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Issue 03 | January 2012

Dear Reader,

Since 1st of July, I have taken over full responsibility for the Tubing Division of SCHOTT Glass India from Mr. Mohan Joshi, he has assumed the position of “Representative Director” and supporting the activities of all of SCHOTT’s business units in India.

My previous positions as production manager at SCHOTT in Germany and Singapore helps me to meet the challenges of glass tubing production. My goal is to improve SCHOTT Glass India’s market share in this happening progressive market. A regular upcoming topic, which is currently pursued by FDA is “Particles in Glass Containers”. We hope our summary regarding this topic is helpful for you.

We are planning a “Fiolax Academy” in North India this year and hope to meet you personally during the event.

Sincerely,Georg SparschuhGeneral Manager SCHOTT Glass India Pvt. Ltd.

Editorial

Georg SparschuhGeneral Manager

SCHOTT Glass India Pvt. Ltd.

Information LetterPharmaceutical Glass Tubing

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SCHOTT FIOLAX® ad in “Pharma Express“ Magazine

For the first time SCHOTT Tubing showed one of its products in a print advertisement in India. To promote FIOLAX® also within the community of pharmaceutical companies we placed an ad in one of the important magazines in India, the “Pharma Express”. You will find the ad in the first third of the magazine.

Update on status of quality seal

In the meantime, 75 % of our cus-tomers are using the quality seal logo. With more than one year experience of this launch we can safely assume that we need 800,000 labels a year. The project is quite successful in terms of visibility in pharmaceutical companies and the message clearly conveys that the product is made out of SCHOTT tubing. Our customers are regularly ordering these labels from us which clearly indicates that they see a perceptible benefit using this seal.

From the tubing side we had op-portunity to visit few big injectable companies and we could see the quality seal logos on the boxes in their warehouse supplied by our customers

Member of OPPI

SCHOTT is represented by Mr Mo-han Joshi as member of the Material management and Global sourcing committee in the “Organization of Pharmaceutical producers of India” (OPPI)

New contact at SCHOTT Glass India

Since August 2011, Mr Santosh Jadhav has joined SCHOTT Glass India in sales and marketing and is responsible for pharmaceutical as well as technical tubing, he is based in our Mumbai office.

Worth knowing

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Since the drugs to be filled are becoming more and more sensitive, it is important when producing primary packaging that the surface is as constant and inert as possible. Apart from the difficulties which the drug itself causes regarding stability and cleanness, if possible the drug should not have any reaction with the glass surface which changes it and would lead to alterations in the primary packaging. A fault which gained more importance last year were particles in the filled packag-ing. This type of particle can, e. g. consist of dust, fibers, glass splinters or so-called flakes which are caused by glass attack. The following expla-nations especially summarise the subject of flakes.

Appearance and Proof

Flakes are glass particles which are caused by delamination of the glass surface and can be seen as suspen-sion parts in the filled drugs. They have a typical appearance. Most of them are very thin or wafer-thin cylindrical particles.

They can be formed after autoclav-ing or after the filled product has been stored for some time and are visible as suspending particles.

These particles are mechanically very unstable because they are extremely thin. Thus, if the container is shaken or even after transport, it may be possible that the ori ginal shape is no

longer visible and there are only a lot of very small “dust-like” particles. Then, it is almost impossible to identify their nature.

If one looks at the particles under a microscope using a cold light source, they are usually easy to identify due to their typical shape. Furthermore, when the drug has been removed, an iridescent layer (Picture 3) can often be recognised on the surface.Picture 1: Flake

Picture 3: Iridescent layer

Picture 2: Ampoule with

suspending Particles

“ Particles in Containers: Flakes”

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If the surface of such an emptied container is etched with a solution of hydrofluoric acid w (HF) = 5 % (1 Vol %) and hydrochloric acid w (HCl) = 1% (9 Vol %), for 10 min-utes, then rinsed with distilled water and dried at 110 °C for 1 hour, (Picture 4) the delaminating process can be made visible as a typical ring. By doing this, the rough parts of the surfaces become even more marked or the flakes are finally released.

A further method of proving this is to filter off the solution. Picture 5 is typical for this. A larger flake of approx. 0.3 mm in size can be re cognized here. The white back- ground is the filter paper. When using clear glass the main chemical composition of such a flake is typi-cally SiO2 and Al2O3.

Origin

The glass surface of not well pre-pared glass containers can be attacked by some formulation. In this case even water is sufficient to cause an attack. If the pH values are higher (> 8,5), this can increase dramatically, i. e. the time it takes until there is a visible change in the glass surface or the particles become visible in the medicine is shorter, the higher the pH value becomes. An exact prediction on how quickly the corrosion continues can only

be obtained by making storage tests and stability tests on each individual medicine.

Glass container production takes place at very high temperatures >1400 °C during which evaporation of the glass components (mainly alkali borates) takes place. This can be observed during forming the container by the fact that “mist” develops for a short time in the container and by the fact that whitish deposits which are mainly soluble in water, develop on the cold packaging (see also Newsletter No. 3 and No. 9). The chemical composition of the ampoules/vials surface has therefore changed locally: Due to the alkalis evaporat-ing, the amount of silicon oxide has increased in the same manner as the oxides of Sodium and Boron in the condensation zones. It is unchanged on the parts which were not so strongly heated (Graph 1).

If the formation temperatures are low, the amount of evaporation products is so low that one cannot recognize any influence. Only when very high temperatures are con-cerned (so-called surface burning) is this effect visible with the naked eye and the part near the base is saturated with fine condensation points of sodium borate as one can see under a electron microscope (Picture 6).

“ Particles in Containers: Flakes”

Picture 5: Filtered Particel, size approx. 0.3 mm

Picture 4: Glass attack on the inner side of

a 5 ml-vial made of clear glass. Typical ring

with delaminated surface

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Graph 2 (Model for delamination) shows an example of a surface which has been attacked by an alkaline solution. The glass network is broken and Na+ and OH- are deposited instead of the oxygen binding.

Through this, the volume of the layer increases. If it becomes too thick, it simply peels off and can be found as flakes in the solution. Picture 7 shows a layer just before it is about to peel off.

Graph 2: Model for delamination

“ Particles in Containers: Flakes”

Picture 6: Alkaliborate

Graph 1: SIMS Picture of the surface of vial

Graph 2: Model for delamination

Picture 7: Layer just before to peel off

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A chain reaction is concerned when particles are released by glass corro-sion. The state of the surface is not a material property but is conside-rably influenced by the subsequent processes for forming the primary packaging.

The main factors which influence this are:• Formation speed• Temperature• Adjustment of the burners• Annealing conditions• Final sterilisation after filling

the drug

In the past, one has noted that mainly primary packaging which has been processed too hot is affected by flakes. Such containers show a high alkali release before filling and cooling. However the alkali release measure-ment does not give us the only key to flake formation, as in particular annealing has a considerable influ-ence on the solubility of the alkali.

A further factor which influences this is e. g. the treatment of the inner surface with ammonium sul- phate. The surface becomes poorer through treatment with sodium borate – a layer which is rich in silicone oxide is created which in its turns tends to form flakes.

Other risk factors for delaminations can be phosphate, citrate and com- plexing agents in the drug. The glass composition and therefore also the glass properties (proof by the glass powder test method ISO 719) only play a subordinate role here.

To avoid the effect of delamination, the only thing one can do is to ensure that the temperature is as low as possible during forming the containers. However, even in this case, a particularly aggressive me- dicine can cause the formation of flakes. Finally, one must always fall back on long-term test to be able to make an exact statement.

“ Particles in Containers: Flakes”

Literature

(1) K. Rehm:The Effect of the Manufacturing Conditions of Ampoules on the Chemical Resistance of Their Inner Surface Pamphlet No. 293 e. (1965); Jenaer Glaswerk Schott & Gen.,

(2) T. Futagami: Workshop: Pharmaceutical

Packaging and Delivery Systems.Requirements to serve Europe and US; Shanghai June 16, 2005

(3) SCHOTT AG, Mainz: Labornotiz Schott R&D; LN 2005-091:

(4) SCHOTT-Rohrglas GmbH, Mitterteich: Newsletter 3 (12/2002), 6 (9/2003) and 9 (10/2004)

Factors which influence the delamination

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India forges ahead in the market for biosimilars which includes insulin for diabetes patients. Due to afford-ability issues, the local market has been growing slowly, explained K V Subramaniam, President and CEO of Reliance Life Sciences, India.

How ever, economic growth and increasing income levels now put India into a key position among the emerging nations by 2015.

indiaonline.com

According to Steven H Myint, chairman of Chennai-based Green Signal Bio Pharma, the Indian vac-cine market has become one of the leading vaccine manufacturers. With forecasted revenues of $ 800 million, 70 percent of vaccines are being

exported. Global and domestic companies providing affordable, high quality vaccines, play a signi-ficant role on the Indian market.

articles.economictimes. indiatimes.com

Having reached a size of $ 3.5 billion in 2010, the biotechnology sector in India is poised for robust growth. Despite the lack of venture funding, delays in import-export as well as in regulation, insiders predict a

20 per cent growth per annum – mainly driven by the growing demand for biopharmaceuticals, biosimilars and vaccines.

news.in.msn.com

According to a new report by Global Industry Analysts, Inc. GIA, the market for disposable and reusable syringes is on the rise. Main reasons are an aging population requiring intensive healthcare and a rising number of drugs that need to be

administered using syringes. There-by, the market is witnessing a trend towards pre-filled and needle-less syringes which offer higher safety.

strategyr.com

Interesting Links:

India’s share of biosimilars may reach $ 2 billion by 2015

India produces 60 percent of the global health vaccines

India is entering the era of bioeconomy

Syringe market to reach $ 11.8 billion by 2017

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The value of drugs going off-patent between 2016 and 2020 will fall 62 percent from the value in the preceding five-year period. Indian off- patent drug exporters will need other ideas to expand business.

The Economic Times suggests four key growth drivers: Generic Biolo-gics, new drugs, differentiated or specialty formulations and vaccines.

The Economic Times

Vaccines that, if approved, could put an end to some of today’s most challenging diseases could end up as blockbusters a decade from now. Kalorama Information’s report has identified ten emerging vaccines that could account for $ 24.7 billion

in new sales by 2020. Among these are vaccines against Alzheimer’s, AIDS, Hepatitis C and E and Hyper-tension.

www.fiercevaccines.com

Interesting Links:

Growth opportunities for the time when drugs go off-patent

Bestselling vaccines 2020

Please find all interesting links and every issue of this information letter at www.schott.com/tubing/infoletter_in

Imprint: Schott Glass India Pvt. Ltd., Village-Ankhi, Tal. Jambusar, 392 150 Gujarat, India. Phone: +91-2644-220216. FIOLAX®, BORO-8330™ and DURAN® are registered trademarks of SCHOTT AG.