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Significant improvement In the therapeutic monitoring of antieplleptlc drug concentrations In the laboratories partlclparing In the Antleplleptlc Drug Quality Control Program has been observed. In contrast to the 1974 blind survey results where over 50 percent of the laboratories were unsatisfactory, a recent assessment of performance based upon results from monthly proficiency samples demonstrates that 88 percent of the laboratories were performing satisfactory phenytoln assays. The performance on phenobarbital prlmldone, carbamazeplne and ethosuximide assays also demonstrates a marked Improvement. Proficiency testing has significantly improved the routine of

This paper estimates the impact of federal regulation of drug quality on research spending by the pharmaceutical industry. The theoretical approach recognizes that the effects of these regulations on research spending depend upon the reactions of R&D decision makers and the information available during project selection. The information available to R&D decision makers in the 1960s suggests that it would have been difficult for them to forecast accurately regulatory effects on research profitability. As better information developed in the late 1960s and early 1970s, however, regulation had a significant effect on research spending. These differences in response are tested econometrically and prove to be empirically significant. The estimates of current regulatory effects on pharmaceutical R&D spending are quite large.

Different published gas-liquid chromatographic procedures for the estimation of anti-convulsant drugs in plasma have been evaluated and two have been selected as being very suitable, the first for the determination of phenobarbitone, primidone, diphenylhydantoin and carbamazepine and the second for the determination of sulthiame. The performance of the first method has been evaluated in an Antiopileptic Drug Quality Control Scheme.

The following issues are discussed: The dynamics of specifications. The impossibility of any published public document providing the last word in total specifications of a drug substance and its dosage form.The compendium and the compendium process and its weaknesses. The fact that it is still a viable system and that alternatives such as those suggested by the OTA Panel bring with them many, many more inherent weaknesses with no guarantee that there would be an improvement in drug quality and specifications.Suggestions to strengthen the compendium process.“As the World Turns” is a very popular daily TV soap opera. Like most soap operas, it depicts the problems of its leading characters and the efforts that are made to solve their problems and arrive at their Utopia. Thus I thought it most appropriate to entitle this presentation “As the Pharmaceutical World Turns” for we here are trying to solve our problems and arrive at our Utopia. As the Pharmaceutical World Turns, specifications, the “Guiding...

We discuss here the complexity of the doses of traditional Chinese medicine (TCM) prescriptions and herbs from different viewpoints, including the heterogeneity of drug quality, the flexibility of prescriptions, and the diversity of drug effects. Then, the corresponding research ideas and strategies are proposed. We can reveal the actual situation of clinical doses based on in-depth “real-world study” of the safety and effectiveness of TCM prescriptions, create an analytical method for dose-effect relationships in accordance with the features of TCM, and reveal the correlated regular nature of the effectiveness and dosage of TCM prescriptions and herbs.

The radioprotection afforded normal tissues by WR-2721 or S-213-aminopropylamino]ethylphosphorothioic acid varies widely, with some of the most responsive tissues showing low levels of absorbed drug and vice versa. While the oxygen tension of the respective tissues may be contributing to this variation, it can be shown that the drug is not homogeneously distributed within each tissue, and that its location within the sub-cellular compartments can vary widely. Recognition of this variability, when combined with the newly developed HPLC assays for drug quality, should provide new insights into the sources of variation in normal tissue responsiveness to these agents.

Considerations about differences in bioavailability between brand-name drugs and generic formulations of these agents are discussed as are the meaning of drug quality, the national regulatory situation concerning generic substitution, and state-to-state variations in product selection laws. Actual and potential problems with generic substitution are described with regard to current and future prescribing practices. Proposed regulations permitting or mandating substitution of generic alternatives and therapeutic substitutes are mentioned. Although there is no consensus on the proper use of generic drugs, physicians should be aware of potential differences in bioavailability and therapeutic effectiveness that may arise when one drug product is substituted for another. Such differences are of particular concern for certain therapeutic categories such as psychotropic, cardiovascular, and endocrine/metabolic drugs, as well as for special population groups, such as the elderly, infants, and children. If physicians are to prescribe in an optimal manner, they should be knowledgeable about the bioavailability of different drug products and the national and state laws addressing substitution. Generic substitution is linked to current and future policy changes in the area of therapeutic substitution.

How the Bureau of Drugs laboratories and offices obtain chemical data from the scientific literature, from user complaints and product defect reporting systems, from the drug manufacturers, from analyses of drug samples collected from the market, and from analytical research are described. The chemical data thus educed have been used successfully in developing new analytical methods, in establishing better specifications of drug quality, in removing adulterated drugs from the marketplace, in successfully prosecuting purveyors of substandard drugs, and in general assuring that consumers are provided with safe and effective drugs of high quality. Language: en

This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (

Where regulation is weak, medicine transactions can be characterised by uncertainty over the drug quality and efficacy, with buyers shouldering the greater burden of risk in exchanges that are typically asymmetric. Drawing on in-depth interviews (N = 220) and observations of medicine transactions, plus interviews with regulators (N = 20), we explore how people in Ghana negotiate this uncertainty and come to trust a medicine enough to purchase or ingest it. We identify two mechanisms – attempts to mitigate uncertainty through seeking observable signs of quality and attempts to reduce informational asymmetry – that underpin cognitive assessments of a medicine's trustworthiness. However, these ‘cognitive’ forms of trust assessment have limited traction where uncertainty is high and trustworthiness remains unknowable, so a third mechanism comes into play: one based on affective relationships within which transactions are socially embedded. Even these, however, cannot eliminate uncertainty, because of the dispersed and under-regulated nature of wider supply chains. In conclusion, we reflect on the need for careful research on actors' practices and decision-making across supply chains to inform more effective policy and regulation.

Objective: Recently the Laboratory of Dutch Pharmacists (LNA) published a guideline (LNA-procedure P01-2) to assess the pharmacotherapeutic rationale of pharmacy-compounded products. We evaluated this procedure and we investigated the rationale of a representative part of standardised products compounded in our hospital pharmacy. GMP requirements increase the cost of compounding. As a consequence, although every patient should have access to high-quality pharmacy-compounded products through his own pharmacist, it is not feasible to operate a compounding activity in each community pharmacy. Although pharmacy-to-pharmacy distribution of compounded products is forbidden within Dutch law, the Healthcare Inspectorate accepts this if three additional requirements are met. One of these requirements is a product file containing the documented pharmacotherapeutic rationale of the compounded product. Design and methods: LNA-procedure P01-2 was evaluated and adjusted. The primary criteria were simplified and the secondary criteria were reduced from 5 to 2 without loss of information. The adjusted procedure was used to review the rationale of the selected products. Results: 34 products with 36 indications were reviewed. All products except one were classified as effective and safe. For 16 products there was no registered equivalent available in the Netherlands. 14 products had a specific advantage over registered products, for example formulations for children. Conclusion: The LNA guideline procedure to standardise assessment of the pharmacotherapeutic rationale of pharmacy-compounded products is, with a few adjustments, suitable in daily practice. The added value of pharmacy-compounded products is partially based on the lack of registered products and partially on dosage forms that are better attuned to their intended use.

Background Substandard and falsified anti-malarial medicines pose a serious threat to public health, especially in low-income countries. Appropriate technologies for drug quality analysis in resource-limited settings are important for the surveillance of the formal and informal drug market. The feasibility of thin-layer chromatography (TLC) with different solvent systems was tested using the GPHF Minilab in a study of the quality of sulfadoxine/pyrimethamine tablets in Malawi. Methods Twenty eight samples of sulfadoxine/pyrimethamine tablets were collected from randomly selected health facilities of four districts of southern Malawi. A mystery shopper approach was used when collecting samples from illegal street vendors, and an overt approach for the other facilities. Samples were subjected to visual inspection, disintegration testing and TLC analysis. 10 samples were further investigated according to the methods of the US Pharmacopeia using high performance liquid chromatography (HPLC). Results One sample was found to be falsified, containing a mixture of paracetamol tablets and co-trimoxazole tablets. These had been repackaged into paper strip packs labelled as a brand of sulfadoxine/pyrimethamine. TLC with different solvent systems readily proved that these tablets did not comply with their declaration, and provided strong evidence for the active pharmaceutical ingredients which were actually contained. Full pharmacopeial analysis by HPLC confirmed the results suggested by TLC for this sample, and showed two further samples to be of substandard quality. Conclusions Due to the absence of the declared anti-malarial ingredients and due to the presence of other pharmaceutical ingredients, the identified falsified medicine represents a serious health risk for the population. Thin-layer chromatography (TLC) using different solvent systems proved to be a powerful method for the identification of this type of counterfeiting, presenting a simple and affordable technology for use in resource-limited settings.

To the Editor.— Jacobson and coworkers (243:733, 1980) recently presented their experience on the nonequality of two thyroxine preparations. They demonstrated that the 100-μg tablets from Letter and Synthroid were physiologically nonbioequivalent and therefore should not be dispensed interchangeably. We sympathize with their observations from a drug quality viewpoint. The nonequivalence of various thyroxine preparations may stem from the fact that different firms are using raw material (levothyroxine sodium) of different particle size during the manufacturing process. Because of the low solubility of levothyroxine sodium, some firms are employing micronization techniques to enhance solubility, whereas others are using raw material with larger particle size that complies with the requirements of the United States Pharmacopeia . These differences may appear to be minor in nature; however, in this product they have a significant effect on the bioavailability of the active material. The current USP recognizes the effect of particle size on bioavailability

Excerpt Controversy about the relative merits of brand-name and generic prescription is nothing new. For years advocates of generic prescription have argued that generic drugs are cheaper than bran...

Background Two major cities in West Africa, Accra, the capital of Ghana, and Lagos, the largest city of Nigeria, have significant problems with substandard pharmaceuticals. Both have actively combated the problem in recent years, particularly by screening products on the market using the Global Pharma Health Fund e.V. Minilab® protocol. Random sampling of medicines from the two cities at least twice over the past 30 months allows a tentative assessment of whether improvements in drug quality have occurred. Since intelligence provided by investigators indicates that some counterfeit producers may be adapting products to pass Minilab tests, the results are compared with those from a Raman spectrometer and discrepancies are discussed. Methods Between mid-2007 and early-2010, samples of anti-malarial drugs were bought covertly from pharmacies in Lagos on three different occasions (October 2007, December 2008, February 2010), and from pharmacies in Accra on two different occasions (October 2007, February 2010). All samples were tested using the Minilab® protocol, which includes disintegration and active ingredient assays as well as visual inspection, and most samples were also tested by Raman spectrometry. Results In Lagos, the failure rate in the 2010 sampling fell to 29% of the 2007 finding using the Minilab® protocol, 53% using Raman spectrometry, and 46% using visual inspection. In Accra, the failure rate in the 2010 sampling fell to 54% of the 2007 finding using the Minilab® protocol, 72% using Raman spectrometry, and 90% using visual inspection. Conclusions The evidence presented shows that drug quality is probably improving in both cities, especially Lagos, since major reductions of failure rates over time occur with all means of assessment. Many more samples failed when examined by Raman spectrometry than by Minilab® protocol. The discrepancy is most likely caused by the two techniques measuring different aspects of the medication and hence the discrepancy may be the natural variation in these techniques. But other explanations are possible and are discussed.

Background The quality and stability of anti-malarial drugs in the Global South has long been of significant concern. Drug quality can be affected by poor or fraudulent manufacturing processes, while drug stability is affected by temperature and humidity. Knowledge of drug quality and stability is often the unique contribution of pharmacists volunteering on short-term medical mission trips. Objective To determine the quality and stability of artemether-lumefantrine 20/120 mg under ambient storage conditions in rural Mali. Methods One unopened blister pack of artemether-lumefantrine 20/120 mg (IPCA Laboratories, Mumbai) was stored under ambient conditions in a warehouse in a Malian village for one year. A second pack from the same lot number was stored under temperature and humidity controlled conditions in a university laboratory. The active ingredients of tablets from both packages were analysed using thin layer chromatography, nuclear magnetic resonance and infrared spectroscopy. The IPCA samples were referenced for drug identity and content to an identical American made product (Coartem ®, Novartis Pharmaceuticals). Results Thin layer chromatographs, nuclear magnetic resonance and infrared spectroscopy results were identical for both IPCA samples and the reference product. Conclusions The IPCA products contained the same drugs in the same amount as on their package label and were identical to the reference product. It is concluded that they were of good quality. Spectroscopy results demonstrate the sample stored in Mali was stable for one year. Pharmacists volunteering on medical mission trips may dispense this product with confidence. At the end of a mission trip, pharmacists may store left over artemether-lumefantrine under ambient conditions for up to one year without concern for significant degradation of the active ingredients.