In order to conduct a clinical trial in the EC, the sponsor must first submit a valid request for authorisation to the Competent Authority of the Member State where they propose to conduct the trial. This request is known as the Clinical Trial Application (CTA). The content of this application will then be assessed by the competent authority and/or the Ethics Committee to ensure that the anticipated therapeutic benefits to the patient justify any foreseeable risks before a favourable opinion is issued to allow the trial to proceed.
The safety of subjects participating in a clinical trial is the main reason behind many of the changes brought about by the Directive and thus why the need for a common system of authorization has also come about. This requirement within the pharmaceutical industry was previously only applicable to commercial products. However, this change now means that all facilities used for the manufacture or import of Investigational Medicinal Products (IMPs) will be subject to an inspection by the competent authority.
This is to ensure that the principles of Good Manufacturing Practice (GMP) as led down in Annex 13 to the EU guide to Good Manufacturing Practice are being adhered to. On the basis of this inspection, they may become licensed by the competent authority. This authorisation takes the form of a Manufacturing Authorisation for IMPs or MA for IMPs.
Yet, one additional aspect must be fulfilled in order for a facility to be granted a licence. This is the need for the manufacturer or importer to have a Qualified Person (QP) permanently and continuously at their disposal. This person will be named on the licence and will be responsible for the release of batches of clinical trial material before they can be used in a clinical trial.Several scenarios present themselves. The first one is when the IMP has been manufactured within Europe. This is no doubt the simplest case for the QP when discharging their duties. In order to release material of European origin, they must confirm that each batch has been manufactured and checked in compliance with GMP, the Product Specification File (PSF) and the request for authorisation to conduct the trial, i.e. the CTA.
Another scenario exists when a comparator product from outside the EU, with a marketing authorisation (MA) in that country is to be used as an IMP. Under such circumstances the QP can perform release, if documentation is available to certify its manufacture to standards at least equivalent to European GMP. However, in the absence of such documentation, the QP must ensure that each lot undergoes all relevant analyses, tests or checks to confirm its quality.
This can sometimes prove difficult and therefore it is important that the sponsor gives purchase of comparators due consideration. One piece of advice would be that, if possible, comparators should be sourced within Europe or from countries where Mutual Recognition Agreements are already in existence, such as Canada, Australia, New Zealand, Switzerland and Japan. These Mutual Recognition Agreements are based on trust and confidence and are therefore very useful when it comes to importing comparators, as they aim to remove barriers to trade and promote standardization of GMP.
MA: Marketing authorization
MAH: Marketing authorization holder
CA: Competent Authority
QP: Qualified Person
MRP: Mutual Recognition Process
MRA: Mutual Recognition Agreement
EMEA: European Medicines Agency
- The European Medicines Agency (EMEA) is a decentralised body of the European Union with headquarters in London. Its main responsibility is the protection and promotion of public and animal health, through the evaluation and supervision of medicines for human and veterinary use.
BPWP: blood product working party
- The Blood Products Working Party (BPWP) was set up by the CHMP to provide recommendations on all matters relating directly or indirectly to efficacy and safety aspects of blood products.
CHMP: The Committee for Medicinal Products
- The Committee for Medicinal Products for Human Use (CHMP) is responsible for preparing the Agency's opinions on all questions concerning medicinal products for human use, in accordance with Regulation (EC) No 726/2004.
NfG: Notes for Guidance
PtC: Point to Consider
RMS: Reference Member State
Concerned Member States
Application for variation to a marketing authorisation = sNDA or sBLA
MHRA: Medicines and Healthcare products Regulatory Agency - An executive agency of the Department of Health in UK - simiar to FDA in US
SPC or SmPC: Summary of Product Characteristics - similar to Label or Package Insert in US.
- Pescription medications are regulated by governmental bodies to assure quality and appropriate use. In the US, the FDA regulates medications, and requires "labels" to be approved. "Package inserts" are written for health care providers. They contain very detailed information about different drugs. Frequently, there are also official documents for patients, called Patient Information leaflets. The manufacturers prepare this information, and the FDA approves it (sometimes after considerable discussions and negotiations!).
- In Europe, a similar process is used, with the "label" called the Summary of Product Characteristics (SPC, or SmPC). The patient-oriented document is called a "Package Leaflet" or "Patient Information Leaflet" (PILs)
IPMD: The Investigational Medicinal Product Dossier (IMPD)- similar to IND submission in US. IMPD needs to be submitted to the concerned competent authority (CA) in order to obtain the authorization of conducting the clinical trial.
CTA: Clinical Trial Application - similar to IND (investigational new drug)
NICE: The National Institute for Health and Clinical Excellence a counterpart in US is the Agency for Healthcare Research and Quality.
- NICE is a special health aurhority of the National Health Service (NHS) in England and Wales. It was set up as the National Institute for Clinical Excellence in 1999, and on 1 April 2005 joined with the Health Development Agency to become the new National Institute for Health and Clinical Excellence (still abbreviated as NICE).
- NICE publishes clinical appraisals of whether particular treatments should be considered worthwhile by the NHS. These appraisals are based primarily on cost-effectiveness.