Systems Validation

New to the industry is the requirement that all electronically kept records be validated in accordance with the CFR (Title 21, Volume 1, part 11 revised April 1, 2003 requirement. This is particularly true of instances in which the systems are custom-designed and, furthermore, where computer-controlled automated processes are used. There remain many misconceptions about makes up computer validation. The CFR guideline as listed below should be well understood  

Persons who use closed systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, when appropriate, the confidentiality of electronic records, and to ensure that the signer cannot readily repudiate the signed record as not genuine. Such procedures and controls shall include the following  

Subpart — Electronic Records Sec. 11.70 Signature/record linking. 

Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective electronic records to ensure that the signatures cannot be excised, copied, or otherwise transferred to falsify an electronic record by ordinary means. 

---

It follows that there are two kinds of processes required for an arbitrary initial state to relax to an equilibrium state the diagonal elements must redistribute to a Boltzmaim distribution and the off-diagonal elements must decay to zero. The first of these processes is called population decay in two-level systems this time scale is called Ty The second of these processes is called dephasmg, or coherence decay in two-level systems there is a single time scale for this process called T. There is a well-known relationship in two level systems, valid for weak system-bath coupling, that... 

Computer System Validation US Code of Federal Regulations 21 CFR Part 11. 

Qualification and calibration, including recording system. Arrangements for computerised systems validation. 

S Two K Component System. Validation of Orbital Size Effect on the Magnitude of Facial Selectivity... 

Form and System Design Protocol and System Rules System Development System Validation Staff Training... 

Weinberg S, Romoff RM, Stein GC. Handbook of System Validation. Weinberg, Spelton and Sax Inc. 1993 Weinberg S. Validation Compliance Annual, in Weinberg S, Editor, International Validation Forum. Marcel Dekker New York, 1995. 

Ilyukhin, S.V., Haley, T.A., and Singh, R.K., A survey of control system validation practices in the food industry, Food Control, 12, 297, 2001. 

GLP compliance for electronic records does not differ from GLP compliance for paper records. The increased access and distribution of records and documents enabled by electronic systems provide compliance challenges. There are many new questions to answer for example, what is the difference between electronic approvals and electronic signatures The solutions to these challenges lie in ensuring that system validation and management processes are in place, such as SOPs or procedures... 

Also, electronic SOPs and protocols must be available to staff at all test sites for multisite studies. If the electronic documents are to be available at several sites, the validation phase of the system must include functionality testing at each site. Documentation of system validation needs to be available at each test site as well. Electronic SOPs must have a limited life span when printed to avoid the use of an outdated document. This may be achieved by stamping each SOP hard copy Printout not valid after date xx/xx/xx . This practice helps to ensure that system users will not retain printed SOPs long after the electronic SOP is revised. For company SOPs that are to be followed by an outside contractor who has no access to the electronic system, an alternative stamp may be used on the hard-copy SOPs that will be provided to the contractor that defines the date printed or indicates that the SOP is valid for use in a particular study. Whatever procedure is used, it must be clearly documented in an SOP. 

End-user software acceptability testing is frequently performed to satisfy regulatory requirements however, it is also used to ensure system validity and identify deficiencies. 

Define what computer system validation would ultimately entail in a management-approved document, such as a policy statement. 

The Association for Clinical Data Management (ACDM) and Statisticians in the Pharmaceutical Industry (PSI) publish an excellent document called Computer Systems Validation in Clinical Research A Practical Guide, which can be found at http //www.cr-csv.org/. 

The computerized systems, both hardware and software, that form part of the GLP study should comply with the requirements of the principles of GLP. This relates to the development, validation, operation and maintenance of the system. Validation means that tests have been carried out to demonstrate that the system is fit for its intended purpose. Like any other validation, this will be the use of objective evidence to confirm that the pre-set requirements for the system have been met. There will be a number of different types of computer system, ranging from personal computers and programmable analytical instruments to a laboratory information management system (LIMS). The extent of validation depends on the impact the system has on product quality, safety and record integrity. A risk-based approach can be used to assess the extent of validation required, focusing effort on critical areas. A computerized analytical system in a QC laboratory requires full validation (equipment qualification) with clear boundaries set on its range of operation because this has a high... 

Glennon, B. 1997. Control system validation in multipurpose biopharmaceutical facilities. Journal of Biotechnology 59(1-2), 53-61. 

Category 4—Configurable Software Packages These software packages can be conhgured according to user requirements. A supplier audit is usually required to conhrm software has been developed according to a documented quality system. Validation should ensure software meets URS requirements. Full life cycle vahdation is needed. 

---