Core Facility

ATMP

Expert center for the production of Advanced Therapy Medicinal Products.

Services

Facility / Equipment

Clean Room Facility

Three fully equipped clean rooms for the in house production of ATMP.

The Clean Room Facility for cell and gene therapy is located at the 13th floor of the Ee-building. It consists of:

  • One ladies- and a gents changing room (1354, 1356) at the entrance.
  • One sterile disposables storage room (1358).
  • Two clean rooms for hematopoietic stem cell processing (1351a and 1351 b) connected with the central hall through a single lock room (1351).
  • Three clean rooms (1357a, 1359a, 1361a) for the production of ATMP, which are each connected with the central hall through a lock room (1357, 1359, 1361).

The three clean rooms for ATMP production are ± 16 m2 each fully equipped for aseptic processing and in vitro culture. All clean rooms and associated lock rooms are qualified as cleanroom class C. An environmental monitoring program is operational to document the quality of the aseptic processing environment and provide information on environmental trends of the clean areas.

The 3 clean rooms for ATMP production are qualified for genetic modifications at ML-I and ML-II level. The entrance to the cleanroom facility is restricted to qualified personnel and regulated through a personal badge. Next to the clean room facility is a quality control laboratory and  a room for the storage of cryopreserved products.

 

Map of Clean Room Facilities

 

Quality management system

A comprehensive Good Manufacturing Practice compliant quality management system for the in house production of ATMP.

ATMP are medicinal products. Thus the production of ATMP has to comply with Good Manufacturing Practice (GMP) standards. A GMP-compliant comprehensive quality management system is operational, ensuring that all applicable quality and safety rules for the in house production of ATMP are met.

The quality management system includes:

  • Training and qualification of personnel.
  • Selection and qualification of raw materials.
  • Document control.
  • Process validation.
  • Validation, maintenance and calibration of equipment,
  • Environmental monitoring of the clean rooms.
  • Release of ATMP end products by a Qualified Person.
  • Internal audits.
  • Registration of errors, accidents and adverse events.
  • Participation in external proficiency testing programs.

In addition, written policies regarding processing, quality controls, storage, release and transport of cell and gene therapy products are operational.

Support

Preparation of an ATMP-specific product dossier

The ATMP facility supports researchers in writing the IMPD for their ATMP.

The Investigational Medicinal Product Dossier (IMPD) is the basis for approval of clinical trials by the competent authorities. The IMPD includes summaries of information related to the quality, manufacture and control of the Investigational Medicinal Product. An overall risk-benefit assessment, critical analyses of the non-clinical and clinical data in relation to the potential risks and benefits of the proposed study have to be part of the IMPD.

Over the years, the ATMP facility has acquired knowledge and experience on writing an IMPD for ATMP which are intrinsically complex products derived from a variety of biological materials, such as cells, tissues or viral vectors.

The ATMP facility supports researchers in writing the IMPD for their ATMP.

A manual to develop and write an IMPD for an ATMP and an example of a CCMO-approved IMPD for an ATMP are available.

Center of expertise for ATMP

Through the Center of Expertise, developers of ATMP are supported to bring their advanced products to the clinic.

The translation from pre-clinical research with ATMP to clinical application in patients requires extensive knowledge regarding regulatory issues (types of permits required and procedures for obtaining them) and many aspects in relation to the preparation of these medicines (GMP-compliant quality system, clean room facilities, SOP's and product documentation (IMPD) etc.

Specific knowledge and experience regarding the production process of an ATMP or study with an ATMP is often absent with researchers. The constantly renewing regulation is difficult to understand. For most researchers the understanding of these regulations does not have priority.

Through the Center of Expertise, developers of ATMP are supported to bring their advanced products to the clinic. Researchers are supported during the preparatory phase preceding the clinical study. The Center of Expertise helps to navigate through the regulatory framework, to prepare the ATMP-specific dossier including the investigational medicinal product dossier and to obtain the required permits for the production and clinical application of the ATMP. In addition, researchers are assisted with the translation of the research production protocol into a GMP-compliant production protocol. This includes the upscaling of the procedure, the replacement of research grade ingredients with GMP compliant ingredients and the transition of an open production system into a closed production system, when possible. We also advise on the design of in process quality controls and the specification of the release criteria of the final ATMP product.

Training & education

Training

Training and qualification of personnel

The ATMP facility provides a training program for researchers and technicians to qualify for the in house production of ATMP for clinical studies.

ATMP's are produced by staff from the department of the Principle Investigator of the clinical study with a particular ATMP. The ATMP facility offers a training program for researchers and technicians to qualify for the production of an ATMP in a clean room environment.

The training program consists of a basic training on the theory and practice of the quality management system, Good Manufacturing Practice (GMP), clean rooms, clothing and hygiene instructions. The microbiological training program includes a bouillon simulation test and a clean room clothing qualification. Successful completion of the initial training program and continued training  is a prerequisite to qualify for ATMP production in the clean room facility.

News, events & publications

About us

Introduction

ATMP: From bench to bedside 

Scientific progress in cellular and molecular biotechnology and continuous research and innovation has led to the development of novel advanced therapy medicinal products (ATMP), such as somatic cell therapy-, gene therapy- and tissue-engineered medicinal products. However, the translation from pre-clinical research to clinical application in patients is challenging and requires extensive knowledge regarding regulatory issues and the good manufacturing practice (GMP)-compliant production of these ATMP. The mission of the ATMP facility is to support bench-to-bedside development of innovative ATMP-based therapies within the Erasmus MC.

Our team

ATMP Facility Personnel:

Eric Braakman

Facility Manager, Qualified Person

e.braakman@erasmusmc.nl
Tel: 010-7043772
Room: Ee-1391a

Anita Rijken Schelen

Hoofd Quality Assurance

a.schelen@erasmusmc.nl
Tel: 010-7043952
Room: Ee1369

Valentina Lorenzi

Qualified person, Advisor

User Council:

Koen Bezemer
Head of production
Dept. Lung Disease
k.bezemer@erasmusmc.nl
Tel: 010-7043701
Room: Ee-2251

Cor Lamers
Head of production
Dept. Internal Oncology 
c.lamers@erasmusmc.nl
Tel: 010-7041771
Room: Be-430c

Nicolle Litjens
Head of production
Dept. Internal Medicine
n.litjens@erasmusmc.nl
Tel: 010-7035418
Room: Na-516

Valentina Lorenzi
Dept. Pharmacy

Anita Rijken-Schelen
Dept. Hematology

Arnold Vulto
Dept. Pharmacy

Our expertise

The ATMP facility supports bench-to bedside development of innovative ATMP based therapies.

ATMP comprise 3 types of products. These are:

  1. Manipulated somatic cell therapy products.
  2. Gene therapy products.
  3. Tissue engineered products.

ATMP hold great promise for the development of new treatment approaches for a variety of serious diseases. As a result of the implementation of the European Directive 1394/2007 on advanced therapy medicinal products, ATMP are considered to be medicinal products. This implies that the preparation of ATMP for clinical application has to comply with all legal regulations for the production of medicines.

Over the past few years, significant progress has been made in the development of novel ATMP. However, the step from basic and translational research to clinical trials is challenging. This is mainly due to the complex nature of the ATMP production process and the regulatory framework governing ATMP production.

Mission statement
The mission of the ATMP facility is to support ATMP developers within Erasmus MC to bring promising innovative cellular therapies into clinical trials. In order to do this, a core of expertise on ATMP was established in the ATMP Center of Expertise.

The ATMP Center of Expertise supports researchers to navigate through the regulatory framework, to prepare the ATMP-specific product dossier and to obtain the required permits for the production and application of ATMP in clinical trials. In addition, the Center of Expertise  assists in the translation of the research production protocol into a GMP-compliant production protocol and provides clean rooms and a GMP-compliant quality management system for the in house production of ATMP for clinical studies.

The ATMP facility also provides a training program for researchers and technicians to qualify for the production of an ATMP in a clean room environment. Finally, the ATMP facility holds a Good Manufacturing Practice (GMP) license for the production of ATMP. This is a legal prerequisite for the in house production of ATMP for application in clinical trials.

Examples of ATMP:

  • Monocyte-derived dendritic cells loaded with tumor antigens (see figure). 
  • Genetically-modified T lymphocytes expressing a tumor-specific T cell receptor.
  • Ex vivo expanded umbilical cord blood-derived hematopoietic stem and progenitor cells.

GMP License

The ATMP facility holds a manufacturing authorization (108517F) and a GMP certificate (NL/H/15/1004371) for the production of ATMP Cell-therapy medicinal products from the competent authorities in the Netherlands (Ministry of VWS).

Any questions?

Please contact our facility

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