Compliance issues

An important principle that underpins the use of the 5-point ideal standard is that checking compliance with numerical standards is a statistical process. This requires that a standard is defined in terms that allow the use of statistical methods, typically 

Absolute limits cannot be used in statistical assessments of compliance based on sampling such standards need to be translated into percentiles to be used. The reasons for this are that standards are usually set in a precautionary manner, and it is nearly always the case that occasional exceedances of a limit value are acceptable. With such an absolute limit, the risk of reporting failure is strongly influenced by sampling frequency the more sampling, the higher the likelihood that at least 1 sample will fail. This is an important consideration if compliance assessments are to be used to compare regions or nations in a way that has serious implications for poor performers. 

To illustrate this, consider a watercourse that exceeds a threshold 1% of the time. Such a watercourse will always be reported as a failure of the absolute limit if assessed using continuous, error-free monitoring. Table 3.2 shows that if assessed by sampling, this failure will escape detection with a probability that depends strongly on the number of samples.2 With 4 samples, there is 4% probability that at least 1 exceeds the absolute limit. This rises to 41% for 52 samples. In this situation, the illusion of improved performance can be manufactured by taking fewer samples. In the meantime, the true quality might have deteriorated. 

Absolute limits monitored solely by sampling are not true absolute limits. This is because of the mathematical implication that exceedance is permitted at times (or places) when the samples are not taken that is, exceedance is tolerated for a proportion of the time (or places). Such absolute limits are, in truth, percentiles. 

An additional problem lies in setting up the action to secure compliance. An absolute limit must never be exceeded, but what is meant by never Once in a million years The answer to this question defines the absolute limit as a percentile it expresses the proportion of time for which failure is acceptable. This is also the outcome when we select a sampling frequency. There are 31 million seconds in a year, and we might sample 12 of them. This leaves a lot of time when we might fail the absolute limit and not notice it, and this accepted proportion of time defines the percentile Twelve samples a year treats an absolute limit as something like an annual 95th percentile. 

OSHA does not specify how the survey data is to be organized or analyzed. Employers should be able to verify that they have conducted an appropriate hazard assessment to identify the level of PPE required to protect the employee from any recognized hazards. The key here is recognized hazards. 

A certification document should be developed outlining that the workplace has been evaluated for hazards. It should specify the workplace or areas surveyed and should include the name of the person certifying the evaluation. The contents of a hazard assessment cannot be verified without documentation. Without documentation, the certification could be worthless. So to play it safe, some form of a written certification of the hazard assessment should be retained. 

There is no mention that a prior hazard assessment will be acceptable. It is only common sense that OSHA would not expect employers with a previously documented hazard assessment program that meets the new requirements to perform another assessment. Yet there is no way of knowing if this will be acceptable. Employers should use good judgment on what is an effective hazard assessment. Bear in mind, hazard assessment should incorporate any applicable American National Standards 

Institute (ANSI) standards for purchases of PPE after July 5, 1994. Therefore, if the prior assessment does not include this, a reevahiation of the population should be conducted. 

Employers also have new responsibilities to inspect and remove defective or damaged PPE. It is important that employees are instructed to report defective or damaged equipment. 

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If we are going to follow HAZWOPER principles, why should we determine if the operation falls under these requirements The answer is simple. If we follow these principles it will help to make sure that a job is done safely. If the specific work falls in a gray area, using HAZWOPER principles will help to eliminate controversy over any compliance issues. 

Generally, the plant engineering function is responsible for overall plant safety, as well as all compliance issues. The plant engineer must adapt to the constantly escalating federal, state and local regulations that govern these compliance issues. 

Regulatory Compliance Issues in the US Table 64.2 Examples of OSHA-listed chemicals... 

Protocol deviations in the processing phase of the study must be reported to the Study Director without delay. The Study Director will determine any potential impact upon the study that would result from the protocol deviation and will advise the PPI how to proceed with the study. Regardless of the form of communication by which the Study Director is notified of the protocol deviation, a formal description of the protocol deviation must be written by the PPI and submitted to the Smdy Director for an assessment of impact on the study. The assessment of impact by the Study Director should address any scientific and GLP compliance issues. A signed copy of the deviation report is included with the raw data notebook. 

Some QA auditors prefer to audit printouts of the electronic data rather than the electronic data themselves. This may be partially due to a lack of familiarity with electronic auditing or with the computer system and partially to unavailability of the software to QA. There are several arguments in favor of QA auditing the electronic data rather than the paper data. For one, there may be perceived compliance issues related to the printouts that do not exist in the electronic data (such as no initials and date on the hard copy). Also, QA may not be given printouts of all the pertinent data. 

The use of individual passwords increases software security. During a study inspection, QA should ensure that the person physically entering the data is the person that has logged on to the system. If not, this is a GLP compliance issue since the person entering the data will not be the person identified as such in the electronic data. QA personnel should have read-only access to the data in order to avoid any inadvertent changes. 

In the recently released book on worldwide compliance issues (Adherence to Long-term Therapies, Evidence for Action),7 published by the World Health Organization, researchers indicate that the problem of noncompliance is worse in countries in the developing world than in countries in the industrialized world. Many parts of the United States have similar morbidity and mortality rates as countries in the Third World.8 Specific disease states may have significant additional noncompliance ramifications due to the development of drug-resistant strains of bacteria.9 Many times what is necessary is referral to specific clinicians for individualized treatment and monitoring to enhance compliance. The case histories provided in this text will allow you to follow what others have done in similar situations to optimally help patients succeed in improving compliance rates and subsequent positive health outcomes. 

Non-compliance issues appear more prevalent in some non-Western cultures. One study in South Africa revealed non-compliance rates to oral neuroleptics in two-thirds of Black patients and one-half of colored patients compared to only one-quarter of Caucasians (Gillis.Trollip, Jakoet etal., 1987). Cultural and communication factors were considered to be significant barriers apart from those related to cost and social factors. Kinzie et al. (1987) reported that despite prescribing adequate doses of tricyclic antidepressants (TCAs) to depressed Asian refugees,... 

Women who particularly benefit from progestin-only methods, including minipills, are those who are breast-feeding, those who are intolerant to estrogens, and those with concomitant medical conditions in which estrogen is not recommended. Also injectable and implantable contraceptives are beneficial for women with compliance issues. 

New York City, 2nd-6thMay 1999, p.2880-4. 012 DYES IN PETP A LOOK AT FDA COMPLIANCE ISSUES... 

The author acknowledges helpful ideas and suggestions from R. Ornaf, D. Barker, J. Bonilla, and C. Choi of Purdue Pharma. This chapter has been presented in parts in a symposium Regulatory compliance issues in the pharmaceutical industry at the Pittsburgh Conference in Orlando, Florida, March 13, 2003. 

Line management should establish a system to provide consistent information about incidents and compliance issues, together with associated follow-up actions. Progress should be reviewed regularly, and can be recorded on a punch-list-style report showing status, estimated completion date, and whether an item is open or closed. When action items are completed, they can be moved to a closed punch-list for future audit trail purposes. 

During a Nevada field demonstration, approximately 333 yd of soil and debris contaminated with up to 1100 pCi/g of plutonium was processed at the U.S. Department of Defense s (DOD s) and doe s Tonapah Test Range. The actual cost of the demonstration was 138,126. This figure included 8203 for regulatory and compliance issues, 29,614 for mobilization, 78,545 for physical treatment, and 21,764 for demobilization (D21040S, p. 78 D21231X, p. 14). 

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