Patients who are administered medication, have faith in the medicine while having it. There is a belief of getting cured. The trust lies with the prescribing doctor & the pharmacist; who in turn rely on the manufacturer of the medicine for its quality. No one involved in this chain (neither the patient, the doctor or the pharmacist) can make out, if the medicine is genuine or faulty. To preserve this trust, regulators have bought in guidelines which are known as Good Manufacturing Practices (GMP).
No product by itself or by testing, on its own can ensure its quality. As a lot of testing is destructive; hence only few samples from a batch can be tested. This is called as batch testing.
Good Manufacturing Practices (GMP) ensures the quality of products by its implementation at root levels i.e. in processes and in manufacturing.
This includes not just achieving quality but far more than that. There is a clear and detailed list of specifications on every step involved in manufacturing, for example in the process of materials used, manufacturing, operations, packaging etc. There are standard operating procedures being documented for all the activities like handling, storage, testing etc. The facilities like production units, its premises, manufacturing equipment and staff have to be as per the requirements as well.
In clinical trials also the tested products should be manufactured as per the GMP. This is cited in ICH-GCP part 2.12, “Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol”.
In clinical trials there is an added risk to subjects or patients participating, when compared to patients treated with marketed products. For the risk minimization in terms of safety, efficacy, or quality due to faulty manufacturing of Investigational product, the application of GMP to the manufacturer of investigational products is enforced by regulators and verified from time to time. Also, this is done to ensure that there is consistency between different batches of the same investigational product used in the same or different clinical trials.
There are lots of issues when thought from a clinical trial point of view such as administration of the Investigational Product (IP) is different for different trial designs, their packaging is different etc. In addition randomization and blinding add to the difficulty. Further to this, unexplored safety issues can cause multiple problems. It is very difficult to resolve such complexities.
Such challenges require experts or personnel with in-depth understanding of GMP with its applications to investigational products. This being a responsibility of sponsor, has to undertake the ultimate responsibility for all aspects of the clinical trial including the quality of investigational medicinal products. However, such challenges can be met by implementing a highly effective quality system.
1) ICH – International Conference on Harmonisation Good Clinical Practices, Jan 23st 2012, http://ichgcp.net/2-the-principles-of-ich-gcp-2.