IE51360B1

IE51360B1 - Reference system for use in checking the purity of a liquid in a container

Info

Publication number: IE51360B1
Application number: IE1459/81A
Authority: IE
Original assignee: Aerospatiale; Sanofi Sa
Priority date: 1980-07-01
Filing date: 1981-06-30
Publication date: 1986-12-10
Also published as: GR74564B; ES503893A0; IT8167894A0; KR870002748Y1; GB2078950B; IT1145169B; JPS5740637A; DE3166169D1; BE889447A; PT73290A; IL63092A0; FR2486241B1; ATA278281A; EP0043330A1; GB2078950A; LU83462A1; CA1171767A; DK274381A; PT73290B; BR8104248A

Abstract

The invention relates to a reference system for use in the non- destructive checking and detection of foreign bodies or other imperfections in a liquid present in a container capable of being checked by the selected detection system. The system is composed of a set of identical standardized containers all containing the same liquid and each having a single known, deliberate foreign body or imperfection which is stable and reproducible and capable of producing an affect, for example a signal, in the detection system used and which varies in size from one container to another. The system may comprise a set of sealed pharmaceutical ampoules. The foreign body may be a crystal whose growth has been arrested at the required dimensions or a bead of known diameter made of glass, metal or plastic.

Description

REFERENCE SYSTEM FOR USE IN CHECKING THE PURITY _OF A LIQUID IN A CONTAINER_ This invention relates to non-destructive checking systems and is concerned with the detection of foreign bodies, mainly solids, or other solid matter in a liquid present in a container capable of being checked by the chosen detection means, it being possible to carry out the check even after the said container has been finally sealed prior to commercial use.

It is an object of the invention to provide a stable and reproducible reference system which is of use in the detection of such solid matter.

In accordance with the invention, a reference system comprises a set of containers which will normally be the same or substantially the same as the containers the contents of which are to be checked for foreign bodies or solid matter.

All the containers of one set are identical. They all contain the same liquid, but each has one known deliberate, clearly defined foreign body or solid mass which is stable and reproducible, and capable of producing a signal in a detection system and which varies in size from one container to the next.

Sets of standardized containers made in this way may be used to regulate the sensitivity of automatic checking devices, periodically to check the accuracy of the sensitivity of the said devices, or to compare actual solid matter with the standardized solid mass. In these cases of utilization, by means of the invention a high degree of accuracy and great saving of time can be achieved for the automatic checking, compared with the. statistical methods frequently previously used.

The reference system according to the invention may also be used for the information of the personnel carrying out a visual check and as a reference base for such a visual check. For these two uses, the quality of this visual check is thereby appreciably improved. - 3 The reference system according tc. the invention is of especial use for checking liquid pharmaceutical products, especially ampoules of injectable liquids.

In this connection pharmacopoeia require that injectable liquids packaged in ampoules be subjected to rigorous checks. The purpose of one such check is to detect, after the ampoules have been sealed, the presence of foreign bodies of a very varied nature, form and size, such as textile fibres (for example from clothing or atmospheric filters), granular particles, particles of glass, particles from crystallization, or dust. The aim of this detection is to eliminate all the ampoules containing imperfections visible to the naked eye, for example particles, assuming that these are at least 50 micrometres (ji m). This is an empirical method as the detection of certain imperfections depends on the checker's keenness of sight, on the type of lighting and its intensity and also on the form and nature of the imperfection.

Automatic devices are known for detecting solid matter in ampoules by photo-electric means. These, however, do not allow a direct equivalence to be established between the detected solid matter and its actual size, except by lengthy, inaccurate and arbitrary statistical methods.

These methods are not only costly but too removed from the criteria of accuracy and reproducibility which are to be expected from a method of standardization to be used for checking pharmaceutical products.

It was therefore considered necessary to produce a system of standardization for devices of the above-mentioned type in order to achieve a high quality check. It also seemed necessary to create reference means for the staff carrying out the visual checking.

The present invention therefore makes it possible: to overcome the drawbacks of the previous technique, to improve the checking of liquids contained in containers capable of being checked by the selected method of detection, to reduce the cost of the checks, especially the standardization of the checking devices and their accuracy, and - 4 1 to standardize the strictness of the criteria for rejection in the case of visual checking, as a function of the time and the operators.

The liquid present in the set of containers comprising the reference system of the invention may be identical to the liquid to be checked or, more simply, may have properties equivalent to those of the liquid to be checked, in respect of the detection system selected.

The foreign body of solid mass may consist, for 10 example, of a bead made of suitable material, such as glass, metal or plastics. This solid mass may also consist of a crystal the growth or size of which has been arrested at the required dimensions. The essential thing is that the said solid mass is defined, reproducible and stable, i.e. of known and unchangeable material, shape, surface state and size.

The type and size of the standardized solid masses will be chosen as a function of the solid materials actually encountered and of the detection system to be employed which might be, for example, an optical, photoelectrical or electro-magnetic system, or a system using X-rays or gamma radiation.

The size of the solid masses varies from one reference container to another, according, for example, to an arithmetic or geometric progression, so as to cover the entire range of materials which are discernible by the eye or detectable by a machine. When calibrated beads are used they are sorted at the beginning by a known method, for example by sifting. In this way sets of reference containers are produced which are suitable for each type of check and for each machine.

For visual checking a set of reference containers may be envisaged having solid masses ranging from the smallest solid material detectable by the practised eye to the material which will always be easily detected. It is obvious that the sizes of the largest masses are also established as a function of the conditions of - 5 use of the visual checking station and as a function of the criteria essential to this checking, for example as a function of the requirements of pharmacopoeia when pharmaceutical 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 solid mass as soon as the other possible impurities are of an obviously insignificant size in comparison with this standardized mass.

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 at the start to be identical or nearly identical to the ampoules to be checked.

In order to provide a practical example, a set of 2 ml. 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 under the 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 applicatons, such as the checking of fine chemicals, particularly reactive chemicals.

Claims

CLAIMS :

1. Λ reli tuu'e s;..ten for u:;e it; the ih-f ij-.-ti. n of foreign bodies or other solid matter in a liquid pr--.--.nt in a container capable of being checked by the chuser detection system, the reference 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 solid mass 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 solid mass varying from one container to 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 Claim 1, 2 or 3, 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 or 3, wherein the deliberate foreign body is composed of a small bead of a known diameter which varies 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 bead is made of a plastics material.

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

7. 10. A system according to Claim 9, wherein the system comprises a set of 2 ml. standardized ampoules containing a glass bead of a diameter in the range from 30 to 200 um .

8. 11. A reference system according to Claim 1, substantially as herein described.