Jbol Ltd, R (on the application of) v The Health Protection Agency

Urinary tract infection results from the presence and multiplication of micro-organisms in one or more structures of the urinary tract with associated tissue invasion. This can give rise to a wide variety of clinical symptoms. Those who are suspected of suffering from such infection are commonly asked to provide a specimen of urine so that it can be investigated in a laboratory. Routinely, a urine specimen is passed from the body and collected into a specimen container. The specimen of urine is then transported in the container to the laboratory where the specimen may be examined by microscopy, bacteriological culture, or other process.

In these proceedings the Claimant asserts that European Directive 98/79/EC demands that such containers are sterile. The word sterile is used to mean that the container is free from any viable micro-organisms. Since it is not possible to measure the absolute absence of something, however, a product such as a container is considered to be sterile if the chance of a viable micro-organism being present in it is 1 in 1,000,000 or less.

The Claimant is a small innovations company which has designed and patented a device for mid-stream urine collection. Originally the device was known as “Cleancatch Midstream.” Its current device is known as “Whiz Midstream.” Whiz Midstream is sterile in the sense described above.

The Defendant is a body created by statute. It has a number of functions in relation to health which include a) the protection of the community (or any part of the community) against infectious disease and other dangers to health; b) the prevention of the spread of infectious diseases; c) the provision of assistance to any other person who exercises functions in relation to those matters. From time to time the Defendant issues documents entitled “National Standard Methods”. On 1 May 2008 the Defendant issued such a document under the title “Investigation of Urine”. It was given a document reference, namely BSOP41 and the document issued on 1 May 2008 was the sixth version of the document.

The document had a section dealing with safety considerations. Under the heading “SPECIMEN TRANSPORT AND STORAGE” the document specified:-

“Sterile leak-proof container in a sealed plastic bag.”

Under the heading “SPECIMEN COLLECTION” the following appeared:-

“2.2.1

MID-STREAM URINE (MSU)

Recommended method for routine use

The first part of voided urine is discarded and, without interrupting the flow, approximately 10ml is collected into a sterile container. The remaining urine is discarded…..

Clean-catch urine

A reasonable alternative to MSU

Thorough periurethral cleaning is recommended. The whole specimen is collected into a sterile container and then an aliquot sent for examination.”

On 20 October 2009 the Defendant issued version 7 of BSOP41. Version 7 contains a number of changes from version 6. Critically, the following appears:-

“SPECIMEN TRANSPORT AND STORAGE

CE marked leak-proof container^a in a sealed plastic bag

…..

2.2.1

MIDSTREAM URINE (MSU)

MSU is the recommended routine collection method.

Periurethral cleaning is recommended (water is considered sufficient).

The first part of voided urine is discarded and, without interrupting the flow, approximately 10ml is collected into a CE marked leak-proof container^a

The remaining urine is discarded. …..

Clean-catch urine

A reasonable alternative to MSU

Periurethral cleaning is recommended. The whole specimen is collected and then an aliquot sent for examination in a CE marked leak-proof container^a.”

The footnote reads as follows:-

“The requirements of the EU in vitro Diagnostic Medical Devices Directive (98/79/EC Annex 1B 2.1) state that such devices must “reduce as far as possible contamination of, and leakage from, the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen. The manufacturing processes must be appropriate for these purposes.”

It is common ground that BSOP 41 is in the nature of guidance. Mr. Green for the Claimant submits that the guidance contained in the extracts from issue 7 set out above is unlawful since it removes the requirement contained within the Directive (and hitherto contained in the guidance itself) that containers should be sterile.

The Defendant resists this contention. It submits that the relevant provisions of Directive 98/79/EC, properly interpreted, do not require that such containers should be sterile and that the phraseology contained within version 7 of BSOP 41 is entirely consistent with the Directive. The Defendant accepts as it must that its guidance prior to 2009 suggested that containers used for the collection and transportation of urine must be sterile; it argues, however, that this was and never has been a requirement imposed by the Directive. Further, it has adduced evidence to show that over many years the receptacles in general use for urine collection and transport are plastic containers with screw caps (known as “universal” containers) which are not sterile as defined above (although commonly described as if they were).

When these proceedings were commenced there were other grounds of challenge. Ultimately, however, permission to apply for judicial review was granted on the ground identified above. While the other arguments raised originally surfaced as part of the background when submissions were made to me, no useful propose would be served by a discussion of the background which exists between the parties in this case. As I see it, the case now depends upon the proper interpretation of the Directive.

One of the main objectives of the Directive is the maintenance or improvement of the level of health protection attained in member states. The Directive is clear that in vitro diagnostic medical devices should provide patients, users and third parties with a high level of health protection and attain the performance levels originally attributed to them by the manufacturer. Article 2 of the Directive provides that Member States shall take all necessary steps to ensure that devices are placed on the market and/or into service only if they comply with the requirements laid down in the Directive and used in accordance with their intended purpose (defined in Article 1(2)(h) as “the use for which the device is intended according to the data supplied by the manufacturer on the labelling, in the instructions for use and/or in promotional materials”). Article 3 makes it mandatory for devices to meet the essential requirements in Annex 1 of the Directive which apply to them, taking account of the intended purpose of the devices concerned.

The essential requirements contained in Annex 1 which are relevant to the issue before me are as follows:-

“A.

GENERAL REQUIREMENTS

1.

The devices must be designed and manufactured in such a way that, when used under the conditions and for the purposes intended, they will not compromise, directly or indirectly, the clinical condition or the safety of the patients, the safety or the health of the users or, where applicable, other persons, or the safety of property. Any risks which may be associated with their use must be acceptable when weighed against the benefits to the patient and be compatible with a high level of protection of health and safety.

2.

Solutions adopted by the manufacturer for the design and construction of the devices must conform to safety principles, taking account of the generally acknowledged state of the art.

In selecting the most appropriate solutions, the manufacturer must apply the following principles in the following order:

•

eliminate or reduce risks as far as possible (inherently safe design and construction),

•

where appropriate take adequate protection measures in relation to risks which cannot be eliminated,

•

inform users of the residual risks due to any shortcomings of the protection measures adopted.

……

5.

The devices must be designed, manufactured and packed in such a way that their characteristics and performances during their intended use will not be adversely affected under storage and transport conditions (temperature, humidity, etc.) taking account of the instructions and information provided by the manufacturer.

B.

DESIGN AND MANUFACTURING REQUIREMENTS

2.

Infection and microbial contamination

2.1

The devices and their manufacturing processes must be designed in such a way as to eliminate or reduce as far as possible the risk of infection to the user or other persons. The design must allow easy handling and, where necessary, reduce as far as possible contamination of, and leakage from, the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen. The manufacturing processes must be appropriate for these purposes.

2.2….

2.3

Devices labelled either as ‘STERILE’ or as having a special microbiological state must be designed, manufactured and packed in an appropriate pack, according to procedures suitable for ensuring that they remain in the appropriate microbiological state indicated on the label when placed on the market, under the storage and transport conditions specified by the manufacturer, until the protective package is damaged or opened.

2.4

Devices labelled either as ‘STERILE’ or as having a special microbiological state must have been processed by an appropriate, validated method.”

Articles 5 and 9 are also relevant. Article 5 provides that Member States shall presume compliance with the essential requirements referred to in Article 3 in respect of devices which are in conformity with the relevant national standards which have transposed the “harmonised standards” the reference numbers of which have been published in the Official Journal of the European Communities. Article 9 relates to all devices other than those covered by Annex 2 and devices for performance evaluation. It provides that a manufacturer shall, in order to affix the CE marking, follow the procedure referred to in Annex 3 and draw up the EC Declaration of Conformity required before placing the device on the market. The relevant extracts from Annex 3 are as follows:-

“EC DIRECT DECLARATION OF CONFORMITY

1.

The EC declaration of conformity is the procedure whereby the manufacturer or his authorised representative who fulfils the obligations imposed by sections 2 to 5 and, additionally, in the case of devices for self-testing, the obligations imposed by section 6, ensures and declares the products concerned meet the provisions of this Directive which apply to them. The manufacturer must affix the CE marking in accordance with Article 16.

2…….

3.

The technical documentation must allow assessment of the conformity of the product with the requirements of the Directive. It must include in particular:

…..

•

In the case of sterile products or products with a special microbiological state or state of cleanliness, a description of the procedures used.

5.

The manufacturer shall institute and keep up to date a systematic procedure to review experienced gained from devices in the post-production phase and to implement appropriate means to apply any necessary corrective actions, taking account of the nature and risks in relation to the product….”

Devices considered to meet the essential requirements of the Directive must bear the CE mark – see Article 16.

Mr Chamberlain submits that there is nothing in the Directive which expressly requires that containers for collecting and transporting urine must always be sterile or that they must be sterile if that is technically possible. That is no accident submits Mr Chamberlain. He points out that the term sterile is used in the Directive in Annex 1 Part B paragraphs 2.3 and 2.4 that those paragraphs are simply aimed at ensuring that devices are appropriately labelled. Those paragraphs do not purport to stipulate in what circumstances a device must be sterile.

Mr Chamberlain also relies upon the wording of paragraph 1 of Part A to Annex 1 and paragraph 2.1 of Part B. Both those paragraphs, submits Mr Chamberlain, permit of a degree of flexibility and judgment; they cannot be interpreted as requiring that containers are always sterile. Mr Chamberlain focuses, in particular, upon the second sentence of paragraph 2.1 of Part B. The requirement that the design of the device must reduce as far as possible contamination of and leakage from the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen is qualified by the words “where necessary”. Mr Chamberlain points out that this sentence resonates with Article 3 which makes it plain that the essential requirements apply “taking account of the intended purpose of the devices concerned.”

Mr Chamberlain also relies upon European Standard EN14254 which was approved on 23 April 2004. It is common ground that this European Standard also has the status of a national standard; in the UK it is BS EN 14254. The Standard specifies requirements and test methods for single-use evacuated and non-evacuated receptacles, intended by their manufacturers for the primary containment and preservation of specimens, other than blood specimens, derived from the human body, for the purposes of in vitro diagnostic examination. Paragraph 4.1 of the Standard is as follows:-

“4.1.

If a receptacle is intended to collect a specimen for a specific examination where the material of the closure, or container, or the interior coating, or the additive, or accessory, if present, may affect the final results of the examination, then the maximum level of the contamination with that substance, and the analytical method employed, shall be stated by the manufacturer in accompanying literature, or on the label or packaging (see also 11.7). Validation of the suitability of material with regard to a receptacle specifically intended use is the responsibility of the manufacturer.”

Paragraph 4.3 provides that receptacles containing a microbe-supporting additive should be subjected to a validation process to eliminate microbial contamination from the additive and the receptacle interior and that validation of the process is the responsibility of the manufacturer.

Mr Chamberlain submits that the contrast between these two paragraphs demonstrate that the Standard clearly contemplates that there may be circumstances in which a receptacle can be less than sterile in the strict sense.

Mr Green, on behalf of the Claimant, also relies upon this Standard. He relies upon paragraph 9 which is in the following terms:-

“9.1

If a manufacturer claims that the interior of the unopened and unused receptacle, or the whole receptacle, is sterile, or has a special micro-biological state, the container interior and any accessory or additive shall have been subjected to a validated process designed to achieve that claim. Validation of the sterilisation process is the responsibility of the manufacturer.

9.2

Sterility is mandatory when the collection system is intended for the culture of the specimen and when the receptacle contains culture media.”

Paragraph 9.1 does not advance Mr Green’s argument. However, paragraph 9.2 is capable of supporting Mr Green’s argument if the container under consideration is properly to be regarded as part of a collection system which is intended for the culture of the specimen and when the receptacle contains culture media.

Paragraph 3 of the Standard contains a number of definitions. For example, the words receptacle, container and specimen are defined. Receptacle is defined to mean a “vessel, whether evacuated or not, intended to contain a specimen, together with any receptacle accessory and additive, with closure in place”; container is “part of the receptacle without the closure, and without any accessory, that contains the specimen”; specimen is “biological material which is obtained in order to detect properties or to measure one or more quantities”. The phrase “the collection system” is not defined.

In order to explain the meaning to be given to the phrase “the collection system” in paragraph 9.2 the Defendant relies upon witness statements made by Professor Brian Duerden. Until recently the Professor was the Inspector of Microbiology and Infection Control for the Department of Health (England); he was also (indeed he may still be) Emeritus Professor of Medical Microbiology at Cardiff University Medical School. In his first witness statement dated 21 May 2010 the following paragraphs appear:-

“Specimen containers containing culture media

21.

There are certain circumstances in which specimen containers containing culture media are used. One example is the ‘e-swab’ for the collection and transport of patient samples for the identification of MRSA (meticillin resistant Staphylococcus Aureus). The e-swab is packaged in a pouch and gamma irradiated. It is therefore sterile in the strictest sense of the term. Sterility by terminal sterilisation is necessary because the swab needs to enter the body to obtain these specimens and is then placed directly in growth medium.

22.

Another example is the combination of a swab and ‘transport medium’ which are packaged together and terminally sterilised. This is the way a clinician might use a swab in order to collect a specimen of, for example, pus or exudate from a wound. In this example, however, the ‘transport medium’ is designed to maintain the viability of the bacteria but to prevent overgrowth of any bacteria present in the sample, not to encourage their growth (in contrast to the ‘e-swab’), above. Again, sterility by terminal sterilisation is necessary because the swab needs to enter the body to obtain a specimen.

Collection system

23.

I am aware that BSEN 14254 uses the term ‘collection system’ but does not define it. In some circumstances a set of products is used in combination to collect a sample from a patient and then transport it to the laboratory (as in the swab and medium example of the e-swab described above). In this example, the ‘collection system’ is intended for the culture of the specimen and the receptacle contains culture medium. A further example is the blood collection needle with an attachment that transfers the blood directly into a bottle of liquid medium for culture; this does not need to be sterile. However, the screw-cap (universal) container has many purposes as a receptacle for storing or transporting materials in microbiology and other pathology laboratories. It is not used to directly collect the sample from the patient (as with a swab or needle) but is the receptacle into which the sample is delivered for transport.”

The Claimant has adduced no evidence which contradicts Professor Duerden’s evidence as set out in these paragraphs. However, the Claimant's managing director, Mr Levinson has made a witness statement dated 20 January 2011 in which he discusses paragraph 9.2 of BS EN 14254. He makes the following points. All samples of urine are intended for the culture of the specimen. There is no reason to treat receptacles containing culture media differently from those from which a culture will subsequently be made. He suggests that the reference to “collection system” being intended for the culture of the specimen must be a reference to the whole or any part of the process of collection, storage and transport of a sample. He poses the question what would be the purpose of only mandating sterility of the final stage of the process, if the sample had passed through various non-sterile containers first?

As a matter of interpretation I am satisfied that the mandatory requirement for sterility for “the collection system” referred to in Paragraph 9.2 of the Standard applies only when that system is intended for the culture of the specimen and when the receptacle contains culture media. I see no reason to interpose the word “or” after “and” as the Claimant would have me do. I see no reason to reject Professor Duerden’s view as to what is meant by the phrase “the collection system” in paragraph 9.2. I accept, of course, that ultimately it is for the court and not the Professor to determine the meaning to be given to Paragraph 9.2 of the Standard. However, I accept, too, that the understanding of those who have to wrestle with such documents is not to be lightly set aside especially when that understanding is consistent with the natural meaning to be attributed to the words in question. In my judgment, the answer to Mr. Levinson’s question as posed in the preceding paragraph is that although the sample may have passed through one or more non-sterile containers before the final stage there is such a small risk of contamination of the sample by reason of that fact that the same can reasonably be ignored – as to which see below.

Mr Green accepts that Article 3 of the Directive requires that devices must meet the essential requirements set out in Annex 1 which apply to them “taking account of the intended purpose of the devices concerned.” His primary submission, however, is that the “essential requirements”, properly interpreted, nonetheless dictate that a container which is in use for the collection and transportation of urine should be sterile. He submits that paragraph 2.1 of Part B of Annex 1 requires that the design of any device must reduce as far as possible contamination of the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen. A proper application of the phrase ‘reduce as far as possible’ inevitably means that a device which is sterile must be used. That interpretation, submits Mr Green, also derives support from paragraph 2 of Part A to the Annex.

The difficulty with Mr Green’s interpretation is that it ignores the words “where necessary” which appear in paragraph 2.1 of Part B. Unless those words are to be regarded as superfluous (which cannot be right) the words, inevitably, qualify the need to reduce as far as possible the relevant risk. Whether it is necessary to reduce the relevant risk as far as possible is a matter of judgment. That judgment, of course, is to be exercised taking account of the intended purpose of the device in question and further, the objects of the Directive as spelled out in the Directive itself.

Accordingly it seems to me that the Directive demands that a device must be sterile only when as a matter of reasonable judgment that is considered to be necessary taking account of the intended purpose of the device and the objects of the Directive as a whole.

It is clear that the Defendant has reached the conclusion that it is perfectly permissible and consistent with the objectives of the Directive as a whole that it is not necessary for urine to be collected in containers which are sterile as strictly defined. It is true that it has not provided evidence from the person or persons who reached this conclusion on behalf of the Defendant in advance of the decision to issue version 7 of BSOP 41. However, finding as I do that the evidence of Professor Duerden is both objective and impressive (despite the doubts raised by Mr Levinson) there is before me a substantial body of evidence which demonstrates that the use of “universal containers” for the collection and transportation of urine is permissible when account is taken of their intended purpose and also the objectives of the Directive as a whole.

I should make clear, in summary, what that evidence demonstrates. First, for most of the last 30 years, the universal containers commonly used for collecting and transporting urine have been referred to as “sterile” containers. No doubt in part, at least, that is because universal containers are manufactured in a hot moulding process involving temperatures of 200°C, which kills all bacteria. They are assembled and packaged in aseptic conditions. In consequence of this method of manufacture, universal containers are described as “aseptically produced.” The term ‘aseptic’ is understood to describe a process or procedure designed to prevent or reduce to a minimum the risk of contamination of a product, material or patients’ tissues with living or dead bacteria, fungi or viruses and other biological agents during the process or procedure. If products are manufactured under such conditions they are said to be free from microbial contamination to a sterility assurance level of 1 in 1000 or less.

It is readily apparent that the sterility assurance level of containers and receptacles prepared by aseptic manufacturing processes is different from the sterility assurance level of a product which is sterile in the strict sense. Professor Duerden’s evidence is that the difference between a sterility assurance level of 1 in 1000 and 1 in 1,000,000 is not significant. He goes on to say that the possibility of contamination from containers with less than a 1 in 1000 chance of not being sterile compared with sterile containers is many orders of magnitude less than other risks of contamination during specimen collection. Those other risks arise according to the Professor because the urine inevitably passes through an area which is itself frequently contaminated by bacteria from the skin, urethra, vagina, or from faeces. While the Claimant does not accept the evidence of Professor Duerden it has adduced no evidence which persuades me that I should reject it.

In the light of my interpretation of the Directive and the evidence adduced on behalf of the Defendant I do not consider that the Defendant acted unlawfully when it decided to remove from its guidance the requirement that urine should be collected and transported in sterile containers.

That is not the end of this challenge. Mr Green submits that the guidance actually issued is opaque; it ought to be declared as unlawful since those obliged to comply with the Directive would find it impossible to understand the guidance now issued.

The relevant part of the guidance for collection and transport of urine is that it should be contained within a “CE marked leak-proof container”. No one who is familiar with the Directive and the regulations transposing the Directive into domestic law will find any difficulty in understanding what is meant by a CE marked container. A CE marking can be applied to a device only if the requirements of Annex 3 of the Directive are satisfied.

As I have identified, however, the guidance must be read in conjunction with a footnote. The footnote purports to reproduce the relevant part of the Directive (i.e. Annex 1 Part B paragraph 2.1). However, the words “where necessary” are not included in the footnote with the consequence that the footnote is capable of being read as though the Directive requires that all devices used for collection and transportation of urine must reduce as far as possible the relevant risk. In that sense the footnote is capable of misleading an uneducated reader. Whether it would mislead any person to whom the guidance is sensibly directed, however, must be a matter of considerable doubt. That said, if the Defendant considers it necessary to retain the footnote as part of the guidance it seems to me that the effect of paragraph 2.1 should be reproduced accurately.

However, the fact that I have highlighted a possible difficulty with the wording of the advice as currently published does not mean that the Claimant has obtained success in the proceedings. My clear view is that the Directive does not require that containers used for the collection and transportation of urine should be sterile. The Claimant has failed to persuade me that its principal argument is correct.

In the light of my view upon the proper interpretation of the Directive there can be no basis for the argument presented by Mr. Green that the effect of the guidance issued by the Defendant is to undermine the Directive. In my judgment this is not a case in which the principles formulated by the European Court of Justice in Commission of the European Communities v UK [2006] IRLR 888 have any application. I accept, of course, that while the provisions of the Directive are aimed primarily at manufacturers of in vitro devices bodies such as the Defendant have an obligation not to act in a way which is contrary to the Directive. As I have found, however, the Defendant has not broken this obligation.

I should not conclude this judgment without some mention of the fact that the hearing before me began with an application by the Claimant to amend its grounds of challenge. Initially, that was joined with an application to adjourn the hearing assuming the application to amend succeeded. After some discussion between Bar and Bench the Claimant decided to pursue its application to amend but not to seek an adjournment in the event that the application was successful. On that basis I invited the Claimant to make submissions not just about the timing of the application to amend (which was, on any view, very late) but also upon the substance of the challenge encompassed by the amendment.

At the conclusion of Mr Green’s submissions on the issues relating to the amendment I made observations which made it obvious that I was very likely to dismiss the application to amend. When Mr Chamberlain began his submissions in reply Mr Green informed both Mr Chamberlain and the court that he did not require Mr Chamberlain to respond to his application to amend. In other words, Mr Green gracefully accepted that his application to amend would fail.

In those circumstances I do not propose to prolong this judgment by dealing, formally, with the application to amend. It suffices to say that the application was brought at the very last minute; that there was no good reason for the delay in seeking to put forward the grounds of challenge and there was no general public interest in litigating the proposed grounds. Had Mr Green pressed his application I would have dismissed it. He acted reasonably and responsibly in indicating that the application to amend was not pursued.

As I have indicated this challenge fails on the main issue between the parties. Further, I cannot conceive that it is appropriate to grant any relief to the Claimant related to the wording of the guidance as currently published. However, the Claimant has not addressed me, directly, on this point and if any point is to be taken about relief that can be addressed at the handing down of this judgment.

I direct that if the parties can agree an order consequent upon this judgment the same should be submitted to the court for approval and if that is done there need be no attendance by anyone at the handing down.