A review about industrialization of Chinese materia medica decoction pieces.

Chinese materia medica decoction pieces (CMMDPs), one of the three pillars of the Chinese materia medica industry, are a key link in the Chinese materia medica industrial chain. Industrialization is the only way for the modernization of CMMDPs. This review mainly summarizes the characteristics, history, current situation and prospect of CMMDPs industry, providing a new reference for promoting the flourishing development of the industrialization of CMMDPs and for serving massive health industry. The literature was collected from databases including Web of Science, PubMed, Elsevier and CNKI (Chinese). CMMDPs industry has the characteristics of regionalism, resource dependency, customer diversity and low industrial concentration. Deeply processed products include traditional Chinese medicine (TCM) formula granules, small-packed decoction pieces, ultrafine decoction pieces, puffed decoction pieces, compressed decoction pieces and instant decoction pieces. Integration of treatment and processing at the place of origin is emerging. However, there is still room for improvement, for example, the manufacturing technologies of CMMDPs industry need to be continually improved. The management of CMMDPs' normalized production also needs to be strengthened. The quality of CMMDPs should be strengthened supervision and it should establish the objective and feasible quality evaluation system for CMMDPs. At present, China has attached unprecedented importance to the development of TCM, and issued a number of supporting policies, sparing no effort to support its development.

Introducing the Alba® Primary Packaging Platform. Part 2: Inorganic Extractables Evaluation.

Sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failure as worst-case scenario.This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, substances coming from the production process, or silicone oil droplets or other particles.The Alba primary packaging platform was designed to have the same interface between the drug and the glass container surface on the different primary packaging containers in order to minimize the emergence of instabilities at later stages of formulation development. Alba containers are internally treated with an innovative cross-linked coating based on silicone oil lubricant, and the additional rubber components have been selected to minimize the possible differences between the container typologies.This paper shows in great detail the reduction of the inorganic extractables released and the comparability of the performances of the different containers obtained using Alba technology.The improvement has been demonstrated by stressing the containers with different extract solutions; Alba-coated containers show a strong reduction of inorganic extractables and of corrosion degree compared to spray-on siliconized and bulk products. The containers included in the Alba platform present comparable results, and this represents a strong advantage during the drug formulation development by facilitating the transition from one container to another.LAY ABSTRACT: The sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failure worst-case scenario.This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, substances coming from the production process, or silicone oil droplets or other particles.The Alba primary packaging platform was designed to minimize these problems associated with the interaction between the drug and its primary packaging. This paper shows in great detail and with robust data the inorganic extractables release reduction and the delamination risk mitigation obtained using the Alba technology.

Comparing Physical Container Closure Integrity Test Methods and Artificial Leak Methodologies.

The sterility of drug products intended for parenteral administration is a critical quality attribute (CQA) because it serves to ensure patient safety and is thus a key requirement by health authorities. While sterility testing is a probabilistic test, the assurance of sterility is a holistic concept including adequate design of manufacturing facilities, process performance, and product design. Container closure integrity testing (CCIT) is necessary to confirm the integrity of a container closure system (CCS), until the end of a product's shelf life. The new and revised United States Pharmacopeia (USP) General Chapter <1207> is a comprehensive guidance on CCI. Nevertheless, practical considerations including the choice of CCIT methods, the acceptance criteria, or the positive control samples (artificial leaks) must be addressed by the pharmaceutical manufacturer.This study is the first to provide a systematic comparison of four commonly used physical CCIT (pCCIT) methods [Helium (He) leak, vacuum decay, laser-based headspace analysis (HSA), and dye ingress] and four commonly used modes of creating artificial leaks (laser-drilled micro holes, copper wire introduced leaks, and two types of capillary leaks).The results from these experiments provide comprehensive data to allow a direct comparison of the capabilities of the individual methods. The results confirmed that the He leak detection method, which is considered the "gold-standard" for pCCIT regarding method sensitivity, indeed demonstrates the highest detection sensitivity (lowest detection limit). In comparison to the dye ingress method, HSA and vacuum decay also demonstrated better detection sensitivity in our study.Capillary leaks with orifice diameter (capillary leak with flow according to an ideal orifice) and micro holes yielded similar leak rates, whereas capillaries with nominal diameters yielded significantly lower leak rates. In conclusion, method sensitivity cannot be compared by means of a leak diameter, but requires the consideration of multiple impacting factors (e.g., path length, uniformity).LAY ABSTRACT: Sterility of drug products intended for parenteral administration is a critical quality attribute to ensure patient's safety and is thus a key requirement by health authorities. The absence of microbial contamination must be demonstrated by container closure integrity (CCI) of the container closure system (CCS). Currently, the revised United States Pharmacopeia (USP) General Chapter <1207> provides the most extensive guidance on how CCI should be assessed. Nevertheless, practical considerations on the choice of an appropriate CCIT method, artificial leaks or the choice of an acceptance criteria are lacking and must be addressed by the pharmaceutical manufacturer.This study provides a systematic comparison of four commonly used physical CCIT (pCCIT) methods [Helium (He) leak, vacuum decay, laser-based headspace analysis (HSA) and dye ingress] and four commonly used modes of creating artificial leaks (laser-drilled micro holes, copper wire introduced leaks, and two types of capillary leaks).

Holistic Considerations in Optimizing a Sterile Product Package to Ensure Container Closure Integrity.

A new major chapter dealing with container closure integrity was released by the United States Pharmacopeial Convention. Chapter <1207> provides a significant amount of education and guidance concerning test methodologies to prove that a system is integral and safe for use. The test method used is only one of the major considerations in approaching the challenge of proving an integral system. This paper takes a holistic review of all the major considerations needed in qualifying a new vial system for container closure integrity. There is substantial interplay among many aspects in the process of sealing a vial. This review helps to define major risks that need to be considered and mitigated and reinforces the need to understand the maximum allowable leakage limit that is acceptable for a specific drug application. A typical risk-based approach considers materials, test methods, process, people, environment, and equipment. Each of these aspects is considered in some detail along with a recommended process flow for building a best practice, science-based approach. This approach will inform decision making for evaluating the correct combination of components and assuring they are assembled and tested in an appropriate manner. This work, once completed, can be the basis for a vial system platform or specific drug application qualification.LAY ABSTRACT: Container closure integrity is a fundamental requirement of every sterile drug package. With recent upgrading of compendia standards and guidance around this issue, there is an opportunity to better define a best practice approach to a complicated subject. It is important to recognize that there is substantial interplay among the components of the system, the process of assembly, and the test methods that are used. This paper takes a holistic approach to discussing these issues and identifying the risks that must be considered in assuring an integral container over the shelf life of a drug product.

The importance of vial composition in HPLC analysis: An unusual case of phosphorous pseudorotation.

Glass HPLC vials are ubiquitous in analytical laboratories and vendors have developed many varieties to meet the various needs of scientists. As such there may be multiple types of vials being used simultaneously in a single laboratory without much consideration as to which is best suited for analytical method development and validation. This study highlights the possibility of vial composition as a potential factor that impacts solution stability. Here we describe a case where the type of HPLC vial used results in an interesting phosphorous pseudorotation driven by the mild alkalinity of glass.

[Suggestions to strengthen quality management of herbal decoction pieces--based on production chain of herbal decoction pieces].

With the development of society and the improvement of people's living standards, the effect of Chinese medicine in treatment and health care is more and more prominent. The herbal decoction pieces are the important part of Chinese medicine,it can be applied directly to clinical treatment and it's also the raw material of Chinese patent medicine. Therefore, the quality of herbal decoction pieces is quite important. The parts of the production of herbal decoction pieces are numerous, and there are possibilities of adverse effects on the quality of the herbal decoction pieces in every part. In this paper, we based on the production chain of herbal decoction pieces, analyzed the main problem that affect the quality of herbal decoction pieces in the part of selection of Chinese herbal medicines, planting, purchasing, processing, packaging, storage and transport, such as the poor quality of seed and seedlings of plant-based Chinese medicines, some plants left their place of origin and have been introduced in the place that is not suitable for this kind of plant, the insufficient growth time and the excessive harmful substances. The purchasers and the accepters lack of professional knowledge and professional ethics. The mechanism of processing is not clear, the standards can not be uniformed, and lack of qualified person in processing, etc. So we suggest: intensify the basic research of key scientific issues. Improve the quality of persons who work in herbal decoction pieces; Establish an "integration" mode of operation in herbal decoction pieces enterprise; Breeding high quality plant resources, establish the large-scale planting basement; Make the packing of herbal decoction pieces standard; Establish the modernization traditional Chinese medicine logistics enterprise.

[To accelerate pace of studying standard pieces of Chinese medicine as standard material].

OBJECTIVE: To elucidate the necessary and research of accelerating basic research of Chinese standard pieces as standard materials. METHOD: According to over 10 years accumulated experience and be keenly aware of the author, the evaluation method of standardized processing technology and Chinese pieces quality, aimed at consummated the standard material of the quality evaluation of Chinese herbal pieces at the current situation, and inaccordance with the need of improving quality standard system of Chinese herbal pieces, illustrate the necessity of accelerating basic research of Chinese standard pieces as standard materials; from the technical specification for collecting and processing of raw materials, and the technical specification, homogenized sample, packaging, storage and etc., for processing of candidate standard pieces, determine the methods and steps of technical specifications for standard pieces as the standard substance, determine the methods and steps of technical specifications for standard pieces as the standard substance. RESULT AND CONCLUSION: To speed up the basic research of standard of Chinese medicine pieces as of standard material is very necessary. The research objective is to specificate the processing technical for a number of standard pieces, to identify technical specifications and to ascertain the guiding principle and technical specification of decoction pieces as standard substance. This research will provide basic scientific data relevant national departments to apply for the accreditation of the standard substance.

Increasing the reliability of production schedules in a pharmaceutical packaging department.

This paper studies quantitative methods for evaluating the potential benefits of introducing new advanced tracking technologies in the pharmaceutical industry with special reference to radio frequency identification (RFID). RFID technology is an effective way for increasing the quality of the data that are used to generate production schedules, but there is a lack of scientific research to quantify the return on investment that can be achieved in practice. In this work, we distinguish two major sources of data unreliability: one is the inherent stochasticity of operations, which cannot be reduced by RFID, and the other one is the data estimation error, which can be significantly reduced by RFID. We focus on the marginal contribution of the latter quantity to the productivity of the packaging department of a pharmaceutical plant, propose a systematic method for assessing this impact and discuss its implementation in a practical test case. Our results confirm that advanced tracking technologies in combination with effective scheduling procedures show a significant potential for improving productivity. Extensions to other production environments and their issues associated with scheduling problems are also discussed.

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model.

BACKGROUND: Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. METHODS: We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. RESULTS: Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. CONCLUSIONS: The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child.

Placebo preparation for the proper clinical trial of herbal medicine--requirements, verification and quality control.

Randomized controlled trials (RCT) have been recognized as the gold standard for interventional clinical trials. In many clinical trials of herbal medicine, it is very difficult to create a quality placebo. To achieve the purpose of blinding, the characteristics of the real drug and placebo should be identical in color, appearance, smell and taste. The quality placebo should be identical to the real drug in physical form, sensory perception, packaging, and labeling, and it should have no pharmaceutical activity. The aim of this study was to evaluate a placebo capsule and its matching herbal medicine D&G capsule in physical form, chemical nature, appearance, packaging and labeling. The assessment results suggested that the placebo was satisfactory in these aspects. The results demonstrated that a placebo could be created for a RCT involving herbal medicine. This report also discusses the means to acquire patent.

Can bottle design prevent bacterial contamination of nasal irrigation devices?

BACKGROUND: Saline nasal irrigation is a mainstay in the medical management of chronic rhinosinusitis (CRS) with proven efficacy. However, bacterial contamination of irrigation bottles has recently been reported and this may contribute to recurrent infections. Sterilization is effective but could a change in bottle design obviate the need for regular sterilization? METHODS: A total of 20 stable CRS patients were given a NasalCare® (Techworld Corporation, Inc., Downington, PA) irrigation bottle to use regularly for 1 week. This bottle incorporates a 1-way valve to prevent irrigant regurgitation. Swabs were taken from their sinonasal cavity and 3 sites on the bottle-nozzle, valve, and inner surface. RESULTS: This study cultured a range of organisms from all sites of the bottle, including common CRS pathogens such as S. aureus, P. aeruginosa, and E. coli. Whereas the bottle's inner surface had the lowest bacterial recovery rate, the frequent culture of organisms at this site suggests a 1-way valve cannot completely prevent irrigant reflux. The high rate of organism detection at the nozzle and valve of the bottle is concerning, as bacteria at these sites may be transported to the nose during nasal douching. CONCLUSION: Saline irrigation will continue to be an essential component of CRS management. However, despite employing a 1-way liquid valve in this study, nasal irrigation bottles can still become contaminated with bacteria. Thus, patient education, irrespective of bottle design, will be essential in preventing bacterial contamination of nasal irrigation devices. The results of our survey suggest this message is not getting across to our patients.

On developing a process for conducting extractable-leachable assessment of components used for storage of biopharmaceuticals.

Extractables and leachables are product-related impurities that result from product contact with components such as gaskets, stoppers, storage bags, cartridges, and prefilled syringes that are used for processing, storage, and/or delivery of biopharmaceuticals. These impurities are a concern for patients due to potential effects on product quality and safety. It is possible that such an impurity could directly impact the patient or indirectly impact the patient by interacting with the protein therapeutics and forming protein adducts. Adducts and leachables may or may not be detected as product-related impurities in routine stability indicating assays depending on the rigor of the analytical program. The need for the development of a thorough and holistic extractable and leachable program based on risk assessment, review of existing literature, and consolidation of industry best practices is discussed. Standardizing component use within an organization enables streamlining of the extractable-leachable program. Our strategy for an extractable-leachable program is divided into different stages, each stage detailing the activities and the department within the organization that is responsible for execution of these activities. The roles and responsibilities of the key stakeholders are identified. The integration of analytical activities with health-based risk-assessment information into the design of an extractable-leachable program is highlighted.

[A comparative analysis of inner wrapping and package inserts for medicines containing Panax ginseng C. A. Meyer]. / Análise comparativa de embalagens secundárias e bulas de medicamentos contendo Panax ginseng C. A. Meyer.

The information provided on package inserts and inner wrapping of eight products containing Panax ginseng from different manufacturers was compared internally and checked against data from the scientific literature. The inserts included extensive text, containing abundant information on indications for use, but no scientific evidence in humans. All the inserts lacked information on potential adverse effects and drug interaction. There was no standardization as to dose regimens, particularly in relation to the dried extract and ginsenoside concentration. The eight inserts thus showed no concern over standardization, indication for usage, or possible side effects and drug interactions.

Proposed rule: current good manufacturing practice in manufacturing, packing, or holding dietary ingredients and dietary supplements.

The Dietary Supplement Health and Education Act (DSHEA) was enacted in October 1994 to promote the health of Americans by ensuring easier access to safe dietary supplements. Many supplements such as vitamins, minerals, herbs and amino acids have been reported to be helpful in chronic conditions (i.e., heart disease, cancer and osteoporosis). Under DSHEA, dietary supplements can be marketed without prior FDA approval; the burden is on this agency to show that a marketed dietary supplement is unsafe. However, DSHEA retained the FDA's authority to issue regulations that require the manufacture of dietary supplements be in compliance with current good manufacturing practice (cGMP) standards, which are needed to ensure their quality. Several quality-related concerns of marketed dietary supplements that came to light since the passage of DSHEA prompted the FDA in 2003 to propose rules for cGMP for the manufacture, packaging and holding (storage) of dietary supplements. This review will present the highlights of these proposed rules, focusing on the legislative history of DSHEA, rationale for proposing cGMPs along with a general discussion of the specific requirements. Given the voluminous nature of the specific details, the reader is directed to the pertinent FDA publications for details. In this analysis, selected scientific and legal issues are also discussed to promote a better understanding and implications of these rules.