25th Oct 2011, 10:32 AM
11. When does Paragraph 26 (Annex 13 IMP Labelling Requirements) apply?
All IMP for use within a clinical trial must be labelled in accordance with paragraph 26 of annex 13. This applies to not only the investigational product but also to any comparators and placebos used.
In some cases, however, abridged labelling is permitted. Paragraph 26 lists the information which should appear on labels, but does allow some flexibility if the absence can be justified. This is often referred to as abridged labelling and is agreed on a trial-specific basis. The cases where this form of labelling is permitted are as follows:
- For marketed product used within its marketing authorisation, the product can be labelled according to dispensed medicine requirements if this was approved as part of the CTA. However, sponsors may wish their products be labelled following the guidance in Paragraph 32 of Annex 13
- if the IMP being used is a drug product in a vial which needs to be reconstituted aseptically for the purposes of administration, then the vial would need Annex 13 labelling.
For further information please see Annex 13 (external link)
Last edited by MHRA Super Moderator; 25th Oct 2011 at 06:49 PM.
25th Oct 2011, 10:37 AM
12. Is it necessary for a pharmacy to obtain QP certification documents when receiving clinical trial stock?
There is often confusion between IMP release and QP certification ? those managing IMP should be clear on the distinction between these two processes, as the answer differs.
QP certification is the process whereby the QP certifies that the prepared IMP is both manufactured to EU GMP standards and that the product has been assembled as requested and approved in the CTA.
Release is defined as approval to ship IMP to a site when all the required approvals (as defined in Article 9 of 2001/20/EC) are in place and release should only happen after QP certification has been achieved for that batch.
It is normally expected that the pharmacy has the documentation of QP certification for each batch of IMP.
If the NHS trust is sponsoring the trial, the responsibility for technical release may be contracted out to a contract manufacturing organisation as defined in a technical agreement. In such cases, the trust pharmacy only needs confirmation by the sponsor or sponsor?s representative that QP certification has taken place and the product is ready for use.
If the pharmacy is acting on behalf of a host organisation, they must have assurance from the sponsor that QP certification has been performed. Such assurance may be a copy of the QP certification document or a letter or email confirmation from the sponsor.
25th Oct 2011, 10:40 AM
13. Where can I find guidance on the manufacturing requirements for non-investigational products (NIMPs)?
Non-investigational products (NIMPs) are products which are not the object of the investigation, but supplied to a subject in a trial and used as per protocol eg support or rescue/escape medication or preventative, diagnostic or therapeutic treatment to ensure adequate medical care for subjects.
Sponsors must ensure NIMPs are of suitable quality for human use. Guidance on NIMPs is included in Volume 10 Clinical Trials Notice to applicants. Supply of NIMPs with an MA in the Member State or other EU Member State is recommended. However, if they are not licensed in the UK they may be considered to be ?Specials? and appropriate approvals / licenses obtained.
Additional guidance relating to NIMPs is available as follows:
In Chapter III of Volume 10 (external link)
On the MHRA website
Last edited by MHRA Super Moderator; 25th Oct 2011 at 06:51 PM.
25th Oct 2011, 10:43 AM
14. Do pharmacies always have to be involved in the receipt and storage of investigational medicinal product (IMPs)?
There is no legal requirement for pharmacy involvement. However, lack of pharmacy involvement has often been associated with negative inspection findings in that often poor record keeping and accountability have been identified.
The Institute of Clinical Research and the Royal Pharmaceutical Society of Great Britain has produced guidance on this topic, which states that, ‘When a clinical trial is taking place in a hospital all IMPs should be stored and issued by the hospital pharmacy and managed to the same standards as licensed medicines. IMPs must not be stored in offices, clinics or ward areas unless by prior agreement with pharmacy’.
The guidance can be found here (external link)
25th Oct 2011, 10:46 AM
15. Is there any legislation which states how and where the code breaks for clinical trials should be stored?
The guidance from the Pharmaceutical Society states that ’The pharmacy should, where possible, hold the code breaks’
The storage location of any code breaks is not specified in the legislation.
What is of concern is the security of the blinding (ie that the blind cannot be broken without it being detected or code breaks removed/accessed by unauthorised personnel), ensuring that the ability to unblind is in place prior to or at the same time that IMP is made available to the investigator and that there is the ability to promptly unblind for a particular subject in an emergency. ICH GCP requires (section 5.13.4, 8.2.17) a documented procedure to be in place to describe how this is to be done. If the investigator only holds the envelopes (or IVRS access codes), what would happen should the investigator be unavailable? Is there an alternative way of breaking the blind? The pharmacy may have a role to play in the process, for example, would the pharmacy be contacted if the investigator/sponsor was unavailable? And is there a documented procedure for this to enable locum staff to follow this procedure? It is the robustness of the process that is important, how it is achieved is the responsibility of the sponsor/organisation.