Q&A Session at the QP Forum 2010 in London, UK
What is the QP’s Responsibility with regard to moving a Clinical Site
a) within the same city?
b) to another city?
The QP has to assess that medication has been:
- properly stored in the site that will be closed
- properly shipped to the receiving site
This means ensuring that all environmental conditions are within specs.
It doesn’t differ whether you move a site within a city or to another city.
We request that a drug transfer form is filled in indicating that medication has been stored and shipped properly.
The monitor is signing off, as well as the local and global trial manager and the QP.
Should a QP audit CROs and investigators or can a QP rely on GCP-auditors of own company?
How can this sharing of responsibility be realised?
The QP can rely on the information provided by the GCP auditors.
Within J&J a system has been set up to ensure the QP is informed in case critical issues are
observed during a GCP inspection. In this situation an escalation meeting is organised to decide what to do with the medication on site.
What is the better option: staff developing the formulation will also manufacture the IMP (and than suddenly have to face GMP) or should they hand it
over to another group who doesn’t know the formulation very well but is familiar with GMP?
Both scenarios are acceptable. Within my organisation phase 1 material is often produced by the formulation group under supervision of QA.
They are properly trained to do these activities.
What is the usual/normal level of complaints for pre-filled syringes and auto-injectors?
There is no “usual complaint rate” for pre-filled syringes, as the type and application of the syringes may vary widely – staked needle, double chamber etc... But a “window” may be 5 ppm to 25 ppm...
There is dispute, whether for auto-injectors higher rates are acceptable or to be expected. Auto-injector may be complex and made of several components. So failures must be anticipated. On the other hand,
auto-injectors should reduce the number of mishandling of the syringe. So a slightly higher number of complaints should be acceptable.
A product (sterile eye drops) meets all specifications. However during production some microbiological monitoring results were not o.K.. Can I release the batch?
Microbiological monitoring data are not describing the microbiological status of the batch itself. Monitoring data are considered to give information about the controlled environment. A level excursion in micro
monitoring may be an indicator that there are deviations from the usual process, but they do not automatically indicate a microbiological problem of the batch. Following a positive outcome of a risk assessment of the
non conforming monitoring results (type of contamination, level of contamination, place of the monitoring, other monitoring data, trending) it might well be possible to release the batch.
Who should sign the Quality agreement? QP only? QA? Legal? Head of production/QC? Business?
Quality Agreements should be considered GMP documents. Therefore involvement of the Legal Departments should be limited – not to complicate and extend the process. According to the latest revision of chapter 7
of the EU GMP Guide (“Outsourced activities”) ...
7.12 A contract should be drawn up between the Contract Giver and the Contract Acceptor which specifies their respective responsibilities and communication processes relating to the outsourced activities.
Technical aspects of the contract should be drawn up by competent persons suitably knowledgeable in related outsourced activities and Good Manufacturing Practice.
The revision of chapter 2 of the EU GMP Guide (“Personnel”) states<
2.7 The heads of Production and Quality Control generally have some shared, or jointly exercised, responsibilities...
– the approval and monitoring of contract manufacturers;
Taken these two chapters in mind, I would advocate for the Head of production and QCto sign a Quality Agreement. The QP must be informed, but there is no obligation for him/her to sign the Quality Agreement.
How much (if at all) you can increase or decrease a batch size without the need for re-validating?
It depends on various aspects. The most important ones should be determined in a risk-evaluation (Product/Process/Specifications …). If you don’t change the equipment and just vary some none critical parameters,
some qualification-steps may be sufficient. Even in cases of 1:10 change mostly a prospective validation is not needed, a concurrent validation is possible.
Importing a product from a 3rd country; what do I need? GMP Certificate? Import License? How do I get these? Do I also need them for APIs?
In case of finished medicinal products you need an Import Licence, which you will get from your competent Authority. In some member states, the same is required for test sera, test antigens or active substances,
which are of human, animal or microbial origin or are manufactured using genetic engineering. In those states you also need a Certificate of Compliance of the competent authority in the case of import of finished
products and test sera, test antigens or active substances, which are of human, animal or microbial origin or are manufactured using genetic engineering from third Countries, which are not MRA-Partners.
This is not necessary for the import of IMPs.
In case of import of active substances, which are not of human, animal or microbial origin or are manufactured using genetic engineering are imported from third Countries, you need a Certificate of Compliance of the local
competent authority (from the local Authority for your supplier abroad).
In France, only pharmacists can become a QP. Do you think this will change someday?
According to our information, there is currently no plan to change the French “Code de la santé publique” to allow a non-pharmacist to hold the position and responsibilities of a QP meaning to officially certify the
pharmaceutical product batches for their release to the market.
Fully electronic systems: is an electronic signature acceptable for: CoA? Audit report? Batch Certification? PQR?
Yes, it is (or it should be) acceptable to use an electronic signature for CoAs, Audits Reports, Batch Certifications, PQRs etc. provided this signature is a true electronically certified signature.
However, a number of situations are not acceptable. For example some CoAs can be found bearing the sentence “this is an electronic document and therefore it does no need any signature” or signed “Head of QC” with no name.
This is not fair enough because a pharmaceutical signature should always belong to a named individual, not to a system and not to a function.
What are the most critical elements of the supply chain requiring QP involvement?
First of all QPs must define their relevant supply chain, for many companies this starts from procurement of the raw materials (e.g. APIs, excipients, packaging components etc.), ending when the product reaches the customer.
The QP then needs to identify what input is required at each stage, then either personally provide that input or delegate the activity to another person or department within the company and ensure that he is kept informed.
Examples of such activities may include selection of suppliers of API’s, audit of suppliers, all relevant activities to manufacture of the product and its testing, transportation of the product to the distribution centres and wholesalers as relevant.
Where does the responsibility of the QP end? When product is handed over to wholesaler/RP?
Normally once the product is delivered to the customer it is assumed that the customer will take responsibility for the product from the point of receipt. If the product is supplied to a wholesaler, it very much depends on who owns the product,
if the wholesaler has purchased the goods, then they should take responsibility, however, if the product at the wholesalers belongs to the QP’s company, then the QP continues to have the responsibility for the goods whilst at the wholesaler.
The responsibility for the product at each stage of it life cycle should be clearly defined in the internal procedures, and where external parties involved (e.g. wholesalers) in the Technical (Quality) Agreement between the company and the wholesaler.
It is possible for the QP to delegate this responsibility to the RP at the wholesaler, but this must be clearly defined (including the limitation which may apply) in the technical agreement. Please note that the QP retain s the responsibility for recall
of the products in the market place as well as ensuring that any product complaints have been fully investigated and appropriate corrective actions taken.
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