Table 3 Screening Technologies – Current Use, Benefits, and Limitations

Africa

▪ Thermo Fisher Scientific’s Handheld Raman, TruScan

▪ Global Pharma Healt Fund’s Minilab

▪ Pharmacies support the use of STs to detect SFs.

▪ TruScan use was seen as reducing SF prevalence.

▪ Minilab primarily used to check antimalarial medicine quality.

▪ TruScan’s associated cost; reference standards requirements; time for library development; inability to work through packaging; software ease of use; training requirements; after-sales service; maintenance; and repairs.

▪ Minilab cannot perform dissolution testing; results were not sufficiently quantitative, limiting its use in litigation.

▪ Pharmacies, manufacturers, and distributors were not using ST; most felt that NAFDAC was responsible for assuring the quality of medicines within the local marketplace

▪ Manufacturers indicated that cost and the lack of available information on STs limited their uptake.

▪ Thermo Fisher Scientific’s Handheld Raman, TruScan

▪ TruScan spectrometers employed to detect SF at some ports of entry.

▪ MCAZ noted that Minilabs would be particularly useful at the ports of entry.

▪ Ministry of Health would like to place TruScan units at all ports of entry and across the supply chain if funding were available.

▪ Although regulators, manufacturers, and pharmacies expressed interest in using portable STs, none reported widespread use.

▪ Most cited lack of ST affordability as a limiting factor; some, insufficient information about comparing available technologies.

Americas

▪ Raman spectrometers used by a manufacturer for its quality control of raw material and finished product active pharmaceutical ingredient identification

▪ Thermo Fisher’s Handheld near infrared spectrometer, Phazir used by a manufacturer for identifying starting materials

▪ Raman spectrometers save reagents and identify material outside of the quality control laboratory; this speeds operations and prevents contamination because there is no need to open multiple drums.

▪ NIR is fast and simplifies product identification.

▪ Lack of information on availability and cost of non-Raman technologies; difficulties procuring and importing new technologies^a.

▪ A manufacturer did not use any STs, but relied on testing by an anti-counterfeit laboratory focused on product security in the Latin American region.

▪ Pharmacies do not use STs; they rely solely on the National Traceability System to ensure medicine quality^b

▪ Handheld near infrared spectrometer was used by a manufacturer.

▪ STs are not used by COFEPRIS; pharmaceutical analyses are currently done in laboratory by compendial methods.

▪ STs were not used by distributors or pharmacies.

▪ Handheld near infrared spectrometer is used for API identification during production; this manufacturer was evaluating the benefits of near infrared compared with Raman.

▪ Raman has the broadest scope of use based on the chemical characteristics related to the components used by the manufacturer.

▪ ST awareness is expected to grow under new legislation that manufacturers need to identify raw materials, active ingredients, and excipients in containers unless the vendor has been pre-qualified.

▪ COFEPRIS does not recognize ST technologies for confirming medicines quality because the Mexican Pharmacopoeia does not recognize these methodologies for testing or have a standardized way to deploy or interpret the results.

▪ Raman, alternative light source, and Ion Mobility Spectrometers .

▪ ST technologies are validated prior to field use.

▪ Alternate light source and Ion mobility spectrometers have successfully detected SFs entering the U.S.

▪ Raman spectroscopic tests are well characterized, with accumulated knowledge on how to use them in quality testing; instrument vendors provide training; maintenance is low, simple, and affordable.

▪ Raman and near infrared distinguish among organic substances, inactive ingredients, and most active ingredients in pharmaceuticals and final products.

▪ Maintaining and updating spectral libraries are the biggest challenges the FDA faces.

▪ The cost of commercial devices is high compared to in-house developed alternate light source technology.

▪ Using Raman to test certain products with fluorescence and low-dose concentrations is problematic without further offline processing of results.

▪ Raman cannot reliably authenticate all of its medicines, a manufacturer commented; the results depend on the complexity of the chemical composition.

▪ Independent pharmacies in one state do not use any STs, citing expensive ST instrumentation and a perception that the quality of commercially available products has already been ensured.

Eastern Mediterranean

▪ Handheld STs are not used by regulators or manufacturers.

▪ Pharmacies do not use STs, but some use two-dimensional barcoding.

▪ STs for raw materials that are imported into Egypt, some of which have been substandard in the past, would help the manufacture of products for domestic consumption^c.

▪ Reasons for not using STs included:

▪ Lack of knowledge about the benefits of STs

▪ ST training costs

▪ ST results are insufficient grounds for taking action against a poor quality product; full compendial laboratory analysis is necessary.

▪ SF medicines are perceived as too low to justify purchase and use such of ST, according to a regulator; STs would probably not improve PMS activities or the ability to detect poor quality medicines.

▪ STs are affordable for multinational pharmaceutical companies but not for smaller manufacturers, according to a manufacturer.

▪ STs are not used by the JFDA.

▪ Handheld Raman and near infrared are used for identification of raw materials by Jordanian manufacturers.

▪ STs are not used at the pharmacy; however, barcoded pricing is obligatory and can trace products from the pharmacy shelf back to the manufacturer.

▪ JFDA quality control laboratory noted that handheld ST devices could reduce overall workload of analysts, but preferred that the purchase of traditional lab equipment instead of “costly” STs.

▪ Near infrared spectrometers were cheaper and safer for users than other currently available STs; and the vendor provided training.

▪ Challenges JFDA faced when it did use ST (TruScan) included: limited spectral library; short battery life and lack of a backup battery; large size; lack of touchscreen function; high cost; and lack of in-country customer service.

▪ JFDA cannot use ST results as evidence of SFs in reports.

Southeast Asia

▪ State FDA used mobile testing vans equipped with Thermo Fisher Scientific’s MicroPhazir RX 4.0 handheld near infrared; SciAps Inspector 300 Raman spectrometer; and Elvatech Pro X-Ray Fluorescence spectrometer.

▪ vHandheld Raman and near infrared spectrometers were used by Customs.

▪ Handheld near infrared spectrometers were used by manufacturers; internal spectral library was shared with other manufacturing facilities.

▪ Regulators and manufacturers noted that: NIR spectrometers are easy to use, non-destructive of the dosage form, and work through packaging; Raman spectrometers are lightweight and fast; after spectral libraries have been developed, they can be used to analyze samples quickly.

▪ State FDA is considering using automated sterility, microbial enumeration, and microbial identification systems to reduce laboratory time testing products.

▪ Manufacturers noted that spectral libraries are product-specific, and some raw material spectra can be shared easily.

▪ Regulators and manufacturers noted that:

▪ Key limitations of STs relate to spectral library development, maintenance, expansion, and sharing.

▪ Near infrared spectrometers cannot be used for fixed-dose combination products; on certain coatings; for low-dose products; or for differentiating structurally similar compounds (e.g., azithromycin, erythromycin).

▪ The Raman spectrometers cannot be used for detecting fluorescent compounds or water-based liquid dosage forms; and they do not have peak labeling capabilities.

▪ Manufacturers noted that results obtained with STs are only preliminary. Additional challenges include the complexities of validating and calibrating the technologies and training requirements for staff.

▪ STs were not used by pharmacies that participated in interviews; limiting factors include the cost of ST technology, training, and the developing a quality control system.

Western Pacific

▪ Global Pharma Health Fund’s Minilab

▪ Philippines FDA sentinel sites use Minilab for initial screening of medicines from retail outlets.

▪ There are plans to provide Raman spectrometers or handheld X-ray fluorescence spectroscopy to regional field offices for product screening. This would enable Philippines FDA laboratories to maximize their resources because only

▪ Confirmatory testing of suspect pharmaceutical samples would be necessary.

▪ Challenges of using Minilab include:

▪ Tracking the supplies and importing certain reagents needed to run tests^d.

▪ Training FDA and Department of Health staff to use Minilab, which is compounded by frequent staff turnover.

▪ Thermo Fisher Scientific’s Handheld Raman TruScan is used by manufacturers.

▪ Handheld near infrared and Raman spectrometers are carried by NIFDC mobile vans; they also carry smaller versions of lab-based high performance liquid chromatography.

▪ Mobile vans and handheld spectrometer technologies do not require chemical reagents.

▪ High performance liquid chromatography testing uses an abbreviated, quick result protocol; suspicious samples are sent to a quality control laboratory for full compendial testing.

▪ APIs and finished pharmaceutical product manufacturers send numerous samples to provincial regulators for spectral library development; and an annual report with this screening data is prepared for the Chinese Food and Drug Administration.

▪ Development of spectral libraries is a major challenge associated with the use of near infrared and Raman. Spectral libraries are not shared among provinces, which makes communicating findings between provinces a challenge.

▪ Training is an issue because vendors conduct training at the time of purchase.

▪ STs are not used by manufacturers or pharmacies to screen finished products in the market.