ATMP Service Packages

Strategic & regulatory consulting service

This service package is a strategic consulting support and serves as a general, always on call support. Valicare assures to answer your questions regarding legal good manufacturing practice (GMP) compliance. If necessary, Valicare will draft statements on the topic of interest to you. If required, we are also happy to provide you with suggestions and arrange contacts for support services beyond consulting.

Regular training services

This service package is also a strategic measure to ensure GMP compliance of your company. The GMP training courses required at least once a year are conducted by our Valicare team as basic training or on various key topics defined by you.

GAP analysis

The objective of this service package is to check your GMP compliance. A Valicare team with a GMP auditor checks the prerequisite of your infrastructure and your laboratory processes in a one to two day audit. You will receive an audit report and a list of recommendations, optionally also a complete project plan.

Concept and project plan

The standardization of laboratory processes is a precondition for the transition to a validated GMP-compliant process and is supported by us in detail within this service package. It starts with a joint concept workshop, during which Valicare obtains an overview of your overall project. In consultation with you, Valicare draws up a comprehensive project plan with the corresponding milestones and schedules.

Implementation of project plan

For the implementation of the project plan, Valicare takes over the project management, if required, subsequent to the concept workshop. Within the scope of this service package, Valicare offers the following services in detail according to the motto “filling the GAP”:

• Process workshops: Organizing workshops to record and describe all relevant processes (user requirement specification (URS), “from bench to bedside”) is a basic precondition for good collaboration.
• Process analysis & development: The analysis, development and optimization of all relevant processes (material procurement, manufacturing, quality control (QC), monitoring, product release, storage and transport) is carried out in each case by means of a written process record. Clearly presented as flow diagrams and reports on the development of processes, they also serve for further risk assessment and can be kept as a clear appendix in a dossier to be submitted to the authorities.
• Risk assessment: In the course of a risk-based approach regarding the use of raw materials or the development of processes, the risks must be named and assessed within an analysis. A further development of these processes takes place via iterative risk analyses. In addition, a pharmaceutical quality system (PQS) always includes risk management.
• Concept development: Cleaning and hygiene concepts for personnel and premises as well as GMP training concepts have to be developed and trained.
• GMP documentation: The generation of higher-level GMP documents (site master file (SMF), validation master plan (VMP), hygiene master plan, standard operating procedures (SOPs) for quality assurance) and project- or process-specific specification or protocol/reporting documents (process SOPs, batch protocols, qualification and validation plans and protocols) allow standardization and reliable traceability of your manufacturing processes.
• Material specification: Consultation on the classification and specification of the goods required for the manufacturing and packaging process simplifies the preparation of the specifications, which are prerequisite for the process.
• Product specifications: Consulting on establishing important specifications to characterize your ATMP, for cellular, tissue and genetically engineered products, can clarify issues and simplify the creation process.
• Qualification & validation: Risk-based qualifications of all premises, supply systems and devices required for the GMP process are an unavoidable requirement. Research regarding suppliers for goods and excipients including supplier qualification is also fundamental and can be facilitated by empirical values regarding proven primary and secondary suppliers. The validation of GMP-relevant processes, including cleaning, analytical methods for quality control and the IT systems, are also complex procedures that could be relieved from you.
• Personal management: Establishing personnel concepts for executive and key positions as well as recruiting new employees require experienced personnel management. The induction and training in GMP topics and the preparation of training, hygiene and clothing concepts are central issues that we are happy to take on for you.

Computer system validation

Computer system validation (CSV) is a special type of validation. In the course of testing devices used in the manufacture of ATMPs, they must first be classified. This includes all computerized systems in manufacturing, quality control, data processing, and quality assurance that have an impact on the quality of the product. Examples are the computer of the personnel in quality assurance, on which, for example, deviations are processed, the analysis system, with which the product is analyzed, or the process control unit at the bioreactor. Valicare has concepts for both existing and new systems and has successfully implemented them in a large number of projects.

Validation of analytical methods

All methods used in the process to check specifications must be valid. This can be ensured by various processes. In the case of methods described in the pharmacopoeia, it must be ensured whether verification is sufficient, or whether this method must be adapted to test the product specifications. If the methods are established in the laboratory, their risk based development and adaptation must be documented in a development report. A subsequent method validation serves to demonstrate the suitability and reproducibility of this test method. Valicare supports you at this stage in all aspects, starting with the risk-based definition of the specification, through the definition and development of the analytical methods and the initial analytical method validation (AMV), to the recurrent review/revalidation and any adaptation.

Process transfer, process translation

Valicare prepares the process transfer from your research environment to the manufacturing site with the appropriate documents by qualifying the relevant GMP environment and performing and documenting the validation of the process. Services related to logistics and good distribution practice (GDP) measures are also part of our competencies.

Application for manufacturing authorization according to § 13 AMG

Valicare advises and supports you in applying for the ATMP manufacturing permit according to § 13 AMG (Arzneimittelgesetz, German Medicines Act) with all required documents and the corresponding time schedule to ensure an efficient project progress. The documents and concepts required for the manufacturing authorization application (master documents, contracts etc.) are designed, drafted and prepared for timely submission.

Accompanying start of manufacturing

The start of the GMP-compliant manufacturing of the ATMP and the continuous optimization of the process is the objective of this service package. The (extended) manufacturing authorization and/or the approval according to § 4b AMG as a prerequisite for the manufacturing of the ATMP is already available at this point of time. If required, Valicare provides temporary key functions of the pharmaceutical operation in interim management and takes over the start-up of manufacturing until the first preparations are manufactured that can be used in patients within the scope of the § 4b approval.

In parallel, your future personnel will be trained in the manufacturing processes and successively handed over responsibility and key functions. The position of qualified person (QP) can also be taken by Valicare on a longer-term basis if desired.  

Turnkey GMP solutions

If you do not have a GMP-compliant contract manufacturer for the manufacturing of your ATMP, Valicare offers you a turnkey manufacturing solution. Our valicare.tainer system can be planned and implemented as a GMP-compliant manufacturing facility at your site within 12 months. This is realized according to the requirements of your manufacturing process and handed over to you including equipment, quality control unit and, if necessary, personnel.

Contract manufacturing

If you decide to produce at a contract manufacturer organization (CMO), our experienced senior GMP consultants will take over its qualification and ensure that the necessary competence and the technical and regulatory requirements for the successful  GMP-compliant manufacturing of the ATMP are in place, e.g. by conducting an on-site audit at your contract manufacturer.

Accompanying clinical studies

The evaluation, planning and set-up of clinical trials, initially phase I, are the focus of this service package. The initial application for approval of a clinical trial must be submitted to the PEI in electronic form. The electronic application is submitted using the Common European Submission Platform (CESP). With regard to attachments and documents, the regulations on good clinical practice (GCP) and the 3rd Notice on Clinical Trials in Humans are applicable. Valicare can support you in the preparation of certain documents that become necessary during this phase:

• Support with scientific advice  
• Development reports
• Support with the voluntary harmonisation procedure (VHP) process 
• Documents for the submission of a clinical trial
• Test plan, synopsis
• Investigator's brochure (IB)
• Investigator medicinal product dossier (IMPD)
• Monitoring reports, clinical study reports (CSR)
• Annual development safety update report (DSUR)
• Generation of an informed consent for the use of data

Organization of clinical studies and study logistics & management of investigational medicinal products

The practical planning of clinical trials is a key issue that Valicare can support specifically with a comprehensive concept for supplying the study centers with the investigational medicinal products. In collaboration with the study centers and on the basis of the study protocol, an assessment is made of demand. According to the stability of the test product as well as the shelf life of the comparative and auxiliary preparations, the manufacturing of batches, labeling, intermediate storage, and deliveries to the individual study centers are planned. A diligent system of tracking each dose, monitoring temperature data and organizing return deliveries from the study centers as well as qualified destruction of study medication complete the service regarding medicinal product supply.

Automation

Manufacturing of ATMPs is currently mainly done manually. However, the state of science and technology is currently experiencing a trend towards automation, especially with regard to an efficient market supply. Valicare will be happy to support you on the way to automation. Together with you, we check the feasibility of automation, help you to formulate your requirements in a URS and support you in the selection and qualification of the appropriate suppliers, the qualification of the plant as well as the transfer of your manual process into an automated process, including validation.

Pharmaceutical development

Within this service package, we relieve you with the pharmaceutical development of your ATMP, which is required for the application of the central marketing authorization at the EMA. For this purpose, a continuous optimization of the processes within the scope of a pharmaceutical development is aspired. Valicare supports you by means of iterative risk analyses to analyze this process, which defines measure plans and development goals in the different stages of development, with which critical quality attributes (CQA) as well as critical material attributes (CMA) and critical process parameters (CPP) are controlled.

Archiving

As required by the ATMP GMP Guideline, all traceability documents must be retained for 30 years. This can be paper-based or electronic. However, the availability of electronic data in particular and the security of storage must be ensured by protective measures. Valicare supports you in creating an archiving concept that takes into account the retention periods for ATMPs. Valicare also helps you to qualify the necessary premises or service providers. 

Data security

The aim of this service package is to support you in handling your data in compliance with the law. According to the Basic Data Protection Regulation (Datenschutzgrundverordnung, DSGVO), encryption of data records is necessary. However, it must also be possible to decrypt the personal data for up to 30 years. Here, Valicare can advise you and provide you with assistance on good practice data linkage (GDP). This is necessary due to the linking of different personal data sources, e.g. in clinical studies. Valicare can provide you with concepts to manage your data infrastructure, data flow, data audit/quality assurance according to the DSGVO, as well as ethical aspects. Central to this are the key variables of the linkage process. Thus, you have the possibility to ensure a long-term data usage.

ATMP pharmacovigilance system

The ATMP pharmacovigilance system is designed to collect and evaluate information on ATMP safety and to prevent serious adverse events associated with ATMP use. We can assist you in reporting and preparing reports on ATMP pharmacovigilance to enable targeted measures that can improve ATMP safety. The PEI offers reporting forms as templates on its homepage, which you should integrate into your quality management (QM) system.