GMP/GxP Consulting

GxP-compliant quality management systems: Key to efficient and faultless operation

Ensure the quality of your products by setting up a QMS. Valicare's experts will support you with consulting, document preparation & implementation.

To ensure the proper quality of pharmaceutical and biotechnological products, numerous sets of rules of Good Practices (GxP), have been published. They cover a wide range of areas to ensure the safety of medicinal products, such as:

• Good Manufacturing Practices (GMP)
• Good Clinical Practice (GCP)
• Good Laboratory Practice (GLP)
• Good Distribution Practice (GDP)

All these regulations require a dedicated quality management system for the respective companies. This must cover on the one hand general quality assurance measures, such as training or self-inspection, and on the other hand very individual procedural instructions for the company-specific activities.

Standard Operating Procedures (SOPs) as well as all supplementary quality management documents (QMS) should be optimally tailored to each other and to the company's organization in order to enable efficient and faultless work in accordance with the respective rules.

The relevant supervisory authority checks the legally compliant design of your QMS and can only grant your company a permission for the activity in question if all processes are described in compliance with the regulations.

Valicare GmbH provides professional support to create and implement your GxP-compliant quality management system!

We can offer the complete set-up and creation of documents for your QMS as well as the focus on certain specified tasks.

GMP: Good manufacturing practice | European Medicines Agency (europa.eu)
GCP: ICH E6 (R2) Good clinical practice | European Medicines Agency (europa.eu)
GLP: Good laboratory practice compliance | European Medicines Agency (europa.eu)
GDP: Good distribution practice | European Medicines Agency (europa.eu)

Key to efficient and error-free operation

GMP concepts describe general procedures for quality assurance tools essential for operation of a GMP system and thereby confirm, that product and processes are compliant to the guidelines and regulatory requirements.

This comprises a multitude of documents like work instructions, standard operating procedures, concepts for training, qualification, validation, deviation and change control management, handling of OOS results, self-inspections and much more.

As these documents assure efficient and error free operation of the GMP unit, they should fit to each other and to the size of the customer side.

 An essential prerequisite for the efficient and practical application of the quality assurance tools is the deep knowledge about options and variation. This and the exact description of the requirements and processes allows the adequate adaption of the tools to the real need of your GMP system.

The Valicare GmbH offers support for implementation of GMP concepts as a pure consulting service whereat our experts evaluate the situation and based on this give advices to the customer only.

On the other hand Valicare GmbH provides extensive preparation of instructions for each quality assurance tool required for this GMP unit.

Review of planned and existing installations

Design review is a well-established consultancy service of Valicare GmbH. By this procedure planned or already built technical equipment and installations are approved on quality by design criteria, suitability and GMP compliance.

The normal scope of a design review could range from viewing a single room or a whole facility. Besides GMP compliance the production capacity and customers product spectrum is important for the evaluation and will obviously be in focus of the executing consultant.

Valicare’s consultant team has already executed a multitude of design reviews and can offer this consulting service in each mode usual in the market.

For design review detailed technical documentation about the equipment and installations are required. An on-site presence of our consultants is mostly not necessary or needed.

Within Valicare GmbH and through the strong obligation to our mother, Syntegon Packaging Technology GmbH, comprehensive competencies about classical pharmaceutical and biotechnological production lines also for advanced therapy medicinal products and special drugs, exist.

Commonly the design review set up is prepared by one person. The documents then are checked and evaluated in presentation mode by two or three experts. In a protocol or a report of that discussion customer will get detailed descriptions of any inconsistencies or deviations observed.

Also the provided technical and organizational concepts were followed and scrutinized on the basis of known or defined process parameters.

All discussions will be closed results-orientated and all issues will be evaluated and documented in detail. Customer will get the report of the discussion meeting and a presentation of the results on demand.

Gap analysis: comparison between current and target state

Gap analysis is a classic management tool to align the current and target state.

Gap analysis relates either to the entire GMP system or to individual subareas and is an active comparison of the established current state with the requirements specified by local or international GMP regulations. For example, the GMP guideline part 1 (chapter 6. Quality Control) describes the performance and documentation of a gap analysis in the context of analytical method transfers. Other sections include qualification and validation or deviation/change management.

Valicare GmbH has successfully carried out a large number of such gap analyses and offers this consulting service for all GMP systems. If, for example, you are in the process of preparing for an internal, external or upcoming regulatory inspection, we can support you with full commitment and professional expertise by our trained and experienced consultants.

The consultant generally first checks the company-specific documentation and creates a gap analysis plan. Based on the gap analysis plan, the consultant conducts the analysis on site. The results of document and on-site checks are documented and the observations and identified deviations from the target and required state are discussed. All document deficiencies and gaps identified on site, e.g. in production, warehouse or laboratory, are listed separately in the analysis report. The consultant supplements the deficiencies listed in the final report with proposals for appropriate corrective actions and with addressed associated regulations.

A common scope for a gap analysis consists of one consultant day for preparation and for the system dependent on-site analysis (two days for subsystems to five days for the entire site), as well as two additional consultant days for reporting the results.

We would be pleased to arrange an individual procedure for you based on your specific system and questions.

Temporary assumption of management functions

Most of our natural scientists and engineers are familiar with being in management positions and instruct project teams regardless whether the current exercise is located inside Valicare’s or customer’s organization.

Our employees represent expertise and competence in nearly all positions of the quality management functions like for example quality management representative, qualification & validation manager, GMP training manager, etc..

If you need personnel compensation for example for parental leave or for other short-term vacancies, our competent interim managers will support you for up to 12 month, limited to leadership positions only.

As a special service each interim manger has a personnel back up at Valicare GmbH office, who is well-informed about the current situation at the customer-site, so that he or she can replace the interim manager without a long transition period, if this will be necessary. Continuity as well as additional availability during capacity intensive business periods is ensured.

Our interim manager are very flexible and their work is charged on hourly basis only. A fixed price offer including all incidentals can be submitted on special request.

If you need compensation of a quality management function independent whether short- or long-term, contact us please and let us check for a suitable profile.

The good manufacturing practice environment requires  qualification of suppliers to ensure drug quality and safety.

The EU GMP Guidelines as well as ICH Q10 and the national AMWHV (German Ordinance for the Manufacture of Medicinal Products and Active Pharmaceutical Ingredients, Arzneimittel- und Wirkstoffherstellungsverordnung) specify requirements for assuring quality of the product between the customer and contractor or supplier. In addition to suppliers of goods (manufacturers and intermediaries of starting materials, active ingredients and excipients; contract manufacturers of intermediate and finished products, packaging materials, plants, systems, spare parts, computer systems etc.), suppliers of services (with regard to calibration, maintenance, repair, pest control, storage, logistics, transport, distribution, development, manufacturing, testing, release, archiving, cleaning, clothing, consulting, third-party audits, etc.) must also be assessed in this context.

The aim of supplier qualification is, on the one hand, to safeguard supply chains throughout the product lifecycle and, on the other hand, to ensure robust internal processes in compliance with the relevant regulatory requirements.

Supplier qualifications are risk-based, with the scope and depth of the assessment depending on the process-specific risk level.

As part of risk management and on the basis of regulatory requirements, audits must be carried out by adequately trained personnel from the manufacturer or by third parties on site at the supplier's premises or by means of questionnaire audits, depending on the criticality of the goods/services. Furthermore, already qualified suppliers must be regularly re-evaluated or requalified.

Assured supply chain with qualified suppliers and robust processes is ultimately the basis for reducing complaints and ensuring medicinal product safety.

Thus, all supplier qualification actions contribute to the overall goals of medicinal product safety, efficiency and compliance.

Regulations:
AMWHV
EU GMP Guideline, Parts I and II
CH Q10 Pharmaceutical Quality System

GxP requirements from R & D to Investigational Medicinal Products

Prior to the introduction of medicinal products to the market, the regulations of Good Practice (GxP) have to be followed during production and development.

These include in particular, Good Manufacturing Practice (GMP), Good Laboratory Practice (GLP) and Good Distribution Practice (GDP).

During the product life cycle of a medicinal product, quality requirements increase continuously from research and development through the different clinical phases to market maturity. Already in the course of development and formulation, the first compliance measures for Good Manufacturing Practice (GMP) have to be implemented. These basically include all GMP relevant topics which are to be applied on a risk-based approach according to the respective development stage.¹

In case medicinal products shall be manufactured for a clinical trial, a manufacturing authorisation and a corresponding GMP certificate are already required for this purpose.²

Upon request, the respective regulatory authority will conduct an on-site inspection to verify compliance with national law and EU GMP requirements. Prior to this, an appropriate quality management system must have been established, which demonstrates suitable measures to ensure the proper quality and safety of the medicinal products according to EU standards. In Particular, the following aspects must be documented and ensured: description of the internal processes, the suitability of all premises and facilities, the conformity of materials used, the qualification of the personnel and the quality of external services.

We offer full services along the entire product life cycle:

GMP in R & D

• Development of GMP-compliant processes and methods (including CPP and CQA)
• Definition, description, adaptation and verification of QC test methods
• Validation: production, analytic, cleaning & transfer
• Special services for ATMPs

GMP for manufacturing of investigational medicinal products, including the relevant application to obtain or extend your authorisation/ GMP certificate (according to § 13 or § 72 AMG):

• Generation of the Site Master File
• Preparation of Standard Operating Procedures (SOPs) and related forms
• Qualification of premises, facilities and equipment as well as the preparation of the corresponding documentation
• Validation of processes, methods, systems and transport management procedures
• Creation of hygiene concept
• Scientific Advice
• Support in the selection of key personnel
• Training of employees
• Identification, selection and qualification of external service providers
• Audits and contractual agreements for external services (e.g. suppliers, analysis, transport)
• Audits to prepare the QP Declaration for the import of products into the EU
• Investigational product specific requirements: Labelling, provision through just-in-time processes, return shipments and destruction
• Mock inspection: in preparation for the inspection
• Support during the audit
• Consulting scale up/scale out and automation processes
• Special GMP services for ATMPs

GDP for investigational medicinal products:

• Logistics for clinical supplies: storage & distribution
• Support in procurement of comparator medication
• Supply chain optimisation

With the support of our experienced professionals, you will accelerate your entry into the pharmaceutical/biotech market!

1 ICH Guideline on Pharmaceutical Development Q8(R2); in development: ICH Q14 Analytical Procedure Development and Revision of Q2 (R1) Analytical Validation; WHO Working Document QAS/20.865 (Nov. 2020) Good Practices for Research and Development Facilities;

2 for the manufacturing authorisation: according to § 13 (1) of the German Medicines Act; for the import authorisation: according to § 72 of the German Medicines Act; format according to: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/basicformat_manufacturersauthorisation_en.pdf