The answer is clear: NO. Annex 1 (𝘔𝘢𝘯𝘶𝘧𝘢𝘤𝘵𝘶𝘳𝘦 𝘰𝘧 𝘚𝘵𝘦𝘳𝘪𝘭𝘦 𝘔𝘦𝘥𝘪𝘤𝘪𝘯𝘢𝘭 𝘗𝘳𝘰𝘥𝘶𝘤𝘵𝘴) does not apply to ATMPs manufacturing. However, it is surprising that we still find professionals in the field and specialized consultants who defend the opposite and, sometimes, even some poorly informed inspectors.

The position of the regulatory agencies is clear; the Guidelines of Good Manufacturing Practice specific to Advanced Therapy Medicinal Products in volume 4 of the GMPs were written precisely to cover this type of therapies in a specific way. Something different is that, for a specific point, the guidelines for ATMPs comment that it applies in the same way as described in Annex 1 or, also, that it is good practice to consult Annex 1 as a guide when we detect an ambiguous or missing point in the part corresponding to the ATMPS. However, in the latter case, it would be something that would not apply directly and that would have to be analyzed.

The guidelines for ATMPs of the GMPs already considers that these types of therapies are sterile, in fact, they address the requirements of production in closed systems and the requirements of the aseptic process simulation, to give a few examples. On the other hand, it must be taken into account that the regulatory agents, when drafting the part relating to ATMPs, not only took into account that they are sterile therapies, but also the specificity of this type of product when establishing certain requirements (the production restrictions, for example, of a small molecule, cannot be equated with those of a therapy based on cells or viral vectors).

What is a GMP washing machine?

In pharmaceutical industry, automatic cleaning is usually associated with the acronym CIP (Cleaning In Place) and certainly, CIP systems are very common in applications such as tanks, reactors and others. On the other hand, the acronym COP (Cleaning Out of Place) is not so much well known. GMP washing machines are the genuine COP equipment, but in our country these devices are not as widespread as one would expect. Why there is not enough effort being made in COP automation?

There may be several reasons that would explain this situation. I suspect that one is a certain lack of knowledge about the state-of-the-art technology. When you think of a washing machine for contact parts, many times we assimilate it to what a dishwasher can do. E.g. small parts such as tablet punches, dosing pumps and nozzles, and above all, glass containers and instruments. There is also some belief that cleaning of parts with complex shapes requires the flexibility and dedication of manual washing and that it is very difficult to automate. The truth is that GMP washers are much more complex than a professional dishwasher and they offer custom made solutions for multiple parts in the same cycle, from containers of all types, sizes and shapes to hoses, pieces and utensils.

Another aspect that slows the investment is the price issue. These are ancillary equipment, non-directly productive and when investments are planned, they are always a second priority. Sometimes, when they are considered, they are wrongly compared with other product categories like laboratory washing machines and budgets are not properly managed.

In order to properly approach the matter of cleaning automation in pharma, we should understand the advantages and benefits that the GMP washers are offering.

Know the benefits and return on investment

Since it is not production equipment but ancillary, we should assess the savings it could provide in terms of operating costs. A short list of them could be:

• Savings in hours of personnel dedicated to manual cleaning. Release from tedious, repetitive and little value tasks.
• Savings in training and qualification of personnel. Elimination of the rotation problem.
• Saving for lowering the frequency of inspections by supervisory personnel.
• Savings in the use of consumables: detergents, tools, clothing and EPIs of operators (about 1/3 or 1/4 of the costs in manual).
• Savings in energy and water consumption (PW and WFI)
• Increase of productivity due to reduction of down time due to cleaning of parts.

The advantages of automation

Investment in GMP washers provides other improvements, especially related to quality assurance and labour safety. These are:

• Reliability. In a manual process, after training, we must rely on the execution by the operator; its discipline and rigor in carrying out the task according to the validated protocol. These two qualities cannot always be properly monitored. Instead, automatic equipment works with recipes; a set of parameters that make up a cycle, with a continuous monitoring of critical parameters which are fully reproducible and, therefore, validatable.
• Flexibility. Contrary to what people believe, GMP washing machines have great flexibility in terms of cleaning parts or design of pieces and can process a wide variety of materials in the same cycle. From containers to hoses, connections and parts of very diverse nature: steels, plastics, resins, rubber and others. Production can be organized straight forward in batches and adjusted to the process.
• Efficiency. As mentioned, automation allows you to optimize consumption; both due to the amount of water, detergents and energy needed and due to reduced cycle times. In addition, it allows to ensure the proper drying of the load, an important issue since water residues over the cleaned components can favour microbial growth.
• Safety and ergonomic. Working with washing machines allows limiting the risks arising from the manual cleaning of contaminated parts. Operator exposure is eliminated according to what types of chemicals. Cleaning can also pose risks due to the use of hot water, detergents or even steam.
• Compliance. GMPs advocate that everything that is automatable should be automated. The reason is very simple; the ability of a machine to always reproduce the same and in the same way is always superior to that of a person.

Project Considerations

In order to prepare the investment, and to ensure a correct budget allocation, it would be necessary to prepare the URS in which the different stakeholders should participate; engineering, maintenance, production and quality control. By incorporating all these perspectives, we assure that the project will be developed properly, without last minute surprises.

In general, there are three major issues that should be very well resolved before starting and budgeting a GMP washer installation project:

• Identifying and grouping the parts to be washe: Unlike what is commonly believed, there are very few products that cannot be washed with a GMP washing machine. From critical parts in contact with the product such as format pieces (punches, dies,…), containers (IBCs, drums, mixing containers, …) to production components (valves, housings, hoses, etc.) and accessories (freeze drying trays, carrousels, etc.).  Parts washing are done by batches or loads with a specific cycle. To ensure proper cleaning of each part, it is necessary to transmit them to the supplier. From here, the most appropriate chamber size is selected, and load racks are designed to adapt to the load. The design of racks is not only for support purposes, they are custom designed using 3D scanning technology.Thanks to the custom design, the placement of the parts is univocal, ease and intuitive, ensuring proper coverage during washing and full drainability.

  

  Rack 1: Dosing pumps, injectors, storage tank and others

  Rack 2: Valves, connectors, hoses, intermediate tanks and others

  The rack, by itself, is piping system that, by means of quick coupling devices and multiple injection points, injects pressurised jets of water to the internal surfaces of the parts to be washed, cleaning by mechanical, chemical and temperature effect.

• Degrees and types of residues. In general, you have a good knowledge of the residues that your products entail since it is already being cleaned manually. Possible contaminants such as residues of active ingredients or excipients, residues of lubricants or detergents, microbial load, etc. may require specific solutions.
• Location of the equipment. Ensure that the dimensions of the equipment and the architecture of the room are compatible. The washing equipment is usually very compact and requires a footprint quite reduced with respect to its load capacity but still has a significant size and the rooms are not always provided for this type of equipment. It is also necessary to consider the services for the operation of the equipment, especially those more critics such as the WFI that may entail a significant additional cost.

Comparative table between manual vs automatic cleaning

Introduction: the problem of the Annex 1 draft around VH2O2 to ‘sterilize surfaces’

As many of you may already know, the draft of the new Annex 1 (v12) questions vaporized hydrogen peroxide (VHP/VH2O2) cycles as a method of surface sterilization for parts of indirect contact with the product. It is argued that VH2O2 has no penetration capacity, and that sterilization implies being able to penetrate to ensure the level of sterility. The truth is that the VHP/VH2O2 cycles show some fragility and sometimes positive indicators are detected unexpectedly. In the EU pharmacopoeia there is no explicit reference to VH2O2 as a method of sterilizing surfaces. On the other hand, there are references in the USP or even articles of the PDA that support the use of peroxide to sterilize or decontaminate surfaces.

Section 5.5 “Direct and indirect contact parts should be sterilized. Direct contact parts are those that the product passes through, such as filling needles or pumps. Indirect product contact parts are equipment parts that come into contact with sterilized critical items and components”
Section 8.12 “For sterile products that cannot be filtered, the following should be considered: i. All product and component contact equipment should be sterilized prior to use.”
In the case where vH202/VHP cycle is applied as the only bio-decontamination process for the barrier and process equipment non-product contact surfaces and in the same cycle ‘surface sterilization’ of in-direct product contact parts this would have to be justified using QRM principles. Such principles would need to recognize the different requirements for cleaning and bioburden control for bio-decontamination of non-product-contact process equipment/ barrier surfaces and ‘surface sterilization’ of in-direct product contact surfaces.

In the context of aseptic filling, eliminating this practice leads necessarily to an “out of place” sterilization: disassembling feed hoppers, guides, and other elements from inside the isolator, taking them to an autoclave chamber for sterilization and then reassembling them trying not to contaminate them.

This situation can involve problems such as that the autoclave chamber does not have enough capacity, the development of new SOPs, training and qualification of operators, productivity losses due to line stoppage, etc.  A real headache.

Photo: Courtesy of Dara Pharmaceutical Packaging

Differences between sterilization and biodecontamination

This article tries to clarify the concepts of sterilization and biodecontamination to understand the problem and try to find solutions.

1. Sterile, sterility and sterilization concepts

The first term is a binary concept. One thing, it’s either sterile or it’s not. It cannot be “half sterile”. By sterile we mean that product with total absence of viable particles.

As for the second term, sterility, or level of sterility assurance (SAL), it is a microbiological concept that designates the probability that a product undergoing a sterilization process contains a viable microorganism. This probability is, by definition, 10e-6.

And what does sterilization mean? According to the ISO 14161 standard for Sterilization of medical devices, sterilization is that process that can be validated starting from a microbial load of 10e6 until reaching the SAL of 10e-6. This literally means that a sterilization process must achieve a 12-log reduction.

In practice, it is impossible to prove such effectiveness. Why? Because to demonstrate this empirically, 1 million samples should be manufactured, each of them inoculated with populations of 10e6 spores and sterility tests of each one of them should be carried out. As this is virtually impossible, microbiologists use empirical data and mathematical formulas to calculate the lethal effect of heat and time needed in a sterilization process to secure the SAL.

2. Biodecontamination

Some studies have determined that VH2O2 has a penetration capacity of only 10-20 nm. A spore of Bacillus stearothermopillus is up to 3-μm long and 1-μm wide. Sometimes, during the manufacture of the indicators, agglomerations of spores (“clumping”) can occur and then the peroxide will not be able to penetrate beyond the first layer. This results in the indicator being positive, regardless of whether the process achieves a good distribution and has got contact with all surfaces. These indicators are called “rogue BI” because they give a false result. False as to the fact that the peroxide has contacted the surface, but true as to the positive is because it has not been able to penetrate inward. Hence the fragility of VH2O2 cycles and why it cannot be considered a sterilization process. In the case of autoclave sterilization, this would not happen since, under conditions of pressure and temperature at 121°C, the steam penetrates perfectly to reach the surface and these indicators would result negative. For this reason, in VH2O2 processes or cycles we should use the word ‘biodecontamination’ and not ‘sterilization’, which is reserved for penetrating processes.

3. Cleaning, bioburden and risk analysis

Does this mean that on surfaces it is impossible to achieve a SAL level (10-6) with VH2O2? Well, in theory, no. To achieve this, the process of cleaning and sanitizing surfaces should reduce biological contamination (bioburden) to a monolayer of microorganisms. The new annex seems to tells us that, if the VHP/VH2O2 cycle is used for decontamination of the isolator and filling machine of non-product contact parts and we want to take advantage of it as surface sterilization of indirect contact parts, we should use QRM or risk analysis techniques (see the quote above in bold) for those most critical parts, putting effort in the study of cleaning and bioburden.

Looking for solutions

Therefore, if we manage to sanitize at bioburden levels <10e3 and we design a 9-log reduction VH2O2 biodecontamination process, the process will achieve the SAL (10e-6). Unfortunately, there are no indicators with populations of 10e9 to validate these processes. Quite recently, at the Congress of Rapid Microbiology organized by A3P Spain Committee, the use of innovative microbiology techniques to better ensure aseptic processes was discussed. One of the speakers, the consultant Gilberto Dalmaso, defended that the pharmaceutical microbiologists should take the initiative and innovate in this aspect. He pointed out that the same Draft V12 of Annex 1 encourages the use of rapid microbiology methods with this sentence: “The use of appropriate technologies (e.g. RABS, Insulators, Robotic systems and environmental monitoring systems and / or rapid microbiology tests) should be considered to increase the protection of the product against contamination of personnel, materials, …”. We will see how it finally turns out, but it is time to take advantage of innovative technologies of rapid microbiology. One of them is the enzymatic indicators.  These indicators allow quantifying the lethal effect of peroxide by correlating the mortality of a population of spores with the remaining activity (RLU) of the enzyme Adenylate Kinase (tAK). Certainly, implementing such a process requires multiple tests and generating data over a period to validate it. However, the benefit in the form of productivity and risk reduction more than outweighs such effort and some multinational companies are already taking advantage of this tool.

This graph, taken from the article “Real-World Vapor Phase Hydrogen Peroxide Decontamination” by James Agalloco, is very illustrative to clarify concepts. As mentioned, neither 9-log reduction nor 12-log reduction to achieve a 10e-6 SAL can be tested experimentally. In the case of sterilization, we rely on the penetration capacity of the steam to ensure that SAL 10e-6 has been reached, while, with biodecontamination, assuming a maximum biological load of 10e3 we should develop a cycle that reaches a reduction of 9-log to have a lethality level of 6-log (or SAL 10e-6).

Conclusion

Biodecontamination and sterilization are analogous processes that involve killing populations of microorganisms but have different connotations. Sterilization is penetrating and this offers the necessary confidence to achieve the level of sterility (10e-6) according to the calculations of microbiologists. In contrast, biodecontamination is a more fragile process because it is superficial. It offers no such confidence and requires further attention. Therefore, it is necessary to carry out bioburden studies in the most critical areas and develop robust cycles. To validate a level of biodecontamination close to sterility, we must demonstrate that our cleaning and sanitization process achieves a low bioburden (<10e3) and then perform a VH2O2 cycle that allows reducing up to 9-log. Enzymatic indicators, which are part of the group of rapid/alternative microbiology techniques, are the perfect tool to support logarithmic reduction studies greater than 6-log and help validate such processes.

Here I continue with 2 more common misconceptions that I have heard saying in different forums or at some point during the technical negotiation phase for biodecontamination projects. They are very common and perhaps, some reader will be surprised. I hope these explanations are quite clear, but, in any case, there is a lot of literature that corroborates that these beliefs are not correct. For more information, the reader can download some related articles here.

Misconception nº3 – The more concentration of H2O2 in gas phase we have in the isolator, chamber, or room, the faster and better we will decontaminate.

As explained before, biodecontamination is not a process that depends solely on concentration. Initial temperature and relative humidity are factors that also influence on the lethality of the process.  A typical case is that of an isolator coupled to an autoclave chamber or a freeze dryer. A simple test can be done to show that, although the concentration reached is the validated one, if the surface of the autoclave door is hot, the indicators located there do not turn. Why? Because being on that warmer surface does not produce microcondensation of H2O2 and, therefore, not enough liquid-phase contact occurs to kill the entire population of spores. Therefore, the reading of the concentration, which measures quantity in gas phase and at a certain point, gives biased information.

This is a lesson learning for those who entrust everything to concentration sensors. The information they provide is only one of the parameters of the process, which can be used for monitoring, but taking it as the main driver of the cycle control can lead to distortions. Currently, there are sensors that not only monitor the concentration, but also the humidity, temperature, and saturation of the vaporized mixture of H2O+H2O2 (the PEROXCAP HPP 272 from Vaisala). These sensors give a more complete information that you must know how to interpret, but let’s not forget, it is taken at a very specific point.

A derivative of the missconception of searching for high concentrations is the unnecessary complication of cycles. To achieve high concentrations, dehumidification systems must be provided, which involves more components and sophistication. It is obvious that, if we inject hydrogen peroxide having a high initial humidity, we will have less space available to vaporize it before it saturates and condenses. However, I have been able to observe cycles with 10% initial humidity and dwell phases with concentrations of up to 1200 ppm that have had difficulties in achieving a lethal effect in a homogeneous way.  In that specific case, the control of the cycle was carried out from a concentration sensor at the output of the generator. The recipe allowed to set up a target concentration and to keep it constant, new peroxide was introduced from the top while drained at the bottom. With the enzyme indicators we verified that, due to the flow of air from top to bottom, the VH2O2 was not properly reaching the upper parts. Despite the glaring lack of uniformity of the cycle, if you only looked at the graph, everything seemed perfect. The graphs were brilliant, with very pronounced preconditioning and aeration phases as well as a very flat exposure phase, with practically no variation in concentration.  However, the development of the cycle was a long process due to the lack of reproducibility of the BI results and at the end, there was no choice but to extend a lot the exposure phase, leading to an excessive consumption of peroxide.

In short, the misconception of considering that the more concentration we achieve, the faster and better we will decontaminate may lead to design of systems and cycle developments with very low efficiency.

Misconception nº4 – VHP hydrogen peroxide vapor is sterilizing while misting is only sanitizing. 

This misconception is one more derivative of considering that a vapor in ambient conditions behaves like a gas and, therefore, achieves similar effects to those of ethylene oxide, for example. In fact, the manufacturer that led the development of the VHP technology did so thinking initially in finding an alternative to ethylene oxide sterilization. Around that time, in the early 1990s, many hospitals began to phase out their ETO sterilization equipment due to its occupational hazards and the increasing awareness of its risks. The only alternative was the massive use of single-use medical devices. However, there were many devices, such as endoscopes, that needed to be reprocessed and needed to be sterilized. Several manufacturers saw that peroxide could be an alternative and equipment initially designed to sterilize lumens and internal spots came onto the market. But they all failed to ensure the sterility level of 10-6 in a wide variety of heat-labile products. The problem was (and still is) that, unlike ethylene oxide, peroxide vapor does not behave like a gas and diffuses/penetrates in a poorly way. Today,  in the hospital sector there are VHP sterilizers, but because of their use is quite limited and regulators like the FDA severely restrict their use to certain product types and forms, total volume of loads, etc. If you are interested in knowing how VHP is used to sterilize in the hospital sector and the difficulties it entails, I recommend this article: Keys to success with vaporized hydrogen peroxide sterilization.

On the other hand, the VHP showed greater viability for another application: the airborne disinfection of surfaces, and in the pharmaceutical sector, especially for isolators. In that context, the VHP was an alternative to other chemical disinfectants such as formaldehyde and peracetic acid, which had some contraindications. Those latter left residues on surfaces and could be highly toxic even at low concentrations. Thus, the success and widespread use of VHP or VH2O2 versus other chemical disinfectant methods is not due so much to its greater power or ability to sterilize/disinfect, but rather to the fact that it does not leave residues, is not carcinogenic and, although it is toxic, it is so at much higher concentrations.

In short, either it’s produced with hot flash vaporization or it’s cold vaporization by nebulization technology, hydrogen peroxide vapor does not have sufficient penetrating capacity to guarantee reduction levels of 10^-6 in items with complex shapes and/or significant bioburden and therefore, in no case is can be considered a sterilization process.

P.S. As I’m aware that this last statement can contribute to even more confusion. In my next post I will explain more precisely the difference between sterilization and biodecontamination in the pharmaceutical context and I will comment on the controversy that exists with the new Annex 1 of the GMP regarding not considering peroxide as a sterilizing process.

I have been working in the development of Solidfog Technologies‘ biodecontamination systems business for more than 7 years. I have witnessed the excellent results achieved with their technology. It is a different and an innovative solution, designed to meet the standards and expectations of the pharmaceutical manufacturing companies. Getting the first projects in Spain was not an easy job. At first, in my presentations, I could notice some disbelief in the audience. There were certain “dogmas” that no one questioned, and this fact prevented the necessary mind openness to understand that other solutions could provide greater advantages. In order to be able to explain myself better, I began to investigate the scientific background and the reasons why of the airborne H2O2 biodecontamination, both vaporized and nebulized. After a few years doing challenge tests and cycle development, I think I have gained enough practical experience to reiterate that, such misconceptions are spoiling the development of projects and/or the optimization of biodecontamination processes.

Faced with this situation, I have been encouraged to write this blog in which I will quote some of the misconceptions or myths that I have heard saying about biodecontamination with H2O2. I will try to explain clearly and concisely why such statements are wrong.

Misconception nº1 – The H2O2 vapor (VHP) has a higher biocidal capacity than dry fog or nebulized H2O2.

This belief comes from the idea that direct vaporization allows to reach high levels of H2O2 concentration in the atmosphere. On the other hand, nebulization is perceived as a less efficient process with distribution in liquid phase. That’s not true. How does the misting that produces dry fog really work? This type of nebulization produces an aerosol or suspension of liquid particles in a gaseous medium. These particles have the ability to move occupying all the available space, but at the same time, because they are so small, they also vaporize. This vaporization occurs until the mixture saturates the environment. Then, no more particles evaporate and begin to be visible as dry fog. Therefore, dry fogging can be seen as a method of cold vaporization, as opposed to direct vaporization, which requires a heat source.

The key question to discern about the biocidal capacity of one method or another is: What is the mechanism that produces the death of microorganisms? If H2O2 is an oxidizing substance that destroys DNA and proteins in cells, what is the best way to distribute the biocide and come into contact with microorganisms? Studies carried out by Beatriz Unger-Bimczok et al (Influence of Humidity Hydrogen Peroxide Concentration and Condensation on the Inactivation of Geobacillus st.) showed that there was a direct relationship between condensation and the lethal effect. Very briefly, they observed that very high sporicidal rates can be achieved with low concentrations (ppm of H2O2) in the environment providing the humidity level was high. These experiments showed that the biodecontamination process is in fact a two-stage process. To achieve decontamination, it must first be vaporized, and second, the vapor must condense. Some referrals such as Tim Coles, in his article Understanding the VH2O2 decontamination process, have called this primary condensation ‘microcondensation’. This occurs when the mixture reaches saturation. In fact, this condensation, which is invisible to the naked eye, is the true cause of the sporicide effect because it is highly concentrated H2O2. In short, if the aim of the process is to decontaminate surfaces and microorganisms are on surfaces, let’s focus on bringing H2O2 to surfaces. This will be better achieved by causing H2O2 microcondensation than by producing a high concentration of H2O2 in gas phase.

In conclusion, the key element in biodecontamination is about how the vapor distribution process is handled and how to ensure that microcondensation occurs on surfaces, and not about the vaporization technology itself and/or about the achieved environmental concentration. The technology that provides a more homogeneous distribution of H2O2, with lower peroxide consumption and in less overall time, will be the one that will offer the greatest advantages and benefits. In this sense, nebulization has enormous potential that is worth exploring.

Misconception nº2 – The dry vapor of H2O2 (VHP) is not corrosive, meanwhile wet vapor and misting are. 

This other statement comes from the misconception that VHP is a gas and this allows a dry process without condensation, avoiding corrosion. But VHP is not a gas, it is a vapor. The VHP generator tries to obtain environmental conditions with low humidity and high concentration. However, even under these environmental conditions, H2O2 and its diluent, H2O, are below their boiling point. Under these conditions, steam does not behave like a perfect gas. In other words, in the environmental conditions existing in clean rooms, vaporized H2O2, whether generated directly by heating or nebulization, can condense even when the relative humidity is much lower than 100%. In reality, H2O2 and H2O do not condense simultaneously due to its different boiling points and/or vapor pressure. A mixture of H2O2 and vaporized H2O will saturate earlier (Relative Saturation) than would happen being only water vapor (Relative Humidity). And it is precisely when reaching 100% relative saturation, that the molecule of greater molecular weight (H2O2) will condense before condensing water (H2O). This primary condensation, called microcondensation, is the real responsible for the sporicidal effect and happens in all biodecontamination processes.

As for corrosion, as described above, whether the process is dry or wet, there will be condensation of H2O2. The question is not to exceed a certain amount of condensation and what level of concentration that condensation entails. Injecting a 35% solution of H2O2 (common in vaporization processes) allows to reach higher environmental concentrations, but also brings a  much more concentrated condensate, which is more corrosive. On the other hand, the solutions commonly used in nebulization, which have a concentration between 8 and 12%, are less aggressive. An excess of condensation, for example, due to a colder area in a room, could be corrosive if we use H2O2 at 35% and much more tolerable if the solution used is 12%. So one thing makes up for the other.

In conclusion, the risk of corrosion, if it would be associated with condensation, can be present in one system or the other and, in any case, its degree of affectation is more related to a poor definition of the process than to the technology used.

To be continued…

Surely you will have heard it during 2019. The German group Bosch has sold its entire Packaging Technology division to an investment group and it has become an independent company.

Bosch Packaging Technology ahora in now Syntegon. Syntegon is the name chosen as the company’s brand. The company has born as a consolidated industrial group, with a number of 64,000 machines sold, 6,100 employees, 2,000 registered patents, clients in 140 countries and 30 sites between factories and offices.

The brand name wants to reflect fundamental aspects in technological advancement such as the search for synergies within the group (SYNergy), its focus on technology (TEchnology) and the proactivity to create a better future (Go ON).

The square of the logo wants to simply represent the importance of packaging as a media to protect the product.