System validation standards

Weinberg SB. System Validation Standards. Dubuque, lA Kendall/ Hunt, 1990. 

All computer systems performing regulated operations must be validated. To support computer systems validation, standard instmments, microcontrollers, and smart instrumentation are functionally tested (black box test) and the installed versions recorded. 

Actually, the FDA issued a general call for system validation, and then tacitly endorsed System Validation Standards (Dr. Sandy Weinberg, 1989). 

Science cannot be performed without an accurate system of measurement, which is globally standardized and compulsory. Units and standards of measurement are agreed upon and harmonized on an international basis by the Bureau International des Poids et Mesures in Sevres, France, and by the International Organization for Standardization in Geneva, Switzerland. The units and standards are then laid down in national laws. Nearly all countries have accepted the Systeme International d Unites (SI units) as their system of measurement. This also applies to countries that had been accustomed to use British units like Australia, Canada, South Africa and the United States. In Britain, SI units are official from January 2010. The valid standards are available from the competent bureaus, for example Bureau International des Poids et Mesures, www.bip.fr National Measurement Institute (Australia), www.measurement.gov.au National Institute of Standards and Technology (NIST, USA), www.physics.nist.gov/ Pubs/SP811/... 

Once the appropriate dissolution conditions have been established, the method should be validated for linearity, accuracy, precision, specificity, and robustness/ruggedness. This section will discuss these parameters only in relation to issues unique to dissolution testing. All dissolution testing must be performed on a calibrated dissolution apparatus meeting the mechanical and system suitability standards specified in the appropriate compendia. 

This chapter defines the terms, responsibilities, requirements and recommended procedures involved in pre-installation, installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ), which are all part of a typical HPLC system validation process. As the FDA does not publish a definitive reference or cookbook for these procedures, the suggestions herein are only recommendations. These have been successfully incorporated into formal standard operating procedures (SOPs) that have been implemented at a number of larger pharmaceutical establishments. As long as proper SOPs... 

We have to make a distinction here between electric controllers (e.g. PID controllers) with a proportional valve as actuator and mechanical diaphragm controllers. In a regulation system w/ith electric controllers the coordination between controller and actuator (piezoelectric gas inlet valve, inlet valve A/ith motor drive, butterfly control valve, throttle valve) is difficult because of the very different boundary conditions (volume of the vessel, effective pumping speed at the vessel, pressure control range). Such control circuits tend to vibrate easily when process malfunctions occur. It is virtually impossible to specify generally valid standard values. 

Test can be defined as an examination of an item or system to determine compliance with its specifications. Under this definition test would include operations to calibrate or standardize but would also include the process of total system validation. 

Computer system validation activities must ensure that all computer systems operating on the GMP environment perform consistently to the required standards. 

Preparation of standard procedures Document review Validation glossary Critical parameter assessment GMP criticality and risk analysis Process validation methodology Computerized system validation Preparation of validation plans Preparation of project and quality plans Manufacturing data specification... 

Description of process/environment Quality-related critical parameters Purpose and objectives of the system Major benefits of the system Special requirements Specific training needs System operating strategy Related GMP compliance/regulations Physical and logical boundaries System GMP risk assessment System validation rationale Life-cycle documentation Assumptions and prerequisites Limitations and exclusions Quality-related critical parameters/data Standard operating procedures System requirement specification Supplier and system history... 

Ensure that the software code or configuration is to a standard that will ensure clear understanding and support maintenance and modification of the software throughout the system validation life cycle... 

In 1980, the European Organization for Quality Control (EOQC as it was called then, now only EOQ) devoted its seminar in Geneva to validation of manufacturing processes. The discussions were conducted by three working groups general considerations, administration, and control, equipment and support systems, and standard operations. The results of these discussions were summarized in the following commonly accepted conclusions [5] ... 

The quality attributes applicable to all procedural controls are that they are appropriate, clear, and consistent with related procedures, adhere to regulatory, industry, and company standards, and are approved, available, accessible, followed, controlled, and periodically reviewed. The SLC process must be consistent with the applicable computer systems validation procedural controls. 

It is fascinating how, in many highly standardized environments, a computer systems validation (CSV) group works with the product just before it goes to production, or when it has just been put into internal use. 

This last equation, valid at extremely low concentrations and lacking the troublesome diameter a, is known as the Debye-Hiickel limiting law for ionic activities and has been well verified in aqueous and some non-aqueous systems. The standard state for these electrical activity coefficients is the infinitely dilute solution in which /, = 1. 

Eli Lilly s site at Indianapolis, Indiana, U.S.A., had an important inspection by the FDA in 1990. This included a review of the company s computer systems validation, which resulted in the company not only developing a computer validation methodology with supporting procedures but also establishing a program to validate its other computer systems across the world to this new standard. In the following year Europe had its first taste of the new expectations for computer systems validation. 

There were no written standard operating procedures for, but not limited to, system validation, hardware and software change control, revalidation,... [FDA Warning Letter]... 

Validation Plans record standards, methods, and personnel involved to assure quality through the system development life cycle and to establish the adequacy of the performance of the computer system. The term Validation Master Plan is typically used for large or multiple computer system validation projects. Validation planning should be initiated at the earliest practicable opportunity and may be reviewed and updated through subsequent stages of the project. 

Software changes Assess software updates for compatibility with the existing software with particular emphasis on any changes made. In terms of system or standard software products, there is normally a bug fix list and details of new, modified, and removed features. Supplier s documentation should include an analysis of the impacts of the patch on their system, and this should be used by the customer to assess the extent of testing required to validate the patch implementation. These documents should be assessed to determine the effects of the change and any appropriate testing performed and incorporated into a validation dossier. 

It is not typical to receive a separate functional and design specification these are often included as part of the building s environmental control package. If this proves to be the case, then it is not necessary to rewrite these specifications. The recommended approach is to create a matrix that references those parts of the environmental control package that are relevant to the computer system validation requirements for the critical functions. Also, ensure that this matrix is mapped back to the URS in order to ensure that the URS is met. This matrix will form the basis of the Requirement Traceability Matrix (RTM), which is intended to assure that all requirements have been addressed, that the functionality is appropriate, consistent, and meets predefined standards, and that the system is appropriately tested. The functional/design specification or the relevant sections of the environmental control package should typically address ... 

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