In the previous assessments of Kymriah, Yescarta, Tecartus, and Zolgensma, the G-BA had defined specific QA requirements for the use of these cell and gene therapies in Germany. SHI funds will only reimburse these therapies if hospitals and clinics meet the QA requirements. Now, a new directive, covering all cell and gene therapies, will replace these individual requirements.
These therapies are classed as Advanced Therapy Medicinal Products (ATMPs) because of the way they are produced and act in the body. They contain components of living cells or nucleic acids and represent innovative therapies for various diseases. But the use of these treatments comes with high risks. Thus, the G-BA can stipulate QA requirements for outpatient clinics and hospitals. The legal basis is § 136a paragraph 5 SGB V.
The aim of these requirements is to increase the treatment quality and patient safety by minimizing complications. For example, centers offering these treatments more routinely, rather than only in rare cases, are expected to have better outcomes. But on the other hand, these requirements limit the number of clinics and hospitals being able to offer ATMPs.
Details of ATMP QA directive
The directive describes, among other things, the minimum requirements for treatment facilities, such as certain professional qualifications of the staff, spatial and medical equipment, and a minimum number of cases. Only if the hospitals and clinics meet these minimum requirements, the SHI funds will reimburse the ATMPs. The G-BA also used learnings from the real-world experience of the use of Zolgensma and the CAR-T treatments in the development of the directive.
This new directive defines consistent requirements for all cell and gene therapies. In addition, it specifies how the centers should prove they are meeting them, and details the quality controls. The directive uses the following structure of requirements:
- Qualification of the care provider:
- Medical staff: e.g. specialist qualification, several years of professional experience in a specialized institution/department / clinic, the minimum number of cases for treatment with specific diagnoses, participation in a study
- Care staff and other staff: e.g. specialized training (e.g. intensive care), codes for staff
- Structure and processes:
- Structures: e.g. specialist departments/clinics, operating theater equipment and capacity, rooms meeting special hygiene requirements
- Process and organization: e.g. surgery teams, on-call services, diagnosis (e.g. by treatment team / interdisciplinary case conferences), preparation, production, transport, treatment of complications
- Other quality assurance measures: use to generate knowledge, e.g. registries (for quality assurance purposes)
The G-BA published the first draft of this directive (called ATMP-QS-RL) on 4 Nov 2021. Currently, the BMG is reviewing the draft. Once accepted by the BMG, it will come into force, and the previously defined QA requirements for Kymriah, Yescarta, Tecartus, and Zolgensma are no longer valid.
Quality controls for ATMPs
The staff of the “medical services” (German: “Medizinischer Dienst”) will check whether hospitals and clinics follow these strict quality requirements. The medical service is the socio-medical advice and assessment service for statutory health and long-term care insurance. It ensures that the services of the SHI and care insurances benefit all insured persons under the same conditions according to objective medical criteria.
On 19 Nov 2021, the G-BA published the rules for these quality controls as new section 4 for the directive, called MD-QK-RL. The BMG is currently reviewing the new section, and the quality controls have not come into force yet.
Controls can happen on certain occasions, e.g. before the first service is provided, but also if there are specific reasons. After the checks, the “medical services” team summarizes the results of all required quality requirements in a control report.
If the minimum requirements are met, they will also issue a corresponding certificate. Hospitals and clinics will have to renew this certificate after the first year and then every two years.
Hospitals also can request a new control check to prove that they have eliminated any deficiencies that the “medical services” may have previously identified.
Interim regulation
On 5 May 2022, the G-BA published an interim regulation that is in place in the time period for transitioning from the old individual requirements for CAR-Ts and Zolgensma to the new ATMP-QS-RL directive.
CAR-Ts for B-cell malignancies
- If the service providers already have received approval from the “medical service”, then this certificate will remain valid.
- If service providers have not received a certificate for treatments in multiple myeloma or follicular lymphoma of grade IIIb yet, they can continue to offer the treatments if they meet the minimum requirements.
- Service providers have to demonstrate that they meet the minimum requirements by 4 Nov 2022.
- Additional regulations were agreed which are concerning control procedures that are already ongoing.
Zolgensma for SMA
The G-BA has extended the date for proving the minimum requirements to 4 Nov 2022.