Guidelines on Good Manufacturing Practice for Investigational medicines

10/02/2023 -

In clinical trials there may be added risk to the subjects compared to patients treated with authorised medicinal products.

Investigational medicinal products are therefore manufactured by applying manufacturing practice which ensures the quality of such medicinal products in order to safeguard the safety of the subject and the reliability and robustness of clinical data generated in the clinical trial (article 63, paragraph 1, Regulation (EU) n° 536/2014).

Guidelines on good manufacturing practice for investigational medicinal products (Annex 13) complement Commission Delegated Regulation (EU) 2017/1569 of 23 May 2017 supplementing Regulation (EU) No 536/2014 on the Good Manufacturing Practice for investigational medicinal products for human use and arrangements for inspections.

Guideline "LD.13. Manufacture of Investigational Medicinal Products" of the Good Manufacturing Practice Guide was replaced by Annex 13 (Guidelines on good manufacturing practice for investigational medicinal products), in France (ANSM decision of 29/12/2022).

These guidelines apply to manufacture or import of investigational medicinal products for human use.


An investigational medicinal product is a medicinal product which is being tested or used as a reference, including as a placebo, in a clinical trial (article 2(5) of Regulation (EU) No 536/2014).

The production of investigational medicinal products involves added complexity in comparison with authorised medicinal products by reason of:

  • Lack of fixed routines
  • Variety of clinical trial designs and consequent packaging design
  • Randomization and blinding
  • Possible incomplete knowledge of the potency and toxicity of the product
  • Absence of full process validation
  • Use of authorized products which have been re-packaged or modified in some way

The increased complexity in manufacturing operations requires a highly effective quality system and personnel with a thorough understanding of and training in the application of Good Manufacturing Practice to investigational medicinal products.


The application of Good Manufacturing Practice (GMP) for the manufacture and import of investigational medicinal products is intended to ensure that:

  • Subjects are not placed at undue risk
  • The results of clinical trials are unaffected by inadequate quality, safety or efficacy arising from unsatisfactory manufacture or import
  • There is consistency between batches of the same investigational medicinal product used in the same or different clinical trials 
  • Changes during the development of an investigational medicinal product are adequately documented and justified

The GMP applicable to medicinal products are a legislative reference enforceable during inspections of pharmaceutical undertakings performed by the competent authorities.


Definitions:

  • Investigational medicinal product: a medicinal product which is being tested or used as a reference, including as a placebo, in a clinical trial.
  • Subject: an individual who participates in a clinical trial, either as recipient of an investigational medicinal product or as a control.
  • Manufacturing: total and partial manufacture, as well as the various processes of dividing up, packaging and labelling (including blinding) (article 2(24) of Regulation (EU) No 536/2014).
  • Placebo: a control product that does not contain an active substance (a dummy treatment) that is given to people taking part in a Clinical Trial.

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Tags : #Exploitant pharmaceutical site , #Pharmacovigilance