Advanced therapeutic medicinal products include gene therapy, somatic cell therapy, and tissue engineered products or a combination thereof. ATMPs are biological medicinal products as defined in Directive 2001/83/EC of the European Parliament and of the Council, insofar as they have properties for curing or preventing diseases in humans or if they act in or on the human body to restore, correct or modulate human physiological functions mainly by pharmacological, immunological or metabolic action. The European Union has specifically adopted a regulation harmonizing the rules governing the circulation of these medicinal products, Regulation (EC) No 1394/2007 of the European
Parliament and of the Council, in order to take account of the specific nature of these biotechnological medicinal products and their complexity of use.
A gene therapy medicinal product is a biological medicinal product for use in or on humans having
the following characteristics:
- It contains an active substance containing or consisting of a recombinant nucleic acid which
is used in or administered to humans to regulate, repair, replace, add or remove a nucleic
- Additionally, its therapeutic, prophylactic or diagnostic action must be directly related to the
recombinant nucleic acid sequence it contains or to the product resulting from the
expression of that sequence.
Vaccines against infectious diseases are not gene therapy medicinal products.
Somatic cell therapeutics
A somatic cell therapy medicinal product is a biological medicinal product for use in or on humans which has the following characteristics:
- It consists of cells or tissues which have undergone substantial processing such that biological characteristics, physiological functions or structural properties relevant to the intended clinical use have been altered, or
- it consists of, or contains, cells or tissues which are not essentially intended to perform the same function(s) in the recipient as in the donor. This intended purpose is also called „non- homologous use“, and
- properties for the treatment, prevention or diagnosis of diseases by pharmacological, immunological or metabolic effects of the cells or tissues it contains are attributed to it and it is used or administered for that purpose in humans.
Tissue engineered products
A tissue engineered product is a biological medicinal product for use in or on humans that has the following characteristics:
- It contains or consists of biotechnologically engineered cells or tissues, and
- it is thought to be capable of regenerating, restoring or replacing human tissue.
Cells or tissues are considered to be biotechnologically engineered if they meet at least one of the following conditions: the cells or tissues have been substantially engineered to achieve biological characteristics, physiological functions or structural properties relevant to the intended regeneration, restoration or replacement. Or, the cells or tissues are not intended to perform essentially the same function(s) in the recipient as in the donor (non-homologous use). Products which exclusively contain or consist of non-viable human or animal cells and/or tissues and which do not act primarily pharmacologically, immunologically or metabolically are not considered tissue engineered products.
Market Access and Reimbursement of ATMPs
ATMPs are approved as biological drugs by the EMA. Market access and reimbursement of drugs in Germany generally corresponds to that of innovative drugs or, if applicable, to the regulations on orphan drugs if an orphan drug status exists. In general, ATMPs are subject to the early benefit assessment procedure (AMNOG). An application for exemption from the early benefit assessment can be submitted to the Federal Joint Committee at least 3 months before market entry only if the expected sales volume is of minor importance, i.e., less than 1 Mio Euro.
Nevertheless, it has been shown that the Joint Federal Committee does not always treat ATMPs as drugs but has evaluated them as new treatment method in accordance with § 135 SGB V, depending on the scope and proportion of medical services provided when the ATMP is used. Examples are the gene therapy C-Cure® and the biotechnological tissue products Holoclar® and Maci®. Due to the novelty of the ATMPs, it must be stated that the use of different legal procedures has reimbursement consequences due to specific requirements associated with the different assessment procedures. From this point of view, the early benefit assessment according to § 35a SGB V provides benefits for the companies in terms of clear formal guidelines for the AMNOG dossier and a defined time-line for the evaluation as well as the price negotiations. If an ATMP is assessed according to the early benefit assessment, the new product is immediately reimbursable at market entry, the price can freely be freely chosen by the pharmaceutical entrepreneur and the final reimbursement price is negotiated within 6 months. The price negotiations are based on the outcome of the benefit assessment and the comparators.
In contrast, classifying an ATMP as a new treatment method means that the product is not reimbursable for the time being, since the so-called authorization reservation applies for the outpatient sector. The reservation of authorization states that new treatment methods are not
covered by statutory health insurance (SHI) and cannot therefore be used or prescribed by doctors at the expense of the SHI until the Joint Federal Committee (Gemeinsame Bundesausschuss – G-BA) has voted in favor of them. GBA examines whether a certain examination or treatment method is available for a sufficient, expedient and economical care of the insured, taking into account the generally recognised state of medical knowledge. The regulation according to § 135 SGB V differs from the early benefit assessment according to AMNOG with regard to the entitled applicants, the time requirements and pricing. Applications for the evaluation of new examination and treatment
methods according to § 135 SGB V can only be submitted by impartial members of the G-BA, a Federal Association of Statutory Health Insurance Physicians, the Statutory Health Funds, or the Hospital Association.
Price Negotiations for ATMPs
As long as ATMPs fall into the scope of the early benefit assessment, price negotiations follow the logic of innovative drugs. The systematic and framework of the price negotiations is outlined in § 130b SGB V.
Price negotiations are determined by the results of the benefit assessment, the price level of comparative therapies, and European reference prices.
Especially gene therapies as one-time treatments create new challenges for the price negotiations between companies and payers. Annual therapy costs for chronic diseases have to be compared in terms of benefits, risks and costs to new ATMPs. The mechanism and duration of action offers the chance to negotiate new pricing and payment models.
Please contact us for any further discussion on new payment models, price strategies and negotiation aspects which are related to ATMPs in the outpatient and hospital sector.