Good Manufacturing Practices (GMP)

Introduction, review and support of quality systems

The efficiency and functionality of the quality systems is a fundamental prerequisite for GMP compliance. There should be tailor-made solutions that are adapted to the size and structure of the company.

On the one hand, GMP Advice supports the introduction of such systems, and on the other hand, a critical review is carried out with particular attention to documentation in order to make the quality systems leaner and more effective:

Deviations

Review and maintenance of the quality system for deviations, revision of associated SOPs, introduction of monitoring.


Corrective and preventive actions (CAPA)

Review and maintenance of the quality systemfor corrective and preventive measures, revision of associated SOPs, introduction of monitoring for overdue corrective and preventive measures.


Change Control
Review and maintenance of the quality system for change control, revision of associated SOPs, introduction of monitoring for overdue measures.


Process validation incl. revalidation

For existing processes according to ICH Q7: risk-based definition of critical and non-critical process parameters, creation of validation protocols and reports or revalidation protocols and reports.


For new processes: Implementation of the contemporary “LifeCycle model of validation”. Based on the findings from process development, a “control strategy” is defined, then the suitability of the process and control strategy is checked in the so-called traditional form executing conformity batches and finally verified over the entire product life cycle in the sense of “ongoing process verification”.


In detail:

  1. Validation phase
    Evaluation of development data as a prerequisite for planning scale-up and conformity batches (including determination of critical quality attributes, CQA and critical process parameters, CPP).
  2. Validation phase
    Checking the robustness of the process in the scale-up phase and defining a product-specific control strategy.
  3. Validation phase
    Producing conformance batches in the production environment and checking the control strategy. The number of conformity batches that are required prospectively before marketing authorization and, if necessary, concomitantly after marketing authorization is determined risk-based.
  4. Validation phase
    Continuous verification of process suitability by means of trending and review of the continuously generated process data (Ongoing Process Verification, OPV).


Cleaning validation
Most pharmaceutical companies use facilities and equipment not just for one product, but for multiple products. You are therefore obliged to provide evidence that existing residues from the preliminary product are below previously specified limits. This happens as part of cleaning validation and cleaning verification studies. It is necessary to make extensive preparations so that these can be carried out in accordance with GMP. A cleaning process for an object or device can be described as effective if it is demonstrably and reproducibly able to remove residues of process input materials and cleaning agents as well as microbiological contaminants up to a limit value previously specified on a scientific basis. This ensures that the quality and safety of the subsequently manufactured products are not affected. I advise you on all questions, but also carry out complete projects, from the analytical method to be validated to the finished cleaning validation report.


Equipment qualification including requalification

In order to use equipment in pharmaceutical production, they must have undergone extensive qualification in advance and the life cycle concept must be applied. I will support you with all related questions and will be happy to advise you on the following topics:


  • Carrying out risk analyzes according to ICH Q9
  • Creation of user requirement specifications (URS)
  • Acceptance of systems from the manufacturer (Factory Acceptance Test – FAT)
  • Acceptance of systems at the installation site (Site Acceptance Test – SAT)
  • Support in the planning, coordination and implementation of qualifications and requalifications
  • Support with initial calibrations as part of qualification
  • Preparation of master SOPs for qualification
  • Creation of GMP-compliant qualification documents (protocols and reports)
  • Training of employee


In order to reduce the effort required for regular requalifications in accordance with GMP, it is possible to establish a risk-based strategy that also gains the approval from the authorities. GMP-Advice presents this strategy to you and supports you on this journey.


Review computerized systems
GMP-relevant computerized systems such as process control systems should be subjected to a regular review in accordance with the GAMP5 guideline for the validation of automated systems. For this purpose, quality-relevant activities and parameters are systematically recorded and evaluated. The aim is to provide documented evidence that GMP-relevant computerized systems are in a validated state.

I will support you in introducing a review for computerized systems and take care of adequate documentation that can be created with a manageable amount of effort.


Internal audits

If you would like to obtain an independent opinion on the GMP status and thus on the GMP compliance of your company, GMP-Advice will carry out internal audits for you in all GMP-relevant departments. These can be system-, process- or, for example, deviation-oriented. In an audit report, all observations are categorized as critical, major or minor and, if necessary, corrective and preventative measures are defined together with you. If you wish, I can also track the implementation of the measures using a database so that you can access the current status at any time.


Audit trail review
Annex 11 of the EU GMP Guide stipulates that the ongoing operation of computerized systems is monitored accordingly. For this purpose, an audit trail review must be carried out at regular intervals. The aim is to provide documented evidence that the audit trail was checked at an appropriate, defined frequency for abnormalities regarding data integrity (e.g. creation, processing, modification and deletion of data). If you have not yet implemented this requirement in your company or would like to review the existing system, GMP-Advice will be happy to support you in establishing a functional and simple system including documentation.


Product quality review (PQR)
In order to verify the stability of a process for a pharmaceutical product and to identify long-term trends in quality-relevant parameters on a product and thus changes in product quality, as well as to identify opportunities for improvement for products and processes, a PQR is required according to the GMP regulations. I will create a PQR for you according to your specifications or establish a SOP according to ICH Q7 that will enable you to write a PQR that can withstand the critical scrutiny of an authority.


Batch Record Review

Before product batches are released, the complete batch documentation must be subjected to an intensive review to provide evidence that all work associated with the manufacture and testing of pharmaceutical products has been carried out in accordance with the manufacturing and testing instructions.

My service also include carrying out batch record reviews. If this is not yet or not fully established in your company, I will support you in implementing a GMP-compliant system.

GMP-Advice checks your batch records for completeness and compliance with good documentation practice. A basic review of the manufacturing and testing documentation can also be carried out to check whether all required information is included..


Batch release (preparation, documentation)
Every batch of a pharmaceutical product must be released in accordance with national and international GMP guidelines. This requires extensive prerequisites that must be implemented in advance. I will advise you on how to create these requirements so that the release for placing on the market can be performed.


Structure and organization of GMP documents
I will develop a GMP-compliant documentation system for you and with you that implements all the requirements of the GMP regulations. These are essentially specifications and verification documents for all GMP-relevant areas. I will also accompany you in the introduction of an electronic document management system to promote the digitalization of business processes and at the same time reduce bureaucratic obstacles.


Individual support on site

If your qualified person according to §15AMG or another function in quality management is no longer able to carry out the defined tasks, GMP-Advice can provide quick, flexible and uncomplicated support through an on-site service by taking over routine activities in the QM system.