ATMP - Critical Deficiencies during an Inspection in the Netherlands

With the increase in facilities and operations involved in the manufacture of Advanced Therapy Medicinal Products (ATMPs), the number of inspections by the supervisory and licensing authorities in such facilities is also rising. As a consequence, it is not excluded that deficiencies are found in the course of such inspections and that corresponding deviation reports are issued.

On 25 February this year, the competent authority in the Netherlands inspected ERC The Netherlands B.V., which officially deals with research and development on health and nutrition. This inspection resulted in a deviation report in the EUDRA GMDP dated 19 April.

The report states that the ERC The Netherlands B.V. is concerned with:

"Human Investigational Medicinal Products
1 Non-Compliant Manufacturing Operations
1.1  Sterile products
   1.1.1  Aseptically prepared (processing operations for the following dosage forms)
           1.1.1.4  Small volume liquids
   1.1.3  Batch certification

1.3  Biological medicinal products (list of product types)
   1.3.1  Biological medicinal products (list of product types)
           1.3.1.3  Cell therapy products
   1.3.2  Batch Certification (list of product types)
           1.3.2.3  Cell therapy products"

This concerns an ATMP that is used autologously and allogeneically and with which the patient is treated several times.

According to the result of the inspection it must be assumed that the establishment does not fulfil the requirements for good manufacturing practice listed in the principles and guidelines of good manufacturing practice according to Directive 2003/94/EC.

A total of thirteen (n=13) deficiencies were identified during the inspection, one of which was classified as a critical deficiency.
These were mainly related to five main components that lead to the safety and efficacy of their product not being adequately ensured:

• Quality and safety of starting materials is not guaranteed. Inspection of chemicals and consumables is insufficient.
• The quality and safety of the final product is not guaranteed. The product is not sufficiently defined and characterized.
• The effectiveness of a gama irradiation step, and therefore the safety of the product, is not guaranteed.
• The change for the transition from Contractor 1 to Contractor 2 for gamma irradiation of cells has not been carried out as referred to in the GMP for ATMPs.
• Prevention of (cross) contamination is not sufficiently guaranteed. 
• The environmental monitoring program and personnel monitoring are inadequate.

Normally, a recall would be an appropriate measure, but since the distributed products had already been applicated, this was no longer possible. However, distribution was suspended.

Further details can be found on the page of the Website of EUDRA GMDP.