GB2078950A

GB2078950A - Reference system for checking liquid purity

Info

Publication number: GB2078950A
Application number: GB8120205A
Authority: GB
Original assignee: Sanofi SA; Airbus Group SAS
Current assignee: Sanofi SA; Airbus Group SAS
Priority date: 1980-07-01
Filing date: 1981-06-30
Publication date: 1982-01-13
Also published as: CH643952A5; FR2486241A1; AT389768B; CA1171767A; DE3166169D1; ATA278281A; BR8104248A; IE811459L; IE51360B1; PT73290A; EP0043330B1; KR830006689A; LU83462A1; DK274381A; GR74564B; FR2486241B1; ES8301537A1; GB2078950B; PT73290B; IT8167894A0

Description

1 GB 2 078 950 A 1 SPECIFICATION These, however, do not allow a direct

equivalence to be established between the detected imperfection Reference system for use in checking the purity of a and its actual size, except by lengthy, inaccurate and liquid in a container arbitrary statistical methods. These methods are not 70 only costly but too removed from the criteria of This invention relates to non-destructive checking accuracy and reproducibility which are to be ex systems and is concerned with the detection of pected from a method of standardization to be used foreign bodies, mainly solids, or other imperfections for checking pharmaceutical products.

in a liquid present in a container capable of being It was therefore considered necessary to produce checked by the chosen detection means, it being 75 a system of standardization for devices of the possible to carry out the check even after the said above-mentioned type in order to achieve a high container has been finally sealed prior to commer- quality check. It also seemed necessary to create cial use. reference means forthe staff carrying outthe visual It is an object of the invention to provide a stable checking.

A15 and reproducible reference system which is of use in 80 The present invention therefore makes it possible:

the detection of such imperfections. to overcome the drawbacks of the previous techni- In accordance with the invention, a reference que, to improve the checking of liquids contained in system comprises a set of containers which will containers capable of being checked by the selected normally be the same or substantially the same as method of detection, to reduce the cost of the the containers the contents of which are to be 85 checks, especially the standardization of the check checked for foreign bodies or other impurities. ing devices and their accuracy, and to standardize All the containers of one set are identical. They all the strictness of the criteria for rejection in the case contain the same liquid, but each has one known of visual checking, as a function of the time and the deliberate, clearly defined foreign body or imperfecoperators.

tion which is stable and reproducible, and capable of 90 The liquid present in the set of containers compris producing a signal in a detection system and which ing the reference system of the invention may be varies in size from one container to the next. identical to the liquid to be checked or, more simply, Sets of standardized containers made in this way may hve properties equivalent to those of the liquid may be used to regulate the sensitivity of automatic to be checked, in respect of the detection system checking devices, periodically to check the accuracy 95 selected.

of the sensitivity of the said devices, or to compare The foreign body or imperfection may consist, for actual imperfections with the standardized imperfec- example, of a bead made of suitable material, such tions. In these cases of utilization, by means of the as glass, metal or plastics. This imperfection may invention a high degree of accuracy and great saving also consist of a crystal the growth or size of which of time can be achieved for the automatic checking, 100 has been arrested at the required dimensions. The compared with the statistical methods frequently essential thing is that the said imperfection is previously used. defined, reproducible and stable, i.e. of known and The reference system according to the invention unchangeable material, shape, surface state and may also be used for the information of the person- size.

nel carrying out a visual check and as a reference 105 The type and size of the standardized imperfec base for such a visual check. For these two uses, the tions will be chosen as a function of the imperfec quality of this visual check is thereby appreciably tions actually encountered and of the detection improved. system to be employed which might be, for exam The reference system according to the invention is ple, an optical, photoelectrical or electro-magnetic of especial use for checking liquid pharmaceutical 110 system, or a system using X-rays or gamma radia products, especially ampoules of injectable liquids. tion.

In this connection pharmacopoeia require that The size of the imperfections varies from one injectable liquids packaged in ampoules be sub- reference container to another, according, for exam jected to rigorous cheeks. The purpose of one suck ple, to an arithmetic or geometric progression, so as check is to detect, after the ampoules have been 115 to cover the entire range of imperfections which are sealed, the presence of foreign bodies of a very discernible by the eye or detectable by a machine.

varied nature, form and size, such as textile fibres When calibrated beads are used they are sorted at (for example from clothing or atmospheric filters), the beginning by a known method, for example by granular particles, particles of glass, particles from sifting. In this way sets of reference containers are crystallization, or dust. The aim of this detection is to 120 produced which are suitable for each type of check eliminate all the ampoules containing imperfections and for each machine.

visible to the naked eye, for example particles, For visual checking a set of reference containers assuming that these are at least 50 micrometres ([t may be envisaged having imperfections ranging m). This is an empiral method as the detection of from the smallest imperfection detectable by the certain imperfections depends on the checker's 125 practised eye to the imperfection which will always keeness of sight, on the type of fighting and its be easily detected. It is obvious that the sizes of the intensity and also on the form and nature of the greatest imperfections are also established as a imperfection. function of the conditions of use of the visual Automatic devices are known for detecting imper- checking station and as a function of the criteria fections in ampoules by photo-electric means. 130 essential to this checking, for example as a function 2 GB 2 078 950 A 2 of the requirements of pharmacopdia when phar maceutical products are being checked.

The reference containers are normally chosen at the outset so as to be identical or similar to the containers to be checked. If necessary they should undergo a special treatment so that they are free from any other detrimental imperfections.

These reference containers will be judged to contain only a standardized imperfection as soon as the other possible impurities are of an obviously insignificant size in comparison with this standardized imperfection.

In the case of pharmaceutical checks the aim of the invention is, more particularly, a reference system consisting of a set of ampoules having the characteristics set out above. In this case the standardized ampoules are preferably pharmaceutical ampoules selected atthe start to be identical or nearly identical to the ampoulesto be checked.

In order to provide a practical example, a set of 2 mi. standardized ampoules was made according to the invention and filled with pharmaceutical-quality (pyrogen free) water, each ampoule containing a glass bead of a diameter ranging from 30 to 200 micrometers. This set of ampoules has given very satisfactory results on a detection device manufactured underthe Trade Mark STRUNCK and on another device of the APM type which is manufactured under the Trade mark ROTA.

Whilst of particular use in the checking of pharmaceutical products, it will be appreciated that the reference system of the invention can be used in various applications, such as the checking of fine chemicals, particularly reactive chemicals.

Claims

1. A reference system for use in the detection of foreign bodies or other imperfections in a liquid present in a container capable of being checked by the chosen detection system, the system comprising a set of identical standardized reference containers all containing the same liquid and each having a single known, deliberate foreign body or other imperfection which is stable and reproducible and is capable of producing an effect on the detection system used, the size of the foreign body or other imperfection varying from one containerto the next in the set.

2. A system according to Claim 1, wherein the liquid contained in the reference containers is identical to the liquid to be checked.

3. A system according to Claim 1, wherein in respect of the chosen detection system the liquid contained in the reference containers has properties equivalent to those of the liquid to be checked.

4. A system according to Cibim 1, 2 or3, wherein the deliberate foreign body is composed of a crystal the growth or size of which has been arrested at the required dimensions.

5. A system according to Claim 1, 2 or3, wherein the deliberate foreign body is composed of a small bead of a known diameter which var es from one container to the next.

6. A system according to Claim 5, wherein the bead is made of glass.

7. A system according to Claim 5, wherein the bead is made of metal.

8. A system according to Claim 5, wherein the 70 bead is made of a plastics material.

9. A system according to anyone of Claims 1 to 6, wherein the reference containers are composed of sealed pharmaceutical ampoules containing an injectable liquid which are identical or substantially 75 identical to the ampoules to be checked.

10. A system according to Claim 9, wherein the system comprises a set of 2 ml. standardized ampoules containing pyrogen-free water each containing a glass bead of a diameter in the range from 80 30 to 200 Itm.

Printed for Her Majesty's Stationery Office by Croydon Printing Company Limited, Croydon, Surrey, 1981. Published by The Patent Office, 25 Southampton Buildings, London, WC2A lAY, from which copies may be obtained.

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