Aseptic Manufacturing Research Articles

Financial assessment of aseptic preparation facilities in European hospital pharmacies

BackgroundThe drug manufacturing conditions in hospitals have become increasingly demanding and the use of a Controlled Atmosphere Area (CAA) in the preparation unit is now mandatory.PurposeTo make an inventory of...

A Two-Stage Strategy for Sterilization of Poly(lactide-co-glycolide) Particles by γ-Irradiation Does Not Impair Their Potency for Vaccine Delivery

This study evaluated the feasibility of using γ-irradiation for preparing sterile poly(lactide-co-glycolide) (PLG) formulations for vaccines. PLG microparticles were prepared by water-in-oil-in-water double-emulsion technique and lyophilized. The vials were γ-irradiated for sterilization process. Antigens from Neisseria meningitidis were adsorbed onto the surface of the particles and were characterized for protein adsorption. Antigens adsorbed onto the surface of the irradiated particles within 30 min. Mice were immunized with these formulations, and vaccine potency was measured as serum bactericidal titers. The γ-irradiated PLG particles resulted in equivalent serum bactericidal titers against a panel of five N. meningitidis strains as the nonirradiated PLG particles. The use of PLG polymers with different molecular weights did not influence the vaccine potency. The PLG particles prepared by γ-irradiation of the lyophilized formulations replace the need for aseptic manufacturing of vaccine formulations. This approach may enable the use of PLG formulations with a variety of antigens and stockpiling for pandemics.

Minimizing human intervention in intravenous admixture practice

I recently read a commentary by Agalloco et al.[1][1] regarding aseptic manufacturing. It reinforced precepts of United States Pharmacopeia (USP) chapter 797[2][2] and caused me to wonder about the evolution of the i.v. room as we know it. The first point of wonder is that there was a time when

Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro.

In this study we determined, for the first time, the ability of microorganisms to traverse microneedle-induced holes using two different in vitro models. When employing Silescol membranes, the numbers of Candida albicans, Pseudomonas aeruginosa and Staphylococcus epidermidis crossing the membranes were an order of magnitude lower when the membranes were punctured by microneedles rather than a 21G hypodermic needle. Apart from the movement of C. albicans across hypodermic needle-punctured membranes, where 40.2% of the microbial load on control membranes permeated the barrier over 24 h, the numbers of permeating microorganisms was less than 5% of the original microbial load on control membranes. Experiments employing excised porcine skin and radiolabelled microorganisms showed that the numbers of microorganisms penetrating skin beyond the stratum corneum were approximately an order of magnitude greater than the numbers crossing Silescol membranes in the corresponding experiments. Approximately 10(3) cfu of each microorganism adhered to hypodermic needles during insertion. The numbers of microorganisms adhering to MN arrays were an order of magnitude higher in each case. We have shown here that microneedle puncture resulted in significantly less microbial penetration than did hypodermic needle puncture and that no microorganisms crossed the viable epidermis in microneedle-punctured skin, in contrast to needle-punctured skin. Given the antimicrobial properties of skin, it is, therefore, likely that application of microneedle arrays to skin in an appropriate manner would not cause either local or systemic infection in normal circumstances in immune-competent patients. In supporting widespread clinical use of microneedle-based delivery systems, appropriate animal studies are now needed to conclusively demonstrate this in vivo. Safety in patients will be enhanced by aseptic or sterile manufacture and by fabricating microneedles from self-disabling materials (e.g. dissolving or biodegradable polymers) to prevent inappropriate or accidental reuse.

Evaluation of alcohol wipes used during aseptic manufacturing

During aseptic manufacturing and specifically during the transfer of items into an isolator, disinfection of surfaces is essential for reducing the risk of final product contamination. Surface disinfection can be carried out by a variety of methods, however the most accepted current practice is a combination of spraying with 70% alcohol and wiping. The aim of this study was to evaluate the effectiveness of two wipe systems by determining their ability to remove, kill and transfer bacterial contaminants from standardized surfaces. The protocol used to achieve these objectives was based on a newly published method specifically designed to test wipes. Alcohol impregnated wipes performed better at reducing microbial bioburden than the alcohol spray/dry wipe applications. Impregnated wipes drastically reduced (1-2 log(10) reduction) a small bioburden (approx. 2 log(10)) of spores of Bacillus subtilis and methicillin-resistant Staphylococcus aureus from the surface, but failed to remove (<0.2 log(10) reduction) Staphylococcus epidermidis. The alcohol spray/dry wipes did not manage to remove (<0.2 log(10) reduction) spore or bacterial bioburden from surfaces and was able to transfer some viable micro-organisms to other surfaces. Both wipe types showed poor antimicrobial efficacy (<1 log(10) reduction) against the test bacteria and spores. As far as the authors are aware this is the first time that such a practical study has been reported and our results suggest that the best wipes for surface disinfection in aseptic units are the alcohol (IPA) impregnated wipes when compared with the dry wipes sprayed with alcohol. The impregnated wipes performed better than the dry wipes sprayed with alcohol and should be used for surface disinfection in aseptic units.

Product Development of Probiotics as Biological Drugs

Elements of product and manufacturing-process design are described for product development of live biotherapeutic biological drugs. Product design uses the history and the phenotypic and genotypic characterization of the selected strain. The quality and integrity of the selected strain can be ensured by preservation in a qualified cell-bank system. Manufacturing-process design includes step-by-step description, including the necessary process-input parameters and the expected output results. The active ingredients in the biological drug are usually manufactured using aseptic processing. The manufacture of the final dosage form of live biotherapeutics requires bioburden control or aseptic manufacture, as appropriate. Specifications for live biotherapeutics must comply with regulations for licensed biological products. Evidence of stability for the duration of the shelf life, as well as stability under the recommended conditions of use, must be provided for licensure.

Assessment of Performance of Manufacturing Procedures in a Unit for Production of Investigational Anticancer Agents, Using a Mixed Effects Analysis

PurposeTo identify the magnitude and sources of variability of a generic, aseptic manufacturing process for experimental anticancer agents employed at our facility, and to estimate the effects on product quality.Materials and MethodsIn-process and quality control data of all products manufactured according to this generic process (composed of weighing, dissolution, filtration, filling, semi-stoppering and lyophilization) over a 3-year period were retrospectively analyzed using mixed-effects analysis.ResultsVariability in the filling process was shown to be marginal and of minor importance for product quality in terms of content and content uniformity. An overall content of 101% was found with batch-to-batch and vial-to-vial variability up to 4.21% and 2.57%, respectively. Estimation of the overall batch failure revealed that structural bias in content and a high batch-to-batch variability in content were the most prominent factors determining batch failure. Furthermore, content and not content uniformity was shown to be most important parameter influencing batch failure. Calculated Process Capability Indices (CpKs) calculated for each product showed that the process is capable of manufacturing products which will routinely comply with the specification of 90–110% for content. However, the CpK values decreased dramatically using the specification of 95–105% as required for approved drug products.ConclusionThese results indicate that at the early stage of product development less tight specification limits must be applied to prevent unnecessary batch rejection of investigational agents.

Standards for Specialized Nutrition Support: Home Care Patients

Standards for Specialized Nutrition Support: Home Care Patients

Achieving Sterility in Medical and Pharmaceutical Products

The Need for Sterility Sterility and Sterility Assurance Sterilization by Gamma Radiation Sterilization by Saturated Steam Dry Heat Sterilization and Depyrogenation Sterilization by Ethylene Oxide Sterilization by Filtration Aseptic Manufacture Maintenance of Sterility Parametric Release and Other Regulatory Issues

Book Review

Aseptic Pharmaceutical Manufacturing - Technology for the 1990′s Edited by Wayne P. Olson ad Michael J. Groves Published by Interpharm Press Inc. P.O. Box 530 Prairie View, IL 60069 Price $85 U.S. inclusive of shipping, outside U.S. add 20% handling charge to cover air speeded delivery. First edition 1987, 430 pages, hard-cover.Recombinant Lymphokines and Their Receptors edited by Steven Gillis published by Marcel Dekker, Inc., New York and Basel, 1987 $89.75, 325 pages, hard cover.