Na podlagi druge alinee prvega odstavka 107. člena in prvega odstavka 91. člena Ustave Republike Slovenije izdajam
U K A Z
O RAZGLASITVI ZAKONA O RATIFIKACIJI EVROPSKEGA SPORAZUMA O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV, PROTOKOLA K EVROPSKEMU SPORAZUMU O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV TER DODATNEGA PROTOKOLA K EVROPSKEMU SPORAZUMU O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV (MESIRT)
Razglašam Zakon o ratifikaciji Evropskega sporazuma o izmenjavi reagentov za tipizacijo tkiv, Protokola k Evropskemu sporazumu o izmenjavi reagentov za tipizacijo tkiv ter Dodatnega protokola k Evropskemu sporazumu o izmenjavi reagentov za tipizacijo tkiv (MESIRT), ki ga je sprejel Državni zbor Republike Slovenije na seji 19. julija 2000.
Št. 001-22-143/00
Ljubljana, dne 27. julija 2000
Predsednik
Republike Slovenije
Milan Kučan l. r.
Z A K O N
O RATIFIKACIJI EVROPSKEGA SPORAZUMA O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV, PROTOKOLA K EVROPSKEMU SPORAZUMU O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV TER DODATNEGA PROTOKOLA K EVROPSKEMU SPORAZUMU O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV (MESIRT)
1. člen
Ratificirajo se Evropski sporazum o izmenjavi reagentov za tipizacijo tkiv in Protokol k Evropskemu sporazumu o izmenjavi reagentov za tipizacijo tkiv, sklenjena v Strasbourgu 17. septembra 1974, ter Dodatni protokol k Evropskemu sporazumu o izmenjavi reagentov za tipizacijo tkiv, sklenjen v Strasbourgu 24. junija 1976.
2. člen
Sporazum, protokol in dodatni protokol se v izvirniku v angleškem jeziku in v prevodu v slovenskem jeziku glasijo:
EUROPEAN AGREEMENT
ON THE EXCHANGE OF TISSUE-TYPING REAGENTS
The member States of the Council of Europe, signatory hereto,
Considering that tissue-typing reagents are not available in unlimited quantities;
Considering that it is highly desirable that member States, in a spirit of European solidarity, should assist one another in the supply of these tissue-typing reagents, should the need arise;
Considering that such mutual assistance is only possible if the character and use of such tissue-typing reagents are subject to rules to be laid down jointly by the member States and if the necessary import facilities and exemptions are granted,
Have agreed as follows:
Article 1
1 For the purposes of this Agreement, the expression “tissue-typing reagents” refers to reagents of human, animal, plant and other origin, used for the determination of tissue-typing.
2 The provisions of Articles 2 to 6 of this Agreement shall also apply to cells of known antigenic composition to be used for the investigation of typing reagents.
Article 2
The Contracting Parties undertake, provided that they have sufficient stocks for their own needs, to make tissue-typing reagents available to other Parties who are in need of them and to charge only those costs of collection, processing and carriage of such substances and the cost (if any) of their purchase.
Article 3
Tissue-typing reagents shall be made available to the other Contracting Parties subject to the condition that no profit is made on them, and that they shall be used solely for medical and scientific, i.e. non-commercial, purposes and shall be delivered only to laboratories designated by the governments concerned in accordance with Article 6 of this Agreement.
Article 4
1 The Contracting Parties shall certify that the provisions as laid down in the Protocol to this Agreement have been observed.
2 They shall also comply with any rules to which they have subscribed with regard to international standardisation in this field.
3 All consignments of tissue-typing reagents shall be accompanied by a certificate to the effect that they were prepared in accordance with the specifications in the Protocol. This certificate shall be based on the model to be found in the Annex to the Protocol.
4 The Protocol and its Annex constitute an administrative arrangement and may be amended or supplemented by the governments of the Parties to this Agreement.
Article 5
1 The Contracting Parties shall take all necessary measures to exempt from all import duties the tissue-typing reagents placed at their disposal by the other Parties.
2 They shall also take all necessary measures to provide for the speedy delivery of these substances, by the most direct route, to the consignees referred to in Article 3 of this Agreement.
Article 6
The Contracting Parties shall forward to one another, through the Secretary General of the Council of Europe, a list of the national and/or regional reference laboratories, empowered to issue certificates as provided in Article 4 of this Agreement and to distribute imported tissue-typing reagents.
Article 7
1 This Agreement shall be open to signature by the member States of the Council of Europe, who may become Parties to it either by:
(a) signature without reservation in respect of ratification or acceptance, or
(b) signature with reservation in respect of ratification or acceptance, followed by ratification or acceptance.
2 Instruments of ratification or acceptance shall be deposited with the Secretary General of the Council of Europe.
Article 8
1 This Agreement shall enter into force one month after the date on which three member States of the Council shall have become Parties to the Agreement, in accordance with the provisions of Article 7.
2 As regards any member State who shall subsequently sign the Agreement without reservation in respect of ratification or acceptance or who shall ratify or accept it, the Agreement shall enter into force one month after the date of such signature or after the date of deposit of the instrument of ratification or acceptance.
Article 9
1 After the entry into force of this Agreement, the Committee of Ministers of the Council of Europe may invite any non-member State to accede thereto.
2 Such accession shall be effected by depositing with the Secretary General of the Council of Europe an instrument of accession which shall take effect one month after the date of its deposit.
Article 10
1 Any Contracting Party may at the time of signature or when depositing its instrument of ratification, acceptance or accession, specify the territories to which this Agreement shall apply.
2 Any Contracting Party may, when depositing its instrument of ratification, acceptance or accession or at any later date, by declaration to the Secretary General of the Council of Europe, extend this Agreement to any other territory or territories specified in the declaration and for whose international relations it is responsible or on whose behalf it is authorised to give undertakings.
3 Any declaration made in pursuance of the preceding paragraph may, in respect of any territory mentioned in such declaration, be withdrawn according to the procedure laid down in Article 11 of this Agreement.
Article 11
1 Any Contracting Party may, in so far as it is concerned, denounce this Agreement by means of a notification addressed to the Secretary General of the Council of Europe.
2 Such denunciation shall take effect six months after the date of receipt by the Secretary General of such notification.
Article 12
The Secretary General of the Council of Europe shall notify the member States of the Council and any State which has acceded to this Agreement, of:
(a) any signature without reservation in respect of ratification or acceptance;
(b) any signature with reservation in respect of ratification or acceptance;
(c) the deposit of any instrument of ratification, acceptance or accession;
(d) any date of entry into force of this Agreement in accordance with Article 8 thereof;
(e) any declaration received in pursuance of the provisions of paragraphs 2 and 3 of Article 10;
(f) any notification received in pursuance of the provisions of Article 11 and the date on which denunciation takes effect;
(g) any amendment of or supplement to the Protocol and its Annex under Article 4, paragraph 4, of this Agreement.
In witness whereof the undersigned, being duly authorised thereto, have signed this Agreement.
Done at Strasbourg, this 17th day of September 1974, in the English and French languages, both texts being equally authoritative, in a single copy which shall remain deposited in the archives of the Council of Europe. The Secretary General of the Council of Europe shall transmit certified copies to each of the signatory and acceding States.
P R O T O C O L
TO THE AGREEMENT
GENERAL PROVISIONS
1. Specificity
A. Tissue-typing reagents to be used in cytotoxic techniques on lymphocytes
These reagents must, when used according to the technique recommended by the producer, react with all lymphocytes known to contain the antigen(s) corresponding to the specificity(ies) mentioned on the label. They must not react with any cell known not to contain this antigen (these antigens).
When these reagents are used according to the technique recommended by the producer there must be no evidence of any interfering serological phenomena such as:
(a) prozone effects,
(b) anticomplementarity.
B. Tissue-typing reagents for use in a complement fixation technique on platelets
These reagents must, when used according to the technique recommended by the producer, give complement fixation with all platelets known to contain the antigen(s) corresponding to the specificity(ies) mentioned on the label. They must not give complement fixation with any platelets known not to contain this antigen (these antigens).
When these reagents are used according to the technique recommended by the producer there must be no evidence of any interfering serological phenomena such as:
(a) prozone effects,
(b) anticomplementarity.
2. Potency
A. Tissue-typing reagents to be used in cytotoxic techniques on lymphocytes
The titre of such a reagent is determined by making successive twofold dilutions of the reagent under study in inactivated AB serum from a donor negative for the antigen(s) corresponding to the antibody (antibodies) in the reagent who should also not have been immunised against tissue antigens by transfusion, pregnancy or other means. Each dilution is then tested with lymphocytes known to contain the corresponding antigen(s) in the reagent, using the technique recommended by the producer. The titre is the reciprocal of the figure representing the highest serum dilution in which a significantly positive reaction occurs, the dilution being calculated without the inclusion of the volume of the corpuscular suspension or any other additive in the total volume.
B. Tissue-typing reagents for use in a complement fixation technique on platelets
The titre of such a reagent is determined by making successive twofold dilutions of the reagent under study in 10% inactivated AB serum in Veronal buffer. Each serum is then tested with platelets known to contain the antigen homologous to the antibodies in the reagent, using the technique recommended by the producer. The titre is the reciprocal of the figure representing the highest serum dilution in which a significantly positive reaction occurs, the dilution being calculated without the inclusion of the volume of the corpuscular suspension or any other additive in the total volume.
Further provisions, for tissue-typing reagents to be used in cytotoxic techniques on lymphocytes as well as for reagents to be used in a complement fixation technique on platelets:
3. Preservation
Tissue-typing reagents may be preserved in the liquid or in the dried state. Liquid reagents shall be kept at a temperature not above –70 °C, dried reagents at a temperature not above +4 °C.
Thawing and refreezing of the reagents during the period of storage must be avoided as much as possible.
Dried reagents shall be kept in an atmosphere of inert gas or in vacuo in the container in which they were dried and which shall be closed so as to exclude moisture. A dried reagent must not lose more than 0.5% of its weight when tested by further drying over phosphorous pentoxide at a pressure not exceeding 0.02mm of mercury for 24 hours.
Reagents shall be prepared with aseptic precautions and shall be free from bacterial contamination. In order to prevent bacterial growth the producer may decide that an antiseptic and/or antibiotic shall be added to the reagent. In such cases the reagent must still fulfil the requirements for specificity and potency in the presence of the added substance.
The above also applies to any other additives such as anticoagulants. Reagents, after thawing or after reconstitution, should be transparent and should not contain any sediment, gel or visible particles.
4. Stability and expiry date
Each reagent, when kept under the appropriate conditions of storage, should retain the requisite properties for at least one year.
The expiry date of a reagent in the liquid state as given on the label shall be not more than one year from the date of the last satisfactory potency test. The expiry date can be extended for further periods of one year by repetition of potency tests.
The expiry date of reagents in the dried form as given on the label shall be in accordance with evidence obtained from experiments on stability.
5. Dispensing and volume
Tissue-typing reagents shall be dispensed in such a way and in such volumes that the reagent in one container is sufficient for the performance of tests with positive and negative control corpuscles in addition to the performance of tests with the unknown corpuscles.
The volume in one container shall be such that the contents can, if necessary, be used for the performance of the appropriate tests for potency as described in this Protocol.
6. Records and samples
Written records shall be kept by the producing laboratory of all steps in the production and control of tissue-typing reagents. Adequate samples of all reagents issued shall be retained by the laboratory, until it can be reasonably assumed that the batch is no longer in use.
7. Shipment
Frozen reagents must be shipped in such fashion that they remain frozen until arrival. Care must be taken to protect reagents against inactivation by the entry of CO2. Dried reagents may be shipped at ambient temperatures.
8. Labels, leaflets and certificates
Two labels, one printed in English and one in French, in black on white paper, shall be affixed to each final container and shall contain the following information:
(a) name and address of producer,
(b) name of the reagent as it appears in the heading of the relevant specification,
(c) name and amount of antiseptic and/or antibiotic, if present, or indication of absence,
(d) the volume or, when the reagent is dried, the volume and composition of the fluid needed for reconstitution,
(e) expiry date,
(f) batch number,
(g) conditions of storage,
(h) results of the test for HB-Ag.
Moreover, these labels or the labels of the carton enclosing several final containers, or the leaflet accompanying the containers shall contain the following information:
(a) full name and address of producer,
(b) name of the reagent as it appears in the heading of the relevant specification,
(c) the volume or, when the reagent is dried, the volume and composition of the fluid needed for reconstitution,
(d) date of last potency test,
(e) expiry date (if any),
(f) batch number,
(g) adequate description of the method of use recommended by the producer,
(h) conditions of storage of unopened ampoules and precautions to be taken after opening,
(i) exact composition, including antiseptic and/or antibiotic if any,
(j) statement whether the product contains or does not contain material of human origin.
Each consignment shall be accompanied by a certificate as provided in Article 4 of the Agreement and the Annex to the present Protocol. Examples of label and leaflet are attached to the present Protocol.
SPECIFIC PROVISIONS1
1 To be completed under Article 4, paragraph 4, of the European Agreement on the Exchange of Tissue-typing Reagents.
ADDITIONAL PROTOCOL
TO THE EUROPEAN AGREEMENT ON THE EXCHANGE OF TISSUE-TYPING REAGENTS
The member States of the Council of Europe signatory to the European Agreement on the Exchange of Tissue-typing Reagents (hereafter called the “Agreement”) and to this Additional Protocol,
Having regard to the provisions of Article 5, paragraph 1 of the Agreement, according to which “the Contracting Parties shall take all necessary measures to exempt from all import duties the tissue-typing reagents placed at their disposal by the other Parties”;
Considering that so far as the member States of the European Economic Community are concerned, the undertaking to grant this exemption falls within the competence of the Community, which possesses the necessary powers in this respect by virtue of the Treaty which instituted it;
Considering therefore that for the purpose of the implementation of Article 5, paragraph 1 of the Agreement, it is necessary for the European Economic Community to be able to become a Contracting Party to the Agreement,
Have agreed as follows:
Article 1
The European Economic Community may become a Contracting Party to the Agreement by signing it.
Article 2
This Additional Protocol shall be open to signature by the States signatory to the Agreement, which may become Parties to the Additional Protocol in accordance with the procedure laid down in Article 7 of the Agreement.
Article 3
No State may become a Contracting Party to the Agreement without at the same time becoming a Contracting Party to this Additional Protocol, which forms an integral part of the Agreement.
Article 4
This Additional Protocol shall enter into force on the same date as the Agreement.
Article 5
The Secretary General of the Council of Europe shall notify the member States of the Council and the European Economic Community of:
a. any signature of this Additional Protocol;
b. the deposit of any instrument of ratification or acceptance;
c. the date of entry into force of this Additional Protocol.
In witness whereof, the undersigned, being duly authorised thereto, have signed this Protocol.
Done at Strasbourg, this 24th day of June 1976, in English and in French, both texts being equally authoritative, in a single copy which shall remain reposited in the archives of the Council of Europe. The Secretary General of the Council of Europe shall transmit certified copies to each of the signatory and acceding Parties.
EVROPSKI SPORAZUM
O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV
Države članice Sveta Evrope, podpisnice tega sporazuma, so se
glede na to, da reagenti za tipizacijo tkiv niso na voljo v neomejenih količinah,
glede na to, da je nadvse zaželeno, da si države v duhu evropske solidarnosti med seboj pomagajo pri oskrbi z reagenti za tipizacijo tkiv, če se pokaže potreba po njih,
glede na to, da je taka medsebojna pomoč možna le, če glede lastnosti in uporabe reagentov za tipizacijo tkiv veljajo pravila, ki jih skupaj določijo države članice, in če se pri uvozu odobrijo ustrezne olajšave in oprostitve,
sporazumele o naslednjem:
1. člen
1. V tem sporazumu se izraz “reagenti za tipizacijo tkiv” nanaša na reagente človeškega, živalskega, rastlinskega in drugega izvora, ki se uporabljajo za tipizacijo tkiv.
2. Določbe 2. do 6. člena tega sporazuma se uporabljajo tudi za celice z znanimi antigeni, ki so namenjene raziskovanju reagentov za tipizacijo tkiv.
2. člen
Pogodbenice se zavezujejo, da dajo reagente za tipizacijo tkiv na voljo drugim pogodbenicam, ki jih potrebujejo, če imajo dovolj zalog za lastne potrebe, in da zaračunajo le stroške zbiranja, predelave in prevoza teh snovi ter morebitne stroške njihovega nakupa.
3. člen
Reagenti za tipizacijo tkiv se dajo drugim pogodbenicam na voljo pod pogojem, da z njimi ne ustvarjajo dobička, da jih uporabljajo izključno v medicinske in znanstvene, t. j. nekomercialne namene, in da jih dobavljajo le laboratorijem, ki so jih določile njihove vlade v skladu s 6. členom tega sporazuma.
4. člen
1. Pogodbenice potrjujejo, da upoštevajo določbe protokola k temu sporazumu.
2. Izpolnjujejo tudi pravila, ki so jih sprejele glede na mednarodno standardizacijo na tem področju.
3. Vsem pošiljkam reagentov za tipizacijo tkiv mora biti priložen certifikat, ki potrjuje, da so bili pripravljeni v skladu s specifikacijami v protokolu. Ta certifikat je narejen po vzorcu iz priloge k protokolu.
4. Protokol in njegova priloga sta upravni dogovor, zato ju lahko vlade pogodbenic tega sporazuma spremenijo ali dopolnijo.
5. člen
1. Pogodbenice ukrenejo vse potrebno, da so reagenti za tipizacijo tkiv, ki jim jih dajo na voljo druge pogodbenice, oproščeni vseh uvoznih dajatev.
2. Prav tako ukrenejo vse potrebno, da omogočijo hitro dobavo teh snovi po najkrajši poti prejemnikom, omenjenim v 3. členu tega sporazuma.
6. člen
Pogodbenice si po generalnem sekretarju Sveta Evrope pošljejo seznam državnih in/ali območnih referenčnih laboratorijev, ki so pooblaščeni za izdajo certifikatov, določenih v 4. členu tega sporazuma, in za distribucijo uvoženih reagentov za tipizacijo tkiv.
7. člen
1. Ta sporazum je na voljo za podpis državam članicam Sveta Evrope, ki lahko postanejo njegove pogodbenice s:
a) podpisom brez pridržka glede ratifikacije ali sprejetja ali
b) podpisom s pridržkom glede ratifikacije ali sprejetja, ki mu sledi ratifikacija ali sprejetje.
2. Listine o ratifikaciji ali sprejetju se deponirajo pri generalnem sekretarju Sveta Evrope.
8. člen
1. Ta sporazum začne veljati en mesec po dnevu, ko tri članice Sveta v skladu z določbami 7. člena tega sporazuma postanejo pogodbenice sporazuma.
2. Za vsako državo članico, ki pozneje podpiše sporazum brez pridržka glede ratifikacije ali sprejetja ali ki ga ratificira ali sprejme, začne sporazum veljati en mesec po dnevu podpisa ali deponiranja listine o ratifikaciji ali sprejetju.
9. člen
1. Odbor ministrov Sveta Evrope lahko po začetku veljavnosti tega sporazuma povabi katero koli državo nečlanico, da pristopi k temu sporazumu.
2. Pristop začne veljati en mesec po dnevu deponiranja listine o pristopu pri generalnem sekretarju Sveta Evrope.
10. člen
1. Pogodbenica lahko ob podpisu ali deponiranju svoje listine o ratifikaciji, sprejetju ali pristopu določi ozemlje ali ozemlja, za katera se ta sporazum uporablja.
2. Pogodbenica lahko ob deponiranju svoje listine o ratifikaciji, sprejetju ali pristopu ali kadar koli pozneje z izjavo generalnemu sekretarju Sveta Evrope razširi uporabo tega sporazuma na vsako drugo ozemlje ali ozemlja, navedena v izjavi, za katerih mednarodne odnose je odgovorna ali v imenu katerih je pooblaščena za odločanje.
3. Vsaka izjava, dana na podlagi prejšnjega odstavka, je lahko po postopku, ki ga določa 11. člen tega sporazuma, umaknjena za katero koli ozemlje, navedeno v taki izjavi.
11. člen
1. Vsaka pogodbenica lahko odpove ta sporazum z uradnim obvestilom generalnemu sekretarju Sveta Evrope.
2. Odpoved začne veljati šest mesecev po dnevu, ko generalni sekretar prejme tako uradno obvestilo.
12. člen
Generalni sekretar Sveta Evrope uradno obvesti države članice Sveta in vsako državo, ki je pristopila k temu sporazumu, o:
a) vsakem podpisu brez pridržka glede ratifikacije ali sprejetja;
b) vsakem podpisu s pridržkom glede ratifikacije ali sprejetja;
c) deponiranju vsake listine o ratifikaciji, sprejetju ali pristopu;
d) vsakem datumu začetka veljavnosti tega sporazuma po določbah 8. člena;
e) vsaki izjavi, prejeti na podlagi določb drugega in tretjega odstavka 10. člena;
f) vsakem uradnem obvestilu, prejetem na podlagi določb 11. člena, in datumu začetka veljavnosti odpovedi;
g) vsaki spremembi ali dopolnitvi protokola in njegove priloge na podlagi četrtega odstavka 4. člena tega sporazuma.
V potrditev tega so podpisani, ki so bili za to pravilno pooblaščeni, podpisali ta sporazum.
Sestavljeno v Strasbourgu 17. septembra 1974 v angleškem in francoskem jeziku, pri čemer sta besedili enako verodostojni, v enem izvodu, ki se hrani v arhivu Sveta Evrope. Generalni sekretar Sveta Evrope pošlje overjene kopije vsaki državi podpisnici in vsaki državi, ki je pristopila k temu sporazumu.
P R O T O K O L
K SPORAZUMU
SPLOŠNE DOLOČBE
1. Specifičnost
A. Reagenti za tipizacijo tkiv, ki jih uporabljamo pri limfocitotoksičnih reakcijah
Reagenti morajo, kadar se uporabljajo skladno z metodo, ki jo priporoča proizvajalec, reagirati z vsemi limfociti, za katere je znano, da vsebujejo antigen ali antigene, ki ustrezajo specifičnostim, navedenim na etiketi. Ne smejo reagirati z nobeno celico, za katero je znano, da ne vsebuje tega antigena (teh antigenov).
Kadar se ti reagenti uporabljajo skladno z metodo, ki jo priporoča proizvajalec, ne smejo povzročati motečih seroloških pojavov, kot sta:
a) prozonski učinek,
b) antikomplementarnost.
B. Reagenti za tipizacijo tkiv, ki jih uporabljamo pri postopkih fiksacije komplementa na trombocite
Reagenti morajo, kadar se uporabljajo skladno z metodo, ki jo priporoča proizvajalec, povzročiti fiksacijo komplementa na vse trombocite, za katere je znano, da vsebujejo antigen ali antigene, ki ustrezajo specifičnostim, navedenim na etiketi. Ne smejo povzročiti fiksacije komplementa na trombocite, za katere je znano, da ne vsebujejo tega antigena (teh antigenov).
Kadar se reagenti uporabljajo skladno z metodo, ki jo priporoča proizvajalec, ne smejo povzročati motečih seroloških pojavov, kot sta:
a) prozonski učinek,
b) antikomplementarnost.
2. Jakost
A. Reagenti za tipizacijo tkiv, ki jih uporabljamo pri limfocitotoksičnih reakcijah
Titer reagenta določimo z zaporednimi dvakratnimi razredčitvami reagenta, ki ga preverjamo, v inaktiviranem serumu AB dajalca, ki nima antigena ali antigenov, ki ustrezajo protitelesu ali protitelesom v reagentu; dajalec seruma prav tako ne sme biti imuniziran proti tkivnim antigenom s transfuzijo, nosečnostjo ali kako drugače. Vsako razredčino testiramo z limfociti, za katere je znano, da vsebujejo enak antigen ali enake antigene, kot jih prepozna reagent, z uporabo metode, ki jo priporoča proizvajalec. Titer je recipročna vrednost števila, ki predstavlja največjo razredčitev seruma, v kateri opazimo nedvoumno pozitivno reakcijo; pri izračunu razredčitve ne upoštevamo volumna celične suspenzije ali drugega dodatka v skupnem volumnu.
B. Reagenti za tipizacijo tkiv, ki jih uporabljamo pri postopkih fiksacije komplementa na trombocite
Titer reagenta določimo z zaporednimi dvakratnimi razredčitvami preizkušanega reagenta z 10% inaktiviranega seruma AB v veronalnem pufru. Vsak serum nato testiramo s trombociti, za katere je znano, da izražajo antigene, ki ustrezajo protitelesom v reagentu, z uporabo metode, ki jo priporoča proizvajalec. Titer je recipročna vrednost števila, ki predstavlja največjo razredčitev seruma, v kateri še opazimo nedvoumno pozitivno reakcijo; pri izračunu razredčitve ne upoštevamo volumna celične suspenzije ali drugega dodatka v skupnem volumnu.
Druge določbe, ki se nanašajo na reagente za tipizacijo tkiv, ki jih uporabljamo v limfocitotoksičnih reakcijah ter v postopku fiksacije komplementa na trombocite:
3. Shranjevanje
Reagente za tipizacijo tkiv lahko hranimo v tekočem ali dehidriranem stanju. Tekoče reagente hranimo pri temperaturi, ki ne presega –70 °C, dehidrirane reagente pa pri temperaturi, ki ne presega +4 °C.
Med hranjenjem pri nizkih temperaturah se moramo čim bolj izogibati odmrzovanju in ponovnemu zamrzovanju reagentov.
Dehidrirane reagente shranjujemo v atmosferi inertnega plina ali v vakuumu v steklenički, v kateri so bili dehidrirani in ki mora biti zaprta tako, da se prepreči prodiranje vlage. Dehidrirani reagent ne sme izgubiti več kot 0,5% svoje mase po dodatnem 24-urnem sušenju ob prisotnosti fosforjevega pentoksida pri tlaku, ki ne presega 0,02 mm živega srebra.
Reagente pripravljamo v aseptičnih pogojih in ne smejo biti bakteriološko kontaminirani. Za preprečitev rasti bakterij se lahko proizvajalec odloči, da se reagentu doda antiseptik in/ali antibiotik. V prisotnosti dodane učinkovine mora reagent še vedno izpolnjevati zahteve glede predpisane specifičnosti in jakosti.
Zgoraj zapisano velja tudi za vse druge dodatke, na primer antikoagulante. Reagenti morajo biti po odmrznitvi ali rekonstituciji prozorni in ne smejo vsebovati nobene usedline, gela ali vidnih delcev.
4. Stabilnost in rok uporabnosti
Vsak reagent, ki je primerno shranjen, mora obdržati zahtevane lastnosti najmanj eno leto.
Rok uporabnosti reagenta v tekočem stanju, ki je naveden na etiketi, ne sme biti daljši od enega leta od datuma zadnjega uspešnega preverjanja njegove jakosti. Po ponovnem preverjanju jakosti lahko rok njegove uporabnosti podaljšamo še za eno leto.
Rok uporabnosti dehidriranih reagentov, ki je naveden na etiketi, mora biti v skladu z ugotovitvami preizkusov njihove stabilnosti.
5. Odmerjanje in volumen
Reagente za tipizacijo tkiv pripravimo in razdelimo tako in v takšnih volumnih, da količina reagenta v posamezni steklenički poleg izvedbe testov z neznanimi krvnimi telesci zadošča za izvedbo preizkusa s pozitivnimi in negativnimi kontrolnimi krvnimi telesci.
Volumen posamezne stekleničke mora omogočati, če je to potrebno, da se vsebina uporabi za ustrezno preverjanje jakosti, opisano v tem protokolu.
6. Dokumentacija in vzorci
Laboratorij, ki proizvaja in preverja reagente za tipizacijo tkiv, hrani pisno dokumentacijo o vseh fazah proizvodnje in kontrole. Laboratorij hrani ustrezne vzorce vseh izdanih reagentov tako dolgo, da lahko utemeljeno domneva, da serija ni več v uporabi.
7. Pošiljke
Zamrznjene reagente moramo pošiljati tako, da ostanejo zamrznjeni do prihoda na cilj. Pri tem moramo poskrbeti za zaščito reagentov pred inaktivacijo zaradi vdora CO2. Dehidrirane reagente lahko pošiljamo pri sobnih temperaturah.
8. Etikete, kontrolni listi in certifikati
Na vsaki končni steklenički sta nalepljeni dve etiketi, ena natisnjena v angleškem in druga v francoskem jeziku, v črni barvi na belem papirju, z naslednjimi podatki:
a) ime in naslov proizvajalca;
b) ime reagenta, kot je navedeno v naslovu ustrezne specifikacije;
c) ime in količina antiseptika in/ali antibiotika, če sta prisotna, oziroma navedba o njuni odsotnosti;
d) volumen, ali če je reagent dehidriran, volumen in sestava tekočine, ki je potrebna za njegovo rekonstitucijo;
e) rok uporabnosti;
f) številka serije;
g) pogoji shranjevanja;
h) rezultat preizkusa na HB-Ag.
Te navedbe ali tiste, nalepljene na kartonsko škatlo, v kateri je več posameznih stekleničk, ali kontrolni list, priložen stekleničkam, morajo poleg omenjenega vsebovati še naslednje podatke:
a) polno ime in naslov proizvajalca;
b) ime reagenta, kot je navedeno v naslovu ustrezne specifikacije;
c) volumen, ali če je reagent dehidriran,volumen in sestava tekočine, ki je potrebna za njegovo rekonstitucijo;
d) datum zadnjega preverjanja jakosti;
e) rok uporabnosti (če obstaja);
f) številka serije;
g) ustrezen opis načina uporabe, ki ga priporoča proizvajalec;
h) pogoji skladiščenja neodprtih ampul in varnostni ukrepi, ki jih je treba upoštevati po odprtju ampul;
i) natančna sestava, vključno z navedbo antiseptika in/ali antibiotika, če sta dodana;
j) izjava o tem, ali izdelek vsebuje snovi človeškega izvora ali ne.
Vsaki pošiljki je priložen certifikat, kot je navedeno v 4. členu sporazuma in v prilogi k temu protokolu. Vzorca etikete in kontrolnega lista sta priložena temu protokolu.
POSEBNE DOLOČBE1
1 Izpolnjen mora biti po četrtem odstavku 4. člena Evropskega sporazuma o izmenjavi reagentov za tipizacijo tkiv.
DODATNI PROTOKOL
K EVROPSKEMU SPORAZUMU O IZMENJAVI REAGENTOV ZA TIPIZACIJO TKIV
Države članice Sveta Evrope, podpisnice Evropskega sporazuma o izmenjavi reagentov za tipizacijo tkiv (v nadaljevanju “sporazum”) in dodatnega protokola, so se
ob upoštevanju določb prvega odstavka 5. člena sporazuma, po katerem “pogodbenice ukrenejo vse potrebno, da so reagenti za tipizacijo tkiv, ki jim jih dajo na voljo druge pogodbenice, oproščeni vseh uvoznih dajatev”,
glede na to, da je za odobritev te oprostitve državam članicam Evropske gospodarske skupnosti pristojna Skupnost, ki je za to pooblaščena na podlagi ogodbe, s katero je bila ustanovljena,
glede na to, da je za izvajanje prvega odstavka 5. člena sporazuma potrebno, da Evropska gospodarska skupnost lahko postane pogodbenica sporazuma,
sporazumele o naslednjem:
1. člen
Evropska gospodarska skupnost lahko postane pogodbenica sporazuma, tako da ga podpiše.
2. člen
Ta dodatni protokol je na voljo za podpis državam članicam sporazuma, ki lahko postanejo pogodbenice dodatnega protokola v skladu s postopkom, določenim v 7. členu sporazuma.
3. člen
Nobena država ne more postati pogodbenica sporazuma, ne da bi hkrati postala pogodbenica tega dodatnega protokola, ki je sestavni del sporazuma.
4. člen
Ta dodatni protokol začne veljati istega dne kot sporazum.
5. člen
Generalni sekretar Sveta Evrope uradno obvesti države članice Sveta Evrope in Evropsko gospodarsko skupnost o:
a) vsakem podpisu tega dodatnega protokola,
b) deponiranju vsake listine o ratifikaciji ali sprejetju,
c) datumu začetka veljavnosti tega dodatnega protokola.
V potrditev tega so podpisani, ki so bili za to pravilno pooblaščeni, podpisali ta protokol.
Sestavljeno v Strasbourgu 24. junija 1976 v angleškem in francoskem jeziku, pri čemer sta besedili enako verodostojni, v enem izvodu, ki se hrani v arhivu Sveta Evrope. Generalni sekretar Sveta Evrope pošlje overjene kopije vsaki podpisnici in državam, ki so pristopile.
3. člen
Za izvajanje sporazuma, protokola in dodatnega protokola skrbita Ministrstvo za finance in Ministrstvo za zdravstvo.
4. člen
Ta zakon začne veljati naslednji dan po objavi v Uradnem listu Republike Slovenije – Mednarodne pogodbe.
Št. 500-02/00-6/1
Ljubljana, dne 19. julija 2000
Predsednik
Državnega zbora
Republike Slovenije
Janez Podobnik, dr. med. l. r.
