Overview ATMP literature

On this page, you find our growing collection of articles, publications and other information material concerning ATMP (advanced therapy medicinal products) or TEMP (tissue engineered medicinal products) development, tests, validation and use.

Some summary articles (partyl in German) are these:

GMP for ATMP (Guideline draft 2016) = MUST READ
EMA Workshop presentation about ATMP
Arzneimittel für neuartige Therapien - Broschüre zu ATMP vom Innovationsbüro des Paul-Ehrlich-Instituts
ATMPs fordern neue Regularien

EU Directives and Regulations

Here we have listed links to English or German versions of regulations, directives guidelines etc. concerning MP (medicinal products), vMP (veterinary medicinal products), ATMP (advanced therapy medicinal products), blood, EMA (european medicines agency = EMEA), GCP (good clinical practise), Tisuue, GMP (good manufacturing practise), MD (medical devices). Directives are guiding documents that have to be implemented by national laws in the EU member states. Due to these national implementations, national "flavours" in the specifications are possible. It is therefore, always recommended to read national laws and the respective europpean directives to avoid misinterpretation, e.g. when trying to grasp "industrially prepared". Regulations on the other hand are directly binding european "laws" that do not require further national implementation.Further links to authorities and commitees are listed on our authorities links page.

Document	keyword	Title	Comment
REG 1394/2007	ATMP	Advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004	Link
REG 726/2004	EMA	Laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency	Link
RL 2006/17/EG	Tissue	Implementing Directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells Durchführung der Richtlinie 2004/23/EG des Europäischen Parlaments und des Rates hinsichtlich technischer Vorschriften für die Spende, Beschaffung und Testung von menschlichen Geweben und Zellen = Erweiterung Geweberichtlinie	Link Quelle
RL 2006/86/EG	Tissue	Implementing Directive 2004/23/EC of the European Parliament and of the Council as regards traceability requirements, notification of serious adverse reactions and events and certain technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells Umsetzung der Richtlinie 2004/23/EG des Europäischen Parlaments und des Rates hinsichtlich der Anforderungen an die Rückverfolgbarkeit, der Meldung schwerwiegender Zwischenfälle und unerwünschter Reaktionen sowie bestimmter technischer Anforderungen an die Kodierung, Verarbeitung, Konservierung, Lagerung und Verteilung von menschlichen Geweben und Zellen	Link Quelle
RL 2005/28/EG	GCP	Laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products Festlegung von Grundsätzen und ausführlichen Leitlinien der guten klinischen Praxis für zur Anwendung beim Menschen bestimmte Prüfpräparate sowie von Anforderungen für die Erteilung einer Genehmigung zur Herstellung oder Einfuhr solcher Produkte	Link Quelle
RL 2004/23/EG	Tissue	Setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells Festlegung von Qualitäts- und Sicherheitsstandards für die Spende, Beschaffung, Testung, Verarbeitung, Konservierung, Lagerung und Verteilung von menschlichen Geweben und Zellen = Geweberichtlinie	Link Quelle
RL 2004/27/EC	MP	Amending Directive 2001/83/EC on the Community code relating to medicinal products for human use	Link
RL 2003/94/EG	GMP	Laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use Festlegung der Grundsätze und Leitlinien der Guten Herstellungspraxis für Humanarzneimittel und für zur Anwendung beim Menschen bestimmte Prüfpräparate	Link Quelle
RL 2002/98/EG	Blood	Setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC Festlegung von Qualitäts- und Sicherheitsstandards für die Gewinnung, Testung, Verarbeitung, Lagerung und Verteilung von menschlichem Blut und Blutbestandteilen und zur Änderung der Richtlinie 2001/83/EG	Link Quelle
RL 2001/20/EG	GCP	On the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use Angleichung der Rechts- und Verwaltungsvorschriften der Mitgliedstaaten über die Anwendung der guten klinischen Praxis bei der Durchführung von klinischen Prüfungen mit Humanarzneimitteln	Link Quelle
RL 2001/82/EG	vMP	On the Community code relating to veterinary medicinal products Schaffung eines Gemeinschaftskodexes für Tierarzneimittel	Link Quelle
RL 2001/83/EG	MP	On the Community code relating to medicinal products for human use Schaffung eines Gemeinschaftskodexes für Humanarzneimittel	Link Quelle
RL 95/46/EG	Data	On the protection of individuals with regard to the processing of personal data and on the free movement of such data Schutz natürlicher Personen bei der Verarbeitung personenbezogener Daten und zum freien Datenverkehr = Datenschutzrichtlinie	Link Quelle
RL 93/42/EWG	MD	Medical devices Medizinprodukte	Link Quelle
RL 90/385/EWG	MD	On the approximation of the laws of the Member States relating to active implantable medical devices Angleichung der Rechtsvorschriften der Mitgliedstaaten über aktive implantierbare medizinische Geräte	Link Quelle

FDA, EMA und CAT: Guidelines (GL, GD), Reflection Papers (RP) und Position paper (PP)

Document	Inst.	Year	Title	Comment
GD draft	FDA	2015	Homologous Use of Human Cells,Tissues, and Cellular and Tissue-Based Products	pdf
GD draft	FDA	2014	Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from Adipose Tissue:Regulatory Considerations	pdf
GD	FDA	2014	Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products	pdf
GL	EMA	2013	Guideline on the risk -based approach according to annex I, part IV of Directive 2001/83/EC applied to Advanced therapy medicinal products	Source
GD	FDA	2012	Pyrogen and Endotoxins Testing: Questions and Answers	Source
GL	EMA	2011	Guideline on analytical method validation	Source
GD	FDA	2011	Potency Tests for Cellular and Gene Therapy Products	Source
GD	FDA	2011	Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)	pdf
GL	EMA	2009	Guideline on xenogeneic cell-based medicinal products	Source
GL	EMA	2009	Detailed guidelines on good clinical practice specific to advanced therapy medicinal products	Source
GL	EMA	2008	Guideline on safety and efficiacy follow-up-risk manegement of advanced therapy medicinal products	Source
GD	FDA	2008	Draft: Validation of Growth-Based Rapid Microbiological Methods for Sterility Testing of Cellular and Gene Therapy Products	Source
GL	EMA	2007	Guideline on cell-based immunotherapy medicinal products for the treatment of cancer	Source
GL	EMA	2006	Guideline on human cell-based medicinal products	Source
GL	EMA	2006	Guideline on virus safety evaluation of biotechnological investigational medicinal products	Source
nG	EMA	2003	Note for guidance on the use of bovine serum in the manufacture of human biological medicinal products	Source
RP ?	EMA	2017	Development of non-substantially manipulated cell-based ATMPs1: flexibility introduced via the application of the risk-based approach	pdf
RP	EMA	2014	Reflection paper on classification of advanced therapy medicinal products	Source
RP	EMA	2013	Reflection paper on management of clinical risks deriving from insertional mutagenesis	Source
RP	EMA	2012	Reflection paper on clinical aspects related to tissue-engineered products	Source
RP	EMA	2012	Reflection paper on the use of starting materials and intermediates collected from different sources in the manufacturing of biological medicinal products	Source
RP	EMA	2011	Reflection paper on stem cell-based medicinal products	Source
RP	EMA	2010	Reflection paper on in-vitro cultured chondrocyte containing products for cartilage repair of the knee	Source
sGL	EMA	1997	Replacement of animal studies by in vitro models	Source
PS	EMA	2011	Position statement on Creutzfeldt-Jakob disease and advanced therapy medicinal products	Source

Hygiene monitoring in ATMP production Labs

The monitoring of hygiene or particle load in ATMP (advanced therapeutic medicinal products) producing labs is ofter underestimated. Contamination is a critical factor in such labs as shown in the following publications:

Environmental monitoring in stem cell banks.

Cobo F, Stacey GN, Cortés JL, Concha A.: Appl Microbiol Biotechnol 2006 May;70(6):651-62. Review

Review: production, characterization, and testing of banked mammalian cell substrates used to produce biological products.

Schiff LJ: In Vitro Cell Dev Biol Anim. 2005 Mar-Apr;41(3-4):65-70. Review

Microbiological risk assessment in stem cell manipulation.

Pessina A, Bonomi A, Baglio C, Cavicchini L, Sisto F, Neri MG, Gribaldo L.: Crit Rev Microbiol 2008;34(1):1-12. Review

Medical biofilms.

Bryers JD.: Biotechnol Bioeng 2008 May 1;100(1):1-18. Review

ATMP in clinical trials

ATMPs and TEMPs carry a huge potential for modern medicine. More and more clinical trials are started now.

A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation.

García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA.: Dis Colon Rectum 2005 Jul;48(7):1416-23.