Manu Grover, Product Manager – Pharma, Waters India, gives an insight about the concepts of reverse innovation in LC Detector Technology drawing instances from a case study
The pharmaceutical industry’s steady growth curve is beginning to taper in 2017, thanks to a few unique challenges that have unfolded recently. Pharma R&D productivity has also diminished and the pharma landscape is changing.
The US is the largest pharma market globally and for India too, hence the performance of the US market is crucial for the industry. Single-digit spending growth is forecast for the US market. The US market growth rate declined from 12 per cent in 2015 to 7 per cent to 8 per cent in 2016 with a 6 per cent to 9 per cent growth forecasted through 2021. Despite the slowing growth, the US will account for 53 per cent of forecasted global pharma industry growth of $367 billion through 2021.
In these times of rapid changes, it is not enough for pharma companies to focus solely on selling drugs and medications. Today, the industry aims for more holistic approach with integrated services. There are upcoming trends in the industry to which pharma companies have to respond to. One such innovative trend is ‘reverse innovation or reverse engineering.’
Reverse innovation is any innovation, which is likely to be adopted first in the developing world. Upon adoption of the reverse innovation in emerging world, the product gets distributed globally. Reverse innovation is a response to numerous challenges, which the industry is facing now, such as a slowdown in successful new drug launch, increasing research costs, decreasing revenues due to patent expirations and huge expense to bring a drug to the market as a result of enhanced regulatory hurdles.
There are different levels of reverse innovation, for e.g. in first level, we identify the major ingredients/impurities. This is often used to verify label claims or give guidance to the formulation/analytical chemist, and in next level we need to identify and quantify all impurities, process markers etc. in the system which is needed to ensure that the ANDA will meet approval with consideration to ICH Q3B (R2), impurities in NDA.
There are analytical tools available in the industry today which can help in innovator/generic drug screening like liquid chromatography equipped with Acquity QDa, Evaporative Light Scattering Detectors, Refractive Index Detectors & UV/PDA detectors. Other than conventional liquid chromatography techniques, we have technologies available like FTIR, DSC/TGA, SEM, Microscopy, XRD, LC-MS etc.
Let us explore here through a case study the advantage of Waters ‘Acquity QDa’ w.r.t reverse innovation process.
Acquity QDa is an orthogonal mass detector, that complements UV/PDA detector and gives mass information about the peak of interest. This detector has been designed for chromatographers who lack mass spectrometer (LC-MS) handling expertise.
In this case study, to study the concepts of reverse innovation we procured multiple formulations of API called as ‘Metoclopramide. Metoclopramide is used to prevent nausea and vomiting.
The samples used in case study were Metoclopramide HCl 10mg Tablets from two different brands (Brand X and Y) and Metoclopramide HCl injection 5mg/ml from Brand Y.
All the samples were prepared in a uniform way and were run under identical conditions using liquid chromatography coupled with PDA and Acquity QDa. After analysis, we processed the data using Empower CDS software and compared the data as depicted in the table in Figure-1.
A representative image of how PDA-Acquity QDa gives the spectra and mass no. simultaneously on Empower Software is shown in Figure-2. This data clearly reflects the advantage of an easy to use mass detector Acquity QDa. Based on the data generated using Acquity QDa detector coupled with PDA detector, it was found that USP specified impurity, 4-Amino-5-chloro-N-(2-(diethylamino) ethyl)-2-hydroxybenzamide was found in tablets of brand X and injectable of brand Y only, but no other USP-specified impurities have been found in any samples. We also observed formulation-specific impurities/excipient peaks and they were identified by their mass number.
Hence to conclude, Acquity QDa is going to be ‘must to have’ detector for all R&Ds and QC labs working on generics, complex generics, nutraceuticals etc. It’s a fast screening tool in R&D’s to compare analytical samples like multiple source of API’s, different grades of API, API versus formulation and stressed samples versus unstressed samples. It is useful in QC labs w.r.t cleaning sample analysis/validations, low level genotoxic impurity quantification, unknown peak identifications and OOS/OOT studies.
Acquity QDa is a tool for conducting orthogonal peak purity studies, wherein homogeneity of the peak can be verified or confirmed by selecting the purity tab from Empower Software. Here, we get mass number at start, apex and end of the peak. This unique feature of Acquity QDa along with its ease of use, makes this detector a real universal detector for most of the pharma applications and a must investment for R&D and QC labs.