Our process

According to the definition in the Regulation of the Minister of Health of 9 November 2015 on the requirements of Good Manufacturing Practice, validation is a documented program that gives a high degree of assurance that a specific process, method or system will repeatedly lead to the results which meet the specified acceptance criteria.

The chart below illustrates the model approach to process / system validation.

The different stages of validation and qualification are selected to suit the project at hand, and agreed on with the customer.

See a short description of each of the stages we handle by clicking on each square.

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Description of validation / qualification process

With regard to each qualification and validation project, we design:

a Traceability Matrix, which shows the link between the user’s requirements, the technical documentation and the tests performed;

a Validation Register, which contains a list of documents (technical documents, validation documents, procedures, manuals, training materials, etc.) created during the validation process.

The chart does not contain information about the technical documents to be created by the client or supplied by the vendors. These include, among others:

User Requirement Specification Functional and technical specifications (applicable to IT);

User Requirement Specification

Functional and technical specification
(applicable to IT)

Operating and maintenance manuals, technical drawings, electrical diagrams, pneumatic diagrams, P&IDs, etc. (concerning equipment and installations)

Technology instructions, cleaning procedures, etc. (concerning process validation)

Validated state maintenance procedure (change control, document management, inspection schedules, APRs, etc.)

We perform all our projects on the basis
of the following laws and regulations:

  • 21 CFR Part 210 – Current Good Manufacturing Practice in Manufacturing Processing, Packing, or Holding of Drugs; General (Pharmacy)
  • 21 CFR Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals (Pharmacy)
  • 21 CFR Part 820 – Quality System Regulations (Medical Device)
  • 21 CFR Part 11 – Electronic Records, Electronic Signatures ( Pharmacy and Medical Device)
  • EudraLex – Volume 4 Good manufacturing practice (GMP) Guidelines
  • European Commission Council Directive 93/42/EEC
  • ISO 13485 – Medical Devices
  • ISO14644-1 Cleanroom Standards
  • Regulation of the Minister of Health of 9 November 2015 on the Requirements of Good Manufacturing Practice, as amended
  • Quality Management Systems – Process Validation Guidance (GHTF/IMDRF)
  • ICH Guideline: VALIDATION OF ANALYTICAL PROCEDURES: TEXT AND METHODOLOGY Q2(R1)
  • ICH Guideline: GOOD MANUFACTURING PRACTICE GUIDE FORACTIVE PHARMACEUTICAL INGREDIENTSQ7
  • ICH Guideline: PHARMACEUTICAL QUALITY SYSTEMQ10
  • PIC/S GMP GUIDE
  • PIC/S GMP GUIDE (PART I: BASIC REQUIREMENTS FOR MEDICINAL PRODUCTS)
  • PIC/S GMP GUIDE (PART II: BASIC REQUIREMENTS FOR ACTIVE PHARMACEUTICAL INGREDIENTS)
  • PIC/S GMP GUIDE (ANNEXES)
  • ISPE Good Practice Guide: GAMP® 5: A Risk-Based Approach to Compliant GxP Computerized Systems
  • ISPE Good Practice Guide: A Risk-Based Approach to Electronic Records and Signatures
  • ISPE Good Practice Guide: A Risk-Based Approach to GxP Compliant Laboratory Computerized Systems (Second Edition)
  • ISPE Good Practice Guide: A Risk-Based Approach to GxP Process Control Systems (Second Edition)
  • ISPE Good Practice Guide: A Risk-Based Approach to Testing of GxP Systems (Second Edition)
  • ISPE Good Practice Guide: IT Infrastructure Control and Compliance
  • ISPE Good Practice Guide: Global Information Systems Control and Compliance
  • ISPE Good Practice Guide: Good Engineering Practice
  • ISPE Good Practice Guide: Applied Risk Management for Commissioning and Qualification
  • ISPE Baseline Guide Volume 5: Commissioning and Qualification
  • ISPE Good Practice Guide: Heating, Ventilation, and Air Conditioning (HVAC)
  • ISPE Good Practice Guide: Packaging, Labelling, and Warehousing Facilities (PACLAW)
  • ISPE Good Practice Guide: Process Gases
  • ISPE Baseline® Guide: Volume 4 – Water and Steam Systems (Second Edition)
  • ISPE Good Practice Guide: Approaches to Commissioning and Qualification of Pharmaceutical Water and Steam Systems (Second Edition) 

Find out how our validation experts can support you

Audit

An optional stage performed at the client’s request, which might include:

  • analysis and description of business processes;
  • analysis of validation documents, procedures and instructions;
  • analysis of documents, procedures and instructions for the maintenance of the validated state;
  • development of documentation, procedures, manuals for validation as well as implementation and training.

Risk analysis

The risk analysis process commences together with the validation process and all the subsequent actions (qualification and its scope, the scope of testing and examination, required documentation, etc.) are planned and performed according to a risk-based approach. Several risk analysis tools are used in the whole validation process. The main tool is FMEA and additionally the Ishikawa Diagram, Pareto Analysis and Expert Evaluation are applied.

Validation Plan

A document which is created at the beginning of the validation process and which describes the main stages, assumptions, roles and responsibilities as well as the conditions for successful completion.

Validation Report

A document which summarises the whole validation work in terms of all the activities and tests performed as well as non-conformities discovered. If there are non-conformities, the Report contains their evaluation and specifies how they can be resolved, if any of the non-conformities were not resolved at this stage; it presents the implemented risk-mitigating measures and sets a deadline for the resolution of any open non-conformities. The Report contains a statement that the object of validation is permitted to be used in the manufacturing process. The whole documentation generated during the validation process must be prepared and approved prior to the execution of the Validation Report. This also applies to training materials, procedures, instructions, etc.

Maintenance

GxP regulations not only impose an obligation of validation and qualification but also an obligation to maintain the processes and equipment in the validated state. To this end, we develop various procedures and instructions for training, change control, periodic inspections, incident management, documentation management, etc. We also take an active part in activities aimed at the preservation of the validated/qualified state. This also applies to Audit and Inspection support.

Supplier Audit

Where necessary, for example with regard to IT systems, we perform Supplier Audits.

Testing / Examination Plan

A document defining the scope of testing / examination, prepared on the basis of a prior risk analysis, describing both the conditions precedent for the commencement of testing (e.g. completed infrastructure qualification) and the acceptance criteria. It may also contain information about the roles and responsibilities, the method of documenting test / examination results, how non-conformities are to be managed, etc. as the case may be.

Testing / Examination

Testing / Examination comprises a number of specific tests, for example:

  • in the case of computer systems, these include: positive testing, negative testing, operating limit testing, integration testing, regression testing, user acceptance testing;
  • in the case of manufacturing processes, these include: specification compliance testing, quality testing, physiochemical and microbiological testing
  • in the case of cleaning processes, these include: examination of the residues of active pharmaceutical ingredients, examination of the residues of detergents, microbiological tests

Testing / Examination Report

A document summarising the testing / examination stage in terms of the results produced and non-conformities discovered.

Qualification Plan

A document which is created at the beginning of the qualification process and which describes the main stages, assumptions, roles and responsibilities as well as the conditions for successful completion.

Design Qualification (DQ)

During the Design Qualification process, the design is verified against the user requirements, applicable laws and industry standards. It should be demonstrated during the Design Qualification process that satisfaction of all the necessary requirements was guaranteed already at the design stage.

Factory Acceptance Test (FAT)

Wherever necessary, we participate in Factory Acceptance Tests performed at the equipment vendor’s premises. This enables us to verify the equipment before it is delivered. FATs, if performed properly, may constitute part of the qualification documentation and thus make it possible to reduce the testing scope at the IQ or OQ stage.

Site Acceptance Test (SAT)

Wherever necessary, we participate in Site Acceptance Tests performed at the client’s premises. This enables us to verify the equipment after it is delivered. SATs, if performed properly, may constitute part of the qualification documentation and thus make it possible to reduce the testing scope at the IQ or OQ stage.

Qualification Report

A document which summarises the whole qualification work in terms of all the activities and tests performed as well as non-conformities discovered. If there are non-conformities, the Report contains their evaluation and specifies how they can be resolved, if any of the non-conformities were not resolved at this stage; it presents the implemented risk-mitigating measures and sets a deadline for the resolution of any open non-conformities. The Report contains a statement that the object of qualification is permitted to be used in the manufacturing process. The whole documentation generated during the qualification process must be prepared and approved prior to the execution of the Qualification Report. This also applies to training materials, procedures, instructions, etc.

Process Qualification (PQ)

What is verified during the Process Qualification is whether the process is running in a stable and consistent way, if a product of required quality is being delivered, if the process critical parameters are kept within the permitted tolerance margins. During the PQ process, we test worst-case scenarios, which are processes of the most extreme technological parameters, the lowest tolerance for the critical parameters, etc.

Operational Qualification (OQ)

During the Operational Qualification, all functions are verified as to whether they function correctly – that is in accordance with the user requirements, GMP requirements, pharmaceutical laws and standards and other related standards. What is performed at this stage are both positive and negative tests, tests of operating limits, of all the alarms and interlocks as well as of the safety and measurement systems.

Installation Qualification (IQ)

During the Installation Qualification, all required documents, such as manuals, drawings, certificates, etc., are checked as to whether they have been supplied and are correct, whether all components have been assembled in accordance with the documentation provided, whether the correct software version has been installed, and whether utilities of appropriate efficiency and quality have been connected, etc. Upon the completion of this stage, we must be sure that the installation is correct and will not affect any subsequent stages of qualification.