Long-term expertise in manufacturing processes for ATMPs

Strategic and regulatory consulting services

This service package is a strategic consulting support and serves as a general, on-call support.

• We answer your questions about compliance with legal regulations regarding Good Manufacturing Practice (GMP)
• We draw up statements on the topic of current interest to you
• We provide contacts for supporting services beyond consulting

Regular training services

GMP training must be carried out at least once a year to maintain your company's GMP compliance. You can choose between basic GMP training courses or specify your own key topics. The Valicare team will carry out the training courses according to your wishes.

GAP analysis

We 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 receive an audit report and a list of recommendations as well as an optional project plan. We can accompany you during the audit or provide on-site support.

Concept and project plan

We support you in the standardization of laboratory processes, which is necessary for the transition to a validated GMP-compliant process.

After a joint concept workshop, where we gain an overview of your overall project, we draw up a project plan with the corresponding milestones and schedules. We can also take over project management to implement the project plan.

According to the motto "filling the gap", we offer the following services:

• Concept and process workshops: organizing workshops to record and describe all relevant processes (URS, “from bench to bedside”) is a basic prerequisite for good cooperation.
• Process analysis and development: analysis, development, and optimization of all relevant processes through written process mapping (flow charts and reports), which serve for further risk assessment and can be kept as an attachment to a dossier to be submitted for approval.
• Risk assessment: possible risks of an analysis must be identified and evaluated (risk-based approach). Further development of the processes takes place via iterative risk analyses. Risk management is also always provided in a pharmaceutical quality system (PQS).
• Concept development: cleaning and hygiene concepts for personnel and premises as well as GMP training concepts must be developed and trained.

• GMP documentation: the creation 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 production processes.
• Material specification: advice on classifying and specifying the goods required for the manufacturing and packaging process makes it easier to establish specifications.
• Product specifications: advice on defining important specifications to characterize cell and gene therapies can clarify issues and simplify the creation process.
• Qualification and validation: risk-based qualification of all premises, supply systems, facilities, and equipment required for the GMP process is essential. We also support you in finding and qualifying the right suppliers. The validation of GMP-relevant processes including cleaning, analytical methods for quality control and IT systems are complex procedures that we will gladly take care of.

• Personal management: we establish personnel concepts for executive and key positions and recruit new employees. We will be happy to take care of induction and training in GMP topics and the creation of training, hygiene, and clothing concepts.

Computer system validation

During computer system validation (CSV), all devices used in the production of cell and gene therapies are checked. This includes all computer-based systems that have an influence on the quality of the product. Valicare has concepts for both existing and new systems and has successfully implemented them in many projects.

Validation of analytical methods

All methods used in the process to check specifications must be valid. This can be ensured by various processes. Methods described in the pharmacopoeia require proof of sufficient verification, or whether this method must be adapted to test 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 method. Valicare supports you in all aspects, starting with the risk-based definition of the specification, the definition and development of the analytical methods, and the initial analytical method validation (AMV), right through to the recurrent review/revalidation and any adaptations.

Process transfer and translation

Valicare prepares and accompanies the process transfer from your research environment to the manufacturing site. We qualify the GMP environment, carry out the transfer validation of the process, and prepare all documents. Our expertise also includes services relating to logistics and good distribution practice (GDP).

Accompanying the  start of manufacturing

We will gladly support you in starting GMP-compliant manufacturing of your cell and gene therapeutics and in continuously optimizing the process. The (extended) manufacturing authorization and/or the approval according to § 4b AMG is already available at this time. If required, Valicare provides interim management of temporary key functions within pharmaceutical operations and takes over the start-up of manufacturing until the first preparations can be manufactured for use in patients.

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 on by Valicare experts on a long-term basis, if desired.

Turnkey GMP solutions

Valicare offers you a turnkey solution for the manufacture of your cell and gene therapies. Our valicare.tainer® system can be planned and implemented as a GMP-compliant manufacturing facility at your site within 12 months. It will be adapted to your production process and handed over to you including equipment, quality control unit and, if necessary, trained personnel.

Contract manufacturing

If you decide to have your ATMP manufactured by a contract manufacturing organization (CMO), our experienced senior GMP consultants will take over qualification and ensure that the necessary competence as well as technical and regulatory requirements for the successful GMP-compliant manufacture of the cell and gene therapies are met.

Accompanying clinical studies

Do you want to test your cell and/or gene therapy product? We will gladly support you in evaluating, planning, and setting up a phase I clinical trial. The initial application for approval is submitted to the PEI. The regulations of Good Clinical Practice (GCP) and the 3rd Notice on Clinical Trials in Humans apply regarding annexes and documents. We can prepare the following documents for you:

• Development reports
• Documents for the submission of a clinical trial
• Investigation plan and synopsis
• Investigator's brochure (IB)

• Investigator medicinal product dossier (IMPD)
• Monitoring reports and clinical study reports (CSR)
• Annual development safety update report (DSUR)
• Informed consent form

We will also be happy to offer you:

• Scientific advice
• Support with the voluntary harmonization procedure (VHP) process

Organization of clinical studies and study logistics

The practical planning of clinical trials is a key issue. Valicare can support you with a comprehensive concept for supplying the study centers with the investigational medicinal products. A careful system to track each dose, monitor temperature data, organize return deliveries from the study centers, and the qualified destruction of study medication round off the drug supply service.

Manufacturing authorization and § 4b AMG approval

Valicare advises and supports you in obtaining the manufacturing permit for cell and gene therapy products according to § 13 AMG with all required documents and the corresponding time schedule. The documents and concepts required for the application for the manufacturing authorization are designed, created, and prepared for timely submission.

We also support you with the classification of your ATMP and the preparation of the documents for the application for a § 4b AMG authorization (in Germany). Moreover, we help you to prepare the annual report on the safety of your ATMP (PSUR).

Upscaling and automation

Manufacturing of cell and gene therapy is currently mainly done manually. However, there is a trend towards automation, particularly regarding efficient market supply. Valicare will gladly support you on this path and examine the feasibility of automation together with your experts.

Pharmaceutical development

We support you in the pharmaceutical development of your cell and gene therapy. With the help of iterative risk analyses, we analyze your process and ensure continuous optimization within the framework of pharmaceutical development. Based on the development stage of your cell and gene therapy products, we define action plans and development goals to control critical quality attributes (CQA), critical material attributes (CMA), and critical process parameters (CPP).

Finalization and archiving

Valicare supports you in creating an archiving concept that takes into account the retention periods for cell and gene therapies. We ensure that the availability and security of the storage is guaranteed by protective measures and help you to qualify the necessary premises or service providers.

Data security

We support you in the legally compliant handling of your data in accordance with the General Data Protection Regulation (GDPR) and provide you with guidance on good practice data linkage (GPD). Valicare offers you concepts that handle your data infrastructure, data flow, data checking, and quality assurance in accordance with GDPR as well as ethical aspects. The key variables of the connectivity process are checked centrally. This gives you the opportunity to ensure long-term data usage.

Post-marketing surveillance - Pharmacovigilance system for cell and gene therapies

We support you in establishing your pharmacovigilance system. To improve the safety of your cell and gene therapy product, we help you prepare and establish ATMP pharmacovigilance reports in order to take targeted measures.