UIP Chosen as vendor for ncats drug product development, manufacture, and stability studies
August 2017: The University of Iowa Pharmaceuticals (UIP) is very excited that it has been chosen as a vendor for the NCATS (National Center for Advancing Translational Sciences) Request for Proposal (RFP) No. N01TR-17-2003, “CRO Support for NCATS Drug Product Development, Manufacture, and Stability Studies”. NCATS at the NIH (National Institutes of Health) studies translation on a system-wide level as a scientific and operational problem to accelerate the development of treatments and preventive strategies for a wide range of diseases. Within NCATS, the Division of Pre-Clinical Innovation (DPI) plans, conducts, and uses both internal and contract resources to advance collaborative research projects across the pre-clinical phases of the translational science spectrum. The goal of NCATS in selecting UIP as a vendor is to obtain contract research services to support the development, manufacturing, and stability studies of dosage forms of experimental therapeutics. The UIP application for this contract also included faculty from the UI College of Pharmacy that participate in the UIP Development Consortium (UIPDC). UIPDC is a formal connection between UIP and faculty in the College of Pharmacy where faculty can work with UIP and/or their students on pre-clinical drug development activities.
This project has been funded in whole or in part with Federal funds from the National Center for Advancing Translational Sciences, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN271201700019I.
UIP & Fervent
January 2017: UIP will be working with Fervent Pharmaceuticals to develop its treatment for hot flashes and other vasomotor symptoms. UIP involvement will be focused on formulation development aspects of the Fervent program, and UIP will manufacture development-scale clinical batches for its upcoming Phase II trial. Fervent CEO George Royster is excited about the partnership: “UIP offers Fervent the perfect blend of drug development expertise and experience. They’ve been practicing cGMP-compliant formulation development and product manufacturing for 40 years. I’ve been extremely impressed by their capabilities and their facility, which is the only one of its kind offering the range and scope of services needed by commercial clients like us.” For more information go to:
UIP TO PARTICIPATE IN NIIMBL VIA NIPTE
December 2016: U.S. Secretary of Commerce Penny Pritzker announced on this day an award of $70 million to the new National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), the eleventh institute in the Manufacturing USA network. This is the first institute with a focus area proposed by industry and the first funded by the U.S. Department of Commerce (DOC). UIP is part of NIIMBL through the UI College of Pharmacy via NIPTE (National Institute for Pharmaceutical Technology and Education). NIIMBL will help to advance U.S. leadership in the biopharmaceutical industry, foster economic development, improve medical treatments and ensure a qualified workforce by collaborating with educational institutions to develop new training programs matched to specific biopharma skill needs.
UI BREAKS GROUND ON NEW PHARMACY BUILDING
September 2016: UI officially broke ground on a new $96.3 million pharmacy building that will feature cutting-edge research laboratories, innovative technology, and collaborative learning spaces. The lower level of this new building will be home to UIP’s new sterile products manufacturing area. This new sterile manufacturing area will be approximately 16,000 square feet and include two complete isolator lines, each with its own lyophilizer. This will increase UIP’s batch size capacity approximately 5-fold to 20,000 vials/batch. UIP will continue to retain its ability to make small, IND enabling batches for clinical supplies with this facility.
Analytical Testing Capability Expanded
June 2016: UIP has received two new Waters Acquity QDa Detectors. The ACQUITY QDa Detector is a mass detector designed as a synergistic element of a chromatographic separations system. These detectors can be used to confirm compound identity with qualitative mass spectral data, complementing quantitative optical data, and/or quantify compounds with no or insufficient UV response. We are in the process of bringing these detectors online and should have the systems operational in then month or so.
INTERCEPT PHARMACEUTICALS RECEIVES FDA APPROVAL FOR OCALIVA®
May 2016: Intercept Pharmaceuticals, Inc. received FDA approval for the orphan drug Ocaliva – one of only 22 NMEs (New Molecular Entities) to receive approval by the FDA in calendar year 2016! It is indicated for the treatment of Primary Biliary Cholangitis in patients with an inadequate response to UDCA or as monotherapy – PBC is a disease for which there has not been a significant new treatment in nearly 20 years. Intercept is a long-standing client of UIP’s. UIP’s analytical laboratory is a laboratory of record in their NDA for this drug product.
August 2015-September 2015: UIP has hired an additional group of new employees. New personnel include three Chemists in the Quality Control Group and Ramprakash Govindarajan, Ph.D. who will be heading up our Preformulation/Formulation Development Group. The added personnel have been through their initial training programs and are already beginning to contribute to UIP operations. UIP looks forward to continued growth in the future.
Additional uplc capability added
July 2015: UIP has added a second Waters ACQUITY UPLC H-Class System. This unit can perform HPLC/UHPLC methods up to 1034 bar/15,000 psi (normal HPLC is ~400 bar / 5000 psi). The higher pressure allows for smaller columns with smaller particle sizes which can reduce run times and solvent consumption. The UPLC will have increased resolution and sensitivity. The UPLC is interfaced with a PDA detector and a Corona Veo detector. This unit is online now.
Additional -20 degree celsius storage space
June 2015: UIP has added an additional 1120 cubic feet of freezer storage space. This approximately doubles our existing frozen storage space. The new area is equipped with an INERGEN fire suppression system. The system uses inert gas to purge the storage space of oxygen in the event of a fire.
uplc capability added
April 2015: UIP has added a Waters ACQUITY UPLC H-Class System. This unit can perform HPLC/UHPLC methods up to 1034 bar/15,000 psi (normal HPLC is ~400 bar / 5000 psi). The higher pressure allows for smaller columns with smaller particle sizes which can reduce run times and solvent consumption. The UPLC will have increased resolution and sensitivity. The UPLC is interfaced with a PDA detector and a Corona Veo detector. This unit will be online in June.
New Inspection machine
July 2014: UIP has received and is in the process of qualifying a new FP Developments Model 1270-2017 Semi-Automatic Vial Inspection Machine. The unit improves efficiency and throughput by automatically presenting the magnified vials to the inspector. It is capable of handling vials sized from to 2 mL to 100 mL. The machine is simple to operate through a touch screen control panel and has all smooth surfaces making it easily cleanable.
June 2014: UIP has completed renovation of an approximately 300 square foot space dedicated to equipment storage. The renovation of this space allows for the segregated storage of equipment that has been, or is waiting to be, tested for cleanliness after cleaning. This frees up UIP manufacturing space for use in manufacturing operations which allows us to complete more projects more quickly.
Additional liquids ManufactuRing equipment
March 2014: UIP has purchased and received a new 225 gallon stainless steel mixing tank equipped with a variable speed mixer. This tank will increase UIP capacity to perform non-sterile liquids manufacturing. The unit is expected to be fully qualified and operational soon.
Additional Dissolution Testing Units
December 2013: UIP has received and qualified two new Distek Symphony 7100 Dissolution Units with a Distek Evolution 4300 Autosampler. The new units improve efficiency and throughput as both units can operate independently on a single autosampler. The units increase UIP capacity to perform dissolution testing on immediate release dosage forms as well as dissolution profile testing on extended release tablets and capsules. Both units are in use and fully qualified and operational.
December 2013-January 2014: UIP has hired an additional group of new employees. New personnel include two Manufacturing Specialists in the Non-Sterile Products Group, a Manufacturing Specialist in the Quality Assurance Group, and a Chemist in the Quality Control Group. The added personnel have been through their initial training programs and are already beginning to contribute to UIP operations. UIP looks forward to continued growth in the future.
June-July 2013: UIP has hired a number of new employees. New personnel include a Project Manager in the Non-Sterile Products Group, a Manufacturing Specialist in the Quality Assurance Group, a Facilities Services Specialist to manage the building automated control system, and an Assistant Chemist in the Quality Control Group. In addition, UIP is in the process of filling additional openings for Manufacturing Specialists in the Non-Sterile Products and Quality Assurance Groups and an additional opening for a Chemist in the analytical Laboratory. The added personnel have been through their initial training programs and are already beginning to contribute to UIP operations. UIP is happy to have these additional staff members on board and looks forward to continued growth in the future.
QP ReLEASE services added
December 2012: UIP has developed a relationship with Russell Thomson, Managing Director and Principal Consultant of TPQ Consultancy, Ltd in the United Kingdom to provide QP release services to our clients. Russell has extensive experience across the full range of CMC related activities associated with the development, manufacturing (both clinical and commercial), and registration (from API synthesis to finished product packaging) of a wide range of dosage forms focused in the EU regulatory space. Russell has visited our facility on numerous occasions to conduct QP audits and has provided UIP a GMP Audit Certificate confirming his assessment of the general compliance of the operations and systems of UIP with the requirements, principles, and guidelines of European Commission Directive 2003/94/EC as interpreted in EudraLex – Volume 4 Good Manufacturing Practice (GMP) Guidelines.
NEW HEATED PASTE Filler PurchaseD
July 2012: UIP has purchased a new Model GF SKPMP heated paste filler. This unit can be utilized to fillointments, pastes, and other semi-solids into jars, tubes or othercontainers. The unit is constructed ofstainless steel and fully cleanable. It is especially useful with products that are solids at room temperature, but become liquid when heated. The unit has been fully qualified and has already been used to fill a clinical batch of product.
ENHANCEMENTS IN ENVIRONMENTAL MONITORING FOR UIP CLEAN ROOMS
March 2012: UIP has purchased 4 new Millipore Integritest® 4 automated filter integrity test instruments. These units represent an upgrade of our filter integrity testing equipment. These units perform bubble point, diffusion, enhanced bubble point, and HydroCorrSM tests on a wide range of filters including disks, cartridges and TFF filters. The instruments are designed and qualified to achieve high test accuracy and have readily cleanable surfaces.
University of Rochester and University of Iowa Collaboration
increased solid oral dosage forms capacity
January 2011: UIP’ Non-Sterile Products Group has added a 10 cubic foot V-blender. This additional blender effectively doubles UIP’ solid oral dosage forms capacity from 50-75 kg to 100-150 kg. The unit is expected to be fully qualified and in operation by the end of February.
Additional HPLC Detector Capabilities
August 2010: UIP purchased and qualified a second Corona charged aerosol detector for use in our Quality Control and Method Development Laboratories. These detectors are used with HPLC systems to detect compounds without a good chromophore. Charged aerosol detectors are especially valuable for quantifying related substances and impurities that are present at very low levels. UIP has also added a second Agilent Refractive Index Detector in our Quality Control and Method Development Laboratories. These additional detectors augment our existing detection capability which includes standard UV detectors, as well as an Agilent Diode Array Detector and a Waters Photo Diode Array Detector.
New Cone and Plate viscometer
March 2010: UIP purchased and qualified a new Brookfield cone and plate viscometer. This new viscometer allows rapid determination of absolute viscosity on small samples of semi-solids. This unit provides the precision necessary for development of complete rheological data on semi-solid and liquid formulations.
UPGRADEd STERILE PRODUCTS POTENT MATERIALS HANDLING CAPABILITIES
February 2010: UIP has purchased a custom isolator system from EnGuard Systems. The complete isolator consists of two independent isolators docked together and functions as one isolator. The first chamber enables powders and liquids to be weighed and easily transferred to the second chamber. The second chamber is equipped with a scale, mixer, and containers used for solution preparation. The isolator’s air handling systems consist of HEPA filtration in and out and provides an ISO class 5 environment in a static condition. The isolator’s alarm and monitor system includes differential pressure gauges with visual and audible alarms. The isolator is capable of operating under positive, negative or neutral pressure and can be manually adjusted.
ENHANCEMENTS IN ENVIRONMENTAL MONITORING FOR UIP CLEAN ROOMS
February 2010: UIP has purchased 16 new Climet CI-3100 remote particle counters (including two CI-309A alarm towers and associated data acquisition hardware and software). Installation of these units in strategic locations within UIP Clean Rooms provides greater capabilities for trending and reporting non-viable particulate counts during the manufacturing process for aseptically filled sterile products. Each remote sensor is managed with DataPro 3 software and enables live data visualization via the user interface on dedicated data stations. The DataPro 3 software package will generate a variety of reports compliant with industry and regulatory standards (including EU GMP Annex 1 (2008), ISO 14644-1, and FS209E).
January 2010: UIP director, Mickey L. Wells, PhD, was the primary author of a paper published in AAPS' PharmSciTech journal. The title of the paper is "Investigation into the Dissolution Rate Increase on Storage of Wellbutrin SR® 100 mg Tablets". The paper describes investigation of the cause of dissolution rate increases observed after storage of Wellbutrin SR® 100 mg Tablets (a hydrophillic matrix sustained release tablet) and the ultimate formulation modifications utilized to adress the problem. UIP personnel have extensive experience formulating both hydrophilic matrix and coated sustained release solid oral dossage forms using a variety of polymers.
Lyophilization Cycle Development Equipment In Place
September 2009: UIP has completed installation of a Lyotherm 2 and Lyostat 2 from Biopharma Technology Limited. The Lyotherm 2 provides integrated Differential Thermal Analyser (DTA) and electrical impedance (Zsinφ) capability in a single instrument. The Lyotherm 2 is designed to measure glass transition (Tg'), eutectic (Teu) and melting (Tm) temperatures relevant to freeze-drying formulations. The Lyostat 2 is a fully integrated freeze-drying microscope that enables critical events such as collapse and melting to be observed in situ, as well as characteristics such as skin or crust formation to be observed and identified. The coupled Lyostat 2 and Lyotherm 2 units provide valuable information for both formulation and cycle development processes. With UIP's in-house expertise in lyophilization, the purchase of this system will allow quicker and more efficient development of lyophilization cycles. In fact, already during installation testing and training, UIPDC staff were able to discover a potential solution to a lyophilization challenge presented by a research project.
New Sterile Fill Line
August 2009: UIP has completed qualification of a new Flexicon FP50 Aseptic Filling and Stoppering Machine for use in the Clean Room that serves our Hull 48 square foot lyophilizer in the Sterile Products department. The FP50 is designed to operate at speeds of up to 25 vials per minute, filling from 0.5 to 50 mL per vial with a filling accuracy of better than ± 1% (depending on the fill volume). The entire fluid path of the peristaltic filling system is single use silastic tubing. Self standing glass vials from 2 mL to 50 mL can be filled and stoppered with 13 mm or 20 mm stoppers. The filling and stoppering operations take place within the ISO Class 5 (Class 100) areas in the Sterile Products Clean Rooms in accordance with both FDA and EU regulatory requirements.
July 2009: Renovation of an additional approximately 1,000 square feet of newly acquired space in UIP’ building at the Oakdale Research Park nears completion. This space will allow UIP to consolidate all of its analytical operations in one location. This will increase the flexibility of staff and analytical equipment, enhancing the efficiency of UIP' analytical method development and validation and Quality Control testing services. UIP expects the relocation of personnel into this space to be completed by late summer to early fall. Use of the vacated space at the UIP College of Pharmacy location for other functions will allow for improved personnel and material flows within this facility. Relocations will be accomplished without impact ongoing analytical or manufacturing operations.
Minncare DRY FOG SYSTEM
June 2009: UIP purchased a Minncare Dry Fog System which is currently being qualified for use in the Sterile Products department. The Dry Fog system provides an easy to use process for Clean Room fogging. The combination of cold sterilant and state of the art Dry Fog delivery system enables a rapid and safe delivery of sanitizing solution vapor to even the most hard to reach areas of our Clean Rooms. The Dry Fog equipment produces fine droplets which ensure even dispersion of disinfectant solution throughout a room. These small droplets tend to bounce off solid surfaces, avoiding excessive condensation, corrosion and surface wetting issues. The small droplets penetrate normally inaccessible areas and lead to a more effective sanitization process. The cold sterilant is a peracetic acid and hydrogen peroxide based chemical registered with the EPA for use as a fog to enhance existing cleaning and disinfection processes. It is fully biodegradable and will leave no measurable air residuals once the room has been fully ventilated. The use of this unit will provide an added level of assurance that UIP Clean Rooms have been effectively cleaned for aseptic operations.
Lyophilization Cycle Development Equipment Ordered
May 2009: UIP issued a purchase order for a Lyotherm 2 and Lyostat 2 from Biopharma Technology Limited. The Lyotherm 2 provides integrated Differential Thermal Analyser (DTA) and electrical impedance (Zsinφ) capability in a single instrument. The Lyotherm 2 is designed to measure glass transition (Tg'), eutectic (Teu) and melting (Tm) temperatures relevant to freeze-drying formulations. The Lyostat 2 is a fully integrated freeze-drying microscope that enables critical events such as collapse and melting to be observed in situ, as well as characteristics such as skin or crust formation to be observed and identified. The coupled Lyostat 2 and Lyotherm 2 units provide valuable information for both formulation and cycle development processes. With UIP's in-house expertise in lyophilization the purchase of this system will allow quicker and more efficient development of lyophilization cycles.
CLEAN ROOM OPERATOR TRAINING
February 2009: Anne Marie Dixon, the managing partner of Cleanroom Management Associates, Inc., conducted a 3 day intensive Clean Room operator workshop on site. Ms. Dixon has been actively engaged in the field of Contamination Control since 1976 with extensive experience in the areas of training, strategic consulting and technical writing. Ms. Dixon has trained over 250,000 cleanroom technicians and managers. She is the author of over 90 technical papers and 5 books. UIP is excited to have had the opportunity to have Ms. Dixon in to conduct this training.
New Sterile Fill Line
January 2009: UIP issued a purchase order for a second new Flexicon FP50 Aseptic Filling and Stoppering Machine for use in the Sterile Products department. The FP50 is designed to operate at speeds of up to 25 vials per minute, filling from 0.5 to 50 mL per vial with a filling accuracy of better than ± 1% (depending on the fill volume). The entire fluid path of the peristaltic filling system is single use silastic tubing. Self standing glass vials from 2 mL to 50 mL can be filled and stoppered with 13 mm or 20 mm stoppers. The filling and stoppering operations take place within the ISO Class 5 (Class 100) areas in the Sterile Products Clean Rooms in accordance with both FDA and EU regulatory requirements.
The University of Iowa Pharmaceuticals Development Consortium
January 2009: The University of Iowa Pharmaceuticals Development Consortium (UIPDC) will be officially launched. This organization consists of the University of Iowa College of Pharmacy pharmaceutics faculty and The University of Iowa Pharmaceuticals personnel. This new group will be focused on preformulation, technical feasibility and formulation development projects especially for compounds that present scientific challenges (solubility, stability, polymorphism, etc.). The technical expertise of the pharmaceutics faculty will be utilized in combination with the client-focused management and manufacturing skills of UIP staff to expand pharmaceutical development capabilities at the University of Iowa.
New VIAL WASHER
December 2008: UIP completed the qualification and validation of a new Steriline model RA-AV2 Vial Washer within the Sterile Products department. The Steriline Washer has been validated to clean vials with both 13 mm and 20 mm openings, ranging in size from 2 mL up to 100 mL. Each programmed washing cycle consists of alternating spraying’s of Water for Injection and compressed air, to provide a more effective cleaning process. Both internal and external spraying of Water for Injection and compressed air are performed. The rotary washer utilizes lifting needles for a more thorough internal washing of each container. The control system and audit trail are 21 CFR Part 11 compliant.
May 2008: UIP completed the qualification and validation of a new Flexicon FPC50 Aseptic Filling, Stoppering and Crimping Machine in the Sterile Products department. The FPC50 is designed to operate at speeds of up to 25 vials per minute, filling from 0.5 to 50 mL per vial with a filling accuracy of better than ± 1% (depending on the fill volume). The entire fluid path of the peristaltic filling system is single use silastic tubing. Self standing glass vials from 2 mL to 50 mL can be filled, utilizing 13 mm or 20 mm stoppers and flip-off crimp seals. The filling, stoppering and crimp sealingoperations all take place within the ISO Class 5 (Class 100) areas in the Sterile Products Clean Rooms in accordance with both FDA and EU regulatory requirements.
February 2008: UIP purchased a Vector Lab-1 fluid bed processing unit for use in the Solid Dosage Forms Department. This unit has the capability to perform top spray granulation and Wurster coating operations. While not purchased with rotor capability, this feature can be added if needed. This unit has been fully validated and has already been used to process a number of batches of product. UIP personnel have extensive fluid bed experience working with other fluid beds from both Glatt Air Techniques and Vector. The purchased unit complements our existing Vector Mini Fluid Bed.