One of the most powerful weapons in the pharmaceutical industry’s battle to defeat counterfeiting and circulation of substandard medicines is advanced science. Outsourcing-Pharma (OSP) recently spoke with Pascal Chalus (PC), senior principal scientist of forensic chemistry with Lonza Drug Product Services, about the group and its work.
OSP: Please tell us a bit about the Forensic Chemistry Group—who you are, what you do, key capabilities/responsibilities, and any recent projects or accomplishments you'd like to share.
PC: The Forensic Chemistry Group from Lonza Drug Product Services (DPS) is a team of 15 people with a broad experience range covering areas such as small molecule oral dosage form pharmaceuticals and biopharmaceuticals to trace analysis of narcotics in urine samples.
Our technology portfolio allows very versatile sample analysis - from purely physical parameters down to chemical identification and traces analyses. Therefore, we can characterize excipients, drug substances and drug products from physical appearance to their chemical composition.
We are currently using established techniques such as HPLC or light microscopy and more advanced technologies such as LC-MS, GC-MS, electron microscopy with energy dispersive X-Ray spectroscopy, vibrational spectroscopies, chemical hyperspectral imaging, and X-Ray computed tomography.
Although primarily used for peptide mapping, extractable and leachable analysis, particle investigation and product and process development support are advanced characterization techniques that can also be used for counterfeit detection.
OSP: Could you please share your perspective on counterfeiting and the problems it poses your customers and the rest of the industry?
PC: It is essential to make a clear distinction for people who may not be so close to the subject. Biosimilars (for biopharmaceuticals) or generics (for small molecule products) are not counterfeits; these may have differing formulation from the original pharmaceutical product, but are based on the same drug substance (API), are subjected to (bio)equivalence studies and are given marketing licenses by health authorities after the corresponding assessment.
Biosimilars and generics cannot infringe granted and valid patents, and we are sometimes asked to investigate them to ensure no manufacturing patent infringement. The biosimilar developer’s objective is to broadly bring drugs to patients after patent expiry, with the patients as focus (secure and affordable access to drugs).
On the contrary, a counterfeiter's sole focus is misleading patients and making money without any regulatory control. Indeed, counterfeits may cause a high health risk for the patients. In the best case, patients do not get their treatment; in the worst case, they may be exposed to toxic compounds that may jeopardize their health.
Additionally, counterfeits and the risks they bring to the patients may harm the counterfeited drug's reputation. Therefore, originator companies have an interest to perform surveillance of the market to check for potential counterfeit activities affecting their drugs, as the consequences (including potential damage claims from customers) may be devastating. This situation puts a lot of pressure on originators as counterfeits expand not only for over-the-counter (OTC) drugs but also for prescription drugs.
OSP: What are some of the ways pharma companies and their production partners typically work to try and defeat fakes on the front end?
PC: Pharmaceutical companies ensure that they have both a well-defined product and primary and secondary packaging qualities and characteristics across their global manufacturing supply. For example, they may use exactly the same ink and colors for the logos on the boxes, the same quality of printing. They may also use a different advanced technology of counterfeit fighting, such as holographic label or seals.
OSP: How do the ways mentioned above fall short?
PC: If we go to more advanced techniques, such as radio-frequency identification (RFID) or laser coding, we must realize that they do not represent an ideal way to fight drug counterfeits. Most of the counterfeits are sold online. Unlike with banknotes, which are regularly passed to the banks that have the means to check these and withdraw the counterfeited money, counterfeited drugs go directly from moonlight manufacturers to victims.
Patients, the actual counterfeiting victims, do not have the required equipment to check for the RFID or the laser coding. For a patient, the best way to eliminate the risk is to remember that the companies making counterfeits do so for the sole purpose of making money. This means that the printing on the boxes will most likely be of low quality.
Indications of counterfeits may be blurred logos or logos with strange aspect ratios. What is also often disregarded and may be worth looking into are the leaflets. Counterfeits' leaflets often contain typos or low-quality translations.
Primary packaging is a very good indicator of counterfeiting as well. Original drugs come in blisters, with a strictly defined number of wells, position of the wells, and a sealing method of the blister. If a drug is unexpectedly packaged in another way, one should suspect counterfeits.
If working with tablets, the key aspects to observe are shape, color, quality of the embossing, and printing on the tablet surface.
OSP: What products and technologies does Lonza offer customers that can help prevent, defeat and detect counterfeiting?
PC: In addition to the visual check of the packaging and the lot number check of the drug itself, Lonza offers full analytical services to identify and precisely describe counterfeits to help customers obtain needed evidence.
On the packaging, we would perform physical measurement of the size of printing of the letters and logos on the box and check by spectroscopy if the correct ink was used. On the primary packaging, we can check the nature of the blister with vibrational spectroscopies and the thickness and the layers of the foils with tomography.
For biopharmaceuticals, we would check the stopper material and the glass quality used for the vial by electron microscopy and elemental analysis.
The step beyond packaging is to go for the identification of the drug itself. Most of the counterfeits do not contain the active pharmaceutical ingredient (API) at all or only in very low amounts - as this is the pricey part of the drug. This can be checked by vibrational spectroscopies such as mid-infrared, near-infrared, or Raman spectroscopies.
The distribution of the API and the excipients in tablets may also be checked by using these spectroscopies in hyperspectral imaging mode. In addition, compendial quality control (QC) tests such as HPLC analysis of the drug can show the presence of the correct API in the right amount. X-ray microtomography may support the measurement of the tablet coating quality and thickness.
To check biopharmaceuticals, we measure the solution's viscosity and perform size exclusion chromatography, electrophoresis or other compendial methods that may show that the product formulation is not what it should be. Here again, vibrational spectroscopy (specifically Raman spectroscopy) may be used.
If further characterization is required, our forensic chemistry group can perform peptide mapping of the counterfeit to show that it does not correspond to the original drug. These advanced steps are often not required, as the purpose of counterfeits is to make money and therefore replace the API with a cheap compound. There were cases when capsules of counterfeited drugs were filled with flour or even beach sand (this could be determined by elemental analysis of the powder and shape analysis of the sand particles).
OSP: Is there anything you'd like to add that we didn't touch upon above?
PC: As it is true for luxury products, if a drug is available online or outside a pharmacy on the market for a low price, it is most likely a counterfeit. The difficulty pharma companies face when fighting counterfeits is the time needed to collect evidence; by the time a brand company has set a hand on a counterfeited material, analyzed it, and set up its case for legal action, the website on which it was purchased or the company it was purchased from may have disappeared or been replaced by another entity, making it very difficult to take legal actions.
Therefore, high-speed analytical techniques such as spectroscopies that can move to the field (through handheld devices) could help to speed up actions, including the seizure of stocks of counterfeits by police action.