What would you do if you found a piece of unidentified material in your toothpaste today? Would you use it? Would you throw the whole tube away? Or, would you send a complaint to the company?…
Foreign matter is an issue across all industries – from food to medicines and consumer products
What is Foreign Matter?
Depending on the industry, it goes by many names, from “particulate contamination” to “foreign objects” or “extraneous material”. United States Pharmacopoeia <788> Particulate Matter in Injections defines ‘particulate matter’ as:
“…mobile undissolved particles, other than gas bubbles, unintentionally present in the solutions…”
Essentially, foreign matter is any material or residue that is
not meant to be in the product.
Where Does Foreign Matter Come From?
Anywhere! It could come from anywhere, from the beginning of the production cycle all the way through to the end.
Over the past decade, we, at Resolian, have analysed over 5000 particles, and the graphic and information below is a representation of types of sources particles typically originate from.
- 39% come from equipment, machinery and facilities: e.g. metal particles or rust from degrading machinery, oils and grease from equipment, or particles of degrading gaskets and seals.
- 29% originate from packaging and materials used in the production: such as glass from vials, plastics from containers, and rubber from stoppers.
- 18% are due to human factors: such as hair, fibres from clothing or PPE, pieces of gloves, or other accidental occurrences.
- About 10% of the time, foreign mmater is not that ‘foreign’ after all, and is part of the formulation itself that doesn’t quite look right or that might have precipitated, agglomerated, or changed colour and appearance.
- About 2% originate from the environment, such as insects, dust or other minerals.
- And the rest originate from miscellaneous sources, or due to cross-contamination
Consequences of Foreign Matter Contamination
What happens when you have foreign matter in your products? To put it simply: your product may not look right, act right, or work right.
- Firstly, your product’s quality, safety and performance might be affected.
- You might have to halt production and delay your processes until the foreign matter is identified; or scrap the batches and start from scratch.
- This can lead to loss of finances, damage to reputation, or (depending on the industry) regulatory action.
Solution?
Forensic analysis to determine identity and source. As part of Root Cause Analyses, you need to ask and answer two questions:
- “What is it?”
- “Where did it come from?”
By knowing the identity of your unknown particle, you can find out the source of your problem.
For example, if your particle is a polymer, it could have only come from a polymeric source. Is it a metal? Then, you are looking for a metallic source. Digging deeper, which metal is it? “Stainless steel”. Perfect, which grade of stainless steel?… What do we have in our processes that is made of this particular grade…?
Only by asking these questions can you get to the source of the problem.
Once you find the source, you can fix it to prevent its reoccurrence.
Forensic Analysis of Foreign Matter
As a rule of the forensic thumb, you need to start with the non-destructive techniques first, then progress with the more destructive ones. This is especially crucial in cases where you have only a single particle to work with.
Once you have successfully isolated your particle, you examine it under the light microscope. Despite being a simple technique, microscopy gives you a wealth of information on the size, colour, morphology and behaviour of the particle. You can see whether it is organic, metallic, or a mixture of things. This information, then, allows you to choose the best analytical technique to follow up with.
Speaking of techniques, what can you use? If it looks organic or polymeric, infrared analysis is a good choice. If it is clearly inorganic or metallic, SEM-EDX is the way to go. Other useful techniques include Raman spectroscopy, XRD for crystalline materials, mass spectrometry for full structural elucidation, or ICP-MS or ICP-OES for a more trace elemental analysis.
Once you have the results, you to need interpret the data, which includes searches against databases and libraries to identify spectra, and comparison to suspected sources to determine a match.
This is the crucial part which requires the careful consideration and prior experience of a seasoned expert: just because the particle gives a match to a reference may not always mean that is the only source it could have come from. Conversely, just because the particle did not match any of the references does not necessarily exclude that reference as a source.
All available information must be considered holistically to come to scientifically sound and relevant conclusions.
Foreign Matter Case Studies
Let’s see forensic analysis in action with some case studies.
CASE STUDY 1:
Fibres in an API Blend
- A pharmaceutical company found some fibres in an API blend.
- They sent these fibres to us along with three suspected sources of personal protective equipment (PPE) that were made of fibres i.e. mask, hair net, lab coat.
PROCESS
- We examined the unknown fibres, as well as samples of fibres from the three suspected sources, under the microscope.
RESULTS
- The examination showed all fibres to be translucent white and measuring approximately 20 µm in diameter. However, closer examination of ‘Reference 3’ fibres showed subtle differences in fibre morphology, displaying more twists and turns, which are characteristic of some natural fibres (such as cellulose) as opposed to synthetic fibres.
- We performed FT-IR microscopy on the unknown fibres and the three references.
- Unknown fibres gave a match to polyethylene terephthalate (PET).
- Reference 2 fibres also gave a match to PET, while Reference 1 fibres matched polypropylene and Reference 3 fibres matched cellulose.
CONCLUSION
Taking into account similarities in appearance and chemical composition, the source of the unknown fibres was determined to be Reference 2.
CASE STUDY 2:
Dark Particles in a Tank
Sometimes light microscopy and FTIR analysis alone can help determine the identity of a contaminant; and at other times, we need different techniques. This second case study is one of those.
- A consumer healthcare company found some dark particles on a swab following cleaning of their tank, and they sent the swab for analysis.
- Microscopic examination of the swab showed stained areas containing several small, dark particles. Extraction and further examination of one of these particles showed it to be shiny and metallic-looking, with orange-brown stains over its surfaces.
PROCESS
- SEM-EDX analysis was performed on the particle, which showed the particle to be primarily composed of iron and oxygen.
RESULTS
- Taking into account the elemental composition of iron + oxygen, its shiny and metallic appearance, as well as the presence of an orange-brown layer, the particles on the swab were determined to be iron particles which had oxidized to form rust.
- Pieces of rust coming from the tank indicated that the tank might have started to deteriorate.
CONCLUSION
Armed with this information, the consumer healthcare company assessed the condition of their tank and made the necessary repairs in order to prevent more rust particles from going into their products.
CASE STUDY 3:
Unknown Crystals in Facilities
Occasionally, neither FTIR nor SEM-EDX might give a conclusive result. The third case study is one of those..
- A chemicals company found unknown particles in their facilities and sent these for investigation.
- Under the light microscope, these particles appeared to be mainly green crystals with different coloured inclusions.
- The particles were very hard, and FTIR analysis was not useful.
PROCESS
- Therefore, SEM-EDX analysis was performed to determine its elemental composition.
- Elemental analysis showed a primary composition of silicon, oxygen, carbon, aluminium and smaller amounts of other elements e.g. sodium, magnesium, potassium and iron.
- Solely based on this elemental composition, it was not possible to determine a confirmative ID, therefore we performed elemental mapping to see the distribution and relation of these elements to one another.
- Mapping showed oxygen to be co-located with sodium and potassium, and not with silicon, which indicated that silicon and oxygen were not part of the same species, ruling out silica and silicates as possible indentities.
- Therefore, we performed Powder X-Ray Diffraction on the particles. This showed us that the particle was silicon carbide (SiC), specifically the hexagonal polymorph, which is the more common polymorph of SiC.
RESULTS
- This information, along with the visual characteristics of the particles helped us to narrow it down to green SiC as opposed to black SiC.
- Green SiC is a purer form of silicon carbide that is typically used in precision machining and grinding of hard and brittle materials. It is produced by addition of salt and iron as catalysts, which explained the presence of other elements observed.
CONCLUSION
Armed with this information, the company was able to locate the source of their contamination and deal with it promptly.
FOREIGN MATTER SUMMARY
- Presence of foreign matter contamination can have severe consequences on the product’s quality, safety and performance, leading to financial loss and regulatory action depending on the industry.
- Forensic analysis methods can help identify contaminants and find out where they came from.
- This allows remediation of issues and establishment of measures to prevent reoccurrence, leading to cleaner processes and safer products.
Why Partner with Resolian?
- Proven Expertise:
Specialized team with decades of industry experience in contamination identification at your fingertips. - Bespoke Approach
Dedicated support tailored to your needs delivering high-quality reports backed by scientific evidence and clear conclusions. - Fast Turnaround
Rapid results to keep your operations on track.
Ensure the safety and quality of your vaccines with reliable solutions for foreign particulate matter.
Let’s work together to protect patients and your reputation. 👇
