July 17, 2017
We’re going to kick off our blog with a focus on the Qualified Person (QP) process, as we get a lot of questions on this.
Last week we asked what you would like to know regarding the QP process, and many of you wrote in with your questions. Below, one of our 2017 Sherpa Summer Seminar speakers, Sue Mann, Managing Director and QP Consultant of Sue Mann Consultancy, has answered some of your questions. Some questions submitted needed some background for us to answer, so if your question isn't answered below, we can address it at the Sherpa Summer Seminar on August 10. In the meantime, we hope you find the below information useful!
First, a little background on the QP role
The European Qualified Person (QP) role was established originally via a Directive published in 1975. This required all manufacturing sites (initially only those dealing with commercial products) to have the services of at least one QP to act in a legal capacity to certify batches for release. Time is allowed via the EU process to incorporate EU Directives into national law so for many countries, the legislation wasn’t in place until 1977 or later. As this was new legislation, people already carrying out this role were allowed to become QPs via a transitional process. For many years now, anyone new wanting to become a QP has to go through the so called “permanent” provisions route. The requirement for a QP to certify batches for Investigational Medicinal Products (IMPs) was introduced via another EU Directive published in 2001. It should be noted that in both cases, the legislation was introduced via a “Directive” which means this has to be incorporated into national law. This allows for some differences to emerge as the Directive is reviewed against existing laws so unfortunately, the system is not exactly the same across all EU countries.
Answered - Your questions regarding the QP process
- Is the QP role a batch releasing role?
Not strictly true as the QP role is separate from the role which decides whether to release product either into the supply chain (commercial) or to a clinical site. The legal term is “certification” and the QP is certifying that a batch is suitable for release (for sale or supply).
- Can I contact an EU QP and ask them to act for me as a QP in the EU?
The QP that you contact will only be able to do this if named on a relevant site authorisation. For IMPs, this would be a Manufacturing Import Autorisation (MIA) IMP authorisation. Otherwise the QP cannot act legally on your behalf.
- Does the QP role only involve batch certification?
Not true and in many organisations, the actual batch certification process is only a minor part of the overall role of the QP. The QP must be fully aware of the overall pharmaceutical quality system(s) in place and of any incidents/events that could affect their ability to certify a specific batch of product. The QP has to satisfy him/her self that the batch has been manufactured in accordance with the requirements of EU GMP and in compliance with any site authorisations and product authorisations. Therefore the scope of the role is much broader than the certification process
- Where testing and packaging are concerned, is there only ever one QP involved?
This is not necessarily the case. Take for example a situation where manufacture of IMP is carried out in one EU country but packaging, labelling and randomisation in another. A QP at the first company may formally “confirm” the batch has been made according to EU GMP etc. A QP at the packaging company can take this confirmation into account when they review activities that have taken place at the packaging site. When satisfied with everything, the final QP can then legally certify the batch for release. With complex supply chains, there can be more than one “confirming” QP, but there is only ever one certifying QP.
- What are the differences between QP Certification and Release?
The EU system for IMP release describes a 2 stage process, involving an initial technical green light (QP Certification), followed by a Regulatory green light which occurs when approval by the regulatory authority in that country has been given to perform the CT and ethics committee approval has been granted. Both these have to have occurred before product can actually be released for use in a trial. In the R&D world, often a company is waiting for both of these approvals so although the QP certification is described as happening first, the QP will undoubtedly want to know if the regulatory approval includes any restrictions/constraints which have any impact on the product.
For commercial products, QP certification is the legal step whereby the QP takes personal legal responsibility and liability to ensure the batch is suitable for release. It is always at the final stage of manufacture when the finished pack is available. For commercial products the next step is often a status change in the logistics system which now makes the specific batch of product “available” (to release and sell).
- I'm confused on what Annex 16 entails. Can you please explain it?
This is part of the EU GMP guide and is a supplementary document that provides much more detail on the roles and duties of the QP. It was updated recently and some significant changes were made to the latest version which was issued April 2016. It acts as a key document for all QPs. Of particular note are the following:
- Clarification of the certification process (so this can include earlier confirmation) and is not in itself batch release
- More detail when relying on GMP assessments (typically on site audits) by third parties
- Handling of unexpected deviations – clarification of what is expected/allowed
- Much more detail on expectations regarding sampling and testing of products imported into the EU
- For early phase (Ph 1/2) trials, what are the requirements regarding the need for "Leading" Stability data? And if there are requirements, such as 6 months in front of actual IMP, then are there any leniencies been shown (e.g., for orphan drugs)?
The ICH development stability guidelines need to be considered if wanting to conduct early trials in the EU. Assuming the formal, development stability work being undertaken is in compliance with ICH requirements and therefore includes accelerated conditions; there is a calculation that can be used to apply a shelf life. Depending on the trial design and duration it may be possible to get a trial approved using Investigational Medicinal Product (IMP) with a very short shelf life. This would certainly not be unusual for Phase I trials. Obviously as additional time points in a stability study are reached and more results obtained, assuming these demonstrate a satisfactory stability profile, the company can apply to extend the shelf life. Data would need to be submitted to support this. I am unaware of any formal “relaxation” of these requirements for Orphan drugs. Any decision regarding stability data required for a drug that has been classified as an Orphan drug is likely to be linked very closely to the specific therapeutic area concerned, dosage form and therefore overall patient risk of that development drug.
Was this information useful for you? Do you have any additional questions regarding the QP process? Let us know in the comments below and we can answer them at the Sherpa Summer Seminar on August 10. Speaking of which…
If you’d like to have your clinical supply questions answered in real-time, register for our complimentary Sherpa Summer Seminar where we will tackle the QP process in further detail, along with a few other items (you can check out the agenda here). Join us and the San Diego life sciences community for an afternoon of talks, and an evening of catered BBQ and networking!
About SHERPA Clinical Packaging
Sherpa Clinical Packaging provides clinical trial material management services for clinical studies phases I-IV, including packaging, labeling, distribution, storage and returns and destruction services. We manage trial materials for global studies using our cold-chain expertise and our global distribution network among our other offerings. Our agile managerial and operational systems are built to accommodate ever-changing clinical project requirements and fast turnaround times without sacrificing quality. Sherpa’s responsive team leverages its global expertise to identify and execute creative clinical supply solutions for all clients.
About sue Mann, sUE mANN cONSULTANCY LTd
We are very grateful to Sue for taking the time to answer these questions! She is the managing director and QP consultant at Sue Mann Consultancy Ltd. She has extensive experience in the Pharmaceutical industry, spanning well over 35 years, principally in Quality Assurance / Management / Systems and also in Clinical Trials supply, Technical Management and production support. Sue has knowledge and experience in most major dosage forms, both in R&D and commercial operations. Sue is a Pharmacist, a Qualified Person (EU Directive 2001/83/EC), member of the Chartered Quality Institute and the Research Quality Association (member of the GMP committee). She is also a QP Assessor, working on behalf of the UK MHRA, representing the Royal Pharmaceutical Society.