- Email: [email protected]
Model format for a vaccine stability report and software solutions
Available online at www.sciencedirect.com
Biologicals 37 (2009) 417e420 www.elsevier.com/locate/biologicals
Model format for a vaccine stability report and software solutions Jinho Shin a,*,1, James Southern b, Timothy Schofield c,2 a
Department of Immunization, Vaccines and Biologicals, World Health Organization, 20, Avenue Appia, CH-1211 Geneva 27, Switzerland b 14 Mariners Close, Simons Town, South Africa c Merck Research Laboratories, West Point, PA, USA Received 14 July 2009; accepted 7 August 2009
Abstract A session of the International Association for Biologicals Workshop on Stability Evaluation of Vaccine, a Life Cycle Approach was devoted to a model format for a vaccine stability report, and software solutions. Presentations highlighted the utility of a model format that will conform to regulatory requirements and the ICH common technical document. However, there need be flexibility to accommodate individual company practices. Adoption of a model format is premised upon agreement regarding content between industry and regulators, and ease of use. Software requirements will include ease of use and protections against inadvertent misspecification of stability design or misinterpretation of program output. Ó 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. Keywords: Vaccine stability; Report; Model format; Common technical document; Software requirements
1. Introduction A session of the International Association for Biologicals (IABS) Workshop on Stability Evaluation of Vaccines, a Life Cycle Approach was devoted to a model format for a vaccine stability report and software solutions. The goals of the session were to offer workshop participants an opportunity to provide feedback to the World Health Organization (WHO) regarding the need for and content of a model format and to explore opportunities to develop software in support of the analyses promoted in the guideline. The session was organized into three parts: (1) a presentation by Dr. Jinho Shin of WHO on a model format; (2) discussion from Dr. James Southern, Adviser to the Medicines Control Council of South Africa on the proposed format; and (3)
* Corresponding author. Tel.: þ41 22 791 3890; fax: þ41 22 791 4971. E-mail addresses: [email protected] (J. Shin), [email protected] (J. Southern), [email protected] (T. Schofield). 1 The authors alone are responsible for the views expressed in this publication and it does not necessarily represent the decisions or the stated policy of the World Health Organization and/or the institutions to which the authors are affiliated or represent. 2 Present address: GlaxoSmithKline, 2301 Renaissance Blvd., King of Prussia, PA 19406, USA. Tel.: þ1 610 787 3194.
a presentation by Mr. Timothy Schofield the representative of The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) on software solutions. 2. Model format for stability report e progress and the way forward The objective of developing a model format for reporting stability studies is to assist regulators or file reviewers in evaluating vaccine stability studies. Previously a draft format of a summary protocol for stability testing of intermediate products and final products was proposed as the appendices to the WHO Guidelines on stability evaluation of vaccines [1,2]. This October 2006 draft format, with main focus on stability indicating parameters and recording of test results, was discussed at the 57th meeting of the Expert Committee on Biological Standardization in 2006, but its acceptance was deferred pending further improvement in a way that would accommodate various product-specific issues on stability and not overload manufacturers by avoiding potential unnecessary duplication with other existing formats such as the summary batch release protocol. In April 2008, another draft model format was prepared for comments from the participants of a WHO/KFDA (Korea Food & Drug Administration) workshop on stability evaluation of
1045-1056/09/$36.00 Ó 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.biologicals.2009.08.007
418
J. Shin et al. / Biologicals 37 (2009) 417e420
vaccines held in Seoul. This April 2008 draft format was structured to categorize different stability studies based on study goal, such as i) to propose shelf-life and storage conditions for intermediates and/or final products; ii) to report post-licensure stability monitoring results; and iii) to support changes/variations. At the workshop, the background and the objective of developing a model report format was presented and it was considered important to develop a model format for inclusion in further series of vaccine stability workshops. Also, a drafting group was formed at the April 2008 Seoul workshop. The drafting group, communicating by e-mail exchange after the April 2008 workshop, favored the idea that the content of the model format should be shaped in a more general way no matter what the goal of stability studies are. For instance, the overall content can be a study report style, e.g. including the headings of objective, responsibilities, product information, study design, methods, acceptance criteria, results, discussion, and conclusion. At the October 2008 IABS workshop, Dr. James Southern and Mr. Tim Schofield further provided their thoughts on the scope and analysis of data for the model stability report format. The ongoing plan is to update the existing format considering comments received at the IABS workshop and then go through a further round of consultation. The finally agreed version of the format will be subject to the ECBS review process for adoption as an appendix to the already approved guidelines on stability evaluation of vaccines as previously recommended by the Committee. 3. Thoughts on the WHO model format stability report A standardized format for the provision of information on the stability of a vaccine will facilitate the regulatory review and approval of applications. The full application dossier will contain the information on the vaccine stability testing program and the outcomes; however, a summary that condenses this information and the conclusions, cross-referenced to the full information contained in the dossier, will further facilitate regulatory review. Where applications are in the ICH Common Technical Document format, the information is provided in the Quality Overall Summary, ICH CTD 2.3.S.7 that will contain a summarized description of the stability studies of the Drug Substance (Primary Production Lot for vaccines and/or Intermediates) and ICH CTD 2.3.P.8 that will contain a summarized description of the stability studies on Drug Product (Final Product Vaccine), each including:
In such cases, the report should be set out to provide a clear indication to the regulatory reviewers of the scope of the studies and the outcomes. The report should be cross-referenced to the relevant parts of the full dossier. Analysis of the results of stability studies including determination of degradation rates at different temperature and storage conditions, and the assignment of shelf-life require the use of appropriate and validated statistical methodologies. If there is general agreement on the methods for statistical analysis, this will be of value for applicants and regulatory authorities. The proposed WHO vaccine stability report format could include: I. Reference to WHO guidelines. II. Introduction, describing the nature of the vaccine; rationale for the stability testing program; methods used; and the scope of the report. III. Stability of intermediates: Determination of the stability-degradation rate and establishment of shelf-life. IV. Stability of final product: Determination of the stability-degradation rate and establishment of shelf-life, in the context of release potencies. V. Stressed stability tests: A. Possible program of stability over a range of temperatures e Arrhenius calculation. B. Develop a model of expected temperature excursions. C. Calculate shelf-life after modeled temperature excursion/s. D. Issues that may be considered, numbers of batches, slope consistency, shelf-life). VI. Justification of the packaging and the controls on transport of intermediates and bulks. VII. Justification of proposed category of vaccine vial monitor as appropriate [3]. The report of each of the above sections should consist of a brief introduction indicating how each fits with the Stability Testing Program and a graphical representation of the results, accompanied by a caption setting out the specific conditions for the test. Multiple batches may be superimposed on a single graph if it simplifies interpretation. There should be consideration of the different forms of novel vaccines and whether the stability test program requires modification in special cases (e.g. naked DNA vaccines). 4. Software solutions
Studies undertaken; Results and conclusions; Post-approval stability protocol; Tabulated summary of stability results with graphical representation where appropriate.
The proposed WHO stability report has value where applications for registration are not in the ICH CTD format.
A standard format for a vaccine stability report will be more attractive to industry and regulators if three conditions are met: (1) the content of the stability report satisfies both industry and regulators; (2) industry and regulatory authorities throughout the world accept the format over previously established designs; and (3) stability information can be easily assembled into the report.
J. Shin et al. / Biologicals 37 (2009) 417e420
The content of the stability report is clearly laid out in Guidance for the Industry M4Q: The CTD e Quality [4]. For drug substance, it specifies, ‘‘This section should include a summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions, the proposed storage conditions, and the retest date or shelf-life, where relevant. A tabulated summary of the stability results from 3.2.S.7.3 of Module 3, with graphic representation where appropriate, should be imported directly,’’ and for drug product, ‘‘A summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions of the stability studies and analysis of data should be included. Conclusions regarding storage conditions and shelf-life and, if applicable, in-use storage conditions and shelf-life should be given. A tabulated summary of the stability results from 3.2.P.8.3, with graphic representation where appropriate, should be imported directly.’’ Thus, a standard stability report should include (1) a brief description of the study design, including batch identification, storage temperatures, time points, and stability indicating procedures; (2) intended conditions for storage and use of the vaccine; (3) tabular and graphical summaries of the data; and (4) analyses and conclusions supporting shelf-life and/or release limits. Historically, some or all of these elements have been reported by larger vaccine manufacturers to regulatory authorities. Vaccine manufacturers with a history of licensing products worldwide have instituted internal practices of data management, analysis, and reporting. Smaller companies without marketed products will develop strategies similar to their more mature counterparts. Simple descriptions of study design and proposed storage conditions, together with data listings sometimes supported by graphics, will be the foundation upon which manufacturers will draw their conclusions. However, this limited submission of stability experience will not satisfy the goal of the WHO Guideline on Stability Evaluation of Vaccines [2]. The data should be analyzed according to practices outlined in ICH Q1E [5] and the WHO Guideline in order to effectively establish shelf-life of the vaccine and manage distribution though a proper calculation of release properties. In concert with the 1987 FDA Guideline For Submitting Documentation For The Stability Of Human Drugs And Biologics, the agency provided a SASÒ program for establishment of product shelf-life using methods which have subsequently been described in ICH Q1E. While that guideline was withdrawn, FDA still promotes the use of its programs and has made them available on its website (http://www.fda.gov/cder/ sas/index.htm). To use those programs, however, one must have the SASÒ system installed on their computer, and the statistical acumen to manipulate and interpret the results of the program. The FDA SASÒ program performs calculations for only the simplest stability design, in which several lots are tested independently across a range of stability intervals. Alternative design commonly used in industry, such as studies with multiple images (e.g., vials and syringes) or studies in which all lots are tested in the same assay, require specialized statistical treatment. In addition, the FDA SASÒ program does not provide protection against violations of statistical
419
assumptions (e.g., linearity of stability response, outliers, normality of data, etc.), or calculate release limits. The methods described in the withdrawn FDA guideline and in ICH have also been programmed into other popular statistical software packages, as well as into many stability laboratory information management systems (LIMS). Given the desire for a standardized stability report format, with minimal disruption to internal practices of large vaccine manufacturers using their own data management and reporting conventions, and the need to accommodate various designs and to interrogate the data for statistical assumptions, a software solution might be organized among statisticians, stability analysts, and regulators, through a software developer that is invested in pharmaceutical applications. Ideally the software developer should be an interdisciplinary team of experts in laboratory analyses and statistics and should be familiar with current guidelines regulating pharmaceutical stability and software development. The software might be packaged to be run locally in the stability laboratory or by the regulator, or served over the internet through either a yearly license, or on a per use basis. In addition, ideally the vendor should be capable of offering technical and statistical support to its users. The multidisciplinary team might work with the software developer to achieve the following high level requirements for stability evaluation of vaccines: A user friendly front end to accurately characterize the stability study design and to enter data into the design. Capabilities to assess statistical assumptions and perform analyses appropriate to the specific study design. Determination of release requirements as well as shelflife. Data displays both in the form of tables and graphics, which depict the raw data together with statistical elements consistent with the formal analysis. Clearly expressed conclusions regarding data handling, assumptions, statistical tests, and expiry/release determinations. A report format that is consistent with a standard agreed upon by industry and regulators. Timing of a software solution should be coordinated with other implementation activities, including further workshops. Manufacturers and regulators must agree upon content and format, as well as adoption of the principles laid out in the WHO guideline prior to developing a software solution. Software roll out should be accompanied by training and the technical support available through commercial providers. Successful implementation of the WHO guideline depends upon collaboration among manufacturing and regulatory stability scientists and engineers, together with proper tools for assessing and analyzing vaccine stability data. Acknowledgement The authors thank the following members of a working group on model format for stability report formed at the WHO/KFDA
420
J. Shin et al. / Biologicals 37 (2009) 417e420
joint workshop on stability evaluation of vaccines in Seoul, April 2008: Dr. Silmara Cristiane da Silveira, Agencia Nacional de Vigilancia Sanitaria, Brası´lia, Brazil; Dr. Alda Laschi, representative of the International Federation of Pharmaceutical Manufacturers & Associations; and Dr Anil Sood, representative of the Developing Country Vaccine Manufacturers Network. References [1] WHO Expert Committee on Biological Standardization. Draft guidelines on stability evalution of vaccines. WHO/BS/06.2049, Geneva; 23e27 October 2006.
[2] WHO Expert Committee on Biological Standardization. Guidelines on stability evalution of vaccines. Adopted 2006. To be printed in WHO Technical Report Series. On-line access to an electronic version: http:// www.who.int/biologicals/publications/trs/areas/vaccines/stability/ Microsoft%20Word%20-%20BS%202049.Stability.final.09_Nov_06.pdf. [3] WHO-UNICEF. Quality of the cold chain: WHO-UNICEF policy statement on the use of vaccine vial monitors in immunization services. WHO/V&B/99.18 http://www.who.int/vaccines-documents/DocsPDF99/ www9928.pdf. [4] ICH M4Q(R1), The Common Technical Document For The Registration Of Pharmaceuticals For Human Use: Quality, current Step 4 version dated 12 September 2004 by the ICH Steering Committee. [5] ICH Q1E, Evaluation of Stability Data, current Step 4 version dated 6 February 2003 by the ICH Steering Committee.
Biologicals 37 (2009) 417e420 www.elsevier.com/locate/biologicals
Model format for a vaccine stability report and software solutions Jinho Shin a,*,1, James Southern b, Timothy Schofield c,2 a
Department of Immunization, Vaccines and Biologicals, World Health Organization, 20, Avenue Appia, CH-1211 Geneva 27, Switzerland b 14 Mariners Close, Simons Town, South Africa c Merck Research Laboratories, West Point, PA, USA Received 14 July 2009; accepted 7 August 2009
Abstract A session of the International Association for Biologicals Workshop on Stability Evaluation of Vaccine, a Life Cycle Approach was devoted to a model format for a vaccine stability report, and software solutions. Presentations highlighted the utility of a model format that will conform to regulatory requirements and the ICH common technical document. However, there need be flexibility to accommodate individual company practices. Adoption of a model format is premised upon agreement regarding content between industry and regulators, and ease of use. Software requirements will include ease of use and protections against inadvertent misspecification of stability design or misinterpretation of program output. Ó 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. Keywords: Vaccine stability; Report; Model format; Common technical document; Software requirements
1. Introduction A session of the International Association for Biologicals (IABS) Workshop on Stability Evaluation of Vaccines, a Life Cycle Approach was devoted to a model format for a vaccine stability report and software solutions. The goals of the session were to offer workshop participants an opportunity to provide feedback to the World Health Organization (WHO) regarding the need for and content of a model format and to explore opportunities to develop software in support of the analyses promoted in the guideline. The session was organized into three parts: (1) a presentation by Dr. Jinho Shin of WHO on a model format; (2) discussion from Dr. James Southern, Adviser to the Medicines Control Council of South Africa on the proposed format; and (3)
* Corresponding author. Tel.: þ41 22 791 3890; fax: þ41 22 791 4971. E-mail addresses: [email protected] (J. Shin), [email protected] (J. Southern), [email protected] (T. Schofield). 1 The authors alone are responsible for the views expressed in this publication and it does not necessarily represent the decisions or the stated policy of the World Health Organization and/or the institutions to which the authors are affiliated or represent. 2 Present address: GlaxoSmithKline, 2301 Renaissance Blvd., King of Prussia, PA 19406, USA. Tel.: þ1 610 787 3194.
a presentation by Mr. Timothy Schofield the representative of The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) on software solutions. 2. Model format for stability report e progress and the way forward The objective of developing a model format for reporting stability studies is to assist regulators or file reviewers in evaluating vaccine stability studies. Previously a draft format of a summary protocol for stability testing of intermediate products and final products was proposed as the appendices to the WHO Guidelines on stability evaluation of vaccines [1,2]. This October 2006 draft format, with main focus on stability indicating parameters and recording of test results, was discussed at the 57th meeting of the Expert Committee on Biological Standardization in 2006, but its acceptance was deferred pending further improvement in a way that would accommodate various product-specific issues on stability and not overload manufacturers by avoiding potential unnecessary duplication with other existing formats such as the summary batch release protocol. In April 2008, another draft model format was prepared for comments from the participants of a WHO/KFDA (Korea Food & Drug Administration) workshop on stability evaluation of
1045-1056/09/$36.00 Ó 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.biologicals.2009.08.007
418
J. Shin et al. / Biologicals 37 (2009) 417e420
vaccines held in Seoul. This April 2008 draft format was structured to categorize different stability studies based on study goal, such as i) to propose shelf-life and storage conditions for intermediates and/or final products; ii) to report post-licensure stability monitoring results; and iii) to support changes/variations. At the workshop, the background and the objective of developing a model report format was presented and it was considered important to develop a model format for inclusion in further series of vaccine stability workshops. Also, a drafting group was formed at the April 2008 Seoul workshop. The drafting group, communicating by e-mail exchange after the April 2008 workshop, favored the idea that the content of the model format should be shaped in a more general way no matter what the goal of stability studies are. For instance, the overall content can be a study report style, e.g. including the headings of objective, responsibilities, product information, study design, methods, acceptance criteria, results, discussion, and conclusion. At the October 2008 IABS workshop, Dr. James Southern and Mr. Tim Schofield further provided their thoughts on the scope and analysis of data for the model stability report format. The ongoing plan is to update the existing format considering comments received at the IABS workshop and then go through a further round of consultation. The finally agreed version of the format will be subject to the ECBS review process for adoption as an appendix to the already approved guidelines on stability evaluation of vaccines as previously recommended by the Committee. 3. Thoughts on the WHO model format stability report A standardized format for the provision of information on the stability of a vaccine will facilitate the regulatory review and approval of applications. The full application dossier will contain the information on the vaccine stability testing program and the outcomes; however, a summary that condenses this information and the conclusions, cross-referenced to the full information contained in the dossier, will further facilitate regulatory review. Where applications are in the ICH Common Technical Document format, the information is provided in the Quality Overall Summary, ICH CTD 2.3.S.7 that will contain a summarized description of the stability studies of the Drug Substance (Primary Production Lot for vaccines and/or Intermediates) and ICH CTD 2.3.P.8 that will contain a summarized description of the stability studies on Drug Product (Final Product Vaccine), each including:
In such cases, the report should be set out to provide a clear indication to the regulatory reviewers of the scope of the studies and the outcomes. The report should be cross-referenced to the relevant parts of the full dossier. Analysis of the results of stability studies including determination of degradation rates at different temperature and storage conditions, and the assignment of shelf-life require the use of appropriate and validated statistical methodologies. If there is general agreement on the methods for statistical analysis, this will be of value for applicants and regulatory authorities. The proposed WHO vaccine stability report format could include: I. Reference to WHO guidelines. II. Introduction, describing the nature of the vaccine; rationale for the stability testing program; methods used; and the scope of the report. III. Stability of intermediates: Determination of the stability-degradation rate and establishment of shelf-life. IV. Stability of final product: Determination of the stability-degradation rate and establishment of shelf-life, in the context of release potencies. V. Stressed stability tests: A. Possible program of stability over a range of temperatures e Arrhenius calculation. B. Develop a model of expected temperature excursions. C. Calculate shelf-life after modeled temperature excursion/s. D. Issues that may be considered, numbers of batches, slope consistency, shelf-life). VI. Justification of the packaging and the controls on transport of intermediates and bulks. VII. Justification of proposed category of vaccine vial monitor as appropriate [3]. The report of each of the above sections should consist of a brief introduction indicating how each fits with the Stability Testing Program and a graphical representation of the results, accompanied by a caption setting out the specific conditions for the test. Multiple batches may be superimposed on a single graph if it simplifies interpretation. There should be consideration of the different forms of novel vaccines and whether the stability test program requires modification in special cases (e.g. naked DNA vaccines). 4. Software solutions
Studies undertaken; Results and conclusions; Post-approval stability protocol; Tabulated summary of stability results with graphical representation where appropriate.
The proposed WHO stability report has value where applications for registration are not in the ICH CTD format.
A standard format for a vaccine stability report will be more attractive to industry and regulators if three conditions are met: (1) the content of the stability report satisfies both industry and regulators; (2) industry and regulatory authorities throughout the world accept the format over previously established designs; and (3) stability information can be easily assembled into the report.
J. Shin et al. / Biologicals 37 (2009) 417e420
The content of the stability report is clearly laid out in Guidance for the Industry M4Q: The CTD e Quality [4]. For drug substance, it specifies, ‘‘This section should include a summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions, the proposed storage conditions, and the retest date or shelf-life, where relevant. A tabulated summary of the stability results from 3.2.S.7.3 of Module 3, with graphic representation where appropriate, should be imported directly,’’ and for drug product, ‘‘A summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions of the stability studies and analysis of data should be included. Conclusions regarding storage conditions and shelf-life and, if applicable, in-use storage conditions and shelf-life should be given. A tabulated summary of the stability results from 3.2.P.8.3, with graphic representation where appropriate, should be imported directly.’’ Thus, a standard stability report should include (1) a brief description of the study design, including batch identification, storage temperatures, time points, and stability indicating procedures; (2) intended conditions for storage and use of the vaccine; (3) tabular and graphical summaries of the data; and (4) analyses and conclusions supporting shelf-life and/or release limits. Historically, some or all of these elements have been reported by larger vaccine manufacturers to regulatory authorities. Vaccine manufacturers with a history of licensing products worldwide have instituted internal practices of data management, analysis, and reporting. Smaller companies without marketed products will develop strategies similar to their more mature counterparts. Simple descriptions of study design and proposed storage conditions, together with data listings sometimes supported by graphics, will be the foundation upon which manufacturers will draw their conclusions. However, this limited submission of stability experience will not satisfy the goal of the WHO Guideline on Stability Evaluation of Vaccines [2]. The data should be analyzed according to practices outlined in ICH Q1E [5] and the WHO Guideline in order to effectively establish shelf-life of the vaccine and manage distribution though a proper calculation of release properties. In concert with the 1987 FDA Guideline For Submitting Documentation For The Stability Of Human Drugs And Biologics, the agency provided a SASÒ program for establishment of product shelf-life using methods which have subsequently been described in ICH Q1E. While that guideline was withdrawn, FDA still promotes the use of its programs and has made them available on its website (http://www.fda.gov/cder/ sas/index.htm). To use those programs, however, one must have the SASÒ system installed on their computer, and the statistical acumen to manipulate and interpret the results of the program. The FDA SASÒ program performs calculations for only the simplest stability design, in which several lots are tested independently across a range of stability intervals. Alternative design commonly used in industry, such as studies with multiple images (e.g., vials and syringes) or studies in which all lots are tested in the same assay, require specialized statistical treatment. In addition, the FDA SASÒ program does not provide protection against violations of statistical
419
assumptions (e.g., linearity of stability response, outliers, normality of data, etc.), or calculate release limits. The methods described in the withdrawn FDA guideline and in ICH have also been programmed into other popular statistical software packages, as well as into many stability laboratory information management systems (LIMS). Given the desire for a standardized stability report format, with minimal disruption to internal practices of large vaccine manufacturers using their own data management and reporting conventions, and the need to accommodate various designs and to interrogate the data for statistical assumptions, a software solution might be organized among statisticians, stability analysts, and regulators, through a software developer that is invested in pharmaceutical applications. Ideally the software developer should be an interdisciplinary team of experts in laboratory analyses and statistics and should be familiar with current guidelines regulating pharmaceutical stability and software development. The software might be packaged to be run locally in the stability laboratory or by the regulator, or served over the internet through either a yearly license, or on a per use basis. In addition, ideally the vendor should be capable of offering technical and statistical support to its users. The multidisciplinary team might work with the software developer to achieve the following high level requirements for stability evaluation of vaccines: A user friendly front end to accurately characterize the stability study design and to enter data into the design. Capabilities to assess statistical assumptions and perform analyses appropriate to the specific study design. Determination of release requirements as well as shelflife. Data displays both in the form of tables and graphics, which depict the raw data together with statistical elements consistent with the formal analysis. Clearly expressed conclusions regarding data handling, assumptions, statistical tests, and expiry/release determinations. A report format that is consistent with a standard agreed upon by industry and regulators. Timing of a software solution should be coordinated with other implementation activities, including further workshops. Manufacturers and regulators must agree upon content and format, as well as adoption of the principles laid out in the WHO guideline prior to developing a software solution. Software roll out should be accompanied by training and the technical support available through commercial providers. Successful implementation of the WHO guideline depends upon collaboration among manufacturing and regulatory stability scientists and engineers, together with proper tools for assessing and analyzing vaccine stability data. Acknowledgement The authors thank the following members of a working group on model format for stability report formed at the WHO/KFDA
420
J. Shin et al. / Biologicals 37 (2009) 417e420
joint workshop on stability evaluation of vaccines in Seoul, April 2008: Dr. Silmara Cristiane da Silveira, Agencia Nacional de Vigilancia Sanitaria, Brası´lia, Brazil; Dr. Alda Laschi, representative of the International Federation of Pharmaceutical Manufacturers & Associations; and Dr Anil Sood, representative of the Developing Country Vaccine Manufacturers Network. References [1] WHO Expert Committee on Biological Standardization. Draft guidelines on stability evalution of vaccines. WHO/BS/06.2049, Geneva; 23e27 October 2006.
[2] WHO Expert Committee on Biological Standardization. Guidelines on stability evalution of vaccines. Adopted 2006. To be printed in WHO Technical Report Series. On-line access to an electronic version: http:// www.who.int/biologicals/publications/trs/areas/vaccines/stability/ Microsoft%20Word%20-%20BS%202049.Stability.final.09_Nov_06.pdf. [3] WHO-UNICEF. Quality of the cold chain: WHO-UNICEF policy statement on the use of vaccine vial monitors in immunization services. WHO/V&B/99.18 http://www.who.int/vaccines-documents/DocsPDF99/ www9928.pdf. [4] ICH M4Q(R1), The Common Technical Document For The Registration Of Pharmaceuticals For Human Use: Quality, current Step 4 version dated 12 September 2004 by the ICH Steering Committee. [5] ICH Q1E, Evaluation of Stability Data, current Step 4 version dated 6 February 2003 by the ICH Steering Committee.