Quality Control Of Final Product Research Articles

Review Article-A Concise Overview on Recent Advances in Pharmaceutical Aerosols and Their Commercial Application

For the treatment of various pulmonary disease such as asthma, chronic abstractive disease, pneumonia, bronchitis, and cystic fibrosis, localized drug delivery to the respiratory system has shown to be an increasingly effective and crucial approach. The global market for respiratory inhaler device is being propelled in large part by the increasing prevalence of respiratory disease. The main objective of this article is to present various aspect of pharmaceutical aerosol, including their various types, components, in-process and finished product quality control, and their commercial applications. Aerosol also known as a pressurized device work by continuously or metered applying a small mist spray to activate a suitable valve system. Aerosol is not only used for the treatment of asthma and chronic obstructive pulmonary disease but also used to treat a wide range of other conditions including diabetes, cancer, angina pectoris, bone disorder, and acute lung injury, bone disorders, and tuberculosis. The therapeutic efficacy of pharmaceutical aerosol is affected by wide range of factors, such as the types and characteristics of propellant, active ingredient, container, valve, actuator, spray pattern, valve crimping efficiency, and aerosol particle size. Key words: - Aerosol, types, metered dose inhaler, dry powder inhaler, nebulizers, commercial applications.

Making Anti-CD19 CAR-T Cell Therapy Accessible and Affordable: First-in-Human Phase I Clinical Trial Experience from India

Background: Chimeric Antigen Receptor (CAR) T cells therapy has shown remarkable success in haematological malignancies. However, complexity of the manufacturing platform and exorbitant costs of the available therapy limits their accessibility in limited resource settings including India. Recently, we developed a novel humanized anti-CD19 CAR-T cell therapy (HCAR19) and showed its efficacy in preclinical models (Dwivedi et al, Mol Cancer Ther. 2021). Here we report our experience of HCAR19 manufacturing in an integrated platform for first-in-human Phase-I clinical trial. Further, we performed the cost analysis of CAR-T delivery from development to clinic. Methods: Lymphocytes were collected from 17 patients of r/r B cell malignancies (DLBCL, transformed follicular lymphoma, PMBCL and B-ALL) through apheresis (Fresenius Fomtek or Spectra Optia) upon receiving the regulatory approvals from central and local agencies. CD3+ T cells were enriched and activated using CTS™Dynabeads™ CD3/CD28 for 36-48 hours followed by consecutive double transduction with CD19 encoding lentivirus vector. Final product was harvested, cryopreserved and stored in ultra-low temperature until further use. All steps were carried out in closed gas permeable bags. Final product quality control (QC) assays were performed by flowcytometry, ELISA, analytical and cell-based assays. The cost of CAR T cell manufacturing was calculated for unit economics on fully scale production model by standard costing methodology. The final unit economics included cost of goods and services (COGS), overhead costs, financing costs of infrastructure, R&D and clinical trials costs. The model was scaled towards a 200 patient per annum in a centralized manufacturing facility. Results: Of the 19 patients enrolled in the study, only 17 patients underwent apheresis procedure for harvest of total 5-10 X 109 mononuclear cells. HCAR19 cells from all 17 patients were manufactured successfully in functionally closed integrated manufacturing platform. The required HCAR19 dose was achieved within 8 days of culture (dosage range: 1.78 x 106 - 17 x 106 viable HCAR19/kg). The transduction efficiency of HCAR19 in r/r DLBCL, r/r PMBCL and r/r B-ALL was 37.7 ± 6.64%, 28.8 ± 8.81% and 34.6 ± 9.72% (Mean ± SEM) respectively . The HCAR19 showed a robust expansion (~20-fold) ex vivo and maintained the presence of potent anti-tumor subsets like naïve and central memory T cells (Figure 1a). Final product from all 17 patients qualified the QC release criteria for safety, identity, purity and potency as per specifications. Finally, the unit economics in fully-scaled production model indicated the estimated cost of CAR-T cell delivery was approximately 30,000 USD (or 25,00,000 INR) per dosage including logistics, lentiviral vector cost and quality control (Figure 1b). The major costs incurred were towards consumables, overhead and financing costs of clinical trials and infrastructure. There was very minor components of logistics and utility costs. More importantly, the major contributors of overall low cost of CAR-T delivery in our settings were frugal R&D costs in an academic setting, scalable integrated manufacturing platform, and highly qualified yet economical manpower. Conclusions: We developed a robust, scalable and highly affordable CAR-T cell therapy platform (product and process development, and first-in-human clinical study), and proven its clinical delivery successfully with our first indigenous HCAR19 product. Given the benefit of affordable platform to broader socio-economic base of patients, the cell and gene therapy will be poised for a transformational change as a mass therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Motion feature based melt pool monitoring for selective laser melting process

Since various build defects in the Selective laser melting (SLM) process are found to be associated with the instability of melt pool, the melt pool monitoring is particularly important for the final product quality control. Previous studies focus on the geometric features to describe the changes of the size and shape of melt pool, which are not sufficient to characterize the dynamic variations of the melt pool during the build process monitoring. To solve this problem, a new motion feature is introduced to describe the moving melt pool. The melt pool and spatters are extracted by thresholds combined with the connected component analysis method. The distance between the centroid and the boundary of melt pool is calculated from the unfolded clockwise at a step angle, which constructs a high dimensional feature vector as the motion features. The k-means clustering algorithm is applied to cluster the motion features under varied process parameters, aiming at construct the link between the melt pool states and processing parameter for the quality control. The research results have shown that the extracted motion features can describe the variation of melt pool more accurately than the traditional geometric features, and they can distinguish the moving direction and melted states of over melting, partial melting and defects simultaneously. This research provides a new approach for intelligent online monitoring of the SLM process.

Simultaneous Quantification of Vitamin A and Derivatives in Cosmetic Products by Liquid Chromatography with Ultraviolet Detection

Vitamin A (retinol) and some of its derivatives are a group of fat-soluble compounds used in cosmetic products as bioactive ingredients. Therefore, it is necessary to perform the quality control of final product to ensure their efficacy and safety. A simple and rapid method to determine retinol, retinal, retinyl acetate, retinyl propionate and retinyl palmitate in cosmetics is presented here. The method is based on vortex and/or ultrasound-assisted leaching of the analytes in ethanol followed by liquid chromatography with ultraviolet detection. The analytical performance of the method was evaluated. It has shown high levels of linearity, at least up to 100 µg mL−1; high precision with RSD values below 14% and high sensitivity with low MLODs ranging between 0.3 × 10−4 and 5.9 × 10−4 % w/w, which are enough to monitor these compounds in cosmetic products. The proposed method was successfully applied to seven commercial cosmetic samples to detect and quantify the target analytes, showing the method is suitable for its employment for quality control in cosmetic industries. Cosmetic samples were spiked at two levels of concentration and recovery values around 100% were obtained, showing no significant matrix effects and, therefore, external calibration was adequate for this determination.

To Study the Quality Control Parameters for Uncoated Paracetamol & Nimesulide Tablet in Pharmaceutical Industry

A pharmaceutical uncoated tablet must satisfy certain standards to claim it to be a quality drug. The quality of any drug in dosage form is its safety, potency, stability, patient acceptability and compliance. The quality of tablet needs to be designed from the product development stage. Quality control test for uncoated tablet is strongly related to final product quality because checks performed during production in order to monitor and if necessary, to adjust the process to ensure that the product conform to its specification are the key for the good or excellence quality of a tablet. The main purpose of quality control test for uncoated tablet is to produce a perfect finished product quality control (FPQC) test for tablet are performed with specific quality control test or parameters within acceptance limit or not. The aim of this to study in process quality control test carried for uncoated Paracetamol & Nimesulide.

Development and validation of a simple and reliable alternative method for process monitoring and final product quality control during fatty acid ethyl esters production

As the production of biofuels increase, there is an urgent need to easily analytically control their production at the plant level as well as to assess the quality of the final products. Especially method capable of determining fatty acid ethyl ester content of 96.5% is crucial for utilization in praxis. In this work, a refractive index method with required sensitivity was developed and validated by means of a standard reference gas chromatography method. Validation with a considerable set of real unique samples obtained at pilot scale was performed for both purposes – process monitoring at high conversions and final product quality control. The results confirmed a favourable degree of accuracy with a relative deviation lower than 3.5% from the reference value given by the gas chromatography. Moreover, application of the method for quality control of fresh and long-term stored samples revealed that the deterioration of final products during storage can be detected. The developed refractive index method is thus suitable for the simple and rapid evaluation of the quality of produced fatty acid ethyl esters and for analytical monitoring of their production process.

Pharmacopoeial comparison of in-process and finished product quality control test for pharmaceutical tablets

All Pharmaceutical industries endeavour to produce good quality products which are achieved by allowing in-process and finished product quality control approaches. In-process quality control is concepts that are carried out before, after and during production covering all steps, counting the establishment of specifications, sampling, relevant testing and analytical clearance assuring that the intermediates, packaging materials and finished pharmaceutical tablets conform with approved specifications or standard for efficacy, safety and elegance which assure the consumer that the products perform consistently and in a manner satisfactory for the purpose for which it is recommended. Quality control highlights testing of products for defects which ease the producer to refuse the releases of products or carry out the possible investigation to make pharmaceutical tablets perfect before released into the market. Since different pharmacopoeias have set the diverse specified limits to some extent within which the value ought to fall with respect to be acquiescent as per the standards. Hence by comparing pharmacopoeias, an effort is made to convey the harmonized limits so that the products should meet the requirements as specified in pharmacopoeias specification to confirm the quality of pharmaceutical dosage form. The endeavour of this study is to compare various quality control assessments for pharmaceutical tablets according to different pharmacopoeias standards.

Pharmacopoeial comparison of in-process and finished product quality control test for pharmaceutical tablets

Pharmacopoeial comparison of in-process and finished product quality control test for pharmaceutical tablets

Development and Validation of Analytical Methods for the Identification in Canprophem - АK® Suppositories with the New Original Polyene Antibiotic

Introduction: The paper presents analytical methods for the identification of Roseofungin active pharmaceutical ingredient (API) using thin layer chromatography (TLC) and spectrophotometry in the ultraviolet region, for the drug CANPROFEM - AK® containing the original polyene antibiotic Roseofungin in the form of suppositories. The study established optimal conditions for the experiment, including sample preparation; the Specificity validation characteristic was examined for each method. Results: Method 1 employed the TLC plate pre-coated with a layer of F254 silica gel using n-butanol saturated with purified water as a mobile phase; the substance was identified in UV light at a wavelength of 365 nm. The method makes it possible to uniquely and specifically identify roseofungin in the presence of placebo components. In method 2, the maximum of the ultraviolet absorption spectrum of the solution being tested coincides with the maximum of theultraviolet absorption spectrum of the reference sample solution (364±2 nm). Conclusion: The methods are suitable for solving the intended objectives and are included in the draft analytical normative document on the finished product quality control by the Identification characteristic.

GMP/GACP - new standards for quality assurance of cannabis

In 2015, in Republic of North Macedonia, a new law for narcotics has been adopted, where the changes include legal cultivation of cannabis for medicinal use as well as legal production of cannabis extracts for medicinal use. In order to gain high quality of cannabis and cannabis products for medicinal use and to meet some quality standards that will guarantee consistency, traceability and continuous quality of the product, it is necessary to implement Quality Systems. Good quality system is ISO standard system but for cannabis for medicinal use, GACP, GMP and GLC standards are used more often. Production of cannabis for medicinal use consists of: process of cultivation where GACP standards are applicable, primary processing where GMP standards are the most important and quality control of final product regulated with GLP standard. In this review, explanation of these standards as well as overview of modes of their implementation has been made. Keywords: GxP, GMP, GACP, GLP

Propagation, Purification And Molecular Characterization Of Rvf Virus (Zh 501) Strain For Vaccine Production In Egypt

Rift Valley Fever (RVF) is an endemic disease in Egypt causing disease in animals and humans since the 1977. Full molecular description of the national vaccine strain is a strategic concern to ensure the antigenic makeup of local vaccine is adequate to provide the required protective immunity for the vaccinated animal species and as a tool of final product quality control. Molecular characterization and phylogenetic analysis of Gc gene of M segment of RVF-ZH501 strain which used in local vaccine production in veterinary serum and vaccine research institute (VSVRI) were carried out in this study. RVF-ZH501 strain was propagated by passages on BHK cell line and then purified my plaque purification technique. RT-PCR for amplification of the Gc gene of M segment. Sequence analysis of the obtained PCR product carried out by MEGA7 program. The result of the study revealed that RVF strain ZH501 Gc genomic content has 99.5 % molecular identity to the strains firstly isolated in Egypt in 1977, so still suitable for vaccine production.

Optimization of ibuprofen hydrogel-based Matrix tablet formulation for oral delivery

Objective. Ibuprofen, a nonsteroidal anti-inflammatory drug, is poorly soluble leading to its slow systemic absorption. This study aimed to optimize the formulation of an ibuprofen hydrogel-based matrix tablet to improve its dissolution for better oral bioavailability.
 Methods. Raw material of ibuprofen was subjected to quality control test and compatibility test with the excipients. Six trial formulations were performed, with polyethylene glycol (PEG) 6000 as the matrix for the first three trial formulations and carbopol for the remaining trial formulations. Finished product quality control (FPQC) tests were conducted to choose the best formulations to be compared against the marketed products using comparative dissolution and stability studies.
 Results. Among the trial formulations, Formulation 3 and Formulation 4 displayed highly satisfactory results from FPQC. The results of disintegration tests, comparative dissolution, and stability studies suggested carbopol as the better polymer over PEG 6000 which made Formulation 4 as the best.
 Conclusion. Based on the percent drug release and similarity factor, it was concluded that the formulation optimized in this study was considered to be similar with the standard liquigel.

Lightweight UAV with on-board photogrammetry and single-frequency GPS positioning for metrology applications

This article presents a coupled system consisting of a single-frequency GPS receiver and a light photogrammetric quality camera embedded in an Unmanned Aerial Vehicle (UAV). The aim is to produce high quality data that can be used in metrology applications. The issue of Integrated Sensor Orientation (ISO) of camera poses using only GPS measurements is presented and discussed. The accuracy reached by our system based on sensors developed at the French Mapping Agency (IGN) Opto-Electronics, Instrumentation and Metrology Laboratory (LOEMI) is qualified. These sensors are specially designed for close-range aerial image acquisition with a UAV. Lever-arm calibration and time synchronization are explained and performed to reach maximum accuracy. All processing steps are detailed from data acquisition to quality control of final products. We show that an accuracy of a few centimeters can be reached with this system which uses low-cost UAV and GPS module coupled with the IGN-LOEMI home-made camera.

Marker assay guided standardization of an ayurvedic concentrated polyherbal decoction “CiruvilvāDi KaṣāYam” and its application in industrial quality control

Background: To establish a marker guided standardization technique to assess whether the marketed concentrated kaṣāyam (decoction) prepared in large scale is providing the same phytochemical values of a Laboratory Reference Standard (LRS) kaṣāyam prepared classically from raw materials of Pharmacopoeial quality. Objectives: Manufacturing and standardization of LRS ' Ciruvilvādi kaṣāyam' , including marker assays and its comparison with four different marketed samples. Materials and Methods: pH, Brix and Total solids of samples were determined and compared. HPTLC profile comparison and quantitative comparison with HPLC were done with Gallic acid and Piperine as standards. Results and Conclusion: Results of Brix and Total solids imply that, the manufacturing process of sample IV was significantly different from other samples and LRS. pH value of sample III showed a significant difference as compared to other samples and LRS, indicating a difference in phytochemical contents. Quantification of Piperine and Gallic acid revealed that sample III has a very low Gallic acid concentration and zero Piperine concentration. Sample IV showed a very high concentration of Gallic acid when compared to other samples and LRS. Sample I, II and IV had piperine content but significantly lower when compared to the LRS. In conclusion, the samples (1-IV) which showed difference with the LRS should be made phytochemically comparable to in-house LRS or Pharmacopoeial standards by adopting the marker assay standardization technique. This method helps to identify and rectify the problems related to raw material, in process and finished product quality control.

Formulation and Evaluation of Methyl Phenidate Sustained Release Tablets

Methyl phenidate is a medication that belongs to the drug class called central nervous system stimulants. Methylphenidate is prescribed for treating narcolepsy (uncontrollable sleepiness), and attention-deficit hyperactivity disorder (ADHD). The aim of the current investigation is to design oral twice a daily sustained release matrix tablets of methylphenidate 20mg, used for the treatment of narcolepsy and ADHD which can release the drug for 10 to 12 hours. The matrix tablets were prepared by the wet granulation method using varying concentrations of sustained release polymers HPMC, Eudragit and Ethyl cellulose. The compatibility of the drug with polymers and other excipients was ruled out by FT-IR studies and found to be compatible. The Methyl phenidate powder and the powder-blends of tablets were evaluated for their physical properties like angle of repose, bulk density and compressibility index and found to be good and satisfactory. The manufactured tablets were evaluated for in process and finished product quality control tests including appearance, dimensions, weight variation, hardness, friability, drug content uniformity, and in vitro drug release. The results of dissolution studies indicated all formulations released up to 12 hours and formulation containing ethyl cellulose (5%) i.e. F7 was the most successful formulation with 96.72% drug release at the end of 12 hours. Based on mathematical models the formulation F7 fitted into zero order and Korsmeyer-Peppas plot with 0.942 and 0.999 regression values respectively and show Fickian diffusion mechanism release.

Self-tuning final product quality control of batch processes using kernel latent variable model

A mid-course correction (MCC) strategy based self-tuning final product quality control of batch processes is presented. The method employs KPLS model developed using batch-wise unfolding data set to capture the relationship between the process variables and final quality. The estimators for the future unknown trajectories are accomplished using statistical latent variable missing data imputation method based on multi-PCA models. Then the optimal control problem is formulated such that the solution is constrained to lie in the kernel latent variable space of the model defined by historical batch data set, and heuristic rule is used for weighting factor to balance the control objective and score magnitude. Finally, SQP is implemented to solve the constraint optimization problem. Application to a simulated cobalt oxalate synthesis process demonstrates that the proposed modeling and quality control strategy can improve process performance.

Quick Development of a NIRS Method for the Analysis of Moisture, Protein, and Fat in Nutritional Clinical Products

This work describes the approaches used for the quick development and validation of a near-infrared spectroscopy (NIRS) method for the quantitation of major constituents—fat, proteins, and moisture—in finished and intermediate nutritional clinical products. The document also describes the development of identification and qualification methods for the finished products. The approaches included the acquisition of spectra from previously manufactured batches in addition to production samples. This approach allows the construction of the calibration equations for the quantitation of the three components, the development of identification and qualification methods, and their validation for four kinds of products in less than 3 months. This procedure may need several months, or even years. Calibration equations for intermediate products were also constructed and validated allowing the quantification of the three constituents in any kind of intermediate product, regardless of the source of fat or protein used in the product. The grouping of all kind of products in the same equation in intermediate product leads to a reduction of the time required for the development of the equations. The method was validated according to FDA requirements; the validation procedure is also described. ISO Official Methods of Analysis were used as reference for the construction of the models. The method has been successfully implemented for in-process control and finished product quality control.

Effectivization of open pit hard mineral mining

The authors show the basic ways of making hard mineral mining with open pit method more efficient. The article gives a review of research aimed at improvement of open pit mining methods, intensification of mining, enhancement of mine safety and final product quality control (in terms of Bakchar iron ore deposit and coal deposits located in the Kuznetsk and Kansk-Achinsk Basins).

Blood product recalls in the United States

The blood recall process is intended to remove from use products that may be harmful, but characteristics of recalls nationally have not been reported. We analyzed recalls of all blood products for 2010 and categorized the reason for the recall, the organizations producing the recalled products, and the Food and Drug Administration (FDA) district in which the blood was collected. During 2010, there were 2468 recalls involving 8278 blood products. None of the recalls was considered to have a reasonable probability of causing serious adverse health consequences or death (FDA Class I). The most common reasons for recalls were donation and donor qualification (73%) and finished product quality control (14%). The FDA class of recalls varied by recall reason, month of the year, FDA district, number of units of blood collected per FDA district, and number of units of blood collected by the blood center. The number of recalls per 100,000 units of blood and the reason for recall varied by FDA district and blood centers collecting smaller numbers of units had more recalls. The absence of Class I recalls suggests a high level of quality and safety in the US blood supply. Organizations that collected larger numbers of units of blood had fewer recalls and there may be some FDA influences since the number and reason for the recalls varied by FDA district.

A Comparative Structural and Bioanalytical Study of IVIG Clinical Lots

Intravenous immunoglobulin are important bio-therapeutics used in the replacement therapy for primary and secondary immunodeficiencies, chronic inflammatory disorders and several autoimmune haematologic disorders. Currently, a number of immunoglobulin intravenous (IVIG) products have been approved by the Food and Drug Administration (FDA) and are available commercially. It is known that small differences in the manufacturing processes as well as in the formulations may affect their clinical efficacy and tolerability. Therefore, given the complexity of the multi-step process required for the isolation of IVIG from human plasma, it is necessary to ensure a rigorous quality control of final products. We show here that a set of different bioanalytical techniques can be conveniently used to comparatively characterize, at a quantitative and qualitative level, different lots of IVIG preparations and to unveil randomly occurring impurities which can also affect the overall product stability. We have used circular dichroism, surface plasmon resonance and two-dimensional electrophoresis (2DE), and have demonstrated that this combination of bioanalytical approaches is very useful to improve the quality control of antibodies and to monitor the reliability of the IVIG manufacturing process.