ATMP Manufacturing Solutions

Turnkey cleanroom modules for ATMP manufacturing

Cell therapeutics, gene therapeutics and biotechnology-engineered tissue products are considered advanced therapy medicinal products (ATMPs) under European pharmaceutical legislation.

The number of clinical trials and approvals is increasing extraordinarily fast worldwide. In the future, their enormous potential will enable therapies for a wide range of diseases for which there was previously no cure. Unfortunately up to now, insufficient manufacturing facilities are available. Since ATMPs must be manufactured aseptically and in accordance with good manufacturing practice (GMP) according to part 4 of EU GMP guideline (“ATMP GMP Guideline”), the investment in premises and know-how is high.

The challenge of personnel and premises capacities often cannot be solved internally. Access to external contract manufacturer organizations (CMOs) specializing in ATMPs, of which there are not very many throughout Europe, is difficult and lengthy. They are often fully booked and have long waiting times. Thus, the market supply required in an approval procedure is often not guaranteed.

GMP compliant cleanroom solutions for ATMP development and manufacture

An unique chance is offered here by Valicare. In cooperation with the engineering and project management department of its parent company, the globally active Syntegon Technology GmbH, Valicare created a new concept of cleanroom modular buildings (valicare.tainer) for GMP-compliant development and manufacturing of starting materials up to investigational clinical trial ATMP products (iATMPs). These turnkey GMP-compliant cleanroom modules are tailored to individual requirements.

Valicare's cult.tainer concept primarily relates to the production of ATMPs (cell therapy, gene therapy & bio tissue engineering) while the valicare.tainer overall concept covers a broader scope. It also includes modules for manufacturing starting materials (vectors, plasmids, cell lines, cell banks, etc.), quality control, storage, automation and filling. All modules can be combined customer- and product-specific to fulfill the individual requirements.

cult.tainer - a modular Unit, with a big Variety of Options

The cult.tainer developed by Valicare is a module up to approx. 470 m2 in size that allows individual ATMPs to be manufactured in parallel in two rooms, with additional space integrated for quality control. Regardless of whether somatic cell or gene therapeutics, stem cells or biotechnologically processed tissue products are involved, Valicare is happy to plan and implement your process professionally.

The module contains all rooms required for process and quality control, including storage, airlocks, office, and optional sanitary areas, provided the laboratory will be located on a greenfield site. The cult.tainer can be expanded with a connection module, a large ballroom in cleanroom class C for automation processes and closed systems.

Planning of premises and supporting you to achieve GMP-compliance

Valicare offers the planning of the premises including calculation of the total investment costs (TIC) and the construction of the plant in cooperation with the construction department SIS of the parent company Syntegon Technology GmbH. A special feature is that the services are combined with the necessary accompanying GMP services! Valicare not only hands you the key to a fully GMP-compliant cleanroom equipped and qualified according to your specifications, but also supports you in the development and establishment of the GMP process and system, the necessary personnel management up to commissioning and start-up of manufacturing.

The cult.tainer offers turnkey GMP-compliant cleanroom modules for manual and automated ATMP production.
cult.tainer Management

Valicare offers you a concept workshop to start with, in order to gain a detailed overview of the planned project in dialogue with you. Based on the results, SIS prepares a construction concept, layout and functional specification for the cult.tainer as well as the planning for design, approval and execution. Valicare qualifies suppliers, and in addition to delivery, engineering and installation of the cult.tainer, SIS also performs project management, installation supervision and object support.

cult.tainer to accelerate your ATMP from bench to bedside

Valicare takes over the project management for the GMP process to be established in the cult.tainer and the related tasks (contract design, planning and management of workshops, feasibility studies, generation of a user requirements specification (URS) for the overall process (“from bench to bedside”), research and qualification of suppliers, as well as the pharmaceutical procurement of equipment for the manufacturing, control and storage of the ATMP).

Valicare supports you successively in the planning, construction and set-up of turnkey cleanrooms for GMP-compliant production of ATMPs and in personnel management.
GMP Process Development

Analysis, development, transfer, and implementation of an efficient ATMP manufacturing process under GMP conditions are part of Valicare's core competencies. We are very familiar with the underlying regulatory requirements for ATMPs and take them into account at an early stage when developing the relevant processes (material procurement, manufacturing, quality control, monitoring, product release, transport). Once set up correctly, Valicare ensures translation into a GMP-compliant manufacturing process.
GMP System Establishment
For this purpose, Valicare also offers its special services, such as accompanying consulting, risk and quality management to ensure GMP compliance, up to the application for manufacturing authorization.

In detail, you receive support in the analysis, development and description (standard operating procedures, SOPs) of all relevant processes (manufacturing, quality control, specification tests, storage, transport), the creation of flow diagrams as well as in planning, execution and documentation of all upcoming risk-based qualification and validation tasks. Furthermore, we help you with the following issues:
- Specification and risk-based categorization of goods (raw materials, excipients and starting materials) and intermediate and end products
- Supplier research (first and second supplier) and qualification (quality assurance agreement, QAA, for suppliers of critical goods)
- Document generation for the higher-level quality assurance processes (change procedures, deviation procedures, complaint management, recalls, self-inspection)
- Verification of cleaning procedures
- Data storage/IT concept and validation of computerized systems
- Organizational chart of responsibilities and function holders
- Master documents such as site master file (SMF), validation master plan (VMP) and hygiene master plan (HMP)
- Vendor assignment of responsibility agreements (VAAs)
- Pharmacovigilance system (for clinical investigational medicinal products)
- Application, discussion and support of a scientific advice procedure at the Paul-Ehrlich-Institute (PEI)
- Generation of applications for manufacturing authorization
- Execution support for the clinical trial application and for the ethics vote of the clinical trial
- Management of investigational medicinal product logistic
Technical & Start-up Services

In cooperation with the design department SIS of Syntegon Technology, Valicare manages the rapid construction of the cult.tainer. Subsequently, the qualified and experienced Valicare engineers carry out the qualification and commissioning of devices and supply systems.

With all the necessary competencies in place and manning the regulatory functions required for a pharmaceutical facility, Valicare can – if required- ramp up manufacturing under interim management and hand over keys and manufacturing to you after the first investigational medicinal products (investigational ATMPs or iATMPs) have been generated.
Personnel Management

Valicare handles the recruitment, training and induction of operational personnel and functionaries according to pharmaceutical operational concepts and provides temporary personnel for key positions.
The overall Concept of the valicare.tainer

For decades, Valicare and Syntegon experts have been taking care of topics related to cleanroom and the processes that are carried out there in compliance with GMP and ISO standards. All modules designed for the production of ATMPs comply with the requirements of the EU GMP Guide including Annex 1 and the "ATMP-GMP Guideline". Our experts will be pleased to explain the standards and guidelines applicable to these modules and, if you are interested, can explain in detail how design, technical requirements and requirements for raw and starting materials, intermediate and end products are taken into account.

The flexibility of the cleanroom modules allows a wide range of combination variants.