Quality And Safe. Human Tissues And Cells Purpos. For Human Use

Original Language Title: jakost a bezpečn. lidských tkání a buněk urč. k použití u člověka

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Read the untranslated law here: https://portal.gov.cz/app/zakony/download?idBiblio=67567&nr=422~2F2008~20Sb.&ft=txt

422/2008 Coll.
DECREE


Dated 28 November 2008

Establishing detailed requirements for ensuring the quality and safety
human tissues and cells intended for human applications

Change: 339/2012 Coll.

Change: 45/2014 Coll.

Ministry of Health, pursuant to § 29 of the Act no. 296/2008 Coll., On
ensure the quality and safety of human tissues and cells intended for human application
and amending related laws (Act on human tissues
and cells), (hereinafter the "Act")

§ 1
Subject Matter


This Decree implements the relevant regulations of the European Communities ^ 1)
and provides detailed requirements for

A) the quality system

B) the procurement of human tissues and cells and reception at the tissue
device

C) assessing the medical fitness of the donor, donor selection tissues and cells
laboratory tests required for donors

D) processing, storage and distribution of tissues and cells and the related
quality control and safety

E) monitoring solutions and reporting of serious adverse reactions and events
,

F) the identification and traceability of tissues and cells

G) reporting on the activities of the tissue establishment

H) authorization of tissue establishment, receiving equipment and
diagnostic laboratories and permission for distribution of tissues and cells

I) rules of good distribution practices for distribution of tissues and cells.

§ 2
Basic concepts


For the purposes of this Decree

A) reproductive cells of all tissues and cells intended for purposes
assisted reproduction

B) standard operating procedures Written instructions describing the
steps in a specific process, including the materials and methods to be
used and the expected end product.

§ 3


Quality System
[To § 5 para. 1 point. ) and f) of the Act]

Quality system requirements within the tissue establishment, collection device
or diagnostic laboratory are set out in Annex no. 1
this decree. When creating a quality system to take account of these requirements
extent that is appropriate to the activities to be provided and
which permits the respective operator asks. Subsequently
meet these requirements is maintained in the range corresponding authorized activities.

§ 4

Procurement of tissues and cells

[To § 7 para. 1 point. c) e) of the Act]

Requirements for the procurement of tissues and cells and provide a tissue
processing equipment are set out in Annex no. 2 hereof.

§ 5

Donor selection and laboratory testing of samples from the donor

[To § 7 para. 1 point. c) and d) of the Act]

(1) criteria for assessing health eligibility and selection of donors of tissues and
cells for autologous and allogeneic use, except donors of reproductive cells
are set out in Annex no. 3 hereto.
Requirements for laboratory testing of samples taken from such donors, including requirements
samples for these tests are set out in Annex.
4 of this Decree.

(2) Criteria for assessing health eligibility and selection
donors of reproductive cells, and requirements for laboratory testing of samples taken
these donors are set out in Annex no. 5 of this Decree.

(3) In the case of the removal of organs, tissues and cells from the same donor and their
use the same beneficiary, shall be applied when assessing health
donor eligibility and selection criteria set for organ donor ^ 2).

§ 6

Requirements processes provided by the tissue establishment

[To § 5 para. 1 point. c), d) and f) and § 5 para. 2 point. a) of the Act]

(1) Requirements for receiving, inspection, approval or disposal of tissues and cells
for processing tissue establishments and on the records of these
tissues and cells are defined in Annex no. 6, paragraph 1 of the Decree.

(2) Requirements for methods of processing, packaging, labeling, layoffs
storage, distribution and withdrawal of distributed tissues and cells are
set out in Annex no. 6 paragraphs 2-6 of this Decree.

(3) Range of controls quality and safety criteria implemented under
Activities to ensure that the tissues and cells and their requirements are set out in Annex
no. 6, paragraph 7 of this Decree.

§ 6a

Requirements on procedures for distribution of tissues and cells

[To § 5 para. 1 point. k) and § 20a par. 4 Act]


Rules of good distribution practices for distribution of tissues and cells are laid down in Annex
no. 9 hereto.

§ 7

Serious adverse reactions and events

[K § 3 para. 3 point. b) of the Act]

(1) When a serious adverse reaction or suspected (hereinafter
"serious adverse reaction") to proceed in order

A) in connection with the procurement of tissues and cells have been serious adverse reactions in
living donors, which could affect the quality and safety of tissues and cells
notified immediately tissue establishment which are
tissues and cells provided for processing

B) in relation to the use of tissues and cells in the treatment recipients were
serious adverse reactions observed during or after clinical application
it immediately notified the tissue establishment indicated on the label
tissues and cells, if they can relate to quality and safety of tissues and cells

C) under the leadership of the tissue establishment referred to in subparagraphs a) and b)
serious adverse reactions assessed, evaluated and were intended
their causes and measures; This measure covers all the relevant
tissues and cells, including those that have already been distributed, and include
well as measures to prevent the causes of serious adverse reactions.

(2) If serious adverse events or suspected (hereinafter
"serious adverse events") is progressing

A) so that a serious adverse event immediately notified
tissue establishment which tissues and cells are provided on
processing, in the case of a serious adverse event that occurs
during or following the procurement, which could affect the quality
and safety of tissues and cells

B) so as to promptly reported serious adverse event
tissue establishment indicated on the label tissues and cells in case of a serious adverse event
which is found within the handling of tissues and distributed
cells with their customers and which could affect the quality
and safety of tissues and cells

C) similarly as in paragraph 1. c) even if it is a
serious adverse event that it is found under the activity of tissue
device which could affect the quality and safety of tissues and cells.

(3) When a serious adverse reaction and serious adverse events
for tissues and cells supplied from abroad proceeds tissue establishment
ensure the delivery of these tissues and cells referred to in paragraphs 1 and 2 accordingly.

(4) reporting serious adverse reactions and serious adverse events
State Institute for Drug Control (hereinafter "the Institute") pursuant to §
5, paragraph. 3 of the Act are used forms of notification and reporting templates according || | Annex no. 7 in which

A) listed in Part A of the notice patterns, and in Section 1
pattern notification of serious adverse reactions and section 2 model
notification of serious adverse events

B) in Part B of specified patterns of the assessment report, evaluation and received
measures, in point 1 specimen report serious adverse reactions and section 2 model
reports of serious adverse events.

(5) Notification and report pursuant to paragraph 4 are retained by the Institute.

(6) In the case of assisted reproduction also any bad
identification or confusion of semen, ova and embryos deemed
serious adverse event and proceed in accordance with paragraph 2 accordingly.

§ 8
Traceability


[K § 3 para. 3 point. d) of the Act]

(1) within the tissue establishment to meet the traceability requirements
under § 3 para. 3 point. d) of the Act shall keep records for at least


) The donor identification,

B) identification of the tissue and cell donation involving

First identifying a sampler or a tissue establishment
conducting procurement,

Second Unique identification number of the donation of tissues and cells

Third date of collection,

Fourth instead of taking a

Fifth kind donations, especially in the case of one type or multiple types of tissues and
cells of allogeneic or autologous donation, a donation from a living or deceased donor
,

C) identification of tissues and cells during processing and final packaging
tissues and cells (hereinafter "tissue and cell preparation"), comprising

First data identifying the receiving and delivering a tissue establishment


Second the type of tissue and cell type or tissue and cell preparation by
basic nomenclature of the European Communities,

Third number of the mixture, where appropriate,

Fourth number fraction, where appropriate,

Fifth date of expiry,

6th the state of tissues and cells, especially in quarantine, released for use

7th description and origin of the tissue and cell processing steps applied,
materials and products that come into contact with tissues and cells and may
affect their quality and safety, and

8th data identifying the tissue establishment, which capped the final
packing label and the release of tissues and cells for use

D) use in humans comprising

First date of distribution, or elimination from the tissues and cells and use

Second information identifying physicians, medical facilities and business
natural or legal persons who have had tissue and cell preparation
provided for use.

(2) For operators who are responsible for human application, for
meet the traceability requirements under § 3 para. 3 point. d) of the Act
keep records including at least data identifying

A) tissue device that supplied the tissue and cell preparation,

B) doctors, medical facilities and business
natural or legal persons who have been tissue and cell preparation is provided for use

C) Type of tissues and cells

D) tissue and cell preparation

E) the beneficiary and

F) the date of application.

(3) For the management and record keeping using such a recording
resources from which records are available and legible throughout
keep them under § 3 para. 3 point. d) of the Act, including ensuring the protection
records. If ensure compliance with this condition, the information
store, for example, in electronic form.

§ 9

Identification codes

[To § 5 para. 1 point. e) of the Act]

(1) In order to ensure unambiguous identification under § 5 para. 1 point.
E) of the Act is assigned

A) tissue and cell donation label, which includes a unique identification number
donation and identification of the tissue
equipment assigned to the Institute,

B) Tissue and cell product description which includes

First identification code of the product

Second number of shares, where applicable,

Third date of expiry.

(2) identification code of the product is chosen according to the nomenclature of the European
coding system published by instructing the Department of § 24 para. 1 point.
D) of the Act. The identification under paragraph 1 shall be indicated in the records
kept on tissues and cells and treating them so that
unmistakably traceable, including records of donors, the performance
tissues and cells, and records for compliance traceability.

(3) Use of European coding system may not apply
reproductive cells, if the donation of reproductive cells between a man and a woman
who declare in writing that they intend to jointly
undergo assisted reproduction (hereinafter referred to as "partner donation").

§ 10

Annual Report tissue establishment

(K § 4 para. 1)

(1) The annual report on the activities of tissue device contains a file of data
relating to tissues and cells of redundant tissue establishments
for use in the treatment of beneficiaries, which include

A) the number of donors who donated tissues and cells are forwarded for processing in
tissue establishment, and the number of samples of these donors;
indicate the total number of donors and donations separately for living donors and deceased donors;
for living donor also states separately the number of donors and the number of subscriptions for
autologous and allogeneic to use; the number of donors and donations also referred
for different types of tissues and cells referred to in paragraph 4

B) the amount of tissue and cell preparations

First processed and released for use in the treatment of beneficiaries

Second Distributed in their own health care facility or other
medical facilities in the Czech Republic, if you have not been returned,

Third exported abroad

Fourth storage at the end of the year, and it compliant products intended for
distribution

Fifth discarded, including the reason for exclusion,

C) the total number of recipients of tissue and cellular products,


D) the number of beneficiaries affected by serious adverse reactions

E) the number of serious adverse reactions among recipients according to the nature
serious adverse reactions

F) the names and addresses of medical devices, in which the tissue and cellular
products were distributed.

(2) The annual report on the activities of the tissue establishment also includes a set
data relating to tissues and cells of redundant tissue
device for the production of medicines or other products intended for use in humans
which include || |
A) the number of donors and the number of samples of these donors in the scope of the data according to paragraph 1
. a)

B) the quantities of tissues and cells

First processed and released for further production

Second supplied by manufacturers in the Czech Republic

Third exported abroad

Fourth stored at the end, as regards the compliant tissues and cells
intended for delivery,

Fifth discarded, including the reason for exclusion,

C) a list of processors, which are tissues and cells available for further
production.

(3) The annual report on the activities of the tissue establishment also includes

A) file additional information on activities relating to tissues and cells, the tissue establishment
which treats but does not pass it, including the amount
tissue and cellular products delivered to the Czech Republic from abroad
, || |
B) the total number of reported serious adverse events and
total number of reported serious adverse reactions.

(4) The data in paragraph 1. a), b), d) and e), paragraph 2, point. a) and b) and paragraph 3
point. a) give for the various types of tissues and cells
set instructing the Department in accordance with the requirement to provide reports
European Commission. The amount of tissues and cells or tissue and cell
preparations in paragraphs 1-3 means a number of packages, indicating
the content of tissues and cells in the pack, or give any other quantitative
indication, if not quantity expressed in packaging commonly used and
clear indication for the type of tissues and cells.

§ 11

Notification of distribution or import an urgent need for tissues and cells

(K § 13 para. 2 of the Act)

(1) Announcement of distribution or importation in the case of ensuring urgent needs
tissue and cell preparation for a particular recipient, according
§ 13 par. 2 Act contains

A) identification of notifying the operator of the tissue establishment
gave tissues and cells, including the name or names, place
business and identification number, if assigned, for individuals or business
or name, registered office, address and delivery
identification number, if assigned, for legal entities and
identification marking tissue establishment, and the name and surname of the person responsible
tissue establishment

B) the name and amount of tissue and cell preparation and its
identification code, the name of the country of origin of tissue and cell
data necessary to identify foreign tissue establishment tissues and cells
compiled and leaked to use in therapy,

C) the intended use, date and reason for the supply of tissue and cell preparation

D) data identifying the medical facility and the workplace, where
was an urgent need for tissue and cell preparation and internal
anonymised data to identify the recipient,

E) the date of the notice, name and surname of the person authorized to act on behalf
operator specified in subparagraph a) and signature.

(2) The notice referred to in paragraph 1 shall be provided in any way that is demonstrable
.

§ 12

Application for a license to operate and its changes

(K § 17 para. 4 of the Act)

(1) The application for the authorization of tissue establishment, receiving equipment
or diagnostic laboratories contain information and documents listed in Annex
no. 8 Part A, sections 1-4 hereof.

(2) An application to amend permits operation includes details and documents listed in Annex
no. 8 of Part A, sections 5 and 6 of this decree, which changes
bring a mark. Final provisions

§ 12a

Request for permission to distribution of tissues and cells

(K § 20a par. 2 Act)

Application for permission to distribute tissues and cells contain information and documents
listed in Annex no. 8 of Part B of this Decree.

§ 13


Decree no. 437/2002 Coll., Laying down detailed conditions for assessing
medical examination and a range of living or deceased donor
tissues or organs for transplantation (Decree on health
ability of the donor tissue and organs for transplantation purposes) in the tissues and cells
apply.

§ 14

This Decree shall take effect on the date of its publication.
Minister
:

MD. Julínek, MBA vr
Appendix 1


Quality system requirements

First Quality system of organization and management

01.01 Quality system implementation involves writing set
functional organizational structure, responsibilities and reporting structure
obligations set out in writing the responsibilities of persons involved in procuring,
testing, processing, storage, distribution within the activities
tissue establishment sampler equipment or diagnostic laboratories
(hereinafter referred to as "connected person"), and writing prescribed processes, procedures and
resources for quality control; quality management means the coordinated
activities, which the organization is managed and controlled in terms of quality
. Part of the quality system are all activities that directly or indirectly
contribute to quality. Documented quality system and quality management
applies to all activities for which authorization is
asks.

02.01 For the needs of the tissue establishment provides at least
consulting the doctor who oversees medical activities such as donor selection,
review of clinical outcomes of applied tissues and cells in contact with
clinical users.

03.01 Determine and minimize the risks associated with the use of biological
material and handling, including the risks associated with the procedures
environment and the health status of the people involved.
While minimizing risks to maintain adequate quality and safety of tissues and cells for the intended purpose
their use.

04.01 In the case of contracting some activities Party
before concluding the contract evaluated and selected according to its ability to meet
requirements of the Act and this Decree. The contract specifies the conditions
relationship and obligations of the contract, which must be observed, also including
detailed procedures and responsibilities regarding the records. If it is a contract
closed to ensure the availability of stored tissues and cells
under § 4 para. 2 of the Act, to clarify the requirements for the quality and safety of tissues and cells
and traceability.

05.01 Establishes a documented system, overseen by a responsible person
tissue establishment ^ 3), which demonstrates that the tissues and cells meet appropriate specifications
quality and safety for the release and distribution
.

01.06 Establishes a documented system, which ensures the identification of
every unit of tissue or cells at all stages of the activities to be provided
.

Second Persons involved

02.01 Carrying out various activities to ensure so that the
sufficient numbers of persons qualified for the tasks
to be provided. Their eligibility is evaluated in
appropriate intervals specified in the quality system documentation.

02.02 For each person involved to draw up and update a clear, documented
job description. This ensures that the duties and responsibilities
were clearly documented and understood.

03.02 Before exercising the activities of each person involved in providing vocational
, updated training in the event of changes in procedures or development
scientific knowledge, as well as adequate opportunities for professional development
. The training program is documented. This ensures that each individual


A) is competent to perform the tasks entrusted to it,

B) has an adequate knowledge and understanding of the process and principles that
related to the tasks entrusted to it,

C) understand the business organization, quality system and health and safety regulations
facility in which they work, and

D) has been informed of the broader ethical, legal and regulatory
context of their work.

Third Equipment, materials and products

03.01 Equipment, materials and products used in
undertaken activities are designed and maintained in a manner suitable for their intended purpose
a manner that poses minimal risk to the recipient
tissues and cells and involved persons handling them.


03.02 Identify equipment, materials and products critical
effect on the quality and safety of tissues and cells (hereinafter referred to as "critical"), validated
to be regularly inspected and preventively maintained in accordance with manufacturer's instructions
. Equipment, materials or products that may
affect critical processing or storage parameters, such as
particularly temperature, pressure, particle count, level of microbial contamination, as required
subject to monitoring, alerts, alarms and || | remedial measures to timely detect malfunctions and defects and to
ensure that the critical parameters are maintained within acceptable limits
. The equipment, which measures the critical parameters are calibrated
, whereby using the appropriate traceable standard, suitable for
calibration, if available.

03.03 New and repaired equipment during installation and tested before use
is validated. The test results are documented.

04.03 Maintenance, servicing, cleaning, disinfection and sanitation
critical equipment must be performed regularly and recorded.

05.03 Procedures are now available for the operation of each piece of critical
equipment, detailing the measures to be taken in the event of failure or malfunction
.

06.03 The written procedures DETAILED identification applied
critical materials and products, in particular solutions, added substances,
packaging materials, medical devices, diagnostic in vitro
(hereinafter "diagnostic means").

07.03 In accordance with the requirements for the use of critical materials and products,
in accordance with the manufacturer's instructions and the requirements of other legal
legislation for medical devices; 4) to develop and apply
specification of critical materials and products.
Supplied materials and products are taken over by verifying their compliance with the specification.
The verification of compliance is placed separately.

Fourth Establishments and premises

04.01 Ensure the establishment and premises suitable for the activities that
them to be carried out and where it is needed the appropriate solution
buildings and installations, in which the establishment included.

04.02 If the tissue and cells during the processing of exposed
environment, extends this work in an environment with specified
air quality and cleanliness to minimize the risk of contamination
including cross-contamination between tissues and cells from different donation.
The effectiveness of these measures is validated and monitored.

04.03 Unless the sub-4.4 otherwise specified and if the tissues and cells
exposed during processing environmental effects, without a subsequent
microbial inactivation process ensures the quality of air
equivalent grade A in accordance with Good Manufacturing Practice for medicinal products
in terms of particle counts and microbial counts.
Related background environment is selected so that it is suitable for processing
relevant tissues and cells, but at least corresponds to the class D
purity by GMP in terms of particle counts and
microbial colonies. These requirements for purity environment
apply the requirements of Good Manufacturing Practice for medicinal products in the Community
^ 5).

04.04 A less stringent environment than specified in sub
3.4 are acceptable

A) in the event that a validated microbial inactivation
or validated terminal sterilization process,

B) if it is demonstrated that exposure to tissue and cell environment Grade
has a detrimental effect on the required properties of tissues and cells

C) if it is proved that the method and route of administration tissues and cells for the recipient does not
recipient risk of transmitting bacterial or fungal infection
or

D) if it is not technically possible to carry out the required process in an environment
grade A, mainly due to requirements for specific equipment in
processing area that is not fully compatible with Grade A
purity.

05.04 In the cases referred to in subparagraph 4.4 point. a), b), c) and d)
environment clearly states on the basis of documented demonstration that
chosen environment achieves the quality and safety
least with regard to the intended purpose and method of use of tissues and the cells and the immune status of the recipient
. In each relevant department to provide adequate clothing and
equipment for personal protection and hygiene, and written instructions for hygiene and

Dressing.

06.04 For the storage of tissues and cells are defined storage conditions,
including parameters such as temperature, humidity or air quality,
necessary to maintain the desired properties of tissues and cells.

07.04 Critical parameters, especially temperature, humidity, air quality, the
control, monitor and record to demonstrate that they are
specified storage conditions observed.

08.04 They provide the storage facilities that clearly separate and distinguish tissues and cells
while awaiting a decision on their acceptance or exclusion
(hereinafter "the tissues and cells in quarantine") from those that are already released
and those that were rejected to avoid confusion and
their cross-contamination. For the preservation of certain tissues and cells
collected under special criteria of the storage of tissues and cells
quarantined in places of storage of redundant tissues and cells
reserve Physically separate areas or storage devices or a device inside
secured a clear separation.

09.04 To draw up written policies and procedures for controlled access to individual parts
spaces for their inspection, cleaning and maintenance
waste treatment and recovery provision of services in an emergency situation
.

Fifth documentation

05.01 There will be a system to ensure clearly defined and effective
documentation, as part of the rulemaking documents (hereinafter referred to as "internal
regulation") and records. The documentation system is created so that
guarantee that all activities from procurement to distribution and
quality assurance standard will be implemented, and that all steps
these activities are traceable. Implement and maintain the system
documentation drawn up appropriate regulations specifying management
internal regulations and records management.

05.02 Over the management of internal rules to ensure in particular that
internal regulations approved and regularly reviewed in order
used their versions and history of changes to each
internal regulations were traceable.

05.03 When preparing internal regulations are also taken into account the specific
characteristics and intended use of a particular type of tissue and cells, as determined
necessary to the specific provisions.

05.04 Internal regulations shall include standard operating procedures
training and methodological manuals, forms for recording basic document
about the location and specifications; Specifications include in particular those tissues and cells and specifications
critical materials and products, including
diagnostic reagents for laboratory checks.

05.05 Specifications are drawn up for each tissue and cell preparation and
each type of the package if the details differ. They report the data necessary to ensure
standard package of tissue and cell preparation and
important data to ensure its quality, safety and efficacy.
Specification packaging of tissue and cell preparation containing information on particular


A) type of tissues and cells, tissue and cell type of product and type of packaging
; Also the name of the product and its packaging, if different from the information included
before the semicolon,

B) of origin of tissues and cells, such as from a deceased donor, living donor
of body parts removed from a patient

C) the appearance and composition of the package contents tissue and cell preparation
including quantitative and qualitative data on the components in the package;
Data on the properties and content of tissues and cells in the pack,

D) the primary packaging of tissue and cell preparation of specifications, including
material and method of confinement

E) critical materials and products that come into contact with
tissues and cells, including their roster, a reference to the specification under sub
05.06, purpose and how it is ensured that they are products and
materials suitable for use in a hedge tissues and cells intended
for human use; list also includes materials that come
into contact with tissues and cells during the process and subsequently removed, and
such materials and products for the treatment of tissue and cell
product before administration, and its administration to the recipient, are
if part of the final packaging of tissue and cell preparation

F) checks that are carried out to ensure the quality, safety and

Efficiency of tissue and cell preparation from tissue and cell procurement
after their release, including the sample used, methods of control
frequency of inspections, criteria for evaluation of the inspection results,

G) conditions of storage and transportation of the tissues and cells and tissue and cell preparation
time and their applicability under the circumstances
storage; Also on storage conditions and shelf life of
after handling tissue and cell preparation, for example, after his
opening

H) purpose, for the treatment of recipients or for further manufacturing;
when used for the treatment of recipients to specify the type of application, such as direct
use autologous use, the use of reproductive cells between partners
or other use,

I) marking the final packaging and the information attached to the package of tissues and cells
for their users under § 5 para. 2 point. d)
Act, including information on the correct handling of final packaging, of therapeutic indications,
and possible side effects and contraindications; where it is necessary
show the data relevant to the administration, for example by modifying the contents of the package
before administration, route of administration, inspections carried out in connection with
administration.

They do not are those of the data referred to in point. a) to i), where the
according to Annex no. 8 of point 5 documented and approved by the Institute that
for a specific type of tissue and cell and tissue and cell preparation is not
appropriate figure to use.

06.05 Specification critical material and specifications critical
product coming into contact with tissues and cells include
determination of this material and the product so as to ensure its quality
and safety for human use and were created by standard conditions
procedures. Specification includes in particular data on the composition and purity
material or product referred to only using the trade name
material, product, or their components, but also for the use of chemical and biological
professional terminology. Further includes information about the appearance
packaging, properties and storage conditions are important for the quality and safety
material or product in relation to their use of
quality and safety criteria to be fulfilled and implemented
controls. It also includes evidence that the requirements are met
legislation for medical devices or pharmaceuticals,
where it is needed. Compliance with the requirements of these regulations shall be given through
reference to the decision of the competent authority or, if no such decision
available by reference to other comparable warranty
ensuring quality and safety, which can be as documentation on its own | || verification. Determine the type of quality certificate batch of material or product
if required. If it is a product or material of biological origin
shall also be its origin and manner of acquisition.

07.05 Basic document summarizes the place of the organizational, technical and personnel prerequisites
created to fulfill the requirements of the Act and
regulations, especially the requirements for a quality system. Current basic
documentary about the place is always submitted to the Department before checking in at least
scope of a permit for the activity listed in Annex no. 8
Part A, point 2. F).

08.05 For every critical activity will be determined and documented
materials and products, equipment and people involved who participate in the activities.

09.05 Changes in internal rules and records are reviewed, approved,
endorsed with the date and properly implemented by authorized persons.

5.10 Records are kept so that they are reliable and a true representation
facts and results.

5.11 Records are kept legible and indelible manner, may be
handwritten or made other validated procedure such
electronically or on microfilm. If using a signature, and adds the date
and what is confirmed by signature.

5.12 All records, including raw data, which are important for
quality and safety of tissues and cells shall be kept so that they can be
ensure access for at least 10 years from the date of expiry
usability, clinical use tissues and cells or their removal from
use. This does not affect the provisions of § 3 para. 3 point. d) of the Act.

5.13. Adopting security measures against illegal refilling
data, deletions or changes in the records. In accordance with § 3 para. 3

Point. c) of the Act provides the access to records under the obligations and responsibilities of the people involved
. Establish procedures for resolving data discrepancies
.

6th Quality review

06.01 A system of own checks. Checks on the
entrust employees or external natural or legal persons
which are to be trained and competent, and are independent in relation to
activities that the inspection concerns. Self-monitoring is done
least once every two years to verify compliance with internal regulations and requirements
Act and this Decree. Findings and actions are documented.

06.02 All deviations from the applicable provisions related
quality and safety be investigated and documented. Also documented
decisions on corrective and preventive actions and decisions on the fate
tissues and cells, unless they meet the requirements. About tissues and cells with
decided by written procedure for this purpose under the supervision of the person responsible
tissue establishment. All affected tissues and cells
identify and notify those affected by the findings concerned.

06.03 Corrective action starts and finishes in a timely and efficient manner. After
perform preventive and corrective measures to assess their effectiveness
. The effect of measures and their effectiveness is documented.

06.04 They shall establish procedures for the review of the performance management system
quality to ensure systematic improvement.
Appendix 2


Procurement of tissues and cells and deliver them to the tissue establishment

First Providing information

01.01 Information related to tissue and cell donation provides training
person is able to bring appropriate and clear manner, using terms
which can be easily understood. This also applies to findings
arising from laboratory testing of samples from the donor and their
explanation under § 7 para. 1 point. c) Section 3 of the Act.

02.01 Living donors are before taking the authorized person
provided guidance and information on how to perform the removal of tissues and cells is required
written consent of the donor, as well as the purpose, importance and benefits of treatment
tissues and cells for the purpose of and the nature, consequences and possible risk taking, carried out by
examinations, reasons and impact of their implementation and
law, donors receive their examination results and a clear explanation of
measures to protect donors and protection of donor data and commitment
medical confidentiality. This information is also provided by a person close
donors, if he has to give consent to the collection by another law.

03.01 Part of the internal regulations, the procedure for providing information and
their contents.

Second Consent and donor identification

02.01 The authorized person prior to sampling confirms and records,

A) in accordance with other legislation ^ 6) was provided
guidance and information, the conditions are met and the admissibility of the collection and was acquired
agreement with the procurement of tissues and cells

B) how and by whom the donor has been reliably identified, and

C) that an assessment was made for donor consumption.

02.02 In the case of living donors, the medical officer in charge of obtaining
medical data and records to ensure that the donor

A) understood the information provided and

B) had an opportunity to ask questions and received satisfactory responses,

C) confirmed that all the information provided by him under its
best knowledge, true and complete.

Record confirms the signature of healthcare worker referred to in the first sentence and
donor.

Third Donor evaluation

03.01 Authorized healthcare worker collects and records
health information and behavior donor essential for assessing donor
requirements specified in paragraph 5.

03.02 To obtain the necessary information to apply various appropriate sources, such as


A) the medical records of the donor

B) an interview with the natural person who knew the donor well, if it is a
deceased donor

C) an interview with the doctor,

D) an interview with the general practitioner,

E) the autopsy report,

Including at least one interview with the donor, for living donors.

03.03 For a deceased donor and living donor when justified, are also
perform a physical examination of the donor to detect any signs that may be
themselves sufficient to exclude the donor or

Must be evaluated in the context of the donor's history and its past.

04.03 Authorized healthcare worker fulfilling the conditions for qualification
according to Annex no. 1 section 2 of this Order shall review and evaluate the entire
documentation relating to the donor in terms of its suitability for consumption.
Review and conclusion of the assessment of donor records and confirm the signing.

05.03 If it is a donation of reproductive cells between partners or
autologous donors, no need to proceed under Section 3

Fourth The conditions and procedures to procure tissues and cells and tissue and cells

04.01 The procurement procedures are created so that they are suitable for the type of donor and the type
donated tissues and cells. In the case of a living donor is
these processes also ensured the safety of donors and protect their health and privacy
.

04.02 The procurement procedures protect those properties of tissues and cells that are
required for their ultimate clinical use, and at the same time is minimized
risk of microbial contamination during the process, particularly when tissues and
cells can then be sterilized.

04.03 Access to the collection of deceased donors is limited to persons authorized to
and sampling applies sampling field ready set
standard disinfecting procedure and created using sterile drapes.
Persons involved in the collection have appropriate clothing, which usually means
sterile clothing and wearing sterile gloves, face shields and protective masks
.

04.04 Record instead of taking a deceased donor and indicate the time that has elapsed since the death
to sampling to ensure that the collected tissues and cells
retain the desired biological or physical properties.

05.04 After removal of tissues and cells from a deceased donor is the body of the deceased
reconstructed so that it is as similar as possible to its original anatomical appearance
.

06.04 Record and examine any adverse event that occurs
during collection, and that leads or could lead to damage
living donor and the outcome of any investigation to determine the cause of adverse events
.

07.04 Establishing the policies and procedures to minimize the risk of contamination
tissues and cells, including the contamination of tissues and cells involved
persons who might be infected with transmissible diseases.

08.04 When you subscribe, sterile, high-quality and regularly maintained
instruments and medical devices that are validated or
demonstrated their quality with a special certificate, for the purpose of use
instruments and medical devices for the collection.

09.04 If used tools for reuse, introduced
validated cleaning and sterilization to remove
infectious agents.

4.10 Wherever it is possible, using only
medical devices with CE marking, and the people involved that these funds
used are not adequately trained.

4.11 If it is not possible to carry out the collection of semen in the collection area, may be accepted
semen collected at home, unless the acquiring tissue
in advance agree conditions are met collection and delivery
semen laid down by the tissue establishments and goes if semen
intended for use among partners and donors for their own use.

Fifth Donor documentation

05.01 For each donor to keep and maintain records that contain

) The donor identification, at least the name, personal identification number or date of birth
, if no birth identification number and contact address;
if the donation concerns a mother and child, the identification of both mother and child
,

B) age, sex, medical and behavioral history;
information is collected so as to be sufficient to assess the donor and if appropriate
allow application of the exclusion criteria donors

C) outcome of body examination pursuant to point 3.3,

D) haemodilution formula, where justified,

E) express consent ^ 6) the collection and recording of lessons and providing information to donors or
person close

F) clinical data, laboratory test results of samples from the donor and
results of other tests carried out,

G) for a deceased donor autopsy results; for tissues and cells that can not
stored for extended periods, recorded a preliminary verbal report of the autopsy,

H) proof donor suitability for the chosen recipient, if the suitability

Donor shows such as with donor hematopoietic progenitor cells in
unrelated donation.

05.02 For the transmission of procured tissues and cells, the tissue establishment with
a report that contains a minimum

A) data identifying the tissue establishment, which should be
tissues and cells are passed, including the address,

B) data necessary to identify the donor, including how and by whom the donor
identified,

C) description and identification of procured tissues and cells and
samples for laboratory examination

D) the name and surname of the responsible person receiving equipment ^ 7) and confirm
news by signing

E) date of sampling, sampling time, or start and end time of collection, place
collection and used standard operating procedures, including variations and
events occurred; conditions and the description of the environment where they held
collection, if it is justified;

F) for deceased donor conditions for the preservation of his body; information about whether
body was or was not stored under refrigerated conditions, including preservation and
time when it was cold preservation initiated and terminated,

G) identification of substances and solutions that have come into contact with tissues and cells
during the collection and transport, including batch number,

H) for a deceased donor, the date and time of death mentioned in the inspection sheet
dead.

05.03 If the semen is collected at home, a report on the collection contains at least


A) information that the semen has been collected at home

B) data identifying the tissue establishment, which is to be handed sperm
including addresses,

C) data necessary to identify donors including how and by whom the donor
identified,

D) the date and time of collection.

05.04 Records are kept as required in Annex no. 1
section 5 of this Decree.

05.05 Donor records required for full traceability is kept at
suitable place reserved for storage, review of which is categorized into
checks carried out by the Institute.

6th packing

06.01 After collection, all recovered tissues and cells packaged in a manner that minimizes the risk of contamination
tissues and cells and individuals that carry out
packaging and transportation of the tissues and cells. Tissues and cells stored at temperatures
which retain their desired properties and biological
function.

06.02 Packaged tissue and cells are transported in a container that is suitable for
transport of biological materials and which maintains the quality and safety of transported
tissues and cells.

06.03 Any accompanying samples from donors for testing exactly
marks, so as to ensure identification of the donor from whom the
sample was taken, and that a record of the time and place of collection
sample.

7th Labelling procured tissues and cells

Every package containing tissues and cells at the time of sampling indicated. On
primary tissue and cells containing information identifying the donation and
pack of tissues and cells. If the size of the package permits, indicating further

A) dates of collection and also the time where it is possible

B) an alarm warning

C) additives, if used,

D) "for autologous use only" if it is a donation for autologous use
,

E) data necessary to identify the recipient, if it is a donation for
specific recipient.

If some of the data referred to in point. a) to e) may not be listed on the label
primary packaging shall be provided on a separate sheet, which is associated with
primary packaging or accompanying, if connection to the primary packaging is
possible.

8th Labelling of the shipping container

When the tissues and cells carrying agent, is given on each shipping container at least


A) notice 'tissues and cells - handle with care "

B) identification of the establishment from which the package is shipped, and it
least the name, address, telephone number and contact person in case
complications

C) identification of the tissue establishment, to whom the consignment is destined by
least name, address and telephone number of a contact person who takes
container,

D) the date and time of transport,

E) specifications concerning conditions of transport relevant to the quality and safety
tissues and cells

F) warning "DO NOT IRRADIATE", if it is a cell preparation,

G) notice "BIOLOGICAL DANGER", if it is known that tissues and cells

Are assessed as positive on one important indicator
infectious diseases

H) the warning "FOR AUTOLOGOUS USE ONLY", in the case of donation for autologous use
,

I) specifications concerning storage conditions, such as "DO NOT FREEZE."
Appendix 3


Criteria for assessing the medical fitness of potential donors and
selection of donors of tissues and cells, except donors of reproductive cells

For specific tissues and cell types down the selection criteria for donors
which are relevant and may help in detecting and eliminating potential
donors whose donation could present a health risk to others or
, jde- If a living donor, the health risks to themselves and
according to which they are secured tissues and cells suitable for the purpose for which
to be used. At the same time take into account the detailed guidelines issued by the Council Evropy8
). Evaluation and selection of the donor should be documented.
Donor selection based on an analysis of risks related to the use of specific types of tissues and cells
. Risks are identified by physical examination, medical history
, behavioral history, laboratory tests and
any other appropriate investigation. In the case of a deceased donor also
based on postmortem examination and evaluation of the results of the autopsy and the cause of death.
If the donation properly substantiate on the basis of a documented risk assessment
approved by the responsible person of the tissue establishment's donor
excluded from donation if one of the general criteria listed in this Annex
.
PART
A
Deceased donors


First General criteria for exclusion

01.01 Cause of death unknown, except in cases where autopsy
cause of death after collection and at the same time when none of the
general criteria for exclusion set out in this section.

02.01 History of a disease of unknown etiology.

03.01 Current or previous history of malignant disease, except for primary
basal cell carcinoma, carcinoma in situ of the cervix and
some primary tumors of the central nervous system, which is
be evaluated on the basis of scientific evidence. Donors with malignant diseases
can be evaluated and considered for cornea donation, except donors
with retinoblastoma, haematological malignancies and malignant tumors of the anterior segment of the eye
.

04.01 The risk of transmission of diseases caused by prions. This risk applies
potential donors

A) have been diagnosed with Creutzfeldt-Jakob disease, or
variant Creutzfeldt-Jakob disease, or having a family history of
non-iatrogenic Creutzfeldt-Jakob disease,

B) with a history of rapid progressive dementia or degenerative neurological disease, including
diseases of unknown origin

C) of hormones derived from the human pituitary gland, such as growth hormones
-transplant graft human cornea, sclera and hard
mater or have undergone undocumented
neurosurgical intervention, in the case of risk whereas such a procedure could be used
dura mater,

05.01 Systemic infection which is not at the time of donation, including
bacterial diseases, viral, fungal or parasitic infections
or significant local infection in the tissues and cells to be donated.
Donors with bacterial septicemia may be evaluated and considered for
eye donation but only where the corneas stored in organ
culture in which it is possible to detect any bacterial contamination
tissue.

01.06 History, clinical evidence, or laboratory evidence of infection with human immunodeficiency
(hereinafter referred to as "HIV"), acute or chronic hepatitis B, except
potential donor with established immune
hepatitis C infection with human T cell lymphotropic virus (
hereinafter "HTLV"), type I and II and also the risk of transmission of, or evidence of risk factors
these infections.

07.01 History of chronic, systemic autoimmune disease that could
have a detrimental effect on the quality of the tissue should be removed.
Systemic diseases with adverse impact on the quality of the tissue, such as connective tissue disease and vasculitis
.

08.01 Signs that the results of blood samples from potential donors
invalid due

A) the occurrence of haemodilution, as specified in Annex no. 4 sub-2.3
This decree, if the sample is not available before or haemodilution

B) treatment with immunosuppressive agents.


09.01 Evidence of any other risk factors for transmissible diseases on the basis
risk assessment, taking into account the local prevalence
infectious disease donor travel and exposure history.

1.10 Finding physical signs on the donor's body during an examination by
Annex no. 2 sub-3.3 this decree, implying a risk
communicable disease or communicable diseases.

1.11 Use or effect substance that may be transmitted to recipients in a dose
threatening their health, such as cyanide, lead, mercury, gold
.

1.12 Recent history of vaccination with a live attenuated virus, there is a risk of transmission of infection
.

1.13. Transplantation of xenogeneic grafts.

1.14. Chronic hemodialysis history.

1.15. Storage times and conditions a deceased donor and other causes
which may threaten the quality of tissues and cells for the purpose of their use, for example
death by drowning, the body of the deceased stored before collection
longer than 24 hours at a reduced temperature 4 ° C, the body of the deceased
stored prior to collection for more than 12 hours in an environment where the temperature is lowered.

Second Other criteria for deceased child donors

If it is a child of a deceased donor excludes all children born to mothers infected with HIV or
children who meet any of the exclusion criteria
mentioned in paragraph 1 of this section until it is definitely ruled out the risk
transmission of infection. Infants of mothers infected with HIV, hepatitis B virus
(hereinafter referred to as "HBV"), hepatitis C virus (hereinafter referred to as "HCV") or
HTLV or mothers at risk of such infection,

A) they are excluded from donating whatever the results of the analytical tests
if they are younger than 18 months, and was their mother breastfeeding a
during the previous 12 months

B) can be accepted as donors if they do not become a breastfeeding mother
during the previous 12 months, and analytical tests, physical examinations
and reviews of medical records do not provide evidence of HIV
HBV, HCV, or HTLV .
PART B


Living donor

First Autologous living donor

In the event that tissue collected and cells are to be stored and cultured
performed with the same minimum set of the examination of samples by
autologous donor as allogeneic living donor. Positive test results for infectious diseases
indicators, does not preclude the tissues and cells
or any product derived from them are stored, processed and re-implanted
if

A) for this purpose a suitable isolated area in which
no risk of cross-contamination of other tissues and cells, or
risk of contamination with other substances, or the risk of confusion,
and || |
B) a physician who these tissues and cells called them about finding
informed and clearly confirm that these autologous tissues and cells requires.

Second Allogeneic living donor

02.01 Evaluation and selection of allogeneic living donors were performed according to established procedure
based on health status, medical and behavioral history
that are listed in the questionnaire and surveyed in
interview with the donor makes an authorized healthcare worker || | fulfilling the conditions of qualification and training provided for in Annex no. 1 Section 2
this Decree and based on the results of clinical investigations and laboratory tests
health of the donor. In the case of tissues and cells
for direct distribution to the recipient, also sets criteria with regard to the requirements
doctor who performed the transplant.

02.02 For any donation, the process of procurement of tissues and cells
done so as not to distort or endangering the health of the donor or care giver.
In the case of a donation of cord blood or amniotic membrane
apply these principles to both mother and child.

03.02 With the exception of the section and subsection 1.1 and 1.15
applying the same exclusion criteria as for deceased donors. Depending on the type of tissues and cells
complement other specific exclusion criteria, such as

) Pregnancy; It does not apply to donors of umbilical cord blood, amniotic membrane and sibling donors
hematopoietic progenitor cells

B) breastfeeding

C) in the case of haematopoietic progenitor cells
genetic disease that might endanger the donor or the quality of tissues and cells or
can lead to the transmission of inherited conditions,

D) exposure to ionizing radiation are harmful to health.

Appendix 4


Requirements for laboratory testing of samples from donors, except donors of reproductive cells and
requirements for samples for these tests

First Required laboratory testing of samples from donors

01.01 All donors are carried out at least testing the sample from the donor to the card signs of infection


A) HIV types 1 and 2 (hereinafter referred to as "HIV-1 and 2") by determination of the antibody and
p24 antigen

B) determination method HBV surface antigen (hereinafter 'HBsAg') and
antibodies against HBV nucleocapsid antigen (hereinafter referred to as "anti-HBc")

C) the method of determining HCV antibodies, and

D) determination of syphilis by sub-4.1

02.01 Examination of antibodies to HTLV I shall be performed for donors living
in areas with high prevalence of disease or originating from them, or at
donors who have sexual partners originating from those areas or
donors whose parents originate from those areas.

03.01 If the examination of anti-HBc positive and HBsAg is negative, it should
carry out further investigations and risk assessment, is to be determined
eligibility for clinical use.

04.01 To exclude the presence of active infection with Treponema pallidum
uses a validated testing algorithm. If Je- examination
unreactive, specific or non-specific, there is no obstacle for
release of tissues and cells. When performing a nonspecific tests, not
a reactive result will not prevent collection or acceptance of tissues and cells
if a specific confirmatory test Treponema pallidum
unreactive. A donor whose specimen tests reactive on a specific
Treponema pallidum, will require a thorough risk assessment
to determine eligibility tissues and cells for clinical use.

05.01 Provides for the implementation and evaluation of other biological tests
characters depending on the characteristics of the tissue or cells donated and
donor's history, such as the character D RhD system, features of the system
HLA, malaria, cytomegalovirus, toxoplasma, virus Epstein-Barr
Trypanosoma cruzi.

01.06 In the case of autologous donors reference Annex no. 3, Part B, item 1
hereof.

Second General requirements for laboratory examination

02.01 Only used this type of testing, which is validated for the purpose
used in accordance with current scientific knowledge. Used
investigative kit with CE marking, where possible.

2.2 Investigations were carried out with serum or plasma donors.
Apply to other fluids or secretions such as eye fluid chamber or vitreous
unless it is clearly clinically justified and if the examination is not
validated for the type fluids or secretions.

03.02 If a potential donor has been the loss of blood and the recent
time he was given donated blood, blood components, colloids or crystalloids
, testing may not be valid due to haemodilution of
blood sample from a donor. An algorithm for assessing the degree of hemodilution


A) in the case of a blood sample from death, if it was infused
blood, blood components, colloids or within 48 hours before taking
blood sample or crystalloids were infused in the hour preceding blood sample collection
,

B) in the case of a blood sample after death, was infused
if blood, blood components or colloids during the 48 hours preceding death or
crystalloids were infused in the hour preceding death.

Tissue establishments may accept tissues and cells from donors with plasma diluting
higher than 50% only if the testing procedures used
samples are validated for such plasma dilution, or if the examination
a sample taken prior to transfusion.

04.02 In case of a deceased donor, collecting blood samples for laboratory examination
as close as possible prior to death or, if not possible, what
soon as possible after death, but no later than 24 hours after death.

05.02 In case of a living donor, collecting blood samples for laboratory tests
during the removal of tissues and cells or, if not possible, within 7 days after
removal of tissues and cells.

06.02 In the case of allogeneic living donor

A) repeated blood sampling from a donor and laboratory tests
card signs of infection, at least 180 days after the removal of tissues and cells
Where tissues and cells donors can be stored until completion

Repeated examinations; when tissues and cells are passed for use by
also a result of repeated testing, may be donation sample
taken up to 30 days prior to collection of tissues and cells, and within 7 days after collection
tissues and cells | ||
B) whose tissues and cells can be stored and repeated sampling
from a donor can not be used as the point. a), the provisions
by sub-2.5

07.02 If the sample taken by the sub-2.5 additionally tested also
nucleic acid amplification technique for HIV, HBV and HCV, it is not necessary to perform the relevant
testing for these viruses with a sample of blood sampling repeated
donor. If the processing includes an inactivation process
validated for the viruses concerned inactivation, is also not required
perform appropriate tests for these viruses pattern of repeated blood sampling
donor.

08.02 In the case of collecting bone marrow stem cells and peripheral blood
blood samples for laboratory tests must be taken as soon as possible before
collection of stem cells, but not later than within 30 days prior to the donation.
Donor bone marrow stem cells and peripheral blood does not need to use
provision subsections 5.2 and 2.7.

09.02 When the donor infant may be carried out examination of the mother
donor, thus avoiding unnecessary medical procedure on a child.

Third Testing for transmissible spongiform encephalopathy

U deceased donor cornea, sclera or dura mater is done
examination of the brain of a transmissible spongiform encephalopathy. This test ensures
National Reference Laboratory for the diagnosis of transmissible spongiform encephalopathy
.
Appendix 5


Criteria for assessing health eligibility and selection
donors of reproductive cells, and requirements for laboratory testing of samples from these donors


First Donation between partners when reproductive cells are directly used

For the donation of reproductive cells intended for direct use
partners not necessary to apply the criteria for donor selection and laboratory tests
.

Second Partner donation if they are not reproductive cells directly used

Case of processing or storage of reproductive cells, or gametes
cryopreservation of embryos, applies
meet the following criteria.

02.01 On the basis of medical history and therapeutic indications
physician responsible for the donor states and documented justification for the donation and safety
recipient and the child or children who may be born.

02.02 To assess the risk of cross-contamination is carried
examination in accordance with Annex no. 4 sub-1.1 this decree. The requirement under the first sentence
not be used if the semen is processed for
intrauterine insemination and not to be stored, if the tissue establishment
can demonstrate that the risk of cross contamination and exposure of employees
risk was excluded using appropriate validated procedures.

03.02 Loads and applies a system of separate storage for cases that
test result for HIV 1 and 2, HBV, HCV and syphilis is positive or
results are not available, or where the donor is known to be || | source of infection risk.

2.4 testing for antibodies against HTLV I is performed for donors living
in areas with a high prevalence of these areas or provenance or
with sexual partners originating from those areas or where the donor 's parents originate
from these areas.

05.02 Provides for the implementation and evaluation of other biological tests
characters depending on the donor's history, examination of the recipient,
travel and exposure history, the characteristics of donor cells and
epidemiological situation, such as D character of RhD, malaria,
cytomegalovirus, Trypanosoma cruzi).

2.6 Positive results of examinations need not be an obstacle for donation
partners.

Third Donations other than by partners

The criteria and the evaluation and selection of donors of sperm and ova donation for
other than that specified in paragraphs 1 and 2. It documents the evaluation
donors at each donation. It is part of the general criteria and evaluation
laboratory tests referred to in this paragraph.

03.01 Donors are selected according to age, which provides different legal regulation, according
health, medical and laboratory examinations, medical

And behavioral history to the questionnaire and through a personal
interview performed by authorized healthcare worker
fulfilling the conditions of qualification and training provided for in Annex no. 1 section 2 of this Decree
. Evaluation and selection of donors includes factors that are important and
can help in detecting and eliminating potential donors whose
donation could present

A) the health risks to others, including the future of the child, such as, for example
risk of sexually transmitted and other communicable diseases
genetically conditioned defects and diseases, the risk associated with behavior
donor or donor exposure to significant influence harmful to reproductive health
risk of psychotic disorders with a hereditary predisposition,

B) the health risks to themselves, such as superovulation, sedation
risks associated with the egg collection procedure, the psychological consequences
donation.

03.02 Tests are done donor to HIV 1 and 2, HBV, HCV and syphilis
serum or plasma samples in accordance with Annex no. 4 a subheading 1.1
this decree and called for a negative result.

03.03 In donor sperm is also done testing for Chlamydia trachomatis
with a urine sample nucleic acid amplification technique and
requires a negative result.

04.03 Testing for antibodies against HTLV I performed for donors
live in areas with a high prevalence or derived therefrom or have
sexual partners originating from those areas or where the donor
parents originate from those areas.

05.03 Provides for the implementation and evaluation of other biological tests
characters depending on the donor's history, examination of the recipient, history
exposure, the characteristics of donor cells and epidemiological situation
such as D character of RhD, malaria, cytomegalovirus,
Trypanosoma cruzi.

06.03 In the case of autologous donors, as described in Annex no. 3
Part B point 1. a) hereof.

07.03 Perform genetic screening for autosomal recessive
genes that is under international scientific evidence
known to occur in ethnic donor and evaluate the risk
transmission of inherited conditions, which are known to they occur in
family. Complete information on the associated risk and the measures taken
for its mitigation must be communicated and clearly explained to the recipient.

Fourth General requirements for the laboratory testing of samples from the donor

04.01 Laboratory tests are carried out in accordance with Annex no. 4
subsections 1.2 and 2.2. this decree.

04.02 Blood samples were collected

A) in the case of a donation between partners during the three months before the first
donation, unless the direct use. For other partner donation
from the same donor further blood samples taken within 24 months of the previous
blood sampling,

B) in the case other than donation between partners at the time of each donation, and
case of oocyte donation, blood samples are taken at the latest at the commencement
stimulation.

04.03 Sperm donations other than by partners is kept in quarantine
least 180 days, after which it is required repeated sampling
blood sample from a donor and laboratory tests for the detection of signs of infection
. If the blood sample at the time of sperm donation
additionally tested by nucleic acid amplification technique for HIV, HBV and HCV
not have to perform the appropriate tests for these viruses with a sample of
repeated blood sampling donor. If the processing includes an inactivation process
validated for the viruses concerned inactivation, is also not required
perform appropriate tests for these viruses pattern of repeated blood sampling
donor.
Annex 6


Requirements for receiving tissue and cell processing procedures, marking
layoffs, packaging, storage and distribution of tissue and cells and their
withdrawal from distribution and quality control and safety

First Receipt of tissues and cells in a tissue establishment

01.01 Upon delivery of procured tissues and cells into the tissue establishment
on the basis of documentation verifies that the consignment, including transport conditions,
packaging, labeling, related documentation and samples, meet the requirements
income requirements of Annex no. 2 of this Order and requirements related
specifications of the receiving equipment, including tissue engineering

Requirements and other criteria that are important for maintaining
acceptable quality.

02.01 Until tissues and cells with accompanying documentation
inspected or otherwise verified that they meet the requirements, the tissue and cells
placed in quarantine. Review important information about donors and
obtaining a decision on acceptance or disposal of tissues and cells
performed and recorded competent person.

03.01 The documentation of the tissue establishment procedures are
and specifications against which each consignment is certified tissues and cells
including samples for laboratory examination. Procedures tissue establishment provides
also dealing with unsatisfactory shipments, including shipments
incomplete examination results or documentation to ensure their
department and eliminate the risk of contamination of other tissues and
cells, tissue processing equipment or stores.

04.01 The data and documentation provided by the tissue establishment, except
data and documentation pursuant to point 5.1, containing

A) consent to the removal of tissues and cells, including the purpose for which they can be
tissues and cells are used, eg a therapeutic, research or teaching
use, and including specific instructions for disposal of tissues and || | cells are not used for the purpose for which consent was obtained,

B) the required documentation relating to procurement of tissues and cells and
donor history, as described in Annex no. 2 point 5 of this decree,

C) results of physical examination of the donor, laboratory tests and other examinations
and other information, such as information
according to Annex no. 2 sub-3.2 this decree, if it proceeded,

D) in the case of allogeneic donors, a properly documented review of the complete donor evaluation
selection criteria carried out to authorized
person

E) in the case of cell cultures intended for autologous use, documentation
recipient possible allergies to medications, such as antibiotics.

05.01 In the case of reproductive cells intended for partner donation, the data and documentation provided by
tissue establishments include

A) consent; including the purpose for which they can be used
reproductive cells, eg a reproductive or research use, and
including specific instructions for the removal of tissues and cells are not used
for the purpose for which consent was obtained,

B) data necessary to identify the donor and the type, age and sex of the donor
presence of risk factors and in the case of a deceased donor, also
cause of death

C) data necessary to identify the partner

D) the place where he carried out procurement procedures,

E) the important characteristics of reproductive cells and documentation about them.

01.06 Fails to tissues and cells are income requirements for processing
tissue establishment, placed on a site that is dedicated to the
handover for other purpose pursuant to point 1.4 point. ) and 1.5 point.
) Or to remove them from the application.

Second processing

02.01 The critical processing procedures are validated so that it has been demonstrated that
tissues and cells do not become clinically ineffective or harmful to the recipient
. This validation may be based on studies performed
tissue establishment or on data from published studies or, in the case
of good practices in processing the return
evaluation of the clinical results for tissues and cells processed by the appropriate tissue equipment
and used in the treatment of the recipient.

02.02 It is obvious that validated procedure can be performed to
authorized persons in the environment and equipment tissue establishment
designed for this process to take place in the same way and were permanently set
achieved results.

03.02 In the standard operating procedures to establish procedures so that
were in line with a validated procedure and requirements are met
internal regulations pursuant to Annex no. 1 paragraph 5 of this Decree.

04.02 All procedures are performed in accordance with the approved standard
workflows and ensuring their control.

05.02 If applied in the processing of microbial inactivation procedure is
documented and validated.

06.02 Before introducing any significant change in processing is changed
validated and documented procedure and ensure that the process of introduction

Changes to meet the requirements of Annex no. 1 hereto and requirements
processing of point 2.

07.02 Processing procedures are regularly evaluated critically in order to permanently set
achieved results.

08.02 Procedures for discarding tissue and cells is chosen so as to avoid
contamination of other tissues and cells, the environment and the people involved.

Third Storage and release of products

03.01 For each type of storage conditions for determining the maximum period
storage. When the determination is also possible to monitor deterioration
desirable properties of tissues and cells.

03.02 System location and registration of tissues and cells in quarantine is introduced
so they can not be released for tissues and cells, if not met
all the requirements. Tissue establishments has for this purpose
standard operating procedures detailing the circumstances, responsibilities and
procedures for the release of tissues and cells for distribution.

03.03 System for identification of tissues and cells are formed so that during
any stage in the process can be clearly distinguished released
tissues and cells from nepropuštěných quarantine and from discarded tissues and cells.

04.03 Records are kept as to demonstrate that before discharge
tissues and cells meet all relevant requirements and specifications.
It also includes that all statements required medical records
records processing, examination results and details on the final
packaging or attached to it are verified in accordance with the written procedure and that the release
it was approved and confirmed by the responsible person tissue
devices. If the release of results from the laboratory uses
computer, it is necessary that this procedure has been validated and to be available
footprint allowing to trace who is responsible for releasing results.

05.03 If the introduction of any new criteria for the selection or
donor testing, or if there is any significant change
one processing step to improve quality and safety, carried out
documented risk assessment approved by the responsible person tissue | || facility, under which decides the fate of stored tissues and cells
.

Fourth Distribution and download

4.1.Definují the Critical transport conditions, such as temperature and
time limit in order to maintain the desired properties of tissues and cells.

04.02 The container and package of tissues and cells is chosen so as to ensure that the tissues and cells
stored safely and under specified conditions.
The suitability of the container and the container is validated for the purpose of their use.

04.03 The request form for the supply of tissue and cell preparation for therapeutic use in
recipient will provide the data clearly defining requirement
including data identifying health facilities, workplaces and
doctor requesting delivery of data and issuing requisitions.

04.04 Tissue and cell preparation supplied medical facility for treatment
recipient is accompanied by proof of delivery, which allows to verify compliance with the requirement
requisition for the supply of tissue and cell preparation.

05.04 The tissue establishment shall be determined by the person authorized to assess the need
Download tissues and cells from circulation and to initiate and coordinate the necessary actions in
if necessary.

06.04 To download the tissues and cells from the circulation by writing down
and implement effective procedure, including a description of the steps
responsibilities of those involved in the procedure and announcement of the Institute.

07.04 Provide also practices in the pre-defined period will follow
tissues and cells for the needs of the investigation and re-tracing
whose purpose is, for example, identify any donor who might have contributed to causing the reaction in
recipient to retrieve available tissues and cells from that donor
and inform customers and recipients of tissues and cells procured
donors in this case could be compromised.

08.04 There will be a documented system for the handling of returned
tissues and cells, including the criteria for their return to the warehouse facility
tissue and for any other use.

Fifth Final designation for distribution

05.01 On the primary package label tissue and cell preparation of the state


A) the name of the product, which indicates what type of tissue and cell
product is, the identification code of the product and, where applicable,
batch number,


B) data identifying the tissue establishment leaked product
including addresses and identification marking,

C) the date of expiry,

D) in the case of autologous donation, sign 'for autologous use only "and
information identifying the donor, who is also a recipient

E) in the case of donations, the recipient information identifying the intended recipient
,

F) the term "BIOLOGICAL DANGER", if it is known that the product
assessed as positive on one important indicator
infectious diseases.

If any indication referred to in subparagraphs d) and e) can be placed on
primary package label, is provided on a separate sheet accompanying
appropriate packaging so as to ensure that they are not separated from each other.
If you put all the data referred to in point. a) through f) to allow dimension
primary packaging shall appear on the primary packaging minimum figure
uniquely identifies the product packaging and other data according to importance and
dimensional possibilities, with the remaining data are presented according to the second sentence
.

05.02 On the primary package label tissue and cell preparation or in the documentation accompanying the respective
packaging is also state

A) defining the product description including formulation and indication
characterizing the amount or size of tissues and cells

B) morphologic and functional data, where appropriate,

C) date of distribution,

D) conducted tests of samples from the donor and results

E) instruction for storage

F) instructions for opening the primary packaging and instructions for reconstitution
preparation and handling,

G) shelf life after opening the primary packaging or after
handling of the product

H) guidelines under § 5 para. 3 point. b) of the Act concerning
serious adverse reactions or events and traceability, unless otherwise provided
,

I) notice of the presence of residues of potentially harmful substances (eg.
Antibiotics, ethylene oxide)

J) therapeutic indications, side effects, contraindications or other
notice, to the extent that meets the needs
therapeutic use of the recipient.

6th Marking the outer shipping container

For transport, tissue and cell preparation in the primary packaging
placed into a shipping container, in which states minimum

A) identification of the tissue establishment tissues or cells leaked,
including addresses, identification marking and telephone number

B) identification of the hospital and its work, which has
container to be shipped, including address and phone numbers, and names
last name and phone number of person taking over where it is needed,

C) a statement that the package contains human tissue and cells and inscription
"HANDLE WITH CARE"

D) DO NOT IRRADIATE warning if necessary for use of live
cells, such as stem cells, germ cells, embryos,

E) conditions of transport, such as "keep cool"
"keep upright"

F) safety instructions and method of cooling where it is possible.

7th Quality control and safety

07.01 Quality control and security established and conducted under
Activities to ensure that the tissues and cells comprise at least

A) examination of samples from the donor to assess the medical fitness of the donor
according to § 5 in every tissue and cell donation,

B) laboratory testing of samples from the donor to assess the applicability
tissue and cell donor for a specific recipient, where it is necessary

C) the inspection criteria of quality and safety of tissue and cell
products; checks shall include data characterizing
amount or size of tissues and cells, the active ingredient content and content unwanted
components, indicators are important for the therapeutic effect of the product for its
stability and microbiological control in accordance with specifications laid down,

D) checks referred to in subparagraph c) selected for the purpose of checking the intermediate
during the processing of tissues and cells or before their release, where
is appropriate

E) control of supplied materials and products according to the specifications laid down
before using them, in the case of materials and products critical to the quality
and safety of tissues and cells


F) inspection of premises and equipment including meeting the requirements of their
use in the procedure for which they are intended; physical control,
chemical or biological parameters that are critical for
procedure

G) inspecting the cleanliness of the environment in the environment declared a grade,

H) microbiological control of surfaces, including surfaces in areas where
are treated with tissues and cells and tissue and cell preparations
primary packaging.

For random checks carried out in accordance with the purpose and character sets
control system checks, including their frequency.

07.02 If the scrutiny sampled and determined
validates the procedure for their collection and preservation so that it has been demonstrated that
inspection carried out using a sample of monitored indicators reflect the quality and safety
.

07.03 Elect such samples from the donor and the conditions of their preservation
that meet the requirements for mandatory laboratory testing of donors and
allow storage of samples for these tests for a period to be determined by the operator
tissue establishment. Preservation of samples to ensure
least until a decision on the release of tissues and cells and the conclusion of the results
donor testing. Shelf sample retained for the purpose of his
examination verified.
Annex 7


Announcements and news
PART
A
NOTICE


First Model for the notification of serious adverse reactions or suspected

----------------------------------------------- ---- ------------------------------------
notifying the tissue establishment according to § 7 of Decree no. 422/2008 Coll. (name, address)
----------------------------------- ---------------- ---------------------------------- - Identification
Announcement1)
--------------------------------------- ------------------------------------ ------------ || | Date of notification (year / month / day)
------------------------------------- -------------- ------------------------------------
The person (donor or recipient)
------------------------------------- -------------- ------------------------------------
Date of collection (year / month / day) and place of collection of tissues and cells, in the case of a reaction in the donor
--------------------- ------------------------------ -------------------- ----------------
filing Date (year / month / day), and instead of bringing tissues and cells in case of a reaction in the recipient
----- ---------------------------------------------- ---- --------------------------------
unique identification number for donations
-------- ------------------------------------------- ------- -----------------------------
Date of serious adverse reaction / suspected (year / month / day)
-------------------------------------------------- - ------------------------------------
Type tissues and buněk2) related to the notification identification code
tissue and cell preparation, if connected with the announcement and the country of origin of tissues and cells
, in the case of tissues and cells from abroad
------------- -------------------------------------- ------------ ------------------------
Type of serious adverse reaction / suspected (please druh3) and describe)
----- ---------------------------------------------- ---- --------------------------------
Responsible tissue establishment (name, title, telephone and e- mail)
--------------------------------------------- ------------------------------------ ------

1) shall apply to the identification provided by the Institute.

2) The type of tissues and cells according to § 10 paragraph. 4, or
material or product that has been in contact with tissues and cells (name, batch
manufacturer) if it has a connection with notification.

3) Indicate the type of serious adverse reactions or suspected, according
nature of the reaction, and it

A) transferred bacterial infection

B) carried viral infection including the originator, such as HBV, HCV, HIV 1 and 2
,

C) infection delegated parasites including the type of infection such as malaria,

D) carried malignant disease

E) the further transmission of the disease, which states specifically indicate

F) other sort of serious adverse reaction in a donor, which states
specifically indicate

G) other type of serious adverse reactions among recipients, which states
namely state.

Second Model for the notification of serious adverse events or suspected
-------------------------------------- ------------------------------ -------------
notifying tissue establishment by § 7 of Decree no. 422/2008 Coll. (name, address)

----------------------------------------------- ------------------------------ ----
Identification Announcement1)
------- -------------------------------------------- ------
------------------------ Date of notification (year / month / day)
-------------------------------------------------- -
------------------------------ Date of serious adverse event / suspected (year / month / day) | || ------------------------------------------------ --- ------------------------------

Specification Serious adverse event or suspected
, which may


affect the quality and safety of tissues and cells


in relation to the variation in the ----------------- ----------------------------------------------
Another glitch Failure Error
Tissue / Facilities man (give
cell states)
----------------------------------- ------------------------------ ---------------- procurement

----------------------------------------------- ---- ------------------------------ ---------

examination ------------------------------------------ -------- ---------------------- ---------------------

transportation ------------------------------ --------------------
----------
processing --------------------------------- ------------------ ------------------------------ || | --------------------------------------------- storage
------------------------------ ------

distribution of materials (name
batch manufacturer) -------------------------------------------
------------------------------ --------
other (give states
) | || ------------------------------------------------
--- ------------------------------ Estimated impact of reported serious adverse event / suspected her
- -------------------------------------------------- ------------------------------
Responsible tissue establishment (name, surname,
title, phone number and e -mail)
-------------------------------------------- ------------------------------ -------
1) shall apply to the identification provided by the Institute.
PART B


NEWS

First Specimen reports of serious adverse reaction
notifying the tissue establishment according to § 7 of Decree no. 422/2008 Coll. (Name, address)

Identification announcement (both with notification of serious adverse reactions
/ suspected)

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

Date when the evaluation of serious adverse reactions
closed (year / month / day)

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

Unique identification number for donations

Confirmation of serious adverse reaction (Yes / No)

Change of type of serious adverse reaction (Yes / No)

If yes, please změnu1)

Other changes to the data referred to in the notice
serious adverse reaction / suspected (if yes, please change)

Number of disabled beneficiaries in case of serious adverse reaction in the recipient


Clinical outcome (if known)
-
a full recovery - slight consequences
-
serious consequences - death

Type of tissues and buněk2) and the amount distributed
tissue and cellular products for which have been notified of serious adverse reactions

The result of the evaluation of serious adverse reactions and final conclusions
(describing states)

Preventive and remedial measures (including
describes announcing the implementation date to be determined)

Responsible tissue establishment (name, surname, title,
phone and e-mail)

Report date (year / month / day)

1) Indicate the type of serious adverse reaction / suspected, according to the nature
reaction, and it

A) transferred bacterial infection

B) carried viral infection including the originator, such as HBV, HCV, HIV 1 and 2
,

C) infection delegated parasites including the type of infection such as malaria,

D) carried malignant disease

E) the further transmission of the disease, which states specifically indicate

F) other sort of serious adverse reaction in a donor, which states
specifically indicate

G) other type of serious adverse reactions among recipients, which states
namely state.

2) The type of tissues and cells according to § 10 paragraph. 4, or
material or product that has been in contact with tissues and cells (name, batch
manufacturer) if it has a connection with notification.

Second Specimen reports of serious adverse events
----------------------------------------- ----------- ----------------------------

Notifying tissue establishment according to § 7 of Decree no. 422/2008 Coll. (Name, address)
------------------------- --------------------------- ----------------------- -----
identification announcement (both notifying serious adverse events
/ suspected)
---------------------- ------------------------------ -------------------- --------
date of confirmation of serious adverse event (year / month / day)
------------------------ ---------------------- ---------------------------- ------
date when the evaluation of serious adverse events
closed (year / month / day)
-------------------- -------------------------------- ------------------
---------- Date of serious adverse event (year / month / day)
----------------------- ----------------------------- --------------------- -------
analysis of the main reasons (describe states)
------------------------------ ---------------------- ----------------------------
preventive and remedial measures (including
describes announcing the implementation date to be determined)
----------------------------- ----------------------- --------------------------- -
Responsible tissue establishment (name, surname, title,
phone and e-mail)
----------------------- ----------------------------- --------------------- -------
report date (year / month / day)
---------------------------- ------------------------ -------------------------- -
Appendix 8


Application for a license to operate and its changes
PART
A

First The request for the authorization of tissue establishment, receiving equipment, or diagnostic laboratories
contains a summary of key, which includes


A) the name, business address and identification number, if assigned
, individuals applying for a permit; if asking for permission
legal person, its business name or name, registered address,
mailing address and identification number or a similar indication

B) the name and surname of a statutory representative of a person referred to in subparagraph a)

C) name, surname, education and experience of the responsible person according to § 6 and § 8
Law and contact information on it, and if it is a diagnostic laboratory
person responsible for professional activities laboratory

D) The type and scope of activities to be carried out, including
a list of practices organized in the framework of procurement, processing
, laboratory monitoring, warehousing and distribution, including direct
distribution, which may have an impact the quality and safety of tissues and cells

E) tissues and cell types that are to be the subject of activity; jde- if a tissue
transmitting device, a list of tissue and cell
products to be released; for each product shall be given
types of packaging product and its use, especially if the product is intended for the treatment
recipient or for further production

F) the type of activities to be performed under the contract pursuant to § 10
Act and data identifying the person who is the contracting activity
exercise the extent identification as in a); in the case of
under § 10 paragraph. 2 point. b) of the Act, this fact shall,

G) addresses all points of activity and the type of activity that has to be in that place
implemented; It also applies to the activity under point. f), and

H), telephone, fax and e-mail address of the applicant;
address for the home page information means allowing remote access
case of a tissue establishment.

Second The request also includes

A) proof of authorization to pursue business persons referred to in paragraph 1. a)
related activities to be carried out, for example, demonstrate
certificate of incorporation, not older than 3 months
valid trade license, valid foundation deed; in the case of tissue
equipment or receiving equipment, also demonstrate their integration into
medical device

B) proof of right to use facilities and equipment for the activity to be carried
,

C) proof that ensures compliance in accordance with § 6 para. 2, § 7
paragraph. Point 1. b), § 8 par. 2 and § 10 paragraph. 2 and 4 of the Act,

D) proof of payment of the fee for filing an application and proof of payment
costs for the examination, which is the amount of payment
known in advance,

E) in the case of tissue establishment, a list of customers who are to be supplied
tissues and cells and demonstrate how it will ensure that
requirement under § 4 para. 2 nd, and


F) basic document for the site, which contains information about the particular

First organization, including the integration of all activities and the places where the activities carried
into the overall structure of the organization

Second persons carrying out activities, including their number, qualification
requirements of job training, education, health and sanitation requirements
on the people involved; says the organization chart
functions of executives and their hierarchy, including links to the highest levels of leadership
organization

Third premises and equipment, which may affect quality and safety
tissues and cells, including, for example, incorporated into a building and the system
distribution; submitted to the operating premises plan designating
procedures performed, indicating sustained environmental parameters, such as for example
grade purity, temperature, humidity, and with representation path along which move
donors different tissues and cell types, each
types of tissue and cellular products, materials and products and waste, from the point of entry or
formation in places where space forsake

Fourth system cleaning, maintenance, inspection, repair, calibration and validation,

Fifth management system, internal regulations and record anonymization and protection
data collected by donors and recipients; presents a list of internal
regulations, forms and records patterns developed procedures that
to be provided,

6th critical processes, including their technical and material
ensure quality checks to be carried out and specifications
conditions and implementation procedures

7th conducted validation and calibration,

8th Security and monitoring activities to be carried out on the basis of a contract
and

9th the system's own review of the quality, participation in national or international
external quality control laboratory work based on examination
distributed samples, the system for traceability and monitoring system
serious adverse reactions and events and their
notification.

Third If a tissue establishment permeable tissues and cells application also includes


A) information and documentation pursuant to § 17 par. 3 point. a) of the Act,

First of redundant tissues and cells in the scope of Annex no. 1, sub
05.05 and

Second the procedures organized by the tissue establishment
covering all sub-processes that can affect the quality and safety of tissues and cells
including procedures organized by the contract; submit the basic information about
conditions and implementation of procedures to determine the standard
course of the process, the emergence of a standard tissue and cell preparation and
ensure its quality, safety and efficacy; Also presented is a diagram showing
practice their continuity, including the designation of tissues and cells
entering the process, resulting package
tissue and cell preparations, the indicators monitored during the procedure and conditions and their
tolerances of the critical materials and product and included
checks tissues and cells

B) a list of sampling equipment involved in donations of tissues and cells for tissue
equipment and information about how the poolside
ensure that the requirements of the Act and this Decree, which
critical materials and products collection the device uses including ensuring
requirements of other legislation ^ 9); report also receiving conditions
tissues and cells for processing

C) a list of diagnostic laboratories involved in the mandatory checks
samples from donor tissue establishment, and information about how these laboratories
ensure that the requirements of the Act and this Decree, which
method and laboratory diagnostics uses including meeting the requirements of other legislation
^ 4)

D) report on the development of tissue and cell preparation and justification

First procedures used and parameters important for a standard course
process and to ensure the quality, safety and efficacy
tissue and cellular products,

Second used quality control procedures used samples, diagnostic
resources, and outcomes to be achieved,

Third selection of critical materials and products eaten during collection and processing
, in relation to their use in humans including
materials and products which have been used and subsequently removed; in the case of material

Product or biological origin, a justification of its necessity
use and what measures were taken to minimize the risks of using
biological material including reports on its own
verify the effectiveness of these measures, or by submitting a certificate issued for the || | purpose of use,

Fourth the composition of the tissue and cell preparation and selection of its primary
packaging

E) specimen labeling for each type of packaging tissue and cell
preparation and pattern information and instructions accompanying the package according to § 5, paragraph
. 2 point. d) and § 5 para. 3 point. b) of the Act,

F) report on the validation of critical processes and results of the validation, including validation
quality control procedures,

G) information on the origin and batch marking where it is applicable,

H) the method and results of verification for each of the claimed shelf life
tissues and cells and tissue and cell preparation, including for example the time
declared useful for tissue and cell preparation after his
opening

I) report on the method and results of verification of therapeutic efficacy and undesirable effects
tissue and cell preparation of the recipient,

J) an analysis of the risks that tissue and cell preparation may pose
including measures employed to minimize these risks,
and guarantees the effectiveness of these measures.

Case of tissue and cell preparation traditionally used in
Czech Republic, can be used in point d), f), h), i) and j)
and documents taken from the literature, je- where proof that such information
subject to the same procedures ensure that tissue and cell preparation
and reached the same final packaging of tissue and cell preparation as
product which is the subject of the application. Proof of compliance and documentation was
attached to the application.

Fourth If any item is a request under points 1 to 3 for the type
tissues and cells, tissue and cell preparation process or hinnosti
applicable, indicate the reason for which it can be given. When developing applications
used model application setting guidelines Constitution.
Documents under paragraph 2 by the competent authority may be replaced by a copy of their certified
.

Fifth Permits are subject to change in the person mentioned in point 1. a) and c) changes
kind of activities and persons referred to in point 1. f) changes in location and type
activities mentioned in point 1. g) changes in the data referred to in point 1
point. d) and e) and in paragraph 3. and). In the case of an application for a change
submitted by the operator of the tissue establishment to in paragraph 1. a)
also indicate an identification mark allocated to the tissue establishment
Institute to enable its operation.

6th The application for approval of changes in accordance with paragraph 5 shall indicate the changes, which is
sought. Furthermore, always submit the data referred to in paragraph 1 and complete data
packaging of tissue and cell preparation or a process under the point 3
point. a) in which there is a change. Indicate the data to be
change, including changes to be sought. Accompanied by the new wording
all the documents and information referred to in point 2 and point 3. b) to j)
related to the change. In case of change of the responsible person shall also be indicated
date from which the person has to start fulfilling their obligations.
PART B


Request for permission to distribution of tissues and cells

First Application for a license to operate - the distribution of human tissues and cells
contains a summary of key, which includes

A) the name, business address and identification number, if assigned
, individuals applying for a permit; if asking for permission
legal person, its business name or name, registered address,
mailing address and identification number or a similar indication

B) the desired range of distribution, to be carried out, depending on the type
tissues and cells, and a list of practices organized in the framework of distribution

C) tissues and cell types that are to be subject to distribution

D) address of each site activities and commissioning procedures organized within
distribution locally,

Second The request also includes

A) proof of authorization for the business person of the applicant
related activities to be carried out, for example, demonstrate
extract from the Commercial Register, not older than three months, the trade
valid license or valid foundation deed | ||

B) basic document for the site, which contains information about the particular

First organization, including the integration of all activities and the places where the activities carried
, the overall structure of the organization

Second persons carrying out activities, including their number, qualification
requirements of job training, education, health and sanitation requirements
on the people involved; says the organization chart
functions of executives and their hierarchy, including links to the highest levels of leadership
organization

Third premises and equipment, which may affect quality and safety
tissues and cells, including space for cleaning, disinfection and sanitation
critical equipment,

Fourth system cleaning, maintenance, inspection, repair, calibration and validation,

Fifth management system of internal rules and records;
presents a list of internal regulations, forms and patterns
records prepared for the procedures to be provided,

6th critical processes, including their technical and material
ensure quality checks to be carried out and specifications
conditions and implementation procedures

7th conducted validation and calibration and

8th the system's own review of the quality system
traceability and monitoring system for serious adverse events and their
notification.
Appendix 9


Good Distribution Practice for distribution of tissues and cells

First Quality system requirements

First Quality system of organization and management

Quality system implementation involves writing set
functional organizational structure, responsibilities and reporting structure
obligations set out in writing the obligations of the persons involved, and writing
prescribed processes, procedures and resources for quality control;
quality management means the coordinated activities, which the organization is managed and
checked for quality. The system of quality
all activities that directly or indirectly contribute to quality.
Documented quality system and quality management applies to all activities related to the distribution
.

Second Persons involved

02.01 Performing various activities related to the distributions
thus ensuring that a sufficient number of people involved
qualified for the tasks to be provided.
Their eligibility is evaluated at appropriate intervals specified in
quality system documentation.

02.02 For each person involved to draw up and update a clear, documented
job description. This ensures that the duties and responsibilities
were clearly documented and understood.

03.02 Before exercising the activities of each person involved
providing adequate training and updated training in the event of changes in procedures.
Program training is documented. This ensures that each individual

A) is competent to perform the tasks entrusted to it,

B) have adequate knowledge and understand the processes and principles that
related to the tasks entrusted to it,

C) understand the business organization, quality management system and internal
rules of the establishment in which they work, and

D) has been informed of the broader ethical, legal and regulatory
context of their work.

Third Equipment and facilities

03.01 Equipment used in distribution is proposed and maintains
manner suitable for the intended purpose and in a manner that poses minimal risk to
affecting the quality and safety of tissues and cells and involved
persons handling them.

03.02 Identifies critical equipment, validates be regularly checked and
preventively maintained in accordance with the instructions of the manufacturer.
Equipment which may affect the critical parameters of the distribution of tissues and cells
(eg temperature), subject to the need to monitor, systems
alerts, alarms and corrective actions to be detected early
faults and defects and to ensure that the critical parameters are
maintained within acceptable limits. The equipment, which measures the critical parameters
, calibrated, whereby using the appropriate
traceable standard, suitable for calibration, if available.

03.03 New and repaired equipment during installation and tested before use
is validated. The test results are documented.

04.03 Maintenance, servicing, cleaning, disinfection and sanitation
critical equipment must be performed regularly and recorded.


05.03 Procedures are now available for the operation of each piece of critical
equipment, detailing the measures to be taken in the event of failure or malfunction
.

06.03 Ensure the establishment and premises suitable for the activities related
distribution, including space for cleaning, disinfecting and sanitizing
critical equipment.

Fourth documentation

04.01 There will be a system to ensure clearly defined and effective documentation
both internal regulations and records.
Documentation system is created so as to guarantee that all activities related to the distribution and security
quality standard will be implemented, and that all steps
these activities will be traceable.
For establishing and maintaining a system of documentation to draw up appropriate regulations
providing for the management of internal regulations and records management.

04.02 Over the management of internal rules to ensure in particular that
internal regulations approved and regularly reviewed in order
used their versions and history of changes to each
internal regulations were traceable.

04.03 Internal regulations shall include standard operating procedures
training and methodological manuals, forms and records basic document
about the place.

04.04 Basic document summarizes the place of the organizational, technical and personnel prerequisites
created to fulfill the requirements of the Act and
regulations, especially the requirements for a quality system. Current basic
documentary about the place is always submitted to the Department before checking in at least
scope of a permit for the activity listed in Annex no. 8 of Part B
point 2. d).

05.04 For the activity of distribution is determined and documented and equipment involved
persons who participate in the activities.

06.04 Changes in internal rules and records are reviewed, approved,
endorsed with the date and properly implemented by authorized persons.

07.04 Records are kept so that they are reliable and a true representation
facts and results.

08.04 Records are kept legible and indelible manner, may be
handwritten or made other validated procedure such
electronically. If using a signature, and adds the date and what is
signature confirmed.

09.04 All records related to the distributions are treated as
records for traceability and stored so that they can be
ensure access for at least 30 years from the date of the distribution.

4.10 Adopting security measures against illegal refilling
data, deletions or changes in the records. Establishing procedures for
resolve data discrepancies.

Fifth Quality review

05.01 A system of own checks. Checks on the
entrust employees, or external natural or legal persons
which are to be trained and competent, and are independent in relation to
activities that the inspection concerns. Self-monitoring is done
least once every two years to verify compliance with internal regulations and requirements
Act and this Decree. Findings and actions are documented.

05.02 All deviations from the applicable provisions related
quality and safety be investigated and documented. Also documented
decisions on corrective and preventive actions.

05.03 Corrective action starts and finishes in a timely and efficient manner. After
perform preventive and corrective measures to assess their effectiveness
. The effect of measures and their effectiveness is documented.

05.04 They shall establish procedures for the review of the performance management system
quality to ensure systematic improvement.

Second Transportation of tissues and cells from tissue sampling device to device

02.01 Part of the internal regulations, the procedure for transporting tissues and cells from
sampling device into the tissue establishment, including related
records.

02.02 Tissues and cells, including samples from the donor to the intended examination is
transported in a container which is suitable for the transport of biological
materials and which maintains the quality and safety of tissues and transported
cells. The container and package of tissues and cells is chosen so as to ensure that
tissue and cells are kept safely and under specified conditions.

03.02 A shipping container equipped with a system of continuous monitoring
temperature. The system should not allow outside interference in the recorded values ​​ago

Reading and evaluating the status value of traffic conditions.

04.02 They are transported only tissues and cells labeled in accordance with Annex.
2 with 7.

05.02 Designation of each shipping container contains at least the information
listed in Annex no. 2, section 8.

Third Distribution of tissues and cells dismissed for human use

03.01 When distributing to comply Critical transport conditions laid down
tissue establishments, in particular the temperature and time has to be
maintain the desired properties of tissues and cells.

03.02 The container and package of tissues and cells is chosen so as to ensure that the tissues and cells
stored safely and under specified conditions.

03.03 A shipping container equipped with a system of continuous monitoring
temperature. The system should not allow outside interference in the recorded values ​​before
reading and evaluating the status values ​​of distribution terms.

04.03 The request form for the supply of tissue and cell preparation for therapeutic use in
recipient will provide the data clearly defining requirement
including data identifying health facilities, workplaces and
doctor requesting delivery of data and issuing requisitions.

05.03 Tissue and cell preparation supplied medical facility for treatment
recipient is accompanied by proof of delivery, which allows to verify compliance with the requirement
requisition for the supply of tissue and cell preparation.

06.03 When you download the tissues and cells from the circulation to follow the procedures and guidelines
tissue establishment tissues and cells withdraws from circulation.

07.03 They are transported only tissues and cells labeled in accordance with Annex.
6 point 5, including accompanying documentation.

08.03 Marking the outer shipping container contains at least the information set out in Annex
no. 6 point 6

Fourth Notifiable

04.01 Adverse events during distribution shall be notified to the tissue
device that leaked the tissues and cells for human applications.

04.02 Adverse events in the transport of procured tissues and cells from
sampling device into the tissue establishment to notify tissue
equipment in which tissues and cells are transported.

1) Directive of the European Parliament and Council Directive 2004/23 / EC of 31 March 2004
establishing quality and safety standards for the donation,
testing, processing, preservation, storage and distribution of human || | tissues and cells. Commission Directive 2006/17 / EC of 8 February 2006
implementing Directive of the European Parliament and Council Directive 2004/23 / EC as regards
certain technical requirements for the donation, procurement and testing of human
tissues and cells. Commission Directive 2006/86 / EC of 24 October
2006 implementing Directive of the European Parliament and of the Council
2004/23 / EC as regards traceability requirements, notification
serious adverse reactions and events and certain technical requirements for
coding, processing, preservation, storage and distribution of human tissues and cells
.

2) Act no. 285/2002 Coll., On donation, drafts and transplantation of tissues and organs
and amending certain acts (Transplantation Act), as amended
.

3) § 6 of Act no. 296/2008 Coll., On ensuring quality and safety
human tissues and cells intended for human use and amending
related laws (Act on human tissues and cells).

4) Act no. 123/2000 Coll., On medical devices and change
some related laws, as amended.

Decree no. 336/2004 Coll., Laying down technical requirements
medical devices, amending Government Regulation no. 251/2003
Coll., Amending some Government Orders issued pursuant to Law no.
22/1997 Coll., on technical requirements for products and amending and supplementing
certain laws, as amended.

Decree no. 453/2004 Coll., Laying down technical requirements
diagnostic medical devices in vitro.

5) Rules Governing Medicinal Products in the European Community, EudraLex,
Volume 4 - Human and veterinary medicines: Good Manufacturing Practice
(The Rules Governing Medicinal Products in the European Community
, EudraLex, Volume 4 - Medicinal Products for Human and Veterinary Use
: Good Manufacturing Practice), the current version
published by the European Commission.


6) Act no. 20/1966 Coll., On Public Health Care, as amended
regulations. Act no. 285/2002 Coll., On donation and transplantation
donations of tissues and organs and amending certain acts (Transplantation Act), as amended
.

7) § 8 of Act no. 296/2008 Coll., On ensuring quality and safety
human tissues and cells intended for human use and amending
related laws (Act on human tissues and cells).

9) For example, Act no. 123/2000 Coll., On medical devices and
amendment of related laws, Government Regulation no. 336/2004 Coll.
Establishing technical requirements for medical devices | || amending Government Regulation no. 251/2003 Coll., amending certain
government regulations issued pursuant to Act no. 22/1997 Coll., on technical
requirements for products and amending and supplementing certain acts , as amended
, Czech and pharmacopoeia in the current version.