Analytical Technologies Singapore

Pharmaceutical

Pharmaceutical Cleaning Validation

Detecting and quantifying trace residue concentrations of active pharmaceutical ingredients (API), excipients, and washes during cleaning validation procedures on pharmaceutical manufacturing equipment is one of the single largest costs associated with the manufacture of pharmaceutical drugs. Current cleaning validation cost are dominated by high labor cost of swabbing and ~90 hours of manufacturing equipment down time due to exhaustive lab (HPLC) analysis throughput limitations.

Presently, pharmaceutical companies pill process manufacturing require about 12 hours to blend and press a tablet, the machines are then broken down and washed (4 hours). The swabbing, 25cm2 area at 100 to 300 locations within each piece of manufacturing equipment, extracting residual contamination picked up by each swab, and running each sample through an HPLC instrument, which takes at least 30 minutes per sample accounts for (90 hours) 4 days after manufacturing a single batch of pills to validate that they have adequately cleaned the equipment, within internal and FDA regulations, in preparation for manufacturing a new batch of pills. This is a very laborious process and combined with the idle time of the manufacturing equipment is a very expensive part of pharmaceutical manufacturing cost.

The Photon Systems’ deep UV TraC instrument can reduce the time to validate the cleaning process to less than 4 hours and virtually eliminate equipment down time and eliminate the need for sample collection, extraction and testing with HPLC reducing cost associated with cleaning and turnaround by 1000 times or more.

Photon Systems has already demonstrated to a leading global pharmaceutical manufacturer that we can reduce the cleaning validation process to a few hours. We have currently tested several active pharmaceutical ingredients such as antidepressants of the serotonin-norepinephrine reuptake inhibitor (SNRI) class and beta blockers, cleaning washes such as SumaStar, Diver Wash, and CIP-200, as well as excipients such as microcrystalline cellulose, ethyl cellulose, magnesium stearate, and starch. We accomplished this with a demonstrated ability to detect and quantify APIs down to less than 0.2 mg/cm2. The system and method we have demonstrated has the ability to virtually eliminate the extensive labor cost by eliminating the need for sample collection, extraction, and testing with HPLC and the vastly reduced and materials and time cost associated with machine down time. The cleaning validation cost savings to pharmaceutical manufacturers is still under study, but it is massive.

Pharmaceutical Cleaning Validation Read More »

New literature from Copley provides guidance for better inhaler testing.

New literature from Copley Scientific, the world’s leading manufacturer and supplier of inhaled product testing equipment, highlights the importance of controlling temperature, relative humidity (RH) and electrostatics in the test environment to maximise the integrity and value of inhaler test data. In an application note and white paper, company experts provide insight into the issues and practical guidance for improvement including experimental data demonstrating the performance of EnviroMate™, a benchtop environmental control chamber for inhaler testing. An interesting and informative read for anyone looking to minimise variability in inhaler testing, the new literature is freely available for download.

“Variability in the test environment is a frequently overlooked contributor to poor quality data and out-of-specification results,” said Clair Brooks, Applications Specialist, Copley. “This white paper explains the links between test environment, orally inhaled product (OIP) performance and measured metrics, while the app note provides experimental evidence showing how EnviroMate can help. Both make good reading for those with a problem with temperature, RH or electrostatics control within the lab.”

Establishing a robust environment for inhaler testing’, the recently released white paper, addresses questions such as:

  • Why is OIP testing prone to variability?
  • What is the economic impact?
  • How do changes in temperature, RH and electrostatic charge affect the performance of different classes of OIP – nebuliser, metered dose inhaler and dry powder inhaler?
  • How can environmental conditions influence cascade impactor measurements?
  • What strategies and solutions are available to improve environmental control?

Reducing variability in the inhaler testing environment’ is a complementary application note detailing an experimental study of the performance of an EnviroMate. The resulting data show how the unit delivers constant temperature and RH in the face of variability in an air-conditioned lab typical of those used for inhaler testing.

“During training, customers routinely ask how to tackle sources of variability and improve data integrity, so we’re delighted to add these valuable pieces to our literature library,” concludes Brooks.

Read the white paper here, the app note here, or find out more about the EnviroMate here

New literature from Copley provides guidance for better inhaler testing. Read More »

New, automated shake and fire platforms from Copley cut the burden of MDI and nasal drug product testing

 The latest generation of Vertus® automated shake and fire platforms from Copley Scientific make it easy and intuitive to integrate automation into a wide range of drug product testing workflows to boost productivity, drive down test variability, and simplify training. The Vertus® III+ is the company’s new flagship, fully automated benchtop system for pressurised metered dose inhaler (MDI), nasal spray and nasal aerosol testing. Comprehensively updated to meet testing requirements for an even wider range of device types, it incorporates a greater array of interchangeable test plates and, integrated shot weight measurement. The DecaVertus® III is a complementary, high throughput solution for firing-to-waste, with the capacity to simultaneously discharge 10 devices under identical conditions to those applied by the Vertus III+. Both feature a new exhaust system that eases the handling of highly flammable propellants. Together they present a compelling, highly effective solution for product testing.

The current regulatory and clinical landscape has resulted in a surge of activity in MDI reformulation and nasal drug product development; the Vertus platform can help significantly reduce the associated burden of routine analysis. Automated shake and fire systems eliminate any requirement for manual device actuation, simulating device handling by the patient via parameters such as shaking action, time between doses, and actuation force profile. Through life testing for MDIs, which requires the firing of hundreds of doses to waste, and regulatory guidance that recommends a ‘mechanical means of actuating the pump assembly be employed’ for spraysi are notable drivers for adoption.

The new Vertus systems are compliant with both pharmacopoeial specifications and 21 CFR Part 11.  Vertus and DecaVertus share an arc-like shaking motion consistent with typical analyst technique, enabling device actuation methods developed on the Vertus to be transferred directly to, and rigorously replicated on, the DecaVertus for firing-to-waste. Both shaking angle and firing force ranges have been increased relative to previous models for greater flexibility with respect to test configuration.

Other key features of the new Vertus III+ include:

  • Integrated shot weight measurement for rapid and efficient Uniformity of Delivered Mass testing for nasal solution products, in line with compendial specifications.
  • A re-engineered exhaust port for simple connection to airflow extraction, making it easier to handle highly potent drugs and more flammable propellants such as HFA152a, a low global warming candidate for MDI reformulation.
  • A large, adjustable screen and intuitive user interface allowing easy interaction with minimal training.
  • A new integrated priming and waste module for streamlined, automated testing, notably across the entire contents, with minimal manual input.
  • An extensive range of interchangeable interface plates for test apparatus such as a Spray Force Tester, Thin Layer Chromatography plates (for spray pattern), Alberta Idealised Throat and Alberta Idealised Nasal Inlet, for the comprehensive testing of both innovator and generic products.

Find out more about the next generation of the Vertus family and how they could transform your testing practice.

New, automated shake and fire platforms from Copley cut the burden of MDI and nasal drug product testing Read More »

Copley introduces the new Flow Rate Sensor, a dedicated device for inhaler testing systems.

The new Flow Rate Sensor FRS is the latest addition to Copley Scientific’s orally inhaled and nasal drug product (OINDP) testing portfolio which sets the benchmark for innovative, efficient, and reliable inhaler testing solutions. The FRS is a robust, low resistance, bi-directional flow sensor that delivers rapid data output via a direct interface with a suitable flow controller, streamlining operation and maintaining a reduced test set-up footprint. A product of Copley’s engineering excellence, and designed specifically for inhaler testing, it offers exemplary flow rate measurement for compendial-compliant testing and allows users to accurately track complex inhalation profiles.    

Compendial methods for OINDPs specify the setting of representative flow rates for both delivered dose uniformity testing (DDU) and aerodynamic particle size distribution (APSD) by cascade impaction. Accurate control is especially important for APSD measurement since cascade impactor performance is calibrated as a function of air flow rate. Beyond compendial methods, assessing the impact of inhalation profile characteristics such as rise-time is increasingly common practice as developers work to enhance product performance for specific patient populations.  

The FRS is an easy-to-use device that integrates seamlessly into standard test set-ups to provide consistent and accurate flow measurement for all types of OINDPs including dry powder inhalers, metered dose inhalers, aqueous droplet inhalers, nebulisers, nasal sprays, and nasal powders. Key features include: 

  • Simple, robust design specified for integration, control, and display via the Breath Actuation Controller BAC 100i or Critical Flow Controller TPK 100i
  • Bi-directional flow functionality for flexible installation
  • Rapid data output for in-depth analysis
  • Low flow resistance for high flow testing with minimal impact 

Copley introduces the new Flow Rate Sensor, a dedicated device for inhaler testing systems. Read More »

Introducing the Copley Impactor Genie™ IG 200i, a two-in-one solution for quicker, more efficient inhaled product testing

The new Impactor Genie™ IG 200i from Copley Scientific is a cost- and space-efficient semi-automation tool for regulatory and compendial aerodynamic particle size distribution (APSD) measurement with either the Andersen Cascade Impactor (ACI) or Next Generation Impactor (NGI), the impactors of choice for most orally inhaled and nasal drug products (OINDPs). A two-in-one unit that automates both impaction surface coating and drug dissolution, it improves the speed and productivity of inhaler testing while at the same time reducing variability. The IG 200i headlines a suite of new solutions from Copley, the world’s leading supplier of inhaler testing equipment, that brings first-in-class semi-automation solutions for the ACI and NGI. The full line-up includes the new Impactor Coater™ IC 200i, for collection plate and cup coating, and the enhanced Gentle Rocker™ GR 200i, for drug dissolution; the IG 200i combines the functionality of both. Selecting the option best aligned with laboratory workflows ensures a cost-efficient outcome for every customer.

“These solutions extend valued semi-automation capabilities for the NGI to the ACI. Compact and easy to use, the IG 200i lightens the manual workload when working with either impactor at the same time improving data integrity and easing method transfer,” said Matthew Fenn, Head of Business Development at Copley, “Its dual functionality preserves precious bench space allowing analysts to switch easily between cup coating and drug dissolution as required. A great addition to our semi-automation line-up, the IG 200i is a sound investment for both ACI and NGI users that releases analyst time for higher-value tasks.’

Coating impaction surfaces with a tacky viscous solution minimises the risk of particle bounce, a known cause of inaccurate measurement, notably for dry powder inhalers. Following size fractionation of the delivered dose, drug is recovered from each collection plate or cup of an impactor via dissolution, to generate an APSD for the active pharmaceutical ingredient(s). This too is a manually intensive process that can give rise to variability in the resulting data.

The IG 200i:

  • Accommodates either a complete set of NGI Collection Cups or ACI Collection Plates.
  • Is compatible with a wide range of coating solutions.
  • Applies a uniform coating to each individual collection cup/plate in as little as two minutes using a precision multichannel dispenser.
  • Supports a range of drug recovery methods, with an adjustable rocking speed in the range 10 – 60 rpm.
  • Has a tilting function to aid sample collection.

The new Copley Impactor Genie™ 200i is an all-in-one solution for cup coating and drug dissolution that boosts the efficiency of inhaler testing with the NGI and ACI (Impactor Coater™ IC 200i mode (left) and Gentle Rocker™ GR 200i mode (right), with ACI Collection Plate Tray & Cups.

 

Introducing the Copley Impactor Genie™ IG 200i, a two-in-one solution for quicker, more efficient inhaled product testing Read More »

The new DUSA Shaker™ DTS 100i from Copley: For faster, safer, more repeatable inhaler testing

The DUSA Shaker™ DTS 100i is a new semi-automation solution from Copley Scientific, the global leader in inhaler and nasal drug product testing equipment, that supports quicker, more efficient, regulatory and compendial delivered dose uniformity (DDU) testing. A fully updated version of the original Copley DUSA Shaker, it provides full, fast, repeatable rinsing for Dose Uniformity Sampling Apparatus (DUSA) for metered dose inhalers (MDIs) and dry powder inhalers (DPIs). Benefiting from Copley’s unrivalled understanding of inhaler testing, the robustly engineered DTS 100i accelerates timelines, increases repeatability and accuracy, and releases analysts for higher value work.

DDU testing confirms the consistency of dose delivery across the lifetime of an individual inhaler and across each batch of product. A key step is rinsing the DUSA to recover a delivered dose. This process can be carried out manually, but an automated approach is better from the perspective of ensuring full recovery, health and safety, and efficiency.

The DTS 100i is a modular solution that will slot easily into any existing set-up or workflow and a perfect low-cost, introduction to the benefits of semi-automation. The original DUSA Shaker has been used in busy inhaler testing labs across the world for over a decade; the comprehensively re-engineered and updated DTS 100i offers:

  • Up to 10 times quicker drug recovery, compared with manual practice
  • An intuitive touchscreen interface for easy operation
  • An optimised lateral shaking and/or rotating motion for repeatable, complete rinsing
  • The flexibility to handle full or partial loads
  • Adjustable lateral shaking speed in the range 20 – 200 rpm
  • Extensive data reporting options

The new DUSA Shaker™ DTS 100i from Copley: For faster, safer, more repeatable inhaler testing Read More »