Ncl does not endorse any of the organizations listed below. Liposome production is accomplished by several methods including conventional. Largescale manufacturing methods to produce sterile filtered preparations have been developed which increase the opportunities for gmp production and commercial development. Good manufacturing practice gmp conditions and can be designed to. Andreas wagner vienna, at informed on guiding liposomal therapeutics to clinical evaluationpoints to consider in formulation and process development and highlighted the quality aspects of phospholipids, process validation, analytics, etc. The manufacturing process of the liposomes is well established. Gmp microfluidic production of liposomes was achieved using the nanoassemblr gmp system and a trm nxgen 500 cartridge which uses the same toroidal mixer design with inline dilution and with custom hplc pumps. May 21, 2019 good manufacturing practices gmps are the set of production standards that have been embraced by regulators, retailers and consumers in the food and drug industries. Dexamethasone loaded liposomes by thinfilm hydration.
Polymun scientific immunbiologische forschung gmbh liposome. Webb c, forbes n, roces cb, anderluzzi g, lou g, abraham s. However, current processes used for the manufacture of liposomes present a. Good manufacturing practices gmp pharmaceutical guidelines. An identical study will be done with the gmp clinical trial material ctm after production. Today, they are a very useful reproduction, reagent, and tool in various. Manual aseptic filling of glass vials 2 ml to 20 ml with up to 1,800 vials per fill.
Establishing a gmp manufacturing site for nanoparticles. Gmp applies to both production and quality control. Dotap powder gmp grade, 1,2dioleoyl3trimethylammoniumpropane chloride salt, avanti polar liquids cat. Ca 94043 abstract liposomes can be produced by a variety of techniques such as sonication, highpressure. Annex 3 who good manufacturing practices for pharmaceutical. General part 211 current good manufacturing practice for finished pharmaceuticals part 600 biological products. Applying microfluidics for the production of the cationic. Gmp good manufacturing practices, often refers to the united states good manufacturing practices which are regulations promulgated by the u. The reconstituted membrane had an osmotic behavior similar to that of nondehydrated ones. Good manufacturing practices in active pharmaceutical. Encapsula nanosciences is a specialty company focused on providing liposome research, development and manufacturing expertise in the production of lipidbased nanoparticles, also known as liposomes, to clients and partners in both the academic and industrial sectors.
Water production equipment and water systems should supply quality water. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Click the relevant tabs below for more information on these custom products and services. A supercritical fluid technology for liposome production and. Polymun scientific immunbiologische forschung gmbh. The cationic liposomal adjuvant caf09b, composed of dioctadecyldimethylammonium bromide dda, monomycoloyl glycerol analogue 1 mmg and polyinosinic.
Translating the production of nanomedicines from bench to gmp. Good manufacturing practices gmp for medicinal products. Traditional techniques, such as bangham, detergent depletion, etherethanol injection, reversephase evaporation and emulsion methods, were compared with the recent advanced techniques developed for liposome formation. Polymun has unique knowhow and technology for the development and manufacturing of liposomal and lipid nanoparticle lnp formulations. Contract development and gmp manufacturing of liposomal formulations. Gmp in api development november 1999 2 table of contents. If you are looking for gmpcompliant transfection reagents, please contact us. Indeed, the manufacturing of liposomes presents certain major issues to be. Cdigmp liposomes also showed significantly higher levels of expression of cd80, cd86 and mhc class i. May 08, 2020 a seamless path to scaling up production an example shown here is a liposome formulation popccholesterol 6040 molmol, optimized using the nanoassemblr benchtop and scaled up using the nanoassemblr blaze and the gmp system with minimal process development and identical results. The system permits liposome manufacture regardless of production scale, as scale is determined only by free disposable vessel volumes. Translating the production of nanomedicines from bench to. Formulation development polymun offers the development of liposomal and lipid nanoparticle formulations for all kinds of pharmaceutically active ingredients such as oligonucleotides, small molecules and proteins as well. General part 601 licensing biologics part 610 general biological products standards 16.
Cosmetics good manufacturing practices gmp guidelines on good manufacturing practices 1 scope this international standard gives guidelines for the production, control, storage and shipment of cosmetic products. Supports nanoparticles, including liposomes as well as cytotoxic and potent compounds. A who guide to good manufacturing practice gmp requirements. Good manufacturing practice gmp is the minimum standard that a medicines manufacturer must meet in their production processes. The purpose is not to keep the worker safe but to protect the end user of the product.
Any treatment of materials by a process inteded to make them suitable for further use. The company is certified according to gmp good manufacturing practice. While the guidelines for gmp production are different in europe and the usa, they all focus on the end user and the actual requirements may vary a little. However, most of the advances in liposome research. Pdf gmp production of liposomesa new industrial approach. Haynes opp1094352 mperpeptide liposome immunogen testing. Very high ee reflects the quality of liposome preparation method used. Support formulations containing oligonucleotides, sirna, mrna, peptides, proteins, sparingly soluble compounds and highly potent api. Pics guide to good manufacturing practice for medicinal products pics guide to gmp, excluding annexes 4, 5 and 14, as the m anufacturing principles for. However, these complicated and separate processes make it difficult to maintain scalability, reproducibility and sterility. In our cgmpcompliant manufacturing facilities, we can produce volumes of a. The mixed dry lipids were dissolved in purified gmp grade chloroform mallinckrodt.
Performs lipid synthesis, cgmp manufacturing, liposome formulation, analytical testing of lipid. Guidelines for developing and estrs readytoeat rte. Many countries have legislated that pharmaceutical and medical device companies must follow gmp procedures, and have created their own gm p guidelines that correspond with their legislation. Pe009, the pics guide to gmp for medicinal products. Development and characterization of a liposome imaging agent by. However, these complicated and separate processes make it difficult. Part 210 current good manufacturing practice in manufacturing, processing, packing, or holding of drugs.
Once the parameters are defined, an easy scale up can be p. The choice of raw materials and production methods must be such that the products match entirely with the goals of this gmp. Gmps provide a basic assurance that a product was produced under industrystandard conditions. Technology offer details liposomal formulations for. Combining strong gmps, sops, ssops and haccp will increase the total process control system and help these manufacturers continue to produce the safest products possible. Liposomes were first described by british haematologist dr alec d bangham frs in 1961 published 1964, at the babraham institute, in cambridge.
Clean areas should be ma intained to an appropr iate standard of cleanliness and supplied with air that has passed through. Liposomes, spherical vesicles consisting of one or more phospholipid bilayers, were first. A new adjuvant delivery system cyclic digmpysk05 liposome. Mar 30, 2021 liposomes, sphereshaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid60s. Conventional and dense gas techniques for the production of. Annex 5 supplementary guidelines on good manufacturing. Innomedica has a pharmaceutical gmp production in fribourg, certified by swissmedic since 2014. Good manufacturing practices for pharmaceutical products 3. Mar 31, 2021 contracts can be arranged step by step proof of concept, indepth analysis, gmp production, product license or all in one.
The measurements were conducted in the manual mode. Liposomes, sphereshaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid60s. Bsl3 containment cgmp cleanrooms for the production of organisms or toxins. Production of liposomes has previously been described 5. Gmp and nongmp capability from the gram scale for preclinical to phase iii clinical studies. A supercritical fluid technology for liposome production. Production of liposomes by a microfluidizer 2249 w n m ci w 2% 0 m 0 a c 0. Conventional and dense gas techniques for the production. Jan 05, 2021 liposomes were produced by an innovative method using supercritical carbon dioxide as a dispersing agent. A quality by design strategy was used to find optimal production conditions with specific parameters lipid concentration, dispersion volume, agitation rate, temperature and pressure allowing the production of liposomes with predicted physicochemical characteristics particles size and pdi.
Using microfluidics for scalable manufacturing of nanomedicines from bench to gmp. We describe the process of the transfer, manufacture of new lots, and production of clinical product. Nov 12, 2018 liposomes are currently part of the most reputed carriers for various molecular species, from small and simple to large and complex molecules. The term is also used by some to describe a set of practices they use for their specific industry. Annex 6 who good manufacturing practices for sterile. Characterization of liposomes the liposomes prepared were characterized by their phospholipid contents by. Liposome drug characterisation and analysis according to fda manufacturing and controls cmc guidance including physicochemical properties, cryotem, composition, encapsulation efficiency, in vitro release of the drug product and stability testing. Encapsulation of hemoglobin in liposomes springerlink. There are few methods available for injectable liposome production under good manufacturing practices gmp. Teatime seminar lab to gmp final 1 precision nanosystems.
This guide for training is part 3 of a who guide to good manufacturing practice gmp requirements. Technological aspects of scalable processes for the. May 30, 2020 gmp microfluidic production of liposomes was achieved using the nanoassemblr gmp system and a trm nxgen 500 cartridge which uses the same toroidal mixer design with inline dilution and with custom hplc pumps. Continuous production of liposomes and lipid nanoparticles. Supplementary guidelines on good manufacturing practices for heating, ventilation and airconditioning systems for nonsterile pharmaceutical dosage forms 1. Introduction a liposome is a tiny bubble vesicle, made out of the same material as a cell membrane. A new scalable liposome production system is presented, which is based on the ethanol injection technique. Good manufacturing practices gmp guidelines gmp is a production and testing practice that helps to ensure a quality product. Liposome characterisation and analysis for drug delivery. Scaling up production capacity staggered herringbone mixer shm toroidal mixer trm flow rate capacity 1 20 mlmin high flow rate capacity 20 lh using microfluidics for scalable manufacturing of nanomedicines from bench to gmp. Gmp production of liposomes a new industrial approach j liposome res. Voraueruhl, karola and katinger, hermann 2006 gmp production of liposomes a new industrial approach, journal of liposome research, 16.
Introduction to good manufacturing processes gmps fda. Water systems should be sanitized according to well. Liposome technology for industrial purposes hindawi. A preclinical glp toxicology study in rabbits was conducted by charles river laboratories crl this year 2018 to verify safety of vaccination with mperpeptide liposomes plus alum adjuvant. Independent hvac systems for all gmp production suites compliant and unidirectional personnel, material and product flow successfully audited by ema and fdacompliant clients bsl3 capabilities. Injectable liposome production processes under gmp generally consist of liposome formation, size homogenization, organic solvent removal, liposome concentration control and sterilization. Although the manufacturing of liposome drug products differs depending on the active substance to be encapsulated, the type and properties of lipid components. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation. For each customer, we collaboratively work through a multistage process to define a gmp transition plan that is appropriate for the target application. Leaders in lipid nanoparticle drug delivery systems gmp. Since their discovery, liposomes have been subject to extensive evolution, in terms of composition, manufacturing and applications, which led to several openings in both basic and applied life sciences. Annex 1 1 manufacture of sterile medicinal products 2 document.
C, is currently being clinically evaluated in therapeutic cancer vaccines. Selfinspection, quality audits and suppliers audits and approval items for self. Liposomes were reconstituted in size by including trehalose sugar in the formulation. The outcome of the study suggests that liposomect could be employed as a competitive method for whole body imagebased disease detection and. One of the challenges of gmp nanoparticle production is defining the appropriate level of controls and processes to appropriately manage risk. Number of passes through the microfluidizer m110, processed at 3000 psi. Polymun excellence in biopharmaceuticals and liposomes. Polymun scientific contract development and manufacturing of. Development of a novel onestep production system for injectable. The protection of the liposomal membrane by trehalose was characterized by differential scanning calorimetry and xray diffraction. Pdf a new scalable liposome production system is presented, which is based on the ethanol injection technique. Talicovax19 ready for production 7 innomedica can produce up to 500,000 vaccines per batch as of july 2020. Introduction to good manufacturing processes gmps fda reader. The company encapsula nanosciences manufacturer of.
Good manufacturing practices for active ingredient manufacturers 7 a. Good manufacturing practices european chemical industry. It is clear that this guide is intended as a first step to approach this topic. Food and drug administration covering the manufacture of food, drugs, and cosmetics. Good manufacturing practices gmp who defines good manufacturing practices gmp as that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization ref 27. Cosmetics good manufacturing practices gmp guidelines. Largescale production of liposomes by a microfluidizer by sriram vemuri12, chengder yu, vuthichai wangatorntanakun and niek roosdorp pharmaceutical development, cooper laboratories, inc. Guideline for the development of liposome drug products.
These guidelines cover the quality aspects of the product, but as a whole do not cover safety aspects for the. Development of a novel onestep production system for. Gmp production of liposomesa new industrial approach. Wagner a, platzgummer m, kreismayr g, quendler h, stiegler g, ferko b, vecera g, voraueruhl k, katinger h 2006 gmp production of liposomes a new industrial approach.
1286 199 248 1452 1243 595 1117 1376 1686 1306 35 1521 1637 1312 1666 523 982 1455 978 117 280 408 1767 931 694 1228 1790 1161 1812 893 1564 930 1796 916 997