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In a regular analysis of covariance (ANCOVA) approach to stability analysis, the decision for pooling data from different batches plays a key role in the determination of the shelf life of the drug product. Conventionally, the decision to pool data for the estimate of slope and intercept of common or individual regression lines is made by "no evidence to reject the null hypothesis of no difference." With typically limited observations, a significance level of much higher than 0.05 was recommended for the pooling tests in order to avoid inflation of type-I error rate of the shelf life testing. This logic of the pooling test decision making discouraged the use of replicates to improve power of testing and precision of estimation. The concept of pooling by equivalence test was originally proposed by Ruberg and Hsu in their 1990 article "Multiple comparison procedures for pooling batches in stability studies" Such a concept has evolved to pooling batches based on the shelf life equivalence test by Yoshioka et al. in their 1996 article "Power of analysis of variance for assessing batch-variation of stability data of pharmaceuticals." In this article, an approximation test of shelf life equivalence and a test of chemical value equivalence for the data pooling decision are proposed as an alternative to the conventional ANCOVA approach.

Stability requirements for the worldwide registration of pharmaceutical products have changed dramatically in the past few years. A series of guidelines on the design, conduct, and data analysis of stability studies of pharmaceuticals have been published by the International Conference on Harmonization (ICH); however, the statistical discussion on study design is limited. In this paper, stability designs including full, bracketing, and matrixing designs will be exemplified. The statistical aspects of these stability designs will be discussed in relation to the recent ICH guidelines. The statistical and regulatory considerations on the selection of stability design will also be presented. The stability study should be well designed so the shelf life of the drug product can be estimated with a high degree of accuracy and precision. Several commonly used criteria for design comparison will be presented. Finally, a case study is presented to illustrate the potential problems of an overreduced design from the statistical and regulatory perspectives.

Shelf life of a drug product is defined as the length of time under specific conditions of storage that the product will remain within specifications established to ensure its identity, strength, quality, and purity. The objective of an new drug application (NDA) stability study is to collect and evaluate the evidence in support of the sponsor-proposed shelf life. The proposed shelf life is supported when each batch of the drug products in the study has shelf life no shorter than the proposed shelf life. When the value of the batch mean changes linearly, sometimes batches of the same product may share the same slope or regression line. In practice, batches are pooled to have a common estimate of slope or regression line when there is no significant difference in slope or regression line. Such practice is often applied in pooling across levels of a design factor such as package or strength in a stability study designed with multiple factors. However, falsely pooling different slopes or intercepts may increase false positive rates on the decision of approval for the proposed shelf life. The proposed algorithm used with the simulation technique tries to reduce false pooling rates for testing slope or intercept differences in order to bring down the false positive rates on the decision of approval for the proposed shelf life to the prespecified Type-I error rate of 5 or 10%.

For a traditional multiple batch stability design with no other factor, the conventional analysis is analysis of covariance (ANCOVA) modeling using F-tests based on type I sum of squares to determine whether the batches may be pooled for a common estimate of the linear regression line(s). In the last decade, many multiple factor designs were proposed in stability studies. With the objective of model selection, the generalization of the conventional ANCOVA model using type I sum of squares to designs with multiple factors requires a prespecified hierarchical pooling test ordering to determine whether any of the factors may be eliminated. Different shelf life estimates may be derived using different hierarchical pooling test orderings. On the other hand, setting the hierarchical ordering can be subjective and controversial. The stepwise modeling based on F-tests using type III sum of squares for model determination and factor elimination is proposed to eliminate such difficulties.

We consider the estimation of shelf life of a drug product when the stability data are discrete. When there is no batch-to-batch variation, the proposed shelf life estimator is an approximate 95% lower confidence bound of the true shelf life. In the presence of batch-to-batch variation, the proposed shelf life estimator is an approximate 95% lower prediction bound of the shelf life of future batches. As a result, the proposed shelf life is applicable to all future batches of the same drug product. Testing for batch-to-batch variation based on discrete responses is also discussed.

The objective of this study was to investigate the possible impacts of curing and storage conditions on dissolution of controlled release diphenhydramine HCl pellets coated with EUDRAGIT NE30D. The accumulative percentage of dissolved active drug was used as the response in three statistical experimental design studies: 32 full factorial, Box-Behnken and 2(3) designs. By only considering curing temperature and curing time, both factors were found to significantly affect the dissolution rate, but curing temperature had greater impact than curing time. When considering polymer coating level, curing temperature and curing time together, polymer coating level and curing temperature had important effects on dissolution rate, but curing time became insignificant among these three factors. The addition of the water-soluble additives hydroxypropyl methyl cellulose and mannitol made coating films less sensitive to curing, and there was little or no difference in their effect in the model studied. Lower levels of a water-insoluble additive (kaolin) had little impact on dissolution; however, when the level of water-insoluble additive increased, the coating film became more sensitive to curing, especially at the lower curing temperature of 30 degrees C.

Stability data are often collected to determine the shelf life of certain characteristics of a pharmaceutical product, for example, a drug's potency over time. Statistical approaches such as the linear regression models are considered as appropriate to analyze the stability data. However, most of these regression models in both theory and practice rely heavily on their underlying parametric assumptions, such as normality of the continuous characteristics or their transformations. In this article, we propose and study some rank-based regression procedures for the stability data when the linear regression models are semiparametric with unspecified error structure. Numerical studies including Monte Carlo simulations and practical example are demonstrated with the proposed procedures as well.

Microcapsules of a water-in-oil-in-water (W/O/W) emulsion, which contained a hydrophilic substance, 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (PTSA), in its inner aqueous phase, was prepared by hot-air-drying or freeze-drying the emulsion using a single-droplet-drying method. Pullulan, maltodextrin, or gum arabic was used as a wall material, and the oily phase was tricaprylin, oleic acid, olive oil, or a mixture of tricaprylin and olive oil. An encapsulation efficiency higher than 0.95 was reached except for the microcapsules prepared using gum arabic and oleic acid. The hot-air-dried microcapsules were generally more stable than the freeze-dried microcapsules at 37 degrees C and various relative humidities. The stability was higher for the microcapsules with tricaprylin as the oily phase than for the microcapsules with oleic acid. The higher stability of the microcapsules with tricaprylin would be ascribed to the lower partition coefficient of PTSA to the oily phase. There was a tendency for the stability to be higher at lower relative humidity for both the hot-air- and freeze-dried microcapsules. The volumetric fraction of olive oil in its mixture with tricaprylin did not significantly affect either the encapsulation efficiency or the stability of the hot-air-dried microcapsules.

The design of a stability study is intended to establish a shelf-life based on testing a limited number of batches of a drug product, which is applicable to all future batches of the drug product manufactured under similar circumstances. In the FDA guidelines for stability testing of new drug products, the matrix design is suggested as the alternative statistical design to the full testing approach. In the last few years, the matrix design has received increasing attention from pharmaceutical companies in order to reduce the cost of stability studies. For this, the full and matrix stability test plans were used on three batches of human insulin pharmaceutical preparation stored under a kinetic mean temperature of 22.7 degrees C for 3 years. The statistical method was suggested by Ruberg and Stegeman (Biometrics, 1991, 47, 1059-1069) and Llabrés et al. (Int. J. Pharm. 2000, 204, 61-68), and was used for comparing batches, and the maximum allowable difference in slopes between batches was used as criteria for estimating a common shelf-life. The results obtained show the conservative nature of the matrix approach, although the difference between the matrix and full shelf-life was less than 1 month. The effect of the matrix method on shelf-life was also studied. The results showed that the model for estimating the shelf-life varied as a function of the permutation used, after testing for both slope and intercept poolability at alpha = 0.25. The batches should be pooled for both full testing and matrix design since the critical significance level required to obtain a power of 0.80 was achieved when the maximum allowable difference in slopes between batches was 1%/month, according to Ruberg and Stegeman. In contrast, when the proposed method by Llabrés et al. was used, the results varied in function of the maximum allowable difference in slopes.

Monsel's solution is a common topically applied hemostatic agent used in minor dermatologic and gynecologic surgery. Clinically, because it is often stored for long periods and dispensed from a common source for multiple patients, Monsel's solution is a potential vector for transmission of infection. However, microbiologic inoculation studies and contamination surveys indicate that Monsel's solution has properties that prohibit microbial growth, making it an unlikely vector for nosocomial infection.

Good Distribution Practice of medicinal products for human use is a quality warranty system, which includes requirements for purchase, receiving, storage and export of drugs, intended human consumption. A drug is a specific product and its mishandling is dangerous to human health and life. Therefore it is necessary to strictly control the movement of the drug from the producer to the consumer so that poor quality drugs do not have access to the market. Good Distribution Practice rules set the general requirements for good wholesale distribution practice of drugs, intended for human consumption. In order for company to meet the specified requirements, the drug distribution company must have all suitable and necessary premises, machinery, equipment, the required number of employees and specified documentation. The preparation of the Good Distribution Practice documentation is one of the most important and complex aspects when implementing the Good Distribution Practice in the companies. The article deals with the analysis of results obtained during the research of drug distribution companies in Lithuania. The research revealed that drug distribution companies put emphasis on the equipment of storage premises. Less attention is being paid to the preparation of the documents of Good Distribution Practice. The article thus presents the analysis of Good Distribution Practice documents prepared by the drug distribution companies.

This report presents the recommendations of an international group of experts convened by the World Health Organization to consider matters concerning the quality assurance of pharmaceuticals and specifications for drug substances and dosage forms. Of particular relevance to drug regulatory authorities and pharmaceutical manufacturers, the report discusses activities related to the development of The International Pharmacopoeia and basic tests for pharmaceutical substances and dosage forms, as well as quality control of reference materials, good manufacturing practices (GMP), stability studies, inspection, hazard analysis, procurement, storage and other aspects of quality assurance of pharmaceuticals, and regulatory issues. The report is complemented by a number of annexes, including recommendations on the risk of transmitting animal spongiform encephalopathy agents via medicinal products, guidelines on GMP for pharmaceutical products, a model certificate for GMP and guidance on a GMP inspection report. The final annexes provide guidance on the application of Hazard Analysis and Critical Control Point (HACCP) method to pharmaceuticals, good storage practices and a procedure for assessing acceptability of pharmaceutical products for purchase by United Nations agencies.

Purpose: To assess the proportion of primary care physician (PCP) offices meeting vaccine storage guidelines, identify factors associated with low compliance, and evaluate whether a quality improvement (QI) activity improves compliance., Methods: We examined compliance with guidelines of 721 PCP offices contracted with a national managed care organization in four cities. A QI activity (educational materials, written feedback, and distribution of thermometers) was conducted at baseline and a follow-up assessment occurred within 3 months., Results: Baseline compliance was relatively high, with >80% adherence to most guidelines. For example, 89% of offices had a thermometer; and 83% of temperatures were appropriate. Most units did not have vaccines stored in the door or food/biological materials in the unit (80% and 96%, respectively). Almost all vaccines had not expired. Multivariate analysis indicated that practice location, type of physician, participation in vaccine programs, and using guidelines were associated with compliance. For most of the compliance measures, pediatric offices had the highest compliance. Adherence to guidelines improved after the QI activity; the net change between pre- and post-intervention ranged from +1% to +19%. Measurements most impacted included temperature log posted (19% improvement in refrigerator; 16% improvement in freezer) and no vaccine stored in refrigerator door (14% improvement)., Conclusions: Despite generally high compliance, there are some opportunities for improvement in how PCPs store vaccines. Incorporating an intervention program in existing practice activities can improve storage practices. Further research is needed to determine the possible benefits of targeting interventions to certain types of providers who may be less knowledgeable about recommended guidelines.

Background: Although the standards for vaccine storage required for accreditation of general practices, and the Guidelines for Australian Immunisation are widely available, all research to date suggests that in Australia compliance with these standards has not been readily achieved., Objective: The New South Wales Central West Division of General Practice (NSWCWDGP) and the Public Health Unit of the New South Wales Mid Western Area Health Service (NSW MWAHS) worked together from 1999 to 2001 to produce an intervention that would gather information about current vaccine storage, and provide practical help to storage sites which were not complying with accepted standards., Discussion: Cooperation between a general practice division and the public health unit can deliver coverage of 100% of vaccinators in a large geographic region. We have demonstrated that the lack of a designated person to take on ultimate responsibility for vaccines at a site is associated with less chance of achieving safe storage. Persistent difficulty in 'getting it right' has been documented. One new measure we have suggested and trialled is the installation of affordable commercial thermostats in the domestic refrigerators that are now widely used. Another is the piloting of a general practice division administered mailout program of temperature dataloggers to document the ongoing compliance of vaccine storage sites with accepted standards.

Medication-related errors are a common cause of patient morbidity and mortality. However, a number of strategies use the latest technology, such as computers and associated hardware and software, to reduce medication-related errors. In this era of reduced operating margins for most hospitals, strategies that employ physician order entry and bar code-labeled medication systems may be prohibitively expensive. Cost-efficient methods are available that can make simple changes in the way medications are mixed, stored, prescribed, and delivered, and they have the potential to have a major effect on medication safety. These methods do not rely on purchasing new hardware or expensive software. They include changing the culture within the hospital to one that focuses on patient safety, developing standardized protocols, developing an education program that provides direct feedback, and using protocols for high-risk medications. Coordinating hospital efforts with regional organizations may also be beneficial in reducing the occurrence of medication-related errors.

Background: To promote improved hand hygiene among personnel, a hospital installed dispensers for an alcohol-based hand rinse throughout the facility. Soon after installation, dispensers began to malfunction and continued to do so despite efforts to rectify the problem., Methods: Sixteen months after installation, dispensers in all patient rooms were examined, and surveyors recorded the condition of dispensers, the number of times the dispenser lever was pressed to obtain product, how the product was delivered onto the hand, and a qualitative estimate of the volume delivered., Results: Of 166 dispensers, 2% were broken, 7% had no product container, 5% had an empty product container, 9% contained product but were totally obstructed, and 77% were functional. Of the 128 functional dispensers, 65% delivered product after a single stroke of the lever, 13% after 2 strokes, 9% after 3 strokes, and 13% after 4 or more strokes. Seventeen percent delivered a small volume onto the hand, and 16% squirted the product onto the wall or floor., Conclusion: Evaluation of alcohol-based handrubs should consider not only product characteristics, user acceptability, skin tolerance, and cost but also the design and function of the dispensers that will ultimately be installed.

Unlabelled: Previously the authors showed that prehospital medications were stored outside their recommended temperature range. In response, the state office of emergency medical services (EMS) issued regulations regarding temperature control and monitoring of prehospital medications., Objective: To determine the impact of previous research (on medication storage conditions) on current practices among the mobile intensive care units (MICUs) within the state., Methods: A statewide, structured telephone survey of MICU directors was conducted between April and December 2000. Questions focused on changes in storage and monitoring practices (including modifications to vehicles, medication boxes, and the use of temperature monitoring devices) since the authors' previous research., Results: Thirty-three of 35 (94%) programs (100 vehicles) participated in the survey. Eighty-five percent changed their practices since the research five years ago. Of the five that did not change, three already had temperature control measures in place, while two have not made any changes. Twenty-one (63%) of the programs reported changing specifically because of state regulations. Eighty-one percent of the programs have taken some measure to control temperature. Currently, 63% of the 100 vehicles in use have both heating and cooling devices specifically for the medications, whereas 14% have only a heater and 23% have neither. Thirty-one (94%) MICUs monitor the temperature in some manner: 42% in the vehicle, 58% in the medication box. Of these, 68% are using 30-day electronic temperature data recorders, whereas 32% are using non-recording digital thermometers., Conclusions: This survey demonstrates a positive impact from previous research. Most of the MICUs in the state have changed their practices in controlling and monitoring prehospital medication storage temperature.

Objectives: To describe the implementation of guidelines for vaccine storage in general practice, and their effectiveness in achieving optimum vaccine storage temperatures in fridges., Design: Repeated cross-sectional surveys over time--phase 1 1996/97, phase 2 1998/99, phase 3 1999/2000., Setting: Central Coast, New South Wales., Participants: Phase 1--all general practices on the Central Coast. Phases 2 and 3--samples of practices., Interventions: Each practice was surveyed about how they stored vaccines. A datalogger recorded fridge temperatures over six days. Individual feedback and advice were given., Main Outcome Measures: Proportion of: 1. fridges maintaining a temperature in the 2-8 degrees C range; 2. fridges freezing; 3. practices with one person responsible for vaccine storage; 4. bridge temperature checked daily; 5. fridges storing no items other than vaccines; 6. bridges with thermometers; and 7. associations between storage practices and fridge temperatures., Results: In phase 1, 102 fridges, and in phase 3, a random sample of 36 practices was surveyed. The findings for phase 1 and phase 3 respectively were: 31% and 50% of fridges were in the 2-8 degrees C range; 36% and 25% were <0 degrees C; one person was responsible in 52% and 53% of cases; 20% and 38% reported daily checks; 74% and 94% of fridges had no extraneous items and 53% and 86% of fridges had thermometers. No statistically significant associations were found between vaccine storage practices and bridge temperatures., Conclusions: Despite improvements in vaccine storage practices, a quarter of fridges were freezing, thereby compromising the potency of many of the immunisation schedule vaccines.

Context: Preventing loss of vaccine potency during storage and handling is increasingly important as new, more expensive vaccines are introduced, in at least 1 case requiring a different approach to storage. Little information is available about the extent to which staff in private physicians' offices meet quality assurance needs for vaccines or have the necessary equipment. Although the National Immunization Program at the Centers for Disease Control and Prevention (CDC) in 1997 developed a draft manual to promote reliable vaccine storage and to supplement published information already available from the CDC and the American Academy of Pediatrics, the best ways to improve vaccine storage and handling have not been defined., Objectives: To estimate the statewide prevalence of offices with suboptimal storage and handling, to identify the risk factors for suboptimal situations in the offices of private physicians, and to evaluate whether the distribution of a new National Immunization Program draft manual improved storage and handling practices., Design: Population-based survey, including site visits to a stratified, random sample of consenting private physicians' offices. At least 2 months before the site visits, nearly half (intervention group) of the offices were randomly selected to receive a draft CDC manual entitled, "Guideline for Vaccine Storage and Handling." The remainder was considered the control group. Trained graduate students conducted site visits, all being blinded to whether offices were in the intervention or control groups. Each site visit included measurements of refrigerator and freezer temperatures with digital thermometers (Digi-thermo, Model 15-077-8B, Control Company, Friendswood, TX; specified accuracy +/- 1 degrees C). Their metal-tipped probes were left in the center shelf of cold storage compartments for at least 20 minutes to allow them to stabilize. The type of refrigerator/freezer unit, temperature-monitoring equipment, and records were noted, as were the locations of vaccines in refrigerator and freezer, and the presence of expired vaccines. Other information collected included the following: staff training, use of written guidelines, receipt of vaccine deliveries, management of problems, number of patients, type of office, type of medical specialty, and the professional educational level of the individual designated as vaccine coordinator., Participants: Two hundred twenty-one private physicians' offices known by the Georgia Immunization Program in 1997 to immunize children routinely with government-provided vaccines., Outcome Measures: Estimates (prevalence, 95% confidence interval [CI]) of immunization sites found to have a suboptimally stored vaccine at a single point in time, defined as: vaccine past expiration date, at a temperature of /=9 degrees C in a refrigerator or >/=-14 degrees C (recommended for varicella vaccine) in freezer, and odds ratios (ORs) for risk factors associated with outcomes. We performed chi(2) analysis and Student's t tests to compare the administrative characteristics and quality assurance practices of offices with optimal vaccine storage with those with suboptimal storage, and to compare the proportion of offices with suboptimal storage practices in the groups that did and did not receive the CDC manual., Results: Statewide estimates of offices with at least 1 type of suboptimal vaccine storage included: freezer temperatures measuring >/=-14 degrees C = 17% (95% CI: 10.98, 23.06); offices with refrigerator temperatures >/=9 degrees C = 4.5% (95% CI: 1.08, 7.86); offices with expired vaccines = 9% (95% CI: 4.51, 13.37); and offices with at least 1 documented storage problem, 44% (95% CI: 35.79, 51.23). Major risk factors associated with vaccine storage outside recommended temperature ranges were: lack of thermometer in freezer (OR: 7.15; 95% CI: 3.46, 14.60); use of freezer compartment in small cold storage units (OR: 5.46; 95% CI = 2.70, 10.99); lack of thermometer in refrigerator (OR: 3.07; 95% CI: 1.15,8.20); and failure to maintain temperature log of freezer (OR: 2.70; 95% CI: 1.40, 5.23). Offices that adhered to daily temperature monitoring for all vaccine cold storage compartments, compared with those that did not, were 2 to 3 times more likely to assign this task to staff with higher levels of training, have received a recent visit from the state immunization program, and be affiliated with a hospital or have Federally Qualified Health Center status. In addition, sites using >1 refrigerator/freezer for vaccine storage were more likely to have at least 1 cold storage compartment outside recommended temperature ranges. We found no significant differences in the data reported above between the intervention group (received copy of the draft manual) and the control group (did not receive copy of draft manual), even when controlling for the annual number of immunizations given or the type of office. (ABSTRACT TRUNCATED)

This report presents the conclusions of a WHO Expert Committee commissioned to make recommendations on specifications for pesticides used in public health, with a view to promoting the manufacture and use of high-quality products that are both effective against susceptible vectors of disease and acceptable in terms of safety. These specifications serve mainly for purchase and quality-control purposes, but may also be useful for product registration by WHO Member States. The text includes an outline of the objectives and achievements of the WHO Pesticide Evaluation Scheme (WHOPES) and an overview of recent trends in pesticide usage in the various WHO regions. Analytical methods and quality control of pesticides in developing countries are discussed, and the Committee's recommendations for specifications for various types of pesticides are presented. The Committee also considered pesticide containers and packaging, marking and storage, as well as the problems of disposal of unusable pesticides and their containers. Recommendations for continued collaboration between WHO and other organizations are summarized, as are the Committee's more general recommendations for WHO's future work in the area of pesticides. Annexed to the report are the Committee's recommendations for changes to existing specifications and methods, for new pesticides and formulations, and for new methods.

The stability of methylmercury and inorganic mercury retained on yeast-silica gel microcolumns was established and compared with the stability of these species in solution. Yeast-silica gel columns with the retained analytes were stored for two months at three different temperatures: -20 degrees C, 4 degrees C and room temperature. At regular time intervals, both mercury species were eluted and quantified by cold vapor atomic absorption spectrometry (CVAAS). Methylmercury was found stable in the columns over the two-month period at the three different temperatures tested while the concentration of inorganic mercury decreased after one week's storage even at -20 degrees C. These results are of great interest since the use of these microcolumns allows the preconcentration and storage of mercury species until analysis, thus saving laboratory space and avoiding the problems associated with maintaining species integrity in aqueous solution.

Background: Child immunisation is among the most cost-effective ways of preventing premature child deaths, and the potency of vaccines, crucial for vaccine efficacy, is dependent on effective management of the cold chain at all levels of vaccine handling., Objective: To assess the status of the cold chain at peripheral vaccine stores in Ethiopia., Design: Institution based cross-sectional survey in two rural and one urban administrative areas were included in the study. Sixty seven health institutions providing static vaccination services were included in the study but cold chain system was assessed fully in only sixty four. Data were collected by interviewing health workers and by directly observing the cold chain equipment and records using structured forms., Results: Conditions of the cold chain system were described based on 64 of the 67 centres visited, three were excluded because of non-functioning cold chain. Complete temperature record was observed in 37 (57.8%) of the centres. Thermometer was not available in four (6.3%) and thermometer reading was found to be outside the optimal range in another seven (10.9%) centres. Vaccine storage in the refrigerator was not proper in 47 (73.4%) centres. Majority of the centres had neither trained personnel nor budget for maintenance of the cold chain., Conclusion: There is a real danger of vaccines losing their potency at these centres even if they were potent on arrival. Relevant training for those handling the cold chain, improving the maintenance conditions of refrigerators and introduction of cold chain monitoring devises are recommended.

The presence of reserve nitrous oxide cylinders on anaesthetic machines is not necessary and potentially hazardous, wasteful and polluting. Although reserve nitrous oxide cylinders are routinely present on the anaesthetic machines in many hospitals in the UK, it is our concern that they are not checked or maintained properly. We examined a sample of cylinders and surveyed the practice amongst the anaesthetic staff in our Department with an anonymous questionnaire. This confirmed that: (1) the equipment is not properly maintained, 68% of cylinders sampled having passed a 3-year expiry date; (2) checks are of little practical use, are not routinely performed by anaesthetists, and only 46% of respondents routinely check the nitrous oxide cylinders. In conclusion, the nitrous oxide cylinders are not properly checked or maintained and may represent a safety hazard.

Objective: To test the hypothesis that dairy farms certified in the Milk and Dairy Beef Quality Assurance Program (QAP) were more likely to use prudent drug management practices than farms that were not certified., Design: Cross-sectional study., Sample Population: 141 Michigan dairy farms of which 74 were not certified in the QAP, 30 were involuntarily certified, and 37 were voluntarily certified., Procedure: Dairy producers completed a self-administered questionnaire that focused on herd health management, drug use, record keeping, personnel management, and descriptive characteristics of their farm during 1993. Separate multivariable logistic regression models were developed to determine the association of QAP certification with each of the management practices., Results: Results suggested that farms adopted specific management practices irrespective of certification. Many farms used visible identification and non-emergency veterinary services and discussed residue prevention with employees. Involuntary certification was associated with maintenance of good written treatment records and performance of on-farm drug residue testing. Voluntary certification was weakly associated with use of refrigerated drug storage., Conclusions and Clinical Relevance: QAP certification appeared to have been associated with the adoption of only a few prudent drug use practices, although QAP materials and framework were developed to assist veterinarians in the promotion of disease prevention, client communication, and residue prevention practices on farms. Veterinary care would benefit from the development and encouragement of better record keeping on farms.

Medications have strength, expiration date, and storage conditions printed on the medication bottle or package. Some anesthesia medications require refrigeration to maintain the stated strength and safety until the expiration date. These medications may expire in days rather than years when left at room temperature in anesthesia carts or emergency boxes. The following AANA Journal course discusses anesthesia-related medications that require refrigeration and how long potency and safety is maintained out of the refrigerator and provides a chart for future referral.

Nurses' involvement in immunisation goes beyond simply giving vaccines. Jeannett Martin describes the nurse's overall role and responsibilities in administering these vital drugs.

This study was conducted to determine storage temperatures of drugs carried on rescue vehicles. Recording thermometers were placed inside drug boxes carried on rescue vehicles. Those temperatures were compared with ambient air temperatures, temperatures inside mechanically cooled compartments of the rescue vehicles, and USP-recommended drug storage temperatures. The results indicate that drug storage temperatures in some prehospital rescue vehicles exceed USP guidelines. Mechanical cooling of the storage compartment results in drug storage temperatures within the USP guidelines. Mechanical cooling of drug storage compartments on vehicles is technologically and financially possible.

The injection of insulin is essential for management of patients with type 1 diabetes and may be needed by patients with type 2 diabetes for intermittent or continuous glycemic control. The species and dosage of insulin used should be consistent, and the patient's injection technique should be reviewed periodically with the diabetes-care team. The effective use of insulin to obtain the best metabolic control requires an understanding of the duration of action of the various types of insulin and the relationship of blood glucose levels to exercise, food intake, intercurrent illness, certain medications, and stress; SMBG; and learning to adjust insulin dosage to achieve the individualized target goals established between the patient, family, and diabetes-care team.

The Joint Commission has standards for appropriate storage of medication, as well as food and nutritional products. Learn what the standards say about your staff watching the "fridge."

Introduction: The safety and efficacy of medications stored on air medical helicopters may be adversely affected by extreme temperatures. The purpose of this study was to determine whether temperatures inside an air medical helicopter drug box were within the U.S. Pharmacopeia recommendations for controlled room temperature. This is defined as a temperature between 15 degrees and 30 degrees C (59 degrees and 86 degrees F) with a mean kinetic temperature of less than 25 degrees C (77 degrees F). An additional goal was to determine whether time/temperature indicator labels can reliably monitor mean kinetic temperatures., Methods: Temperatures were monitored with miniature electronic temperature recorders and color-changing time/temperature indicator labels., Results: The mean kinetic temperatures for the summer and winter periods were 25.1 degrees C (77.2 degrees F) and 12.7 degrees C (54.8 degrees F), respectively. In the summer, the electronic recorders logged temperatures exceeding 25 degrees C (59 degrees F) 37% of the time and more than 30 degrees C (86 degrees F) 6% of the time. In the winter, temperatures less than 15 degrees C (59 degrees F) were recorded 83% of the time. The mean kinetic temperatures obtained from the electronic recorder and the time/temperature indicator labels differed by less than 0.7 degree C (1.3 degrees F). The results show that medications on an air medical helicopter are subject to temperatures out of the recommended range and that time/temperature indicator labels can reliably monitor mean kinetic temperatures.

The international acceptance of the definition of controlled room temperature (CRT) has given additional impetus to the use of mean kinetic temperature (MKT) as a method of quantifying temperatures during transport and storage and consequent possible effects on drug product stability. The present paper explores some of the implications of the MKT concept and considers the effect of temperature excursions on MKT values and hence on stability of drug products.

Objectives: To determine whether temperatures inside drug boxes used in the out-of-hospital setting are within the U.S. Pharmacopeia recommendations for "controlled room temperature," which is defined as a temperature maintained between 15 degrees C and 30 degrees C with a mean kinetic temperature less than 25 degrees C, and to determine whether time-temperature indicator labels can reliably monitor mean kinetic temperatures., Methods: Two methods were used to monitor temperatures: miniature electronic temperature recorders and color-changing time-temperature indicator labels. These were placed in drug storage boxes of advanced life support units over three summer months and two winter months., Results: In summer, the electronic recorders logged temperatures exceeding 30 degrees C in all drug storage boxes, ranging from 3% to 29% of the total time. The mean kinetic temperatures by location for the whole period ranged from 21 degrees C to 30 degrees C. In the winter, the electronic recorders logged temperatures exceeding 30 degrees C at one location 2% of the total time. There were significant temperature excursions below 15 degrees C at all locations, ranging from 16% to 90% of the total time. At one location, there were temperature readings below 0 degrees C for 9% of the total time. The mean kinetic temperatures obtained from the electronic recorders and the indicator labels differed by less than 1 degrees C., Conclusions: This study demonstrates that out-of-hospital medications are subject to temperatures both above and below recommended storage temperatures. Time-temperature indicator labels can reliably monitor exposure to elevated temperatures.

Objective: To evaluate the effect of direct feedback of temperature conditions followed by a telephone educational questionnaire to correct adverse vaccine storage, and to determine the consistency of vaccine storage conditions at provider sites over six months., Participants: 32 general practitioner vaccine providers in metropolitan Adelaide., Design: Temperatures were monitored for 14 days using electronic temperature monitors, with repeat monitoring at two and six months. Feedback was given to vaccine providers and an educational questionnaire was administered after initial monitoring., Main Outcome Measure: Number of sites with more than 20% of recordings < 2 degrees C or > 8 degrees C and/or more than 5% of recordings < 0 degree C or > 15 degrees C., Results: 13 (41%) sites had initially suboptimal storage. Following the interventions, storage was corrected in all but three (23%) of these sites. Only 10 (52%) of the 19 initially optimal sites had consistent optimal storage at two and six months., Conclusion: Electronic monitoring with direct feedback of storage temperatures was effective in correcting adverse storage at most suboptimal sites. Vaccine storage at initially optimal sites was not consistent. Our findings have important implications for further research and public health measures aimed at correcting and maintaining optimal vaccine storage.

This paper reviews contemporary trends in the stability testing of pharmaceutical products. In particular, it considers the progress toward globalization and harmonization and indicates stability problems, which probably will be the focus of attention for pharmaceutical scientists and regulators in the near future. Attention is specifically directed to monitoring stability in the channels of distribution.