We are proud to announce that KERASAVE, the completely synthetic with antifungal media by Alchimia, intended for corneal storage at 4°C for up to 14 days, has obtained the De Novo granting by the US government agency Food and Drug Administration (FDA).

A great result was achieved by the Alchimia team, built by constant investments in research and development in a sector, such as eye banking, that requests high-performance medical devices, capable of ensuring safety and maximum effectiveness.

Now, when more than 12 million people in the world are awaiting corneal transplant surgeries, FDA authorizes the use of KERASAVE, one of the most comprehensive and innovative products on the market.

FDA – US Food and Drug Administration has identified KERASAVE as a corneal storage medium with preservatives including antifungals.

As a Class II medical device subject to prescription, KERASAVE will be used to temporarily preserve human cornea tissue between harvesting and implantation.

As a result of this order, KERASAVE is becoming immediately available for use in the USA.

Having registered a medical device according to a De Novo means being the pioneer of a new category of products never existed before.

All those who want to register similar medical device will have to prove to the FDA that the device has the same performance and safety features as KERASAVE, which becomes the reference standard for its category.

Watch the video and learn how to use KERASAVE

The result of the De Novo registration of KERASAVE is available directly on the FDA website
https://www.fda.gov/about-fda/cdrh-transparency/evaluation-automatic-class-iii-designation-de-novo-summaries

Follow us on our social media to see the behind the scenes of the KERASAVE production

In the last few years, there have been hundreds of cases of blindness due to the use of some liquid perfluorocarbons.
There have been various responses from PFCL manufacturers:

• some dealt with the issue as private national affairs;
• others tried to explain what had happened through chemical parameters such as purity;
• others tried to understand what occurs to the ocular cells when they come in contact with a PFCL through biological cytotoxicity tests.

But are we looking deep enough?

According to the study Intraocular toxicity caused by MEROCTANE perfluorocarbon liquid, conducted by a group of scholars from the Instituto Universitario de Oftalmobiología Aplicada (IOBA) – Valladolid – Spain, the question is more complex than that.

Although the release of a product on the market contemplates a series of standardized procedures in compliance with ISO standards, for MEROCTANE (Meran), ALA OCTA (Alamedics) and BIO OCTANE PLUS (Biotech Opthalmology PVT) this was not enough to avoid vision loss to hundreds of people.

During clinical data analysis, the research group asks PFCL producers not only to provide them with impurity-free perfluorocarbons but also to offer guarantees with regard to the biological toxicity of each batch through direct contact cytotoxicity tests in accordance with the international standard ISO 10993-5, capable of detecting the mortality of cells in contact with the product before its intraocular use.

As manufacturer of perfluorocarbons for vitreoretinal surgery, we feel it is our duty to provide our users, who choose us every day in their operating rooms, with clear answers about the safety of our products. This is why we carry chemical and cytotoxicity tests on each lot and report the results on the traceability labels, which are contained inside each product box.

Read the full study: Intraocular toxicity caused by MEROCTANE perfluorocarbon liquid

Interview with Jana D’Amato Tothova, R&D coordinator of Alchimia srl

Il Gazzettino di Treviso – 4th June 2020 – Primo Piano

Stop the Made in Veneto swabs “But we have to be autonomous”
During the health COVID-19 emergency, our laboratories did not stop for a moment. The development of the reagents for diagnostics too. A challenge that two months later does not stop seeing us active in the development of a liquid with inactivant.

Interview with Paolo Signori, President of Alchimia srl

L’Arena – 22th April 2020 – Primo Piano 19

From a garage to TreVir 2020, the first “made in Veneto” sterile medium for the transport of clinical samples for viral diagnosis by molecular analysis against COVID-19 pandemic

“Swabs are essential tools to anchor the good health trend but also to provide a definitive answer to the request of security in re-opening companies,” says the governor of the Veneto region Luca Zaia in an interview with the Corriere of Verona published today.

A motivation, that of return to normal, which prompted the doctors of the Ca’ Foncello hospital of Treviso and researchers of the Paduan company Alchimia Srl led by Jana D’Amato Tothova, Ph.D., to collaborate side by side to deal with the drastic reduction of liquid reagents overseas for designing the first swab made in Veneto able to guarantee the preservation of the viral RNA for the molecular analysis at a later stage.

Roberto Rigoli, Chief and coordinator of the microbiology laboratories in Veneto and Chief of the Laboratory of Microbiology of the Ca’ Foncello hospital, pointed out that this version of inactivant-free swab developed from the Venetian maxi team works well for the emergency room management.

An essential first step made available to doctors and nurses for the management of a health emergency as they hadn’t seen in years. That’s a saying everything will be OK.

Alchimia, one of the leading European manufacturers of medical devices for Ophthalmic Surgery and Human Tissue Processing, announces the incorporation of Alchilife Srl, an Italian Research & Development company specialized in the ophthalmic field, with great expertise in chemistry, biology, biotechnology and bioengineering and experience in the design, development and validation of medical devices.

«We are very proud to welcome Alchilife, R&D department, to our team. This fusion fits perfectly into an organization like that of Alchimia, constantly focused on the continuous improvement of raw materials, methods and processes to ensure even greater safety and innovation in a competitive market such as that of ophthalmology», said Mauro Beccaro, CEO of Alchimia Srl.

Thanks to its numerous publications, Alchilife Srl has brought its contribution to the scientific community through various papers in the ophthalmic field, such as the validated cytotoxicity test by direct contact method on BALB 3T3 and human-derived ARPE-19 cell lines according to ISO 10993-5, the human retina ex vivo and the reactive oxygen species (ROS) studies.

«We believe that this incorporation is the concrete solution that the market needs now, Surgeons and Patients deserve safe products and guarantees on product quality.
Patients first», declared Mauro Beccaro.

The search for a truly reliable cytotoxicity assay on perfluorocarbon liquids (PFCLs) is becoming one of the “hottest” topics in vitreoretinal surgery.

Since the very unfortunate events occurred during the recent years using perfluorocarbon liquids endotamponades, surgeons want to be reassured that these incidents will not reoccur. With this aim, PFCL manufacturers are seriously committed to do their best to provide surgeons with strong evidences on their product safety.

It is now ascertained that completely fluorinated, unreactive PFCL products such as PFO (perfluoro-n-octane) and PFD (perfluorodecalin) are not toxic by themselves; therefore, all research efforts are now focusing on the search of the best design attributes to detect or, more properly, to exclude the presence of impurities that might lead to ocular toxicity.

Nevertheless, the latest literature clearly demonstrates that this topic is still matter of a great debate, and that an overall agreement in this field is lacking.

Currently, two different approaches are in the spotlight: the H-value determination and the in vitro cytotoxicity tests using direct contact methods.

Menz’s group of research from the Pharmpur Gmbh, while highlighting the clinical relevance of the so-called H-value, defined as the residual amount of reactive incompletely fluorinated compounds in PFCLs, proposed that “The H-value is a measure for reactive and underfluorinated impurities that cause toxicity of PFCLs and should be incorporated in each endotamponade specification with a limit of 10 ppm to prove the effectiveness of the ultra-purification required and ensure a safe product”. The proposal was based on the “evidence that […] incompletely fluorinated by-products that inevitably arise during production and are dissolved in PFCL can, even in minutes quantities, lead occasionally to severe toxic reactions”, and that “the reactivity of incompletely fluorinated compounds and their toxicity are closely related”.

The doubts arisen on the H-value determination method included, among other things, its ability to detect only specific underfluorinated compounds of the form RFRH (having reactive C-H bonds) while leaving undetected other potentially toxic chemical compounds – which were identified in the “unsafe” PFCL used in Spain – such as acids, alcohols, and benzene derivatives; in addition, it was recently shown that using an innovative NMR technology “failed to demonstrate the correlation between the H-content and in vitro cytotoxicity test in ARPE-19 and BALB/3T3 cell lines”. Nevertheless, it must be recognized that the Menz’s group of research admitted that “the article is the first contribution in a planned series of publications aimed at providing tools suitable for ensuring patient safety in the ophthalmological application of perfluoro-carbon liquids (PFCL)”.

A growing interest is gaining the in vitro cytotoxicity test by direct contact method on human retinal pigment epithelial cell line (ARPE-19) according to ISO 10993-5 recommendations.

It should be noted that the direct contact method is, among all the methodologies recommended by the ISO 10993-5 standard, highly sensitive and able to detect even weak cytotoxicity. In addition, as stated by the ISO standard, the application of the PFCL directly on human retinal pigment epithelial cell line (ARPE-19) is, as much as possible, similar to the clinical situation in which the product will be used. Instead, other tests included in the ISO 10993-5 such as the extract method do not obey to this requirement and are much less sensitive for testing volatile and immiscible in water substances as the PFCLs: indeed, in the past the use of the extract method led to falsely negative results, with the well-known bad clinical outcomes in Spanish patients.

It is certainly for all the above-mentioned reasons that two groups of research, the Srivastava’s research group from the IOBA Institute (Instituto Universitario de OftalmobiologÍa Aplicada, Spain), and the team of researchers from Alchilife Srl (Italy), in collaboration with Mario Romano, PhD, from the Humanitas University of Milano (Italy), have dedicated a great effort in tuning up reliable direct contact methods. In fact, this approach requires few, yet very important, technical steps that are strictly related to the physical-chemical specifications of PFCLs and crucial for validating the direct contact method. If, from one side, the high-density properties of these compounds help avoiding any sample evaporation or loss of contact with the cells, from the other one they may lead to insufficient contact area and contact time between the sample and the cell layer, cell mortality induced by sample heaviness and inappropriate cell sensibility. Thus, a careful assessment of all risks of possible direct contact test failure must be performed.

All these requirements were fulfilled by the two research groups, and each of them proposed their validated method:

• In a paper published on IOVS (2018), Srivastava et al. commented that their study on ARPE-19 and mouse fibroblast L929 cell lines “suggests applying this new method to avoid occurrence of such cases of blindness”;
• In his presentation at the 18^th Euretina Congress in Vienna, M. Romano affirmed that “The direct contact cytotoxicity test according to ISO 10993-5 is a suitable method to detect the cytotoxicity of PFCLs that was validated using both a quantitative and a qualitative approach in ARPE-19 and BALB/3T3 cell.” This presentation is of particular relevance for Alchimia, since the described method is the one that has always been used to test their PFCLs, as shown on the finished product labels.

Let us conclude with these few considerations:

• Although a uniform evaluation method or cytotoxicity test evaluation has not been established so far, some truly reliable cytotoxicity test methods are becoming available in literature, which might help overcoming the surgeon safety concerns about the use of PFCLs in vitreoretinal surgery;
• A more efficient control by the European Union Authorities is welcome, yet lacking;
• Even the most reliable cytotoxicity tests must be accompanied by very thorough and most accurate chemical-physical tests to guarantee the highest purity of PFCLs.

References

• Pastor JC et al. Acute retinal damage after using a toxic perfluorooctane for vitreo-retinal surgery. Retina 2017;1440–1151
• Menz DH, et al. How to ward off retinal toxicity of perfluorooctane and other perfluorocarbon liquids?
  Invest Ophthalmol Vis Sci. 2018; 59:4841–4846
• Srivastava GK et al. Chemical considerations regarding the H-value methodology and its relation with toxicity determination.
  Invest Ophtahalmol Vis Sci 2019; 60:3363-3364
• Ruzza P et al. H‐content is not predictive of perfluorocarbon ocular endotamponade cytotoxicity in vitro.
  ACS Omega 2019 https://doi.org/10.1021/acsomega.9b01793
• Menz DH et al. Author Response: Chemical Considerations Regarding the H-Value Methodology and Its Relation With Toxicity Determination.
  Invest Ophthalmol Vis Sci 2019;60(10):3365-3367
• ISO 10993-5, 2009. Biological evaluation of medical devices – Part 5: Tests for in vitro cytotoxicity.
• Romano M. et al. Evaluation of cytotoxicity of perfluorocarbons for intraocular use by cytotoxicity test in vitro in cell lines and human donor retina ex vivo. Trans Vis Sci Technol 2019, in press.
• Srivastava GK et al. Comparison between direct contact and extract exposure methods for PFO cytotoxicity evaluation.
  Sci Rep 2018;8(1):1425

From 4 to 7 February Alchimia srl, as a manufacturer of Medical Devices, hosted the US Food and Drug Administration (FDA) government agency for a Level II QSIT audit, all four major subsystems were covered:

• Management Controls
• Design Controls
• Corrective and Preventive Actions (CAPA)
• Manufacturing & Process controls.

NO major observations (FDA 483) were raised, as shown in the Establishment Inspection Report (EIR).

This result demonstrates the compliance of Alchimia srl to Good Manufacturing Practices (GMP).

The FDA approval adds to the quality system certifications, ISO 9001 and ISO 13485, and to the authorizations already issued by national and international regulatory bodies following on-site audits.

The result of the Alchimia’s FDA audit of last February is available online by accessing the Inspection Classification Database made available by the FDA.

It is possible to start the search, entering Al. Chi. Mi. A. Srl (with spaces in between) in the Firm Name field.

After starting the search by clicking the “SEARCH” button at the end of the page, the database will show the Alchimia Inspection classification as “NAI”, which means no action indicated.

On May 31st Alchimia hosted the Ukrainian Center for Medical Certification and prognostication auditors for the annual periodic audit of its Quality Management System with reference to the following product categories: perfluorocarbons, tissue dyes, gas for intraocular tamponade and silicone oils.

During the audit no non-conformities or observations were found, indicating that the AL.CHI.MI.A. Quality Management System complies with the “Technical Regulation on medical devices n. 753 dated 02.10.2013 - Annex 3 Full Quality Assurance System (Ukrainian regulation), ISO 13485: 2016.