Medical Devices (Amendment) Regulations, 2004

Suppliment tal-Gazzetta tal-Gvern ta’ Malta, Nru. 17,532, 23 ta’ Jannar, 2004

L.N. 27 of 2004

PRODUCT SAFETY ACT

(ACT NO. V OF 2001)

Medical Devices (Amendment) Regulations, 2004

IN exercise of the powers conferred by articles 38 to 40 of the

Product Safety Act, the Minister of Finance and Economic Affairs, on

the advice of the Malta Standards Authority, has made the following

regulations:-

(1) The title of these regulations is Medical Devices Citation

commencement.

(Amendment) Regulations, 2004, and they shall be read and construed

as one with the Medical Devices Regulations, 2003, hereinafter referred L.N. 47 of 2003.

to as “the principal regulations”.

(2) These regulations shall come into force on the date of

their publication

Provided that the provisions of the following regulations shall

enter into force on 1 st April 2004

– item 1.2.2 in regulation 2 of these regulations;

– items 3.1.23 to 3.1.34 in regulation 4 of these regulations; and

– regulations 5, 6, 7 and 8 of these regulations.

Immediately after regulation 1.2.1 of the principal regulations, Amends regulation

1 of the principal

there shall be inserted the following regulations

regulations.

“1.2.2. Holders of EC design-examination certificates or

EC type-examination certificates issued before 1 st April 2004 for

medical devices referred to in Article 1(1) of Directive 2003/32

shall apply for a complementary EC design-examination certificate

or EC type-examination certificate attesting to compliance with

the specifications laid down in Schedule XIII to these regulations.

1.2.3. Breast implants placed on the market before 1 st

September, 2003 pursuant to regulation 8.3(a) or regulation

3(b)(iii) of these regulations shall be subject to a conformity

reassessment procedure as Class III medical devices before the 1 st

March, 2004.

1.2.4. Decisions taken by notified bodies before the 1 st

September 2003 under regulation 8.3(a) of these regulations may

not be extended.”.

3. For regulation 2.1.3 and 2.1.3.1 of the principal regulations,

there shall be substituted the following

“2.1.3. Devices shall be divided into Classes I, IIa, IIb and

III. Classification shall be carried out in accordance with Annex

IX of the Directive, which is set out in Schedule IX to these

regulations, read with Directive 2003/12.”.

4. Immediately after regulation 3.1.21 of the principal regulations,

there shall be inserted the following

“3.1.22. “Directive 2003/12” means Commission Directive

2003/12/EC of 3 rd February 2003 on the reclassification of breast

implants in the framework of Directive 93/42/EEC concerning

medical devices;

3.1.23. “animal” means an animal from a bovine, ovine or

caprine species, as well as deer, elk, mink and cats;

3.1.24. “cell” means the smallest organised unit of any living

form which is capable of independent existence and of replacement

of its own substance in a suitable environment;

3.1.25. “derivative” means a material obtained from an animal

tissue by a manufacturing process such as collagen, gelatine,

monoclonal antibodies;

3.1.26. “Directive 2003/32” means Commission Directive

2003/32/EC of 23 rd April 2003 introducing detailed specifications

as regards the requirements laid down in Council Directive 93/42/

EEC with respect to medical devices manufactured utilising tissues

of animal origin;

3.1.27. “inactivation” means a process by which the ability

to cause infection or pathogenic reaction by transmissible agents

is reduced;

3.1.28. “non-viable” means having no potential for

metabolism or multiplication;

3.1.29. “reduction, elimination or removal” means a process

by which the number of transmissible agents is reduced, eliminated

or removed in order to prevent infection or pathogenic reaction;

3.1.30. “source country” means the country in which the

animal was born, has been reared and, or has been slaughtered;

3.1.31. “starting materials” means raw materials or any other

product of animal origin out of which, or with the help of which,

the devices referred to in regulation 2.2 of these regulations are

produced;

3.1.32. “tissue” means an organisation of cells and/or extra-

cellular constituents;

3.1.33. “transmissible agents” means unclassified pathogenic

entities, prions and such entities as bovine spongiform

encephalophathies agents and scrapie agents;

3.1.34. “TSE certificate” means TSE certificate of suitability

issued by the European Directorate for the Quality of Medicines.”.

5. Regulations 4.6 and 4.7 of the principal regulations shall Amends regulation

be renumbered as regulations 4.7 and 4.8 respectively and immediately 4 regulations.

after regulation 4.5.1 of the principal regulations, there shall be inserted

the following

“4.6. Subject to regulation 4.6.2 of these regulations, no

person shall put into service or supply a relevant device (if that

supply is also a placing on the market or if that supply is of a

relevant device that has been placed on the market) if that device

is manufactured utilising either animal tissue which is rendered

non-viable or non-viable products derived from animal tissue

unless–

(a) there is in respect of that device a risk analysis and

risk management scheme which is in accordance with the

requirements of Directive 2003/32; and

(b) the manufacturer of the device has fulfilled his

obligations under the procedures within that scheme.

4.6.1. If collagen, gelatine or tallow is of animal origin and

has been used in the manufacture of a relevant device, then subject

to regulation 4.6.2 of these regulations, no person shall put into

service or supply that device (if that supply is also a placing on the

market or if that supply is of a device that has been placed on the

market), unless that collagen, gelatine or tallow was fit for human

consumption.

4.6.2. Regulations 4.6 and 4.6.1 of these regulations shall

not apply to a relevant device which is not intended to come into

contact with the human body or which is intended to come into

contact with intact skin only.”.

6. Immediately after regulation 5.2 of the principal regulations,

there shall be inserted the following

“5.2.1. All necessary steps shall be taken to ensure that devices

referred to in Article 1(1) of Directive 2003/32 are placed on the

market and put into service only if they comply with the provisions

of these regulations and the specifications laid down in Schedule

XIII to these regulations.”.

7. (1) Immediately after regulation 8.1 of the principal

regulations, there shall be inserted the following

“8.1.1. Before lodging an application for a conformity

assessment pursuant to regulation 8.1 of these regulations, the

manufacturer of medical devices referred to Article 1(1) of

Directive 2003/32, shall carry out the risk analysis and the risk

management scheme set out in Schedule XIII to these regulations.”.

(2) Immediately after regulation 8.12 of the principal

regulations, there shall be added the following

“8.13. Conformity assessment procedures for medical devices

referred to in Article 1(1) of Directive 2003/32, shall include the

evaluation of their compliance with the essential requirements of

the Directive and the specifications laid down in the Annex to

Directive 2003/32, which is set out in Schedule XIII to these

regulations.

8.14. Notified bodies shall evaluate the manufacturer’s risk

analysis and risk management strategy, and in particular

(a) the information provided by the manufacturer;

(b) the justification for the use of animal tissues or

derivatives;

(c) the results of elimination and, or inactivation studies

or of literature search;

(d) the manufacturer’s control of the sources of raw

materials, finished products and subcontractors;

(e) the need to audit matters related to sourcing,

including third party supplies.

8.15. Notified bodies shall, during the evaluation of the risk

analysis and risk management in the framework of the conformity

assessment procedure, take account of the TSE certificate, for

starting materials, where available.

8.16. Except for medical devices using starting materials for

which a TSE certificate has been issued as referred to in regulation

8.15, national bodies shall, through the CIGD, seek the opinion of

the competent authorities of the other Member States on their

evaluation of and conclusions on the risk analysis and risk

management of the tissues or the derivatives intended to be

incorporated in the medical device as established by the

manufacturer.

8.16.1. Before issuing an EC design-examination certificate

or an EC type-examination certificate, the notified bodies shall

give due consideration to any comments received within 12 weeks

from the date on which the opinion of the national competent

authorities were sought.”.

8. Immediately after Schedule XII of the principal regulations, Adds new Schedule

XIII to the principal

there shall be added the following Schedule

regulations.

“Schedule XIII

Based on the Annex of Directive 2003/32

1. RISK ANALYSIS AND RISK MANAGEMENT

1.1. Justification for the use of animal tissues or derivatives

The manufacturer must justify, on the basis of his overall risk analysis and risk

management strategy for a specific medical device, the decision to use animal tissues

or derivatives, referred to in Article 1(1) of Directive 2003/32, (specifying animal species

and tissues) taking into account the expected clinical benefit, potential residual risk

and suitable alternatives.

1.2. Assessment procedure

In order to ensure a high level of protection for patients or users, the manufacturer

of devices utilising animal tissues or derivatives referred to in point 1.1 must implement

an appropriate and well documented risk analysis and risk management strategy, to

address all relevant relating aspects to TSE. He must identify the hazards associated

with those tissues or derivatives, establish documentation on measures taken to minimise

the risk of transmission and demonstrate the acceptability of the residual risk associated

with the device utilising such tissues or derivatives, taking into account the intended

use and the benefit of the device.

The safety of a device, in terms of its potential for passing on a transmissible

agent, is dependent on all the factors described in points 1.2.1 to 1.2.7, which must be

analysed, evaluated and managed. These measures in combination determine the device

safety.There are two key steps that must be considered.

These are

—selecting starting materials (tissues or derivatives) considered appropriate

regarding their potential contamination with transmissible agents (see 1.2.1, 1.2.2

and 1.2.3) taking into account further processing,

— applying a production process to remove or inactivate transmissible agents

on controlled sourced tissues or derivatives (see 1.2.4).

Furthermore, the characteristics of the device and its intended use must be taken

into account (see 1.2.5, 1.2.6 and 1.2.7).

In performing the risk analysis and risk management strategy, due consideration

must be given to opinions adopted by the relevant scientific committees, and where

appropriate to the opinions of the Committee for Proprietary Medicinal Products CPMP,

the references of which have been published in the Official Journal of the European

Union.

B

1.2.1. Animals as a source of material

The TSE risk is related to the source species, strains and nature of the starting

tissue. As the accumulation of TSE infectivity occurs over an incubation period of

several years, sourcing from young healthy animals is considered to be a factor reducing

the risk. Risk animals such as fallen stock, emergency slaughtered and TSE suspected

animals must be excluded.

1.2.2. Geographical sourcing

Pending the classification of countries according to the BSE status in Regulation

(EC) No 999/2001 of theEuropean Parliament and of the Council of 22 May 2001

laying down rules for the prevention, control and eradication of certain transmissible

spongiform encephalopathies 12 , the Geographical BSE risk (GBR) is used when

assessing the risk of the source country. The GBR is a qualitative indicator of the

likelihood of the presence of one or more cattle being infected with BSE, pre-clinically

as well as clinically, at a given point in time, in a country. Where presence is confirmed,

the GBR gives an indication of the level of infection as specified in the table below.

GBR level

Presence of one or more cattle clinically

or pre-clinically infected with the BSE agent

in a geographical region/country

I

Highly unlikely

II

Unlikely but not excluded

III

Likely but not confirmed or confirmed, at a lower level

IV

Confirmed, at a higher level

Certain factors influence the geographical risk of BSE infection associated with

the use of raw tissues or derivatives from individual countries. These factors are defined

in Article 2.3.13.2, point 1) of the International Animal Health Code of the OIE (Office

International des Épizooties), which is available at web-site www.oie.int/eng/normes/

Mcode/A_00067.htm

The Scientific Steering Committee has made an assessment of Geographical BSE

Risk (GBR) of several third countries and Member States, and will continue to do so

for all the countries, which applied for BSE status categorisation, taking the main OIE

factors into account.

1.2.3. Nature of starting tissue

The manufacturer must take into account the classification of the hazards relating

to different type of starting tissue. Sourcing of animal tissue must be subject to control

and individual inspection by a veterinarian and the animal carcass must be certified as

fit for human consumption.

OJ No. L 147, 31-05-2001, P.1.

The manufacturer must ensure that no risk of cross-contamination occurs at the

time of slaughtering.

The manufacturer must not source animal tissue or derivatives classified as

potentially high TSE infectivity, unless sourcing of these materials is necessary in

exceptional circumstances, taking into account the important benefit for the patient

and the absence of an alternative starting tissue.

In addition, the provisions in Regulation (EC) No 1774/2002 of the European

Parliament and of the Council of 3 October 2002 laying down health rules concerning

animal by-products not intended for human consumption must be applied.

1.2.3.1. Sheep and goats

A classification of infectivity in tissues for sheep and goats has been established

based on actual knowledge on the basis of the titres of transmissible agents in tissues

and body fluids from naturally infected sheep and goats with clinical scrapie. A table

was presented in the Scientific Steering Committee (SSC) opinion of 22-23 July 1999

on ‘The policy of breeding and genotyping of sheep’, (as an annex) 13 and further updated

in the opinion of the SSC — TSE infectivity distributed in ruminant tissues state of

knowledge December 2001 — adopted 10-11 January 2002 14 .

The classification may be reviewed in the light of new scientific evidence (for

example using relevant opinions from the Scientific Committees, the Committee for

Proprietary Medicinal Products CPMP and Commission Measures regulating the use

of material presenting risks as regards TSE). A review of the references to relevant

documents/opinions will be published in the Official Journal of the European Union

and will be listed after a Commission Decision has been taken.

1.2.3.2. Cattle

The list of specified risk material (SRM) laid down in Regulation (EC) No 999/

2001 shall be considered as potentially high TSE infective.

1.2.4. Inactivation or removal of transmissible agents

1.2.4.1. For devices which cannot withstand an inactivation/elimination process

without undergoing unacceptable degradation, the manufacturer must rely principally

on the control of sourcing.

1.2.4.2. For other devices, if claims are made by the manufacturer for the ability

of manufacturing processes to remove or inactivate transmissible agents, these will

have to be substantiated by appropriate documentation.

Available on the website of the Commission

http://europa.eu.int/comm/food/fs/sc/ssc/outcome_en.html.

Available on the website of the Commission

http://europa.eu.int/comm/food/fs/sc/ssc/outcome_en.html.

B

Relevant information from an appropriate scientific literature search and analysis

can be used to support inactivation/elimination factors, where the specific processes

referred to the literature are comparable to those used for the device. This search and

analysis should also cover the available scientific opinions that may have been adopted

by a EU Scientific Committee. These opinions shall serve as a reference, in cases

where there are conflicting opinions.

When the literature search failed to substantiate the claims, the manufacturer must

set up a specific inactivation and/or elimination study on a scientific basis and the

following need to be considered

— the identified hazard associated with the tissue,

— identification of the relevant model agents,

— rationale for the choice of the particular combinations of model agents,

— identification of stage chosen to eliminate and/or inactivate the

transmissible agents,

— calculation of the reduction factors.

A final report must identify manufacturing parameters and limits that are critical

to the effectiveness of the inactivation or elimination process.

Appropriate documented procedures must be applied to ensure that the validated

processing parameters are applied during routine manufacture.

1.2.5. Quantities of animal starting tissues or derivatives required to produce one

unit of the medical device

The manufacturer must evaluate the quantity of raw tissues or derivatives of animal

origin required to produce a single unit of the medical device. Where a purification

process is involved, the manufacturer must assess whether it may have the potential to

concentrate levels of transmissible agents present in the animal starting tissues or

derivatives.

1.2.6. Tissues or derivatives of animal origin coming into contact with the patients

and users

The manufacturer must consider

(i) the quantity of animal tissues or derivatives;

(ii) the contact area: its surface, type (e.g. skin, mucous tissue, brain) and

condition (e.g. healthy or damaged);

(iii) the type of the tissues or derivatives coming into contact with the patients

and/or users; and

(iv) how long the device is intended to remain in contact with the body

(including bioresorption effect).

The number of medical devices that could be used in a given procedure shall be

taken into account.

1.2.7. Route of administration

The manufacturer must take into account the route of administration recommended

in the product information, from the highest risk down to the lowest.

1.3. Review of the assessment

The manufacturer must establish and maintain a systematic procedure to review

information gained about their medical device or similar devices in the post-production

phase. The information must be evaluated for possible relevance to safety, especially

(a) if previously unrecognised hazards are detected;

(b) if the estimated risk arising from a hazard is no longer acceptable;

(c) if the original assessment is otherwise invalidated.

If any of the above apply, the results of the evaluation shall be fed back as an

input to the risk managementprocess.

In the light of this new information, a review of the appropriate risk management

measures for the device must be considered (including rationale for choosing an animal

tissue or derivative). If there is a potential that the residual risk or its acceptability has

changed, the impact on previously implemented risk control measures must be re-

evaluated and justified.

The results of this evaluation must be documented.

2. EVALUATION OF CLASS III MEDICAL DEVICES BY NOTIFIED BODIES

For devices falling into Class III under rule 17 15 of Annex IX to the Directive, set

out in Schedule IX to these regulations, manufacturers must provide to the notified

bodies referred to in Article 4 of Directive 2003/32, all relevant information to allow

evaluation of their current risk analysis and risk management strategy.

All medical devices utilising animal tissues or derivatives rendered non-viable except devices intended to

come into contact with intact skin only.

B

Any new information on TSE risk, collected by the manufacturer and relevant for

their devices must be sent to the notified body for information.

Any change in relation to processes of sourcing, collection, handling and

inactivation/elimination and that could modify the result of the manufacturer’s risk

management dossier must be transmitted to the notified body for the purpose of an

additional approval prior to its implementation.”.