The quality, safety and efficacy of ATMPs are dramatically influenced by the raw materials used in the manufacturing process. Successful ATMP manufacturing is therefore dependent on the use of high quality reagents.

Our GMP grade products allow for the safe use in clinical trials and commercial manufacturing in accordance with the guidelines set by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and the global ISO Technical Standard 20399.

USAEU

FDA – Ancillary Materials

USP chapter <1043>: Ancillary materials for cell, gene and tissue engineered products
Tier 2: Low-risk, well-characterized materials, produced in compliance with GMP, and intended to be used as ancillary materials

USP chapter <92>: Cytokines and growth factors used in cell manufacturing

 

 

EMA – Raw Materials

Ph. Eur. General Chapter 5.2.12: Raw materials for the production of cell-based and gene therapy medicinal products
Section 5: Proteins produced by recombinant DNA technology

EudraLex – Volume 4 – Part IV: Guidelines on GMP specific to ATMPs
7.2. Raw Materials:As far as possible, raw materials used in the manufacturing of ATMPs should take into consideration the Ph. Eur 5.2.12 general chapter on raw materials of biological origin for the production of cell based and gene therapy medicinal products.”

FDA – Ancillary Materials

USP chapter <1043>: Ancillary materials for cell, gene and tissue engineered products
Tier 2: Low-risk, well-characterized materials, produced in compliance with GMP, and intended to be used as ancillary materials
USP chapter <92>: Cytokines and growth factors used in cell manufacturing

EMA – Raw Materials

Ph. Eur. General Chapter 5.2.12: Raw materials for the production of cell-based and gene therapy medicinal products
Section 5: Proteins produced by recombinant DNA technology

Despite arising guidance in this area, dedicated regulations for the GMP compliant manufacturing of cell and gene therapies and associated quality regulations for raw materials are still under development. As a result no official certification is given for the manufacturing of GMP grade raw materials, neither in Europe nor in the USA.

Since this kind of GMP certification is not foreseeable in the near future, manufacturers of raw materials have to identify critical quality requirements to meet increasing quality and safety concerns.

We propose and apply the following three critical quality standards for the manufacturing of GMP grade raw materials:

Safety

Although GMP grade raw materials are not intended to be part of the final ATMP they come in contact with them during manufacturing and might therefore have an influence on their safety.

To ensure the safety of your ATMP we offer:

• Raw material and supplier qualification for all our production materials
• Animal-derived component-free and serum-free products (ADCF & SF Policy)
• The use of fully traceable and well-characterized Master Cell Banks
• Low endotoxin and host-cell protein levels

Endotoxin levels
To make sure endotoxin levels don’t influence the safety and reproducibility of your ATMP, we have adapted and revalidated our QC test method for our GMP cytokines. With this method we are able to measure endotoxin threshold values as low as ≤50 EU/mg for all GMP cytokines except IL-2, IL-7, IL-15 and IL-21. For these T cell cytokines we offer even lower endotoxin threshold values of ≤25 EU/mg. This ensures that endotoxin will not influence the activation, metabolism and inhibition of your T cells.

GMP Compliance

Our GMP grade raw materials are manufactured following all applicable GMP guidelines to provide documented evidence of purity, potency, consistency and stability.

We offer the highest GMP quality standard:

• Manufacturing and QC according to Standard Operating Procedures (SOPs)
• Qualified and trained personnel
• Clean room facilities (Class A-D) and qualified equipment
• Validated and consistent processes (manufacturing, cleaning, QC methods)
• Monitoring of product quality by in-process controls (IPC)
• Product release according to pre-defined specifications by an Authorized Person

Quality Assurance performs internal Quality Audits on a regular basis. We in addition audit our suppliers for critical components prior to allowing these products to be used in our manufacturing process.

We have a continuous improvement process in place in which we closely monitor the complete manufacturing process up to final product performance and feedback from the market. Corresponding Corrective and Preventative Action (CAPA) programs are executed.

Regulatory Compliance & Support

In order to obtain a market authorization for an ATMP it is crucial that your GMP grade raw materials are compliant with international guidelines and local requirements.

Our products are compliant to:

• USP <1043>, USP <92>, Ph. Eur. General Chapter 5.2.12 and ISO Technical Standard 20399, as applicable
• ISO 9001:2015 certified Quality Management (QM) system
• Manufacturing in compliance with relevant GMP guidelines
• Change control process, OOS procedure, deviation process, etc. are in place

Our QM system is constantly improved and regularly inspected by a certified body. In addition, audits are conducted by customers on a regular basis.

Regulatory Support – we assist you with your approval process:

• Expert technical and regulatory support (incl. interaction with major regulatory authorities, on-demand customized documentation for regional authorities)
• Change notifications prior to relevant changes
• Drug Master Files for cross-reference (USA only)

In order to stay up-to-date and help improve regulatory guidance we are actively involved in many of the regulatory initiatives and discussions. Together with the USP we have written the first version of USP <92> and were actively involved in the discussions for the setup of Ph. Eur. General Chapter 5.2.12. We in addition actively contributed to the ISO Technical Committee TC276. This committee published the only global best practice guide for raw materials intended for suppliers and users, the ISO technical standard 20399.