UST-37

APPLICATION FOR A HOSPITAL EXEMPTION FOR ADVANCED THERAPY MEDICINAL PRODUCTS

Valid since 1. 09. 2013

•  UST-37.pdf

 

Legal framework:

• Act No. 378/2007 Coll., on pharmaceuticals and on amendments to certain related acts (act on pharmaceuticals, as amended (the “Act on Pharmaceuticals”)
• Decree No. 228/2008 Coll., on the marketing authorisation of medicinal products, as amended (the “Marketing Authorisation Decree”);
• Regulation (EC) No 1394/2007 of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 (the “ATMP Regulation”);
• Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use;
• Commission Directive 2009/120/EC amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products;
• Guideline on Human Cell-based Medicinal Products  (EMEA/CHMP/410869/2006);
• Guidance on Nonclinical Safety studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3 (R2));
• Note for guidance on the quality, preclinical and clinical aspects of gene transfer medicinal products (CPMP/BWP/3088/99);
• Act No. 296/2008 Coll., on safeguarding the quality and safety of human tissues and cells intended for use in man and on amendments to related acts (Act on Human Tissues and Cells), as amended;
• Decree No. 422/2008 Coll., on detailed requirements for the safeguarding of the quality and safety of human tissues and cells intended for use in man, as amended;
• Directive 2004/23/EC of the European Parliament and of the Council on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells;
• Commission Directive 2006/17/EC 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;
• Act No. 123/2000 Coll., on Medical Devices and on amendments to certain related act, as amended;
• Government Regulation No. 336/2004 Coll., setting technical requirements for medical devices, as amended;
• Council Directive 93/42/EEC concerning medical devices;
• Directive 2007/47/EC of the European Parliament and of the Council amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market

Abbreviations used:

• ATMP – advanced therapy medicinal products
• MP – medicinal product
• The Institute – the Institute for Drug Control

Hospital exemption for ATMP is an institute which allows for a certain type of MP defined in Section 49a of the Act on Pharmaceuticals to be manufactured and used as non-authorised ATMPs (gene therapy, somatic cellular therapy, tissue engineering products) which, when seen from the perspective of general manufacturing requirements, are prepared on a non-routine basis but according to specific quality standards, and are to be used in an inpatient healthcare facility with a view of complying with an individual medical requirement for a specific patient.

Terms:

1. Non-routine production 
Non-routine manufacturing process is understood to mean a non-routine process (i.e. non-standard, individually different) which must be tailored, for example, but without limitation, to the features of the input materials and to the needs of specific patients. The fact that the product is autologous is not, without providing further justification, a reason to mark the manufacturing process as a non-standard process.

2. Exclusive professional liability of doctors
Exclusive professional liability of doctors is understood to mean that doctors are liable for the fitness of use of ATMPs in terms of indications and conditions of patients and the set of information provided by the manufacturer for the product or, alternatively, on the basis of results of scientific works involving the product in question.  Doctors are not liable for quality and safety of the ATMP and accuracy of data furnished by the manufacturer to be used as a basis for a doctor’s decision. Manufacturers of ATMPs are responsible for the quality and safety of the ATMP and the accuracy of data they furnish. 

3. Individual medical requirements
An individual medical requirement is understood to mean a decision of a doctor to use (or, alternatively, to request production of) an ATMP for a specific patient. 

4. Miscellaneous 
The scope of production is assessed along with its non-routineness. The number of products manufactured and the number of patients treated in light of the frequency of the illness in question is monitored. Production should not involve any industrial process.

Typically, the number of packs is in the order of units or tens of units.

 As a rule, hospital exemptions should be used when, given the characteristics of a medicinal product or the indication in question, it is not possible to acquire statistically relevant and requisite amount of data (in particular, clinical data) required for centralised marketing authorisation of the ATMP. 

When assessing applications for hospital exemptions, the Institute shall also consider alternatives offered by the authorisation procedure, e.g., the status of medicinal product for rare illnesses (the “orphan drug”), authorisation under specific conditions or conditional marketing authorisation.

Manufacturers are required to comply with quality standards necessary to ensure the appropriate level of quality and safety of MP. 

Medicinal products approved for hospital exemptions can only be used in inpatient healthcare facilities. 

Manufacturers of ATMPs file their applications for hospital exemptions with the Institute (Section 49(3)).  The Institute shall give its opinion on the completeness of the application within 15 days and, within 60 days, it shall give its opinion on professional assessment of the application and documentation furnished. 

Instructions for applicants:

1. Application forms are available from the Institute’s website (www.sukl.cz)
2. Applications are to be completed in Czech.
3. A document evidencing the payment of reimbursement of expenditures must be presented along with the application
4. Preclinical data need to be submitted in the extent required for clinical trials with the type of product in question in line with requirements set in the Guideline on Human Cell-based Medicinal Products (EMEA/CHMP/410869/2006) and in the Guidance on Nonclinical Safety studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3 (R2)). Preclinical data need to be submitted in the format set out in the Investigator’s Brochure.
5. Pharmaceutical documentation is to be submitted in the CTD format as required for clinical trials with the type of product in question.
6. Other relevant documents (e.g. decision to include a medicinal product by the European Medicines Agency, Scientific Advice, …)

Documents to be submitted along with an application for a hospital exemption 

Documents are to be submitted in the Czech language or in the English language, in electronic form on a CD-ROM or DVD and in hard copy as set out in the table below.  

List of documents to be submitted along with an application for a hospital exemption:

Document	Format requirements (hard copy, electronic)
Cover letter, containing, without limitation, a list of documents submitted, including their versions and dates	1 hard copy, signed
Document evidencing payment of reimbursement of expenditures	Electronic copy
Form of application for hospital exemption	1 hard copy, signed + electronic copy (pdf)
Scientific justification of the application (including a rationale demonstrating that the “non-routine production” requirement was met) and analysis of risks and benefits for patients.	Electronic copy
Preclinical and clinical data as set out in the Investigator’s Brochure – see KLH-9, ICH M3	1 hard copy + electronic copy
Summary reports from completed clinical trials, including summary as set out in Annex 9 to Decree No. 226/2008 Coll.	Electronic copy
Overview of all pending clinical trials involving the same MP	Electronic copy
Draft summary information for doctors in the extent of Summary of product characteristics	Electronic copy
Draft Summary information for patients	Electronic copy
Description of indications for which the medicinal product can be used, including rationale	Electronic copy
Pharmaceutical documentation in the CTD format	Electronic copy (CTD format)
Statement by a qualified person	Electronic copy
Copy of the manufacturing permission	Electronic copy
Copy of the permission for activities of a tissue facility (if applicable)	Electronic copy
Copy of the permission for activities of a sample taking facility (if applicable)	Electronic copy
Copy of the permission for activities of a diagnostic laboratory (if applicable)	Electronic copy
Representative analytical certificate of the final medicinal product	Electronic copy
Labelling on packaging (specimen of outer as well as immediate packaging)	Electronic copy
Detailed description of the manner to ensure pharmacovigilance	Electronic copy
Detailed description of the manner to ensure traceability	Electronic copy
Relevant permissions for special trials or products (if available), e.g. GMO, radiopharmaceuticals	Electronic copy
Permission from the Ministry of the Environment pursuant to the Genetically Modified Organisms Act (if requested)	Electronic copy
Permission of the State Office for Nuclear Safety (if requested)	Electronic copy
Documentation for medical device (if applicable)	Electronic copy
List of sites where the MP is to be administered under hospital exemption (including addresses)	Electronic copy
Other relevant documents	Electronic copy
Power of attorney (if applicable)	1 hard copy + electronic copy