUFACTURED, THE US GMP AUDITS HAVE BEEN DONE but the QP audit has not been done – how does a QP address this?
You will need to go through the full QP process. A QP declaration will be needed to certify that the materials have been manufactured according to European GMP standards. As such, QP audits of the supply chain will be needed. The QP can’t blindly rely on a third party audit unless they have full knowledge of the third-party auditor’s capabilities and CV – and feel comfortable accepting this auditor’s report. It is helpful to remember that different QPs have different levels of experiences, which means the requirements that an individual QP lays out for you may differ from QP to QP.
My first IMPD was filed and reviewed in European countries, and the first few batches were released according to those specifications and review process. We’ve now revised our specifications because we haved learned more, and now have IMPD 2 that is being submitted for approval to all the participating countries. What do I have to do with the batches released under IMPD version 1?
If the specification is different in the new IMPD and batch one doesn't meet the new specifications, batch one goes under quarantine. It then needs to be tested according to the new specifications to ensure it conforms.
There may be some exceptional circumstances where batch one is already being used in a particular phase of a study and a particular trial and you might need to repeat medication. In this case you would continue to use batch one because you started with batch one and therefore need to conclude with batch one. There may be some latitude around that, but in general, once you've changed your specifications on your IMPD, you need to move forward with version 2 and your new specification.
This is a crucial difference between the US and European release environments. In the US, a drug stays released once it is released. This is definitely not the case in Europe. If the drug specifications change, the drug goes under quarantine until it is tested to meet the new specifications.
Check back next Thursday, September 14th for our next installment in OUR qp BLOG series where we will discuss:
- Is leading stability data required for QP release and is this different in early stage versus late stage where we may have leading data from either a platform product that’s very similar but not necessarily the same process?
- How do you make sure that the different steps in the supply chain are meeting quality expectations? Would you audit the entire supply chain or would you only go back to the last step in the supply chain?
- After Annex 16 came out, our QP asked us for audit reports from our vendors that we qualified and we pushed back on that. Do the Annex 16 requirements make it difficult to maintain confidentiality agreements with contractors, and how can I navigate this through the QP process?