In house manufacture

MHRA has produced some guidance (Bulletin 18 - The Medical Devices Regulations: Implications on healthcare and other related establishments) covering this issue.

The following additional information is relevant to in-house manufacture of in vitro diagnostics :

1. Since we published guidance in July and August 2003 on the In Vitro Diagnostic Devices Directive1 ('IVD Directive') and its implications for in-house manufacture, we have received a significant amount of information from various bodies on the use of IVDs in an in-house context.

2. In the light of this information, we have sought further legal advice on the extent to which in-house manufacturing of IVDs is covered by the regulatory requirements. Revised guidance is set out below. Previous guidance no longer applies. Please note that this guidance represents the interpretation of MHRA and cannot be taken to be a definitive statement of the law. This can only be given by the courts. Where you have any doubts about your obligations, you should always consult your own professional advisors.

3. By way of background, the IVD Directive applies not only to devices which are placed on the market, but also to devices which are put into service and used in the context of a professional activity, without being placed on the market (article 9.132). However, article 1.5 of the IVD Directive3 exempts 'health institutions' from the provisions of the Directive in certain circumstances:

"This Directive shall not apply to devices manufactured and used only within the same health institution and on the premises of their manufacture or used on premises in the immediate vicinity without having been transferred to another legal entity."

4. The main focus of the queries we have received has been in relation to the use of IVDs which have been manufactured in-house (i.e. the circumstances covered by article 9.13) particularly in the circumstances where an IVD is manufactured and used on samples from a different legal entity.

Summary of Revised Advice

5. In summary, MHRA's view is that the exemption will apply where a health institution manufactures an IVD in-house and then uses that IVD on the premises of manufacture (or on premises in the immediate vicinity) provided that the use of the IVD is intrinsic to the operation of the health institution, and not for some extraneous purpose that does not form part of the health functions of the institution. If these conditions are satisfied, it is irrelevant that a diagnostic service is being provided to a different legal entity – the exemption will still apply.

What is a 'Health Institution'?

6. MHRA's view is that a health institution is a body whose primary purpose is the care and / or promotion of public health. Bodies which clearly qualify as health institutions are NHS trusts and bodies such as the National Blood Authority and the Health Protection Agency. Similarly, MHRA considers that private hospitals and bodies which provide private health care (for example, BUPA) can be treated as health institutions, provided that the primary purpose of those bodies is the care and / or promotion of public health.

7. On the other hand, free-standing laboratories which provide diagnostic services, (which are not part of a body which has as its purpose the care and / or promotion of public health) do not, in MHRA's view, qualify as health institutions. Similarly, were a clinic to be established purely to provide diagnostic services, which did not have as its overall purpose the provision of health care (i.e. care and treatment of patients) or the promotion of public health, MHRA would not consider such a clinic to be a "health institution." This means that the exemption will not apply to such bodies even if they would otherwise fall within the exemption.

8. In general, MHRA's view is that a health institution will be a single legal entity (e.g. a trust, rather than an individual hospital), although there may be exceptional circumstances where it is appropriate to treat two different legal entities as a single health institution. Whether two legal entities can be treated as a single institution will depend on their precise circumstances. It is not sufficient that they both have as their primary purpose the care and/or promotion of public health. There must be some close association and common identity, as well as shared premises and facilities, such that they can genuinely be considered as a single institution. For example, a hospital may be considered a single health institution, even though the premises are shared by an NHS trust and a research laboratory run by the university which operates the hospital's medical school or medical research department. The laboratory may manufacture an IVD which is then used by the NHS trust staff, but such use could be treated as being use within the same health institution.

What Qualifies Health Institutions for the Exemption?

9. There are two distinct circumstances in which the exemption will apply:

i. A device is manufactured and used within the same health institution, on the premises of manufacture;
ii. A device is manufactured and used within the same health institution, on premises in the immediate vicinity (provided the device has not been transferred to another legal entity).

10. As set out above, concern has centred on the use of devices which have been manufactured in-house (i.e. the circumstances covered by article 9.13) and which are not transferred to another body. Our views are set out in summary in paragraph 3 above.

11. Where a health institution manufactures a device and transfers it to a different health institution, the exemption does not apply because the device is not manufactured and used within the same health institution. This means that in most cases, where a device is transferred by a health institution to a different legal entity, the exemption does not apply.

12. MHRA's interpretation is best illustrated by a series of examples:

A health institution manufactures an IVD in-house and uses that IVD on the premises of manufacture, or on premises in the immediate vicinity.

Provided that the use of the IVD by the health institution is intrinsic to its operation and not for some extraneous purpose that does not form part of its health functions, MHRA considers that the exemption will apply. Our revised view is that this is regardless of the identity of the entity to which the diagnostic service is being provided. This would cover an NHS trust hospital providing a routine or specialist diagnostic service to a hospital within a different NHS trust (e.g. the Supra Regional Assay Service); or a body such as the National Blood Authority or the Health Protection Agency providing specialist testing services within its remit to other bodies.

However, MHRA considers that the use by a health institution of a device for an extraneous purpose (e.g. an NHS hospital setting up commercial, diagnostic service available to privately paying patients, which was not part of its NHS functions) is not use 'within' the institution and therefore the exemption does not apply.

A health institution manufactures an IVD in-house, but then transfers that IVD to a different part of the same health institution located on a different site which is not in the immediate vicinity.

The exemption does not apply, because although the IVD is manufactured and used within the same health institution, the use of the IVD is not on the premises of manufacture or on premises in the immediate vicinity.

A health institution manufactures an IVD in-house, but then transfers it to a different legal entity, which is based on the same premises.

In general, the exemption does not apply because the device is not manufactured and used within the same health institution. However, if the two separate legal entities can be treated as on health institution and the legal entity which uses the IVD does so on the premises of manufacture (assuming that the use of the IVD is part and parcel of the operation of that health institution), then the exemption does apply. An example might be the manufacture of an IVD by a university research laboratory on trust hospital premises (as part of a joint health partnership), which is then used by the hospital to test NHS patients.

However, MHRA does not consider that the exemption would apply if a commercial manufacturer set up on hospital premises and manufactured IVDs which were then used by the hospital - MHRA would not regard the hospital and manufacturer together as a 'health institution'.

A health institution manufactures an IVD in-house, but then transfers it to a different legal entity, which is based on nearby premises.

In the example above, the university research laboratory and hospital are on different premises, albeit nearby. The exemption does not apply.

What about modification of IVDs bought from a Third Party?

13. In our view, the regulatory requirements apply whenever a device has been modified to such an extent that it can be considered as a new device. If it is appropriate to treat the modified device as a new device, then the modifier is in the same position as if he had manufactured a device from scratch for the purposes of the regulatory requirements - i.e. if he is placing the device on the market, or falls within article 9.13, he will need to follow the appropriate regulatory procedure. Health institutions will get the benefit of the exemption in the normal way. There are no hard and fast rules about when a modified device should be treated as a new device and every situation will need to be looked at individually. The question is whether the device has been subject to important changes which modify its original performance. MHRA can give advice in individual cases.

14. Similarly, MHRA considers that where a person or body uses a device bought from a third party, in the context of his professional activity, in a way which makes important changes to its original purpose, that person will need to comply with article 9.13 unless the health institution exemption applies.

Further guidance

15. For guidance on the IVD Directive more generally, see Guidance Note 19 - Guidance Notes on In Vitro Diagnostic Medical Devices Directive 98/79/EC. For more detailed enquiries on the matters covered by this note, please contact MHRA on era@mhra.gsi.gov.uk or phone on 020 7084 3300.

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1 98/79/EC, OJ No. L331, 7.12.98, p. 1
2 See definition of "putting into service", regulation 2(1) of the Medical Devices Regulations 2002, as amended.
3 See regulation 33 of the Medical Devices Regulations 2002, as amended.