Pharmaceutical manufacturing involves a lot of technical terms, which might be difficult to understand, if you’re new to the subject. To make things easier, we’ve compiled this Glossary of Common Terms used in the pharmaceutical industry. Hopefully this will help you with all the jargon, and all the different aspects of pharmaceutical manufacturing – everything from the materials used, to the printing techniques!
1. Clean Room Classifications
“Class R” and “ISO” are two different classification systems used in the pharmaceutical industry, to describe just how clean various cleanrooms are. Cleanrooms are enclosed spaces, designed to minimise the introduction, generation, and retention of airborne particles. In the context of the pharmaceutical industry, these can include dust, powder, droplets, aerosols, or other microscopic particles that are suspended in the air. These particles can be generated during the manufacturing, packaging, or transportation of pharmaceutical products, and can pose a risk to product quality and patient safety.
The American Federal Standard 209E (FS 209E) encompasses the following cleanroom classifications: Class 100,000; Class 10,000; Class 1,000; Class 100; Class 10; Class 1 (where ‘Class 1’ is the cleanest). The cleanroom ‘class’ standard has the advantage of being easy to understand, as it relates to a real-world metric. For instance, Class R100,000 is a controlled environment, with a maximum of 100,000 particles per cubic metre of air. Although it was superseded in 1999 by ISO-14644-1, and officially withdrawn in 2001, it’s still widely used by pharma professionals to describe cleanroom standards.
The modern ISO standard uses the following cleanroom classes: ISO 1, ISO 2, ISO 3, ISO 4, ISO 5, ISO 6, ISO 7, ISO 8 and ISO 9. On this scale, ISO 1 is the ‘cleanest’ and ISO 9 is the ‘least clean’ – but remember, an ISO 9 environment is still cleaner than a normal room. For a breakdown of the ISO classification system in reference to the ‘Class R’ equivalents, please see the table below.1
ISO Clean Room Standards and the FS 209E Equivalent
2. CMYK Colour Values
CMYK stands for Cyan, Magenta, Yellow, and Key (Black). It is a colour model used in the printing industry, including the pharmaceutical industry. The CMYK model uses four colours to create a full range of colours, making it ideal for printing high-quality images and graphics. It is subtractive in the sense that it begins with white, and achieves a specific colour by removing colours from the spectrum, until the desired shade or tone is achieved.
3. DIN 53122-1
DIN (Deutsches Institut für Normung) is the German Institute for Standardisation. It’s a national organisation that develops and publishes technical standards for various sectors, including the pharmaceutical industry. DIN 53122-1 is one such standard produced by this organisation, and relates to the “Determination Of The Water Vapour Transmission Rate Of Plastic Film, Rubber Sheeting, Paper, Board And Other Sheet Materials By Gravimetry”. It describes a test method by which manufacturers can test the MVTR (Moisture Vapour Transmission Rate) of different packaging materials.2
4. Flexographic Printing
Flexographic is a term used to describe a printing technique that uses a flexible printing plate to transfer ink onto the surface of the material being printed. This technique is commonly used in the pharmaceutical industry, for printing on packaging materials, such as plastic and paper.
The main disadvantage of flexographic printing is the complexity (and resulting time-consuming nature) of its set-up. If your artwork consists of multiple colours, there will need to be a plate for each colour, so the more colours you want, the more time you’ll need to set it all up. As such, printing plate configuration will determine the viability of flexography for your print. You must balance the volume of orders, against the setup time (and cost) of creating new plates. For medium to large volumes of printing, this is unlikely to be a problem.
In terms of advantages, whatever time it takes to set up is compensated by the fast production speed that flexography offers. One sense in which it’s better than gravure printing is that, because it uses raised bumps to impress images onto a surface (rather than indentations), it accommodates many different inks. This increases the versatility of this printing method, because it can therefore be used to print on both porous and non-porous surfaces.3 The ‘raised bumps’ aspect of flexographic printing is also environmentally friendly, because it allows you to use water-based (as opposed to solvent-based) inks, decreasing your reliance on harmful chemicals.4
5. GMP Standards
GMP (Good Manufacturing Practices) is a set of guidelines that ensure pharmaceutical products are consistently produced and controlled according to quality standards. It’s the minimum standard that pharmaceutical manufacturers must meet in the UK, in terms of their production process.
To meet these standards, manufacturers must ensure that their process produces products that:
· Are consistently high-quality
· Are appropriate for their end-user
· Adhere to the criteria mentioned in the Product Specification document
The purpose of GMP is to minimise any risk involved in pharmaceutical production, which cannot be eliminated through testing the final product.
6. Gravure (also known as ‘Rotogravure’) Printing
Gravure printing is another technique used in the pharmaceutical industry. This technique involves a metal printing cylinder; the desired image is etched or engraved on its surface in a pattern of cavities, which are called ‘cells’. The cylinder rotates through an ink pan, and the cells take up ink. A ‘doctor blade’ scrapes off any excess ink, before the printing cylinder transfers ink onto the material being printed.
This printing technique is great if your production line does not require frequent design changes. For medium-sized print runs, you may want to consider flexographic printing, as the flexible polymer print plate is easier and quicker to produce and is thus cheaper, when switching designs. The drawback is that flexographic plates offer a slightly lower quality of printed image, and wear-out faster, compared to gravure plates. Also, due to its high speed and repeatability, gravure printing offers the most economical high-volume runs.
7. HDPE (High-Density Polyethylene)
Made from petroleum, HDPE (High Density Polyethylene) is a form of thermoplastic material. It’s one of the most versatile plastics, and is commonly used in the pharmaceutical industry for packaging applications, such as bottles and rigid containers. HDPE is known for its high strength and durability, making it an ideal material for packaging sensitive products.
This type of plastic is opaque,5 in contrast to PVC6 and PP,7 which are both transparent, unless coloured with a pigment. HDPE is also more durable than PVC – in terms of failure ratings, HDPE is approximately 200 times more durable. Even so, whilst HDPE has more expansive uses, PVC can be cheaper.8
HDPE has an advantage over PP in that it can be more rigid, due to its higher density. However, this aspect can actually make PP more desirable for the moulding of low-weight products. HDPE and PP both offer some chemical resistance, but PP does not have as good UV resistance as HDPE; PP would need to be stabilised with additives to compete with HDPE in this sense.9 Ultimately, HDPE is cheaper than PP.10 Unlike PVC and PP, HDPE is widely recyclable,11 making it more environmentally friendly than these other options.
8. Heat-Seal Lacquer
Before we get into heat-sealed lacquers, let’s quickly define what heat-sealing is: Heat-sealing is where manufacturers use heat and pressure, to seal one thermoplastic film (or component) to another.
Heat-seal Lacquer is a type of coating used in pharmaceutical packaging, to seal down a lid. It is typically applied to the rim of containers, such as bottles and reagent wells on medical device platforms, to create an airtight seal, and prevent contamination or leakage.12 Heat-sealed lacquer can be coated onto the lidding material in a liquid form.
Virtually all thermoplastics can be made to seal-to themselves, but when it comes to packaging a product that sits better in a blister than in a pouch, it must be considered that the end-user will need to be able to push the pill or capsule through the foil layer. You therefore use heat-seal lacquer to bond the foil lid-stock to the base tray, because using a sheet of plastic would add strength to the push-through layer, making it difficult for the end-user to push the pill or capsule through it. The extra bulk would also add unnecessary cost to the manufacturing.
9. Heat-Seal Laminate Layers
A laminated heat-seal layer, such as a thin film of PE (Polyester) is another type of sealing technique used in the pharmaceutical industry. This layer provides excellent sealing properties, across a wide range of temperatures and speeds, and is very flexible. The PE layer is typically just one layer of a complex layer laminate, that will provide the packaging properties required.
Hydrolysis is a type of chemical reaction, where a molecule reacts with water, resulting in the separation of a chemical bond within that molecule. In essence, the effect of water is to break-up the larger molecule, into two or more smaller sub-components.
Within the pharmaceutical industry, esters and amides are particularly prone to hydrolysis. This poses a problem to pharmaceutical manufacturers, because if a formulation is readily hydrolysable (e.g., methylphenidate), but isn’t protected by packaging of the required MVTR standard, then hydrolysis will occur, and render the drug inactive. For this reason, the moisture barrier materials of pharmaceutical packaging must be considered seriously, preferably in conjunction with pharmaceutical packaging experts like Baltimore Innovations.
11. Hygroscopic Powders
Hygroscopic powders are substances that have the tendency to adsorb moisture from the air. This property can make them difficult to handle and store, as they can become sticky, and clump together, when exposed to high humidity. Hygroscopic powders are commonly used in the pharmaceutical industry for the manufacture of tablets, capsules, and other solid dosage forms.
One example of a hygroscopic powder is sodium iodide. Sodium iodide is known to adsorb moisture from the air, and form lumps and agglomerates in humid conditions.13 To avoid this, it’s usually supplied in a granular form, to expose less surface area to the atmosphere.
12. PET (Polyethylene Terephthalate)
PET (Polyethylene Terephthalate), otherwise known as Polyester, is a thermoplastic material that’s commonly used in the pharmaceutical industry for packaging, and product labelling. PET is known for its transparency and clarity, making it ideal for packaging consumer products which need to be visible. It’s a strong, durable film, that gives tear and puncture resistance, which can be crucial for pharmaceutical packaging.
In addition to its structural properties, PET is also lightweight, making it easy to transport and handle. This makes it an ideal material for packaging products that are sold in large quantities, or products sold into competitive marketplaces. Conversely, it’s worth mentioning that PET does not have the temperature resistance that HDPE is capable of.14 Additionally, PET doesn’t have as good sealing characteristics as you get with PVC.15
13. Pharma Zones
The differences between climates all over the globe can be vast, so clarity is needed when describing the heat and humidity of various Geographic Regions. With this in mind, the ICH16 has created guidelines which divide the world into four different climatic zones, which correspond to the temperature and humidity in those areas. Zone IV is further divided into two subzones (IVa and IVb), based on levels of heat and humidity. The zones are:
· Zone I Temperate
Mild temperatures, and moderate humidity
For example, Germany
· Zone II Mediterranean
Higher temperatures and humidity than Zone I
For example, Lebanon
· Zone III Hot and Dry
High temperatures, and low humidity
For example, Chad
· Zone Iva Hot and Humid
Tropical; High temperatures, and high humidity
For example, Ecuador
· Zone IVb Hot and Very Humid
Temperatures and humidity levels higher than in Zone IVa
For example, Cuba17
14. PP (Polypropylene)
PP stands for Polypropylene. It is another type of plastic that is commonly used in the pharmaceutical industry for packaging applications, such as blister pack trays, bottles and other closures. PP can be made to be translucent, making it an ideal material for packaging that provides a window, through which end-users can see the products inside easily. It also has some resistance to heat and chemicals. If your packaging needs to deal with warm environments, PP is a better option than HDPE, because it can withstand higher temperatures.18
15. PVC (Polyvinyl Chloride)
PVC (Polyvinyl Chloride) is a synthetic plastic material that is commonly used in the pharmaceutical industry for packaging and product labelling. PVC is known for its versatility, as it can be easily moulded or thermoformed into various shapes and sizes, making it ideal for creating different types of packaging. It’s also cost-effective, which makes it an attractive option for manufacturers of lower price products.
PVC is a strong and durable material, and has some resistance to liquid water. This also makes it ideal for packaging products that need to be protected from physical damage. In addition, PVC can be easily printed on, making it suitable for packaging that requires product branding. This type of plastic is stronger and stiffer than HDPE,19 and more durable than PET,20 so it’s a good choice if you need a sturdy plastic. In terms of the negative aspects of PVC, it must be noted that PVC does the most damage to the environment, because in its production and disposal, harmful toxins are released. PVC can also be harmful to human health, so it’s not as good as HDPE in this sense, which is not known to transmit any toxins.21
16. RGB Colour Values
RGB stands for Red, Green, and Blue. It’s a colour model that is used for both printed and electronic media. RGB is a more modern colour reference system than CMYK, and it generates colours by adding the primary colours of red, green and blue together. It achieves the same final outcome as a CMYK reference, but starts from black as opposed to white, and adds colours, to achieve the desired final shade.
17. RH (Relative Humidity)
‘RH’ means Relative Humidity; it’s a measure of the amount of moisture in the air, expressed as a percentage of the maximum amount of moisture that the air can hold, at a given temperature. In the pharmaceutical industry, RH is an important factor to consider, as high RH values can affect the stability of the product, and its shelf-life.
18. Thermal Printing
With Thermal Printing, your image is printed onto thermal paper using heat.22 Thermal paper is a specialised paper that is sensitive to heat; when heat is applied to it, it changes colour to black, blue, or red.23 Applications include the printing of labels, receipts and barcodes.24
There are two types of thermal printing:
· Direct Thermal Printing
o Here, the heat from the thermal printhead is applied to a chemically treated paper that darkens upon contact with heat. As such, it doesn’t use a separate toner, or ink.25 In essence, the hot printhead is selectively discolouring the label, in order to print a message. An example of this would be applying barcodes to shipping labels.26
· Thermal Transfer Printing
o A ribbon containing ink is used on normal paper. The printhead transfers heat to the ribbon, and the warm ink can then be transferred to the paper27 or plastic.28 Thermal transfer printing has the ability to tolerate excessive temperatures or sunlight. This makes it particularly suitable for outdoor applications.
It’s worth noting that thermal printers don’t offer the full colour print options that you can get with other printing techniques. For instance, Gravure Printing employs the CMYK colour range, which can be combined to create any colour, so it’s capable of producing detailed images.29 By contrast, most thermal printers can only print one colour at a time.30 Another drawback of thermal printing is that labels made by direct thermal printing remain heat-sensitive once printed – so there is a risk that they can darken across the whole label if exposed to excessive heat again.31
19. Work-in-Progress Packaging
Work-in-progress (WIP) packaging is a term used to describe containers or vessels that are used to temporarily store semi-finished products, which are in the process of being produced, but have not yet completed all manufacturing stages. For example, this could be an industrial sized polyethylene sack, or a 200-Litre steel drum. Another example could be a 1200-Litre intermediary bulk container (IBC), if the part manufactured material is a liquid.
This might be necessary in a situation where material requires reprocessing (in order to conform to the manufacturer’s specification). Another example might be an occasion whereby the final stages of production are delayed, or are unavailable due to equipment failure, in which case semi-finished goods need to be packed-up at an earlier point in the production line, and stored until the machinery on the final part of the production line is fixed.
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What to Read Next…
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2: “DIN 53122-1:2001,” ANSI Webstore. [Online]. Available: https://webstore.ansi.org/standards/din/din531222001. [Accessed: 31-Mar-2023]
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16: *International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
17: Pharmaguideline, “Climatic Zones for Stability Studies,” Pharmaguideline. [Online]. Available: https://www.pharmaguideline.com/2010/12/different-climatic-zones-for-stability.html. [Accessed: 31-Mar-2023]
18: Essentra Components, “Caps and plugs: How do HDPE and PP compare?,” Essentra Components US, 26-Mar-2020. [Online]. Available: https://www.essentracomponents.com/en-us/news/solutions/general-protection/caps-and-plugs-how-do-hdpe-and-pp-compare#:~:text=HDPE%20products%20aren’t%20known,it%20ideal%20for%20hotter%20environments. [Accessed: 31-Mar-2023]
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28: M. McAlpine, “Printing on plastic,” RSC Education, 01-Jan-2009. [Online]. Available: https://edu.rsc.org/feature/printing-on-plastic/2020214.article#:~:text=For%20the%20past%20two%20decades,directly%20into%20the%20plastic%20substrate. [Accessed: 31-Mar-2023]
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31: F. X. Admin, “What are the disadvantages of thermal printers?,” FreeX, 02-Jun-2021. [Online]. Available: https://getfreex.com/blogs/learn/what-are-the-disadvantages-of-thermal-printers. [Accessed: 31-Mar-2023]