Audits standardized methods

ISO has two important functions in analytical chemistry. The first is to publish descriptions of accepted methods. These are effectively industry standard methods for particular protocols. The second is in laboratory accreditation. For a laboratory to be ISO accredited, compliance with international QA standards must be confirmed by an initial assessment and subsequently from repeated audits by an independent assessor. Since ISO has no legal or regulatory powers, the standards are voluntary. It is unlikely, however, that a forensic analysis which did not conform to an ISO standard would be upheld in court, for example. Most commercial laboratories need to be accredited to remain competitive and to deal with regulatory authorities. Most university labs are not accredited, mainly due to the time and costs involved, and also to the nonroutine nature of much university research. However, university accreditation may become a requirement in the near future, especially for publicly funded research in the UK. The details of laboratory accreditation are discussed by Christie et al. (1999) and Dobb (2004). 

Computer validation should not be undertaken unless fundamental validation controls have been fully understood and implemented within the pharmaceutical or healthcare company s organization. Here we allude to properly qualified personnel, effective document management and change control systems, internal audit procedures, methods of managing the deviations from standard practice thereby exposed, and a culture of continuous improvement (see Chapter 4 for more details). Senior management must not fall into the trap of assuming through complacency or idleness that these controls have been fully instituted In most firms there is usually much that still needs to be done in these areas. Let us examine these controls a little more closely. 

Detailed requirements for alarm philosophy document Alarm system requirements specification Alarm identification and rationalization Alarm and HMl design details with advanced methods Implementation, operation, and maintenance Monitoring and assessment Management of change handling and auditing Standard hence with lesser examples... 

In the calibration of thermal desorption tubes, the same conditions should predominate as in sample collection. Methods such as the liquid application of a calibration solution to the adsorption materials or the comparison with direct injections have been shown to be unsatisfactory. Alternatively, Certified Reference Standards (CRSs) are available (e.g. Markes Int., UK). CRS tubes are recommended in many key standard methods (e.g. US EPA Method TO-17) for auditing purposes and as a means of establishing analytical quality control. CRS tubes are often certified traceable to primary standards, have a minimum shelf life of typically 6 months. They are available ready for use with concentrations... 

The second aspect of quahty documentation is to detail how the work processes referred to in the manual are performed. The QA unit is often the organization responsible for issuing a set of procedures designed to assure conformance to the appropriate standards or to company poHcy. The procedures, often called standard operation procedures (SOP) or quahty operating procedures (QOP), should include such topics as customer complaints, audit protocols, stabihty testing, preparation of COAs, test method vahdation, etc. 

The reason for an Exposition is so that there is a description of the system showing how it works and how it controls the achievement of quality. This is different from the policies and procedures. The policies are a guide to action and decision and as such are prescriptive. The procedures are the methods to be used to carry out certain tasks and as such are task related. They need to be relatively simple and concise. A car maintenance manual, for example, tells you how to maintain the car but not how the car works. Some requirements, such as those on traceability and identification, cannot be implemented by specific procedures although you can have specific policies covering such topics. There is no sequence of tasks you can perform to achieve traceability and identification. These requirements tend to be implemented as elements of many procedures which when taken as a whole achieve the traceability and identification requirements. In order that you can demonstrate achievement of such requirements and educate your staff, a description of the system rather than a separate procedure would be an advantage. The Exposition can be structured around the requirements of ISO/TS 16949 and other governing standards. It is a guide or reference document and not auditable. 

Devise a method of determining when parts of the system were last audited. Decide on the types of audits to be conducted and the level of staff to conduct them. Determine the standards against which the organization is to be audited. 

Demonstrate that audit trails are created and maintained for Date and time of operator entries and actions that create, modify, or delete electronic records (methods, sequences, raw data, results, reports, calibrations, standards, event logs)... 

Traditional analytical methods make extensive use of computers, but typically these methods still require constant restructuring of the data and multiple analytical tools. This endless restructuring wastes time and productivity and also makes the analytical processes difficult to document, audit, and reproduce in real time. This situation also makes it difficult to reconstruct and update analyses in real time when new adverse event data become available or when new questions need to be asked. The application of comprehensive data standards allows the use of integrated, reusable software for analyzing adverse event data. This integration facilitates the reproducibility of the results. 

A laboratory is free to decide which scheme is most appropriate for its own circumstances. Laboratories entering the audit process for the first time may prefer to carry out an initial complete audit to establish if problems exist, followed, after an appropriate interval, by a rolling programme to maintain standards. When auditing to ISO/IEC 17025, the auditor should plan to witness at least one method being carried out. 

An audit program is planned, taking into consideration the status and importance of the processes and areas to be audited, as well as the results of previous audits. The audit criteria, scope, frequency, and methods are defined. The standard operating procedures are also audited according to the plan. 

A QA system describes the overall measures that a laboratory uses to ensure the quality of its operation. Typical items include suitable equipment, trained and skilled staff, documented and validated methods, calibration requirements, standards and RMs, traceability, internal QC, PT, nonconformance management, internal audits, and statistical analysis. 

The purpose of the qualification/audit is for the sponsor to investigate the standard practices of the contractor. Quality as well as technical capabilities should be evaluated. One should determine where the test article will actually be stored, the department that will conduct the in-life portion, make an assessment of procedures (SOPs) for dosing, identify differences between the sponsor s general practices and the facilities operating procedures (proto-col/study-specific procedures (SSPs), and assess the process of interim data exchange and the method of reporting of SOP and protocol deviations to the study director and the sponsor. 

Autoencoders are a unique and specialized class of software. One must remember that coding is a means to an end. Data consistency is the desired result. For this reason, companies will use different dictionaries and methods to code adverse events and drugs. There is no standard other than the dictionaries used for the process. Autoencoders are usually custom systems developed by a company for its own use. Commercial autoencoders do exist, and they generally provide facilities to audit the coding and provide custom dictionaries based on the general dictionaries above. 

Closely related to preventive action is the process audit. Such an audit is performed as part of a laboratory assessment for each test on the proposed scope of accreditation. Performance of a test procedure is observed relative not only to the requirements of the ISO 17025 standard (or ISO Guide 25) but also with respect to performing the ASTM or ISO test method properly. As a minimum, the laboratory must have properly calibrated equipment, the current test method, and trained testing personnel. In addition, a representative number of test demonstrations will reveal whether good laboratory practices are observed in sample preparation, using the correct test parameters and calculating the results. When operators and technicians accept responsibility through such demonstrations, they tend to commit to the quality process. Real improvement occurs with involvement at all levels. 

In order to demonstrate its compliance with the standard a laboratory will normally apply to an external accreditation body or certification body for accreditation or certification against tbe standard. Certification involves confirmation that the quality management system in place in the laboratory is fully implemented and in compliance with the requirements of the standard. Accreditation, however, adds a further element and involves a peer review of the methods used by the laboratory to confirm that they are suitable for the purpose for which they are being offered. Certification involves checking that what is described in the quality manual is carried out, i.e. an external audit (see Section... 

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