Storage and Distribution) (Amendment) Regulations, 2016

L.N. 367 of 2016

HUMAN BLOOD AND TRANSPLANTS ACT

(CAP. 483)

Human Tissues and Cells (Coding, Processing, Preservation,

Storage and Distribution) (Amendment) Regulations, 2016

IN exercise of the powers conferred by article 16 of the Human

Blood and Transplants Act, the Minister for Health, after consultation

with the Licensing Authority, has made the following regulations:-

(1) The title of these regulations is the Human Tissues Citation and

and Cells (Coding, Processing, Preservation, Storage and scope.

Distribution) (Amendment) Regulations, 2016, and these regulations

shall be read and construed as one with the Human Tissues and Cells S.L. 483.04

(Coding, Processing, Preservation, Storage and Distribution

Regulations, hereinafter referred to as "the principal regulations".

(2) The scope of these regulations is to transpose Commission

Directive 2015/565 of 8 April 2015 amending Directive 2006/86/EC

as regards certain technical requirements for the coding of human

tissues and cells.

Regulation 3 of the principal regulations shall be amended Amends

regulation 3 of

as follows

the principal

regulations.

(a)

immediately after the definition "critical", there

shall be added the following new definition

" "donation identification sequence" means the first

part of the Single European Code consisting of the EU

tissue establishment code and the unique donation

number;";

(b) immediately after the definition "donation

identification sequence", there shall be added the following new

definitions

" "EU Coding Platform" means the IT platform

hosted by the Commission which contains the EU Tissue

Establishment Compendium and the EU Tissue and Cell

Product Compendium;

"EU Tissue and Cell Product Compendium" means

the register of all types of tissues and cells circulating in

the Union and the respective product codes under the three

permitted coding systems (EUTC, ISBT128 and

Eurocode);

"EU tissue establishment code" means the unique

identifier for accredited, designated, authorised, or

licensed tissue establishments in the Union. The tissue

establishment code consists of an ISO country code and the

tissue establishment number set out in the EU Tissue

Establishment Compendium, as further specified in

Schedule VII to these regulations;

"EU Tissue Establishment Compendium" means

the register of all tissue establishments which are

authorised, licensed, designated or accredited by the

Member States’ competent authority or authorities and

which contains the information about these tissue

establishments as set out in Schedule VIII;

"EUTC" means the product coding system for

tissues and cells developed by the Union consisting of a

register of all types of tissues and cells circulating in the

Union and their corresponding product codes;

"expiry date" means the date by which the tissues

and cells can be applied, as further defined in Schedule

VII;";

(c)

immediately after the definition "partner donation",

there shall be added the following new definition

" "pooling" means the physical contact or mixing in

a single container, of tissues or cells from more than one

procurement from the same donor, or from two or more

donors;";

(d) immediately after the definition "procurement

organisation", there shall be added the following new

definitions

" "product code" means the identifier for the

specific type of tissue and cell in question. The product

code consists of the product coding system identifier

indicating the coding system used by the tissue

establishment ("E" for the EUTC, "A" for ISBT128, "B"

for Eurocode) and the tissues and cells product number

foreseen in the respective coding system for the product

type, as further defined in Schedule VII;

"product identification sequence" means the

second part of the Single European Code consisting of the

product code, the split number and the expiry date;";

(e)

immediately after the definition "quality system",

there shall be added the following new definition

" "released for circulation" means distribution for

human application or transfer to another operator, e.g. for

further processing with or without return;";

(f)

immediately after the definition "reproductive

cells", there shall be added the following new definition

" "Single European Code" or "SEC" means the

unique identifier applied to tissues and cells distributed in

the Union. The Single European Code consists of a

donation identification sequence and a product

identification sequence, as further specified in Schedule

VII;";

(g) immediately after the definition " "Single European

Code" or "SEC" ", there shall be added the following new

definition

" "split number" means the number which

distinguishes and uniquely identifies tissues and cells

having the same unique donation number and the same

product code and originating from the same tissue

establishment, as further defined in Schedule VII;";

(h) immediately after the definition "traceability", there

shall be added the following new definition

" "unique donation number" means the unique

number attributed to a specific donation of tissues and cells

in line with the system in place in each Member State for

allocating such numbers, as further specified in Schedule

VII;"; and

(i) immediately after the definition "validation", there shall be

added the following new definition

" "within the same centre" means that all steps from

procurement to human application are carried out under the

same responsible person, quality management system and

traceability system, within a healthcare centre comprising

at least an accredited, designated, authorised, or licensed

tissue establishment and an organisation responsible for

human application at the same location.".

Regulation 10 of the principal regulations shall be

substituted by the following

"10. (1) The Authority shall ensure that tissues and cells

are traceable in particular through documentation and the use of

the Single European Code from procurement to human

application or disposal and vice versa. Tissues and cells used for

advanced therapy medicinal products shall be traceable under

these regulations at least until transferred to the ATMP

manufacturer.

(2) The Authority shall ensure that tissue establishments

and organisations responsible for human application shall retain

the data set out in Schedule VI for at least thirty years, using an

appropriate and readable storage medium.

(3) Where tissues and cells retrieved from a deceased

donor by procurement teams operating for two or more tissue

establishments, the Authority shall ensure an appropriate

traceability system across the procurements.".

Regulation 11 of the principal regulations shall be

substituted by the following

" Single

(1)

Without prejudice to sub-

European

regulation (2), a Single European Code shall be

Code.

applied to all tissues and cells distributed for

human application. For the other situations where

tissues and cells are released for circulation, as a

minimum the donation identification sequence

shall be applied at least in the accompanying

documentation.

(2) The provisions of sub-regulation (1)

shall not apply to

(a)

reproductive cells from partner

donation;

(b) tissues and cells distributed

directly for immediate transplantation to the

recipient, as provided for under the Tissues

and Cells (Quality and Safety) Regulations;

(c)

tissues and cells imported into

the Union in case of emergency authorised

directly by the competent authority or

authorities, as referred to in the Human

Blood and Transplants Act;

(d) tissues and cells other than

reproductive cells for partner donation, when

these tissues and cells remain within the

same centre; and

(e)

tissues and cells that are

imported into the Union, when these tissues

and cells remain within the same centre from

importation to application, provided that the

centre comprises a tissue establishment

authorised, designated, accredited, or

licensed to carry out importing activities.".

5. Immediately after regulation 11 of the principal Adds new

regulations to

regulations, there shall be added the following new regulations

the principal

regulations.

" Requirements

The Single European Code referred to

related to the

in the regulation 11 shall, apart from the

application of

requirements provided for under Schedule VII,

the Single

European

be -

Code.

(a)

in eye-readable format;

(b) preceded by the acronym "SEC";

and

(c)

printed with the Donation

Identification Sequence and Product

Identification Sequence separated by a

single space or as two successive lines.

(1)

The Authority shall ensure that

Requirements

related to the

all tissue establishments, including importing

application of

the Single

tissue establishments (as defined in Directive

European

2015/565/EU, as amended) -

Code.

(a)

allocate a Single European Code

to all tissues and cells requiring application

of this code at the latest before their

distribution for human application;

(b) allocate a donation identification

sequence after procuring the tissues and

cells, or when receiving them from a

procurement

organisation,

or

when

importing tissues and cells from a third

country supplier. The donation identification

sequence shall include

(i) their

EU

tissue

establishment code as assigned in the

EU

Tissue

Establishment

Compendium;

(ii) a unique donation number

allocated by the tissue establishment,

unless such number is allocated

centrally at national level or is a

globally unique number as used by the

ISBT128 coding system. Where

allowed, in case of pooling of tissues

and cells, a new donation identification

number shall be allocated to the final

product;

(c)

do not alter the donation

identification sequence once it is allocated to

tissues and cells released for circulation,

unless it is necessary to correct an encoding

error; any correction requires proper

documentation;

(d) use one of the permitted product

coding systems and the corresponding tissue

and cell product numbers included in the EU

Tissue and Cell Product Compendium at the

latest before their distribution for human

application;

(e)

use an appropriate split number

and expiry date. For tissues and cells for

which no expiry date is defined, the expiry

date shall be 00000000 at the latest before

their distribution for human application;

(f)

apply the Single European Code

on the label of the product concerned in an

indelible and permanent manner and

mention that code in the relevant

accompanying documentation at the latest

before its distribution for human application.

The tissue establishment may entrust this

task to a third party or third parties, provided

the tissue establishment ensures compliance

with Directive 2015/565/EU, as amended, in

particular in terms of uniqueness of the code.

Where the label size precludes the

application of the Single European Code on

the label, the code shall be unambiguously

linked to tissues and cells packaged with

such a label through the accompanying

documentation;

(g) notify the competent authority

when

(i) information contained in

the

EU

Tissue

Establishment

Compendium requires an update or

correction;

(ii) the EU Tissue and Cell

Product Compendium requires an

update;

(iii) the tissue establishment

observes a situation of significant non-

compliance with the requirements

relating to the Single European Code

concerning tissues and cells received

from other EU tissue establishments;

(h) take the necessary measures in

case of incorrect application of the Single

European Code on the label.

(2) The Authority shall also

(a)

ensure the allocation of a unique

tissue establishment number to all tissue

establishments

authorised,

accredited,

designated or licensed in Malta. If a tissue

establishment has different physical

locations, but has one system for allocating

unique donation numbers, it may be deemed

to be one and the same tissue establishment.

If a tissue establishment uses two or more

systems to allocate unique donation

numbers, such an entity shall be allocated

separate tissue establishment numbers

corresponding to the number of allocation

systems used;

(b) decide which system or systems

shall be used for the allocation of unique

donation numbers in Malta. Permitted

systems of allocation include national

systems establishing centralised allocation

of the nationally unique donation number or

systems requiring each tissue establishment

to allocate unique donation numbers or

international systems that allocate globally

unique donation numbers that are compatible

with the Single European Code;

(c)

monitor and enforce the full

implementation of the Single European Code

in Malta;

(d) ensure the validation of the data

on the tissue establishments contained in the

EU Tissue Establishment Compendium in

Malta and update the Compendium, in not

later than ten working days for any changes

substantially affecting the authorisation,

accreditation, designation or licence of the

tissue

establishments

concerned,

in

particular for the following situations

(i) when a new tissue

establishment is authorised, designated,

accredited, or licensed;

(ii) when tissue establishment

information changes or is not correctly

recorded

in

the

EU

Tissue

Establishment Compendium;

(iii) when the accreditation,

designation, authorisation or licence

details of a tissue establishment, as

listed in Schedule VIII, change,

including

(A) accreditation, desi-

gnation, authorisation or licence

for a new tissue or cell type;

(B) accreditation, desi-

gnation, authorisation or licence

for a new prescribed activity;

(C) details

of

any

conditions and, or exemptions

added to an authorisation;

(D) suspension, in part

or in full, of a specific

accreditation,

designation,

authorisation or licence for a

particular activity or tissue or

cell type;

(E) revocation, in part

or in full, of an accreditation,

designation, authorisation or

licence

for

a

tissue

establishment; and

(F) situations when a

tissue establishment voluntarily

ceases, in part or in full, the

activity or activities for which it

is

authorised,

accredited,

designated or licensed

Provided

that

when

a

tissue

establishment is authorised by two or more

competent authorities for different types of

tissues and cells or different activities, each

competent authority shall update the

information relating to those activities for

which it is responsible;

(e)

alert the competent authorities of

another Member State when they observe

incorrect information in the EU Tissue

Establishment Compendium relating to the

other Member State or when they observe a

situation of significant non-compliance with

the provisions relating to the Single

European Code relating to the other Member

State;

(f)

alert the Commission and the

other competent authorities when in their

assessment the EU Tissue and Cell Product

Compendium requires an update.

(3) The application of the Single European

Code does not preclude the additional application

of other codes in accordance with the

requirements set out under any other relevant law.

Tissues and cells already in storage on

Transitional

period.

29 October 2016 shall be exempted from the

obligations relating to the Single European Code,

provided the tissues and cells are released for

circulation in the Union within five years

following that date and under the condition that

full traceability is ensured by alternative means.

For tissues and cells which remain in storage and

which are only released for circulation after the

expiry of this five-year period and for which the

application of the Single European Code is not

possible, in particular because the tissues and cells

are stored under deep-freeze conditions, the tissue

establishments shall use the procedures applicable

to products with small labels as laid down in

regulation 13(1)(f).".

6. Part E of Schedule II to the principal regulations shall be

amended as follows;

(a)

immediately after paragraph (f) of point 1 thereof,

there shall be added the following new paragraph

"(g) Single European Code as applicable to the

tissues and cells being distributed for human application or

the donation identification sequence as applicable to the

tissues and cells released for circulation, other than

distributed for human application.";

(b)

for the words "If any of the information" to the

words "that they remain together" in point 1 thereof, there shall

be substituted the following

"If any of the information under points (d), (e) and

(g) above cannot be included on the primary container

label, it must be provided on a separate sheet

accompanying the primary container. This sheet must be

packaged with the primary container in a manner that

ensures that they remain together."; and

(c)

immediately after paragraph (i) of point 2 thereof,

there shall be added the following new paragraph

"(j) for imported tissues and cells, the country of

procurement and the exporting country (if different from

the procurement country).".

7. Schedule III to the principal regulations shall be Substitutes

Schedule III to

substituted by the following

the principal

regulations.

"SCHEDULE III

NOTIFICATION OF SERIOUS ADVERSE REACTIONS

PART A

Rapid notification for suspected serious adverse reactions

Tissue establishment

EU tissue establishment code (if applicable)

Report identification

Reporting date (year/month/day)

Individual affected (recipient or donor)

Date and place of procurement or human application (year/month/

Unique donation identification number

Date of suspected serious adverse reaction (year/month/day)

Type of tissues and cells involved in the suspected serious adverse

Single European Code of tissues or cells involved in the suspected

serious adverse reaction (if applicable)

Type of suspected serious adverse reaction(s)

PART B

Conclusions of Serious Adverse Reactions Investigation

Tissue establishment

EU tissue establishment code (if applicable)

Report identification

Confirmation date (year/month/day)

Date of serious adverse reaction (year/month/day)

Unique donation identification number

Confirmation of serious adverse reaction (Yes/No)

Single European Code of tissues or cells involved in the confirmed

serious adverse reaction (if applicable)

Change of type of serious adverse reaction (Yes/No) If YES, specify

Clinical outcome (if known)

- Complete recovery

- Minor sequelae

- Serious sequelae

- Death

Outcome of the investigation and final conclusions

Recommendations for preventive and corrective actions

".

8. Schedule IV to the principal regulations shall be

substituted by the following

"SCHEDULE IV

NOTIFICATION OF SERIOUS ADVERSE EVENTS

PART A

Rapid notification for suspected serious adverse events

Tissue establishment

EU tissue establishment code (if applicable)

Report identification

Reporting date (year/month/day)

Date of serious adverse event (year/month/day)

Serious adverse event,

Specification

which may affect

quality and safety of

Tissues and

Equipment

Human

Other

tissues and cells due to

cells defect

failure

error

(specify)

a deviation in

Procurement

Testing

Transport

Processing

Storage

Distribution

Materials

Others (specify)

PART B

Conclusions of Serious Adverse Events investigation

Tissue establishment

EU tissue establishment code (if applicable)

Report identification

Confirmation date (year/month/day)

Date of serious adverse event (year/month/day)

Root cause analysis (details)

Corrective measures taken (details)

".

9. Schedule VI to the principal regulations shall be Substitutes

Schedule VI to

substituted by the following

the principal

regulations.

"SCHEDULE VI

Minimum data to be kept in accordance with regulation 10(2)

A. BY TISSUE ESTABLISHMENTS

(1) Donor identification

(2) Donation identification that will include at least

-

Identification of the procurement organisation

(including contact details) or the tissue establishment

-

Unique donation number

Date of procurement

Place of procurement

Type of donation (e.g. single v multi-tissue;

autologous v allogenic; living v deceased)

(3) Product identification that will include at least

Identification of the tissue establishment

Type of tissue and cell/product (basic nomenclature)

Pool number (in case of pooling)

Split number (if applicable)

Expiry date (if applicable)

Tissue/cell status (i.e. quarantined, suitable for use,

Description and origin of the products, processing

steps applied, materials and additives coming into contact with

tissues and cells and having an effect on their quality and/or

Identification of the facility issuing the final label

(4) Single European Code (if applicable)

(5) Human application identification that will include at least

Date of distribution/disposal

Identification of the clinician or end-user/facility

B. BY ORGANISATIONS RESPONSIBLE FOR HUMAN

APPLICATION

(1) Identification of the supplier tissue establishment

(2) Identification of the clinician or end-user/facility

(3) Type of tissues and cells

(4) Product identification

(5) Identification of the recipient

(6) Date of application

(7) Single European Code (if applicable)".

10. Schedule VII to the principal regulations shall be Substitutes

Schedule VII to

substituted by the following

the principal

regulations.

"SCHEDULE VII

THE STRUCTURE OF THE SINGLE EUROPEAN CODE

DONATION IDENTIFICATION

PRODUCT IDENTIFICATION SEQUENCE

SEQUENCE

EU TISSUE

PRODUCT CODE

ESTABLISHMENT

SPLIT

EXPIRY

CODE

UNIQUE

NUMBER

DATE

DONATION

ISO

Tissue

Product

Product

(YYYYM

country establishment NUMBER

Coding

number

MDD)

code

number

System

identifier

6 alpha-

13 alpha-

1 alphabetic

7 alpha-

3 alpha-

8 numeric

alphabetic

numeric

numeric

character

numeric

numeric

characters

characters

characters

characters

characters

characters

".

11. Immediately after Schedule VII to the principal Adds new

schedule to the

regulations, there shall be added the following new schedule

principal

regulations.

"SCHEDULE VIII

Data to be recorded in the EU Tissue Establishment Compendium

A.

Tissue establishment information

1. Name of the tissue establishment

2. National

or

international

code

of

tissue

establishment

3. Name of the organisation in which the tissue

establishment is located (if applicable)

4. Address of the tissue establishment

5. Publishable

contact

details

functional

e-mail

address, phone and fax

B. Details on the authorisation, accreditation, designation, or

license of the tissue establishment

1. Name of the authorising, accrediting, designating or

licensing competent authority or authorities

2. Name of the national competent authority or

authorities responsible for maintenance of the EU Tissue

Establishment Compendium

3. Name of the authorisation,

accreditation,

designation or licence holder (if applicable)

4. Tissues and cells for which the authorisation, accreditation,

designation or license was granted

5. Activities actually carried out for which the authorisation,

accreditation, designation or licence was granted

6. Status of the authorisation, accreditation, designation or

license (authorised, suspended, revoked, in part or in full,

voluntary cessation of activities)

Details of any conditions and exemptions added to the

authorisation (if applicable).".

€1.44