Pharmaceutical Manufacturing Unit Research Articles

Impact of autoclavation on baked-on siliconized containers for biologics

Many pharmaceutical manufacturing units utilize pre-sterilized ready-to fill primary containers for parenterals. The containers may have been sterilized by the supplier via autoclavation. This process can change the physicochemical properties of the material and the subsequent product stability. We studied the impact of autoclavation on baked on siliconized glass containers for biopharmaceuticals. We characterized the container layers of different thickness before and after autoclavation for 15 min at 121 °C and 130 °C. Furthermore, we analyzed the adsorption of a mAb to the silicone layer and subjected filled containers to 12 weeks storage at 40 °C monitoring functionality and subvisible particle formation of the product. Autoclavation turned the initially homogenous silicone coating into an incoherent surface with uneven microstructure, changed surface roughness and energy, and increased protein adsorption. The effect was more pronounced at higher sterilization temperatures. We did not observe an effect of autoclavation on stability. Our results did not indicate any concerns for autoclavation at 121 °C for safety and stability of drug/device combination products using baked-on siliconized glass containers.

Comparison of three automated compounding devices for parenteral nutrition according to four key technical tests

ObjectivesAutomation of parenteral nutrition (PN) preparation is nowadays a recommended practice in order to reduce human errors and thus improve the safety and accuracy of the finished product. Other benefits...

A COMPREHENSIVE REVIEW ON COMPARISON OF GDOCP IN PHARMACEUTICAL MANUFACTURING UNIT AS PER EUROPEAN AND WHO GUIDELINES

To review the good documentation practices in the pharmaceutical industry as per the guidelines provided in the European Commission and WHO (World Health Organisation). GDocP is a systematic method of planning, evaluating, approving, issuing, documenting, preserving, and archiving records. GDocP is a must when operating in an atmosphere of existing GMP. To provide an overview of good documentation practices for those employed in the pharmaceutical and healthcare sectors. The GDocP stands for good documentation practice which can be described as an integral part of quality assurance (QA) and thus related to all aspects of GMP. There are very few articles related to the comparison of GDocP in the pharmaceutical manufacturing unit as per European and WHO guidelines hence we are trying to develop a study on the comparison of GDocP guidelines. Public and private organizations, institutions, and regulatory authorities working and cooperating and with the pharmaceutical industry are involved at the international and national level to reach a consensus on the guidelines and laws for the production of medicinal products for human. This article explains how these participants work and cooperate and set out current regulations along the lines of the European community and WHO referencing, where appropriate, the practiced guidelines, outside space regulatory action referred to above. In this way, the goal is to achieve exceptional standards of quality, protection, and efficacy in the manufacture of health products.

Supply Chain Performance in the era of Digitisation: The role of Electronic Supply Chain Management

The advancements in information technology have enabled the supply chain members to share real-time information, which further facilitates the integration of supply chain members. Since supply chain integration is a prerequisite in achieving superior supply chain performance, the objective of the current study is to determine the relationship between IT-enabled supply chain management (e-supply chain management), supply chain integration, information sharing and the performance of supply chain as a whole. Also, many authors are of the view that e-SCM and information sharing can positively enhance the integration among supply chain members, thus, another objective is to determine whether supply chain integration mediates the relationship between e-SCM and supply chain performance or not. Similar relationship is tested with information sharing as a mediator. For this, samples of 293 respondents are taken from the pharmaceutical manufacturing units and pharmacies in India. Structural equation modelling is applied to test these relationships.

Segmentation Strategies:Empirical Evidences from Pharmaceutical Companies

The Indian Pharmaceutical sector is highly fragmented with more than 20, 000 registered units. The organized sector of India's pharmaceutical industry consists of 250 to 300 companies, which account for 70 percent of products on the market, with the top 10 firms representing 30 percent. Multinationals represent only 35% of the market, down from 70% thirty years ago. Because of differences in the industry structure and combination of market opportunities for domestic companies and multinationals, they are likely to differ on strategic issues. Hence domestic companies and multinational firms need to pursue different strategies to achieve desired goals. The study covers pharmaceutical companies operating in Madhya Pradesh state of India. The data or information required is related to segmentation strategies adopted by these pharmaceutical companies. The participants are selected from the directory of pharmaceutical manufacturing units in India, published by national pharmaceutical pricing authority. ANOVA is used for testing of hypothesis. The results show that there are visible differences in the segmentation strategies followed by different pharmaceutical companies of Madhya Pradesh. Small & medium domestic pharmaceutical companies have very little inclination towards segmentation strategies. MNCs and large domestic pharmaceutical organizations in Madhya Pradesh are following the segmentation strategies but this is also limited to demographic and geographic segmentation mostly. They also follow integrated segmentation strategies to some extent.

Hybrid coagulation, gamma irradiation and biological treatment of real pharmaceutical wastewater

The present study aimed towards the utilization of hybrid approaches for the effective treatment of real pharmaceutical industry wastewater. The focus was to treat pharmaceutical wastewater with low (LSW) and high organic strength (HSW), which was collected from the effluent treatment plant of the representative bulk pharmaceutical manufacturing unit. The hybrid approach included coagulation treatment, biological treatment and gamma irradiation which were employed individually and in sequence to determine the most appropriate treatment sequence for effective remediation of real pharmaceutical wastewater. To compare process performance, gamma-irradiation was employed as pre-treatment and post-treatment stage to biological treatment. To achieve the enhanced removal efficiency using gamma irradiation treatment, oxidant like H2O2 and persulfate ions S2O82- were used and optimized for LSW and HSW. Results indicated that use of H2O2 lead to enhanced COD and TOC removal efficiency when compared to S2O82-. The sequential approach of coagulation, gamma irradiation and biological treatment accounts for the synergistic degradation and detoxification of recalcitrant pharmaceutical wastewaters, and lead to overall 92.7% ± 2.3% and 90.2% ± 2.9% of COD removal of LSW and HSW, respectively. The pre-treatment using gamma-irradiation enabled effective treatment, achieving 58.7% ± 3.2% COD and 80.4% ± 2.1% TOC removal efficiencies for LSW; whereas 62.0% ± 2.9% COD and 71.0% ± 2.7% TOC removal efficiencies were achieved for HSW. Cytotoxicity assessment and cost analysis of the treatment process were examined and analyzed.

Review on Good Documentation practice in pharmaceutical manufacturing unit as per European Union GMP Chapter-4 on Documentation

Good documentation constitutes an essential part of the quality assurance system and is key to operating in compliance with GMP requirements. Documentation requirements of maintaining complete, accurate, truthful and verifiable data in all cGXP documents that are needed to be maintained as per regulatory requirements and various Governmental regulations, laws, rules and statutes/acts. Documentation may exist in a variety of forms, including paper-based, electronic or photographic media. Ensure that the Document should be free from error and during any point if error identify then rectify with proper reason for correcting including sign and date. A system should be in place to indicate special observations and any changes to critical data. GMP Document must have predefined retention period and document must be stored in secure and easy to retrieve or easily available as and when required. Batch Processing and Packaging Instruction must be in place and Contemporaneous entry provision must be available. Instruction and procedure for using equipment; instrument must be clear and specific. Specification with authorization should be available for analysis of Raw Material and Packing Material, Intermediate and Bulk Product, Finished Product.

Toward the Drug Factory Microbiome: Microbial Community Variations in Antibiotic-Producing Clean Rooms

Microbiome projects are currently booming around the globe, enabled by advances in culture-independent microbial community analysis and high-throughput sequencing. One emerging application of microbiome science involves exploring microbial diversity in built environments, and one unexplored built environment is the pharmaceutical factory, notably factories producing antibiotics, as they could be enriched in antibiotic-resistant microbes. To examine the drug factory microbiome, we launched this interdisciplinary hypothesis-generating study to benchmark culture-independent microbiome analysis in drug manufacturing units producing antibiotics and nonantibiotic drugs, against traditional microbial identification and quantification techniques. Over a course of 4 months, we prospectively collected 234 samples from antibiotic (kanamycin and amoxicillin) and nonantibiotic (acetaminophen) production clean rooms within a pharmaceutical factory in Egypt. All samples were analyzed by traditional culture-based methods, and microbial communities of representative samples were profiled by16S rRNA gene sequencing. In addition, antibiotic resistance profiles of some samples were determined, and representative resistance genes were screened. The 16S rRNA analysis revealed a typical predominance of Proteobacteria (36%), Firmicutes (31%), and Bacteroidetes (16%). The microbial composition of the samples was highly affected by the use of water, environmental conditions during the production process, the presence of personnel, and the type of the product. The effect of these factors was confirmed by total aerobic microbial counts and identification of biomarker microbes. In conclusion, these observations can aid in the future for optimal design and management of pharmaceutical manufacturing units, and speak to a greater need for implementing microbiome research in the quality assurance of built environments.

Commentary on Reconstituting Fibrinogen Concentrate to Maintain Blinding in a Double-blind, Randomized Trial in an Emergency Setting

BackgroundThe gold standard of trial design is the double-blind, placebo-controlled, randomized trial. Intravenous medication, which needs reconstitution by the attending clinician in an emergency situation, can be challenging to incorporate into a suitably blinded study. DiscussionWe have developed a method of blindly reconstituting and administering fibrinogen concentrate (presented as a lyophilized powder), where the placebo is normal saline. Fibrinogen concentrate is increasingly being used early in the treatment of major hemorrhage. Our methodology was designed for a multicenter study investigating the role of fibrinogen concentrate in the treatment of the coagulopathy associated with major obstetric hemorrhage. The method has been verified by a stand-alone pharmaceutical manufacturing unit with an investigational medicinal products license, and to date has successfully been applied 45 times in four study centers. There have been no difficulties in reconstitution and no related adverse events reported. ConclusionWe feel our method is simple to perform and maintains blinding throughout, making it potentially suitable for use in other trials conducted in psychologically high-pressure environments. Although fibrinogen concentrate was the focus of our study, it is likely that the method is applicable to other lyophilized medication with limited shelf life (e.g., antibiotics).

Pharmaceutical Industry: Key Issues in Growth in Pakistan & International Market

Pakistan has a very vibrant and forward-looking Pharma Industry. At the time of independence in 1947, there was hardly any pharma industry in the country. Today Pakistan has about 400 pharmaceutical manufacturing units including those operated by 25 multinationals present in the country. The Pakistan Pharmaceutical Industry meets around 70% of the country's demand of Finished Medicine. The domestic pharma market, in term of share market is almost evenly divided between the Nationals and the Multinationals (Ahmed & Saeed, 2012).The National pharma industry has shown a progressive growth over the years, particularly over the last one decade. The industry has invested substantially to upgrade itself in the last few years and today the majority industry is following Good Manufacturing Practices (GMP), in accordance with the domestic as well as international Guidance. Currently the industry has the capacity to manufacture a variety of product ranging from simple pills to sophisticated Biotech, Oncology and Value Added Generic compounds (Aamir & Zaman, 2011).Although Pakistan 's pharmaceutical and healthcare sectors are expanding and evolving rapidly, about half the population has no access to modern medicines. Clearly this presents an opportunity, but much more work needs to be done by the government and industry's stakeholders. The value of pharmaceuticals sold in 2007 exceeded US$1.4bn, which equates to per capita consumption of less than US$10 per year and value of medicines sold is expected to exceed US$2.3 B by 2012 (Ahmed et al., 2011).

Designed Blending for Near Infrared Calibration

Spectroscopic methods are increasingly used for monitoring pharmaceutical manufacturing unit operations that involve powder handling and processing. With that regard, chemometric models are required to interpret the obtained spectra. There are many ways to prepare artificial powder blend samples used in a chemometric model for predicting the chemical content. Basically, an infinite number of possible concentration levels exist in terms of the individual components. In our study, design of experiments for ternary mixtures was used to establish a suitable number of blend compositions that represents the entire mixture region of interest for a three component blend. Various experimental designs and their effect on the predictive power of a chemometric model for near infrared spectra were investigated. It was determined that a particular choice of experimental design could change the predictive power of a model, even with the same number of calibration experiments.

A Study of Pharmaceuticals in India and Kashmir Aspect

The Indian pharmaceutical industry positions among the top five countries by volume (production) and accounts for about 10% of worldwide production. The industry?s gross revenue has grown from a simple US$ 0.3 bn in 1980 to about US$ 21.73 billion in 2009-10. Stumpy cost of skilled manpower and innovation are some of the major factors taking sides of this growth. According to the Department of Pharmaceuticals, the Indian pharmaceutical industry employs about 340,000 people and an approximate 400,000 doctors and 300,000 chemists. The Indian pharmaceutical industry is disjointed with more than 10,000 manufacturers in the controlled and unplanned segments. The products manufactured by the Indian pharmaceutical industry can be generally classified into bulk drugs (active pharmaceutical ingredients - API) and formulations. Of the total number of pharmaceutical manufacturers, about 77% make formulations, while the remaining 23% make up bulk drugs. Bulk drug is an active constituent with medicinal properties, which acts as fundamental raw material for formulations. Formulations are precise dosage forms of a bulk drug or a mixture of bulk drugs. Drugs are available as syrups, injections, tablets and capsules. Based on the pharmaceutical consumer base, the Indian API manufacturing segment can be alienated into two sectors ? innovative or branded and generic or unbranded. In 2009, the worldwide generic drug market was projected to be US$ 84 billion, of which the US accounted for 42%. India‟s generic drug industry is approximate to be US$ 19 bn and it ranks third globally, contributing about 10% to global pharmaceutical production. Pharmaceutical manufacturing units are mainly concentrated in Maharashtra and Gujarat. These regions hold for about 45% of the total number of pharmaceutical manufacturing units in India. Based on the elevated value plant species, J&K has a huge potential for establishing bio-pharmaceutical industry.

Identification of specific organic contaminants in different units of a chemical production site.

Due to the very limited number of studies dealing with the chemical composition of industrial wastewaters, many industrial organic contaminants still escape our view and consequently also our control. We present here the chemical characterization of wastewaters from different units of a chemical complex, thereby contributing to the characterization of industrial pollution sources. The chemicals produced in the investigated complex are widely and intensively used and the synthesis processes are common and applied worldwide. The chemical composition of untreated and treated wastewaters from the chemical complex was investigated by applying a non-target screening which allowed for the identification of 39 organic contaminants. According to their application most of them belonged to four groups: (i) unspecific educts or intermediates of industrial syntheses, (ii) chemicals for the manufacturing of pharmaceuticals, (iii) educts for the synthesis of polymers and resins, and (iv) compounds known as typical constituents of municipal sewage. A number of halogenated compounds with unknown toxicity and with very high molecular diversity belonged to the second group. Although these compounds were completely removed or degraded during wastewater treatment, they could be useful as "alarm indicators" for industrial accidents in pharmaceutical manufacturing units or for malfunctions of wastewater treatment plants. Three potential branch-specific indicators for polymer manufacturing were found in the outflow of the complex. Among all compounds, bisphenol A, which was present in the leachate water of the on-site waste deposit, occurred in the highest concentrations of up to 20 000 μg L(-1). The comparison of contaminant loads in the inflow and outflow of the on-site wastewater treatment facility showed that most contaminants were completely or at least significantly removed or degraded during the treatment, except two alkylthiols, which were enriched during the treatment process. The chemical composition of the inflow samples showed a very heterogenic composition and strongly varied, reflecting that large scale industrial synthesis is carried out in batches. The outflow contained mainly unspecific chlorinated educts or intermediates of industrial syntheses as well as compounds which are known as typical constituents of municipal wastewaters.

Ecopharmacology: Therapeutic Drugs as Environmental Hazards

There is an increasing concern in the medical fraternity regarding the impact of presence of active pharmaceutical ingredients (API) on the environment. In recent years, scientists have detected trace amounts of more than 150 different human and veterinary medicines in environments as far as the Arctic. High level of pollution is seen in the vicinity of large pharmaceutical manufacturing units and effluent river waters from cities. They are known to affect ecosystem in a negative way. Non-targeted population is at the receiving end of the effects of these pollutants, with direct onslaught for years together. Chronic effects are known with continuous inflow of more data, with even acute effects increasingly being reported. A research model has been suggested to bring forth a more realistic and true picture of the effects of these environment pollutants on the flora and the fauna in their natural habitats.

Isolation and characterization of the environmental bacterial and fungi contamination in a pharmaceutical unit of mesenchymal stem cell for clinical use

Design and implementation of an environmental monitoring program is vital to assure the maintenance of acceptable quality conditions in a pharmaceutical manufacturing unit of human mesenchymal stem cells. Since sterility testing methods require 14 days and these cells are only viable for several hours, they are currently administered without the result of this test. Consequently environmental monitoring is a key element in stem cell banks for assuring low levels of potential introduction of contaminants into the cell products.The aim of this study was to qualitatively and quantitatively analyze the environmental microbiological quality in a pharmaceutical manufacturing unit of human mesenchymal stem cells production for use in advanced therapies.Two hundred and sixty one points were tested monthly during one year, 156 from air and 105 from surfaces. Among the 6264 samples tested, 231 showed contamination, 76.6% for bacteria and 23.4% for fungi.Microbial genuses isolated were Staphylococcus (89.7%), Microccocus (4.5%), Kocuria (3.2%) and Bacillus (2.6%). In the identification of fungi, three genuses were detected: Aspergillus (56%), Penicillium (26%) and Cladosporium (18%).The origin of the contamination was found to be due to personnel manipulation and air microbiota. For all sampling methods, alert limits were set and corrective measures suggested.