ISO INTERNATIONAL STANDARD 20688-1 First edition 2020-02 Biotechnology - Nucleic acid synthesis - Part 1: Requirements for the production and quality control of synthesized oligonucleotides Biotechnologie-Synthesedes acides nucleiques- Partie 1: Exigences relatives a la production et au controle qualite des oligonucléotidessynthetisés Reference number IS0 20688-1:2020(E) ISO @IS02020 IS020688-1:2020(E) COPYRIGHTPROTECTEDDOCUMENT ISO2020 All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written permission. Permission can be requested from either IsO at the address below or IsO's member body in the country of the requester: ISO copyright office CP 40i : Ch. de Blandonnet 8 CH-1214 Vernier, Geneva Phone: +4122.749 0111 Fax: +41 22 749 09 47 Email:[email protected] Website: www.iso.org Published in Switzerland ii IS02020-Allrights reserved IS020688-1:2020(E) Contents Page Foreword iv Introduction V 1 Scope. .1 2 Normativereferences .1 3 Terms and definitions. .1 4 Design and selection of suitable oligonucleotides that are fit for purpose .2 5 General quality management requirements .2 5.1 Generalrequirements 2 5.2 Oligonucleotide grading 3 5.3 3 Control of documents 5.4 Qualitymanagementsystem. 3 5.5 Personnel and training 3 5.6 Safetycontrol 3 6 Resource management .3 7 Requirementsforproductionprocess 7.1 General 4 7.2 Oligonucleotide synthesis 4 7.3 Purification 4 7.4 Qualitycontrolinspection 4 7.5 Drying 5 7.6 Formulation. 5 8 Requirements for quality control process 5 8.1 5 General 8.2 Validation and verification of analytical methods 55 8.3 Identityand purity 8.3.1 Identityofthebasesequence 55 8.3.2 Purity 8.3.3 Impurity. 6 8.4 Quantity 6 8.4.1 General. 6 8.4.2 Concentration. 6 8.4.3 Mass 7 8.5 Molar mass and/or base length 7 Melting temperature (Tm) .8 8.6 8.7 Report. 8 8.8 Verificationofcorrectiveactionandimprovements 9 9 Additional requirements for synthetic oligoribonucleotides (RNA) .9 AnnexA(informative)Processchecklist .10 Annex B (informative) List of equipment and devices and their control standards .12 AnnexC (informative)Calculationofmolarmass andmolarnumbers. .14 Annex D (informative) Verification of oligonucleotide sequences using mass analysis .17 Annex E (informative) Accuracy control of measurement instrument with certified .23 referencematerials-Examples. Annex F (informative) Calculation method of Tm values .26 .28 Bibliography @ IS0 2020 - All rights reserved iii