Regulatory controls and standards

DIOGENES also provides access to many other FDA regulatory documents related to quality control and standards for good manufacturing or laboratory practices. These will be discussed in greater detail later in this chapter. 

For instance, equiatomic nickel-titanium alloy (nitinol) is a very attractive material for biomedical applications. However, the high nickel content of the alloy and its potential influence on biocompatibility is an issue for nitinol-composed devices. Corrosion resistance of nitinol components from implantable medical devices should be assessed according to regulatory processes and standard recommendations. It is now well known that nitinol requires controlled processes to achieve optimal good life and ensure a passive surface, predominantly composed of titanium oxide, that protects the base material from general corrosion. Passivity may be enhanced by modifying the thickness, topography, and chemical composition of the surface by selective treatments [46]. 

The first step in designing a stack for air pollution control purposes is to determine exactly what regulatory constraints and requirements exist at the particular site. These constraints and requirements may be so severe that alternative means of air pollution control may have to be sought. In any case, the regulations specify a performance standard to which the stack must be designed, and against which the design can be evaluated. 

Included in this element are requirements for purchasing documents (specifications, drawings, and purchase orders), selection of suppliers, inspection and control of received material and record-keeping. For ESH/PSM, this element would focus on those aspects of the procurement process which support purchasing according to regulatory requirements, safety standards, risk management controls, etc. 

Control systems will play a key role in future distributed plants ]139,145]. As a rule of thumb, plants will be smaller and simpler, but the control systems will be much more advanced, of a standard not known today. Plant personnel for operation and managing will ultimately no longer be required, except for start-up, shutdown, and services. This is a shift from a regulatory to a servo role, supported by a sophisticated sequence control. Control is needed for safety issues, operability, and product quality control. Sensors have a central role to provide the information needed for control and modeling and simulation is needed for process models. 

Analytical chemistry is a critical component of worker safety, re-entry, and other related studies intended to assess the risk to humans during and subsequent to pesticide applications. The analytical aspect takes on added significance when such studies are intended for submission to the U.S. Environmental Protection Agency and/or other regulatory authorities and are thus required to be conducted according to the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Good Laboratory Practice (GLP) Standards, or their equivalent. This presentation will address test, control, and reference substance characterization, use-dilution (tank mix) verification, and specimen (exposure matrix sample) analyses from the perspective of GLP Standards requirements. 

The most cost-effective, technically feasible remediation procedures are not always in agreement with regulatory controls. Environmental regulations, by their very nature, must be applicable for a wide variety of settings and must protect the overall environment. In past years remediation standards were established as general numerical concentrations usually based on drinking water standards or other health-related criteria borrowed from related public health fields. This type of remediation was often generic, not site specific. 

Standardization The instrument response function can vary from analyzer to analyzer. If calibration transfer is to be achieved across all instrument platforms it is important that the instrument function is characterized, and preferably standardized [31]. Also, at times it is necessary to perform a local calibration while the analyzer is still on-line. In order to handle this, it is beneficial to consider an on-board calibration/standardization, integrated into the sample conditioning system. Most commercial NIR analyzers require some form of standardization and calibration transfer. Similarly, modem FTIR systems include some form of instrument standardization, usually based on an internal calibrant. This attribute is becoming an important feature for regulatory controlled analyses, where a proper audit trail has to be established, including instrument calibration. 

The below definition needs some explanatory words (Box 5). A first aspect to consider is that counterfeiting implies the intention to cheat those who receive the medicine - either in the distribution chain or as patients. This is important because it permits to make necessary distinction between counterfeit medicines and sub-standard medicines. Counterfeit medicines are sub-standard because they are manufactured and distributed out of control and their composition is unpredictable. On the other hand, not all sub-standard medicines are counterfeits. Substandard products are genuine products, manufactured by officially licensed manufacturers, which do not meet quality specification set for them. All substandard products are manufactured without compliance with Good Manufacturing Practices (GMP) and other regulatory requirements established by the competent national regulatory authorities in order to ensure that efficacy and safety of medicines is not affected by quality problems. 

Unlike SPC techniques, standard feedback control methods such as PID-control, do exert control upon a process, in an effort to minimize y, — yk. Control in Statistical Process Control is as such not regulatory control, but a semantic means of relating SPC to quality control—a means that often leads to the hybrid term SQC. Ogunnaike and Ray [14, Sec. 28.4] offer advice on when to use SPC and when to use standard feedback control methods When the sampling interval is much greater than the process response time, when zero-mean Gaussian measurement noise dominates process disturbances, and when the cost of regulatory control action is considerable, SPC is preferred. 

Laboratories using these methods for regulatory purposes are required to operate a formal quality control program. The minimum requirements of the program consist of an initial demonstration of laboratory capability and an ongoing analysis of spiked samples to evaluate and document data quality. The laboratory must maintain records to document the quality of data that is generated. Ongoing data quality checks are compared with established performance criteria to determine whether or not the results of analyses meet the demonstrated performance characteristics of the method. When results of spike sample analyses indicate atypical method performance, a quality control check standard must be analyzed to confirm that the measurements were performed in an in-control mode of operation. 

If any individual P falls outside the designated range for recovery, that parameter has failed the acceptance criteria. When this situation occurs, a quality control check standard containing each parameter that failed the criteria must be analyzed independent of the matrix, that is, spiked reagent water, to demonstrate that the laboratory is operating in control. If this second test is failed, the sample results for those parameters are judged to be out of control, and the problem must be immediately identified and corrected. The analytical results for those parameters in the unspiked sample are suspect and may not be reported for regulatory purposes. 

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