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Lithuania: Is the development of advanced therapies in Lithuania being hampered by legal regulation?

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The hospital exemption rule brings ATMPs (‘Advanced Therapy Medicinal Products’) closer to the patient.

Reality is forcing scientists to find new ways in which to effectively treat serious diseases.

One such option is advanced therapies, which are increasingly being introduced into clinical practice. ‘Advanced Therapeutic Medicinal Products’ (or ATMPs) offer patients who have incurable or intractable diseases the possibility of being able to receive innovative and scientifically-advanced drug treatments which have been developed through genetic engineering, or cell and tissue engineering forms of technology.

The registration of ATMPs, as with other new areas of medicinal products, is a complex and lengthy procedure, but the pathway to the patient can be accelerated through the manufacture of ATMPs for specific patients under a doctor’s prescription, or by using what is generally known as the ‘hospital exemption’ rule, as foreseen in Article 28 of European Regulation No 1394/2007 which covers ‘Advanced Therapy Medicinal Products’ (ATMPs), and in Article 29-1 of the ‘Law of Lithuania on Pharmacy’. The hospital exemption rule means that ATMPs which are not subject to the requirement for marketing authorisation are also not manufactured on an industrial basis, instead being produced on an individual patient basis, albeit in accordance with specific quality standards, and are being prescribed for individual patients by a doctor who is working at the specific hospital which is treating the patient, and who assumes professional responsibility for the prescription and use of such ATMPs.

The key point is that, for a patient who has a rare condition for which there are no other alternatives, or for which there are no longer suitable alternatives, a tailor-made medicine is specifically prescribed as an exception because there exists no such registered medicinal product or ongoing clinical trials of such a product.

EU member states must ensure that specific quality standards are respected in the production of ATMP. Not all European countries interpret and regulate the concepts of ‘specific quality standards’ and ‘industrial process’ in precisely the same way but all of them, including Lithuania, have strict legal regulations which relate to the production of ATMPs.

So precisely what are the requirements for any institution which is seeking to produce an ATMP, and which options are available in terms of a patient when it comes to their receiving treatment which uses such medicinal products?

The right to manufacture ATMPs is limited to legal entities which hold a personal healthcare licence and a permit which has been issued by the State Medicines Control Authority within its purview under the republic of Lithuania’s Ministry of Health (hereinafter referred to as the ‘VVKT’). The procedure for issuing such authorisations, along with all standards, safety, traceability, and pharmaco-vigilance requirements for such medicinal products are, inter alia, detailed in those descriptions and forms which have been approved by order of the republic of Lithuania’s Minister of Health.

Production of ATMPs requires premises which are compliant with ‘Good Manufacturing Practice’ (or GMP), along with the required equipment, an effective quality assurance system, sufficiently qualified, experienced, and educated staff, and a documentary system to ensure full production process documentation and traceability. The production process itself is also subjected to a high level of requirements, along with a flow diagram of the entire production process, all of which specifies all necessary biological raw materials, intermediates, additional materials, critical process steps, storage, and transportation. Cells which are used in the production of ATMPs must be collected and tested in accordance with the requirements of the ‘Law on the Donation and Transplantation of Human Tissues, Cells, and Organs of the Republic of Lithuania’ and/or the ‘Law on Blood Donation of the Republic of Lithuania’, and must only be purchased from legal entities which hold the relevant licences and which are registered in Lithuania.

ATMPs are not prescription medicines. A prescription (in the form of a doctor’s prescription) can only be issued by a doctor at the hospital or authorised healthcare facility which is providing in-patient services, at which the medical products in question are to be used by the patient. This is understandable, as only in a hospital will the patient be provided with competent assistance around the clock in the event of an adverse reaction following personalised treatment. The patient must give their consent to such treatment, and the hospital’s medical ethics committee must also approve in writing the administration of the medicine. In special cases, ATMPs can only be administered with the written approval of the medical consortium and the medical ethics committee for that specific personal healthcare facility.

It seems that such strict regulation both of the production and the administration of ATMPs to the patient does not really disadvantage the patient, and that the benefits of receiving individualised treatment with ATMPs in the case of serious diseases where other medicines or treatments do not work or can no longer be used are certainly very likely. The only problem is that the price of ATMPs, when taking into account the huge cost of production, can sometimes be unaffordable for patients.

How can legal assistance help licensed healthcare facilities which intend to produce ATMPs and need to seek authorisation?

As already mentioned, production requires a licence from the VVKT, for which an application and relevant documentation must be submitted. The proper preparation, accuracy, and authenticity of the documentation will determine the on-site assessment by the VVTC staff in regard to whether or not the applicant is ready for production. The more accurately the documents are prepared, the more likely it is that the permit will be granted more quickly, which is why legal advice is absolutely essential for the preparation and completion of the documents.

Another point to remember is the fact that legislation allows for some IMP manufacturing operations and quality testing to be carried out on a contractual basis, ie. an IMP manufacturer may enter into contracts with other legal entities which are authorised to carry out any activities which may be related to cells, tissues, and laboratories for the performance of certain operations and/or quality tests. These contracts shall, in addition to standard terms and conditions, specify the roles of persons who are responsible for the work, along with the division of any such responsibilities, and other relevant aspects. The legal entity which is to carry out the manufacturing operations and quality tests must be prepared for a VVKT audit, and must keep all required records, with the result that legal advice and guidance is often very useful in the run-up to or during an audit.

In conclusion and to answer the title question: no, legal regulation does not hamper the development of advanced therapy, although its requirements are strict and detailed. However, in order to properly prepare the documents which will make it possible to obtain the relevant permits, the involvement of a solicitor is highly desirable.

The post Lithuania: Is the development of advanced therapies in Lithuania being hampered by legal regulation? appeared first on bnt attorneys in CEE.


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