In view of recent experiences from inspections carried out for COVID-19 therapeutics, the World Health Organization (WHO) published a new working document entitled “GOOD MANUFACTURING PRACTICES FOR INVESTIGATIONAL PRODUCTS“. The deadline for comments is 6 January 2021. According to the WHO the current update of the WHO Good manufacturing practices for investigational pharmaceutical products for clinical trials in humans (WHO Technical Report Series, No. 863) document is to bring the guideline in line with current expectations and trends in good manufacturing practices (GMP).
The recommendations in this guideline apply to investigational medicinal products (IMPs) for human and veterinary use. The quality system should incorporate GxP (e.g. GLP, GMP, GCP, GSDP) including quality risk management (QRM).
Specific aspects of the WHO draft document
- Specifications (for starting materials, primary packaging materials, intermediate, bulk and finished products) should be available. They should include the estimated stability, if necessary, under accelerated conditions; and the preliminary storage conditions and the shelf life of the product.
- Change Control
As a result of new experience in the development of an IMP, specifications may be changed by following a documented procedure. Changes should be authorized by a responsible person.
- Qualification and Validation
The extent of qualification and validation (analytical & production procedures) may be different to that necessary for routine production and should be determined based on risk assessment.
- QC & Batch Release
Each batch of product should be tested in accordance with a Product Specification File (PSF) and should meet its specification. Product release can be carried out in two stages: Before final packaging (bulk product testing) and after final packaging (finished product testing). The IMP batch release should only occur after the designated responsible person has certified that the product meets the relevant requirements.
- Reference & Retention Samples
Reference and retention samples of each batch of product should be retained. Retention samples should be kept until the clinical report has been prepared. The storage location of reference & retention samples should be defined in a technical agreement between the sponsor and manufacturer and should allow for timely access by the competent authorities.
- Electronic Records
It is acceptable to store information related to the final packaging as written or electronic records. Electronic systems should comply with the requirements of the WHO guideline for computerized systems.
- Complaints & Recalls
Written procedures should be in place describing the handling of complaints & recalls. Recall procedures should be understood by the sponsor, investigator and monitor, in addition to the persons responsible for recalls.
- Shipping & Transfer
Shipping of IMPs should be carried out in accordance with written procedures laid down in the protocol or shipping order given by the sponsor. A shipment is sent to an investigator after following the defined release procedures, for example, QC and authorization by the sponsor. Both releases should be recorded. The sponsor should ensure that the shipment will be received and acknowledged by the correct addressee as stated in the protocol. Transfer of IMPs from one site to another should be done in exceptional cases only. Such transfers should be justifiable, documented and carried out in accordance with a written procedure.
- Repackaging / Relabelling
Repackaging or relabelling should normally be done by the manufacturer. Records should be maintained and provide full traceability of the product and activities.
The sponsor is responsible for the destruction of unused IMPs. Unused products should not be destroyed by the manufacturer without prior authorization by the sponsor.
- The Product Specification File (PSF) contains all the information necessary on the detailed written instructions on processing, packaging, labelling, quality control testing, batch release, storage conditions and shipping.
More information can be found in “GOOD MANUFACTURING PRACTICES FOR INVESTIGATIONAL PRODUCTS” on the WHO Medicines website under “Working documents in public consultation“.