European Bioanalysis Forum and the way forward towards harmonized regulations
2009; Future Science Ltd; Volume: 1; Issue: 5 Linguagem: Inglês
10.4155/bio.09.96
ISSN1757-6199
AutoresBerthold Lausecker, Peter van Amsterdam, Margarete Brudny-Kloeppel, Silke Luedtke, Philip Timmerman,
Tópico(s)Protein purification and stability
ResumoBioanalysisVol. 1, No. 5 EditorialFree AccessEuropean Bioanalysis Forum and the way forward towards harmonized regulationsBerthold Lausecker, Peter van Amsterdam, Margarete Brudny-Kloeppel, Silke Luedtke and Philip TimmermanBerthold Lausecker† Author for correspondenceF. Hoffmann-La Roche, Pharmaceuticals Division, Non-Clinical Safety, DMPK, Bioanalysis, PO Box, Basel, CH-4070, Switzerland. , Peter van AmsterdamSolvay Pharmaceuticals, Margarete Brudny-KloeppelBayer Schering Pharma AG, Silke LuedtkeBoehringer-Ingelheim and Philip TimmermanJohnson & JohnsonPublished Online:27 Aug 2009https://doi.org/10.4155/bio.09.96AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail It is a great opportunity for the bioanalytical community around the world to exchange views and positions on bioanalysis in a journal that is specifically dedicated to that field in order to foster mutual agreement and to further develop our area of expertise. Everybody in drug R&D recognizes nowadays that a thorough understanding of the circumstances under which experiments and studies, from drug candidate selection to late-phase clinical development, are conducted and samples analyzed is of extremely high importance for the correct selection and development of a new chemical or biological entity (NCE and NBE, respectively). This is true for the assessment of both pharmacokinetic properties and equally for the assessment of pharmacodynamic effects.While the set-up of the study conduct and analysis during the selection process is primarily a company's risk–benefit decision, the process for the development phase is set by the authorities in order to guarantee that a solid data-based risk–benefit assessment of the drug can be made. This is performed in close collaboration between the stakeholders from authorities, pharmaceutical companies and professional organizations, such as the interactions established in the USA between US FDA Center for Drug Evaluation and Research (CDER), the Pharmaceutical Research and Manufacturers of America (PhRMA) and the American Association of Pharmaceutical Scientists (AAPS). In the particular field of bioanalysis, the interaction was set-up and developed in the USA by the FDA and AAPS from the early 1990s via a series of conferences resulting in draft and final guidelines and associated White papers [1–5].For European-based companies, it has always been difficult to identify a common standard to be followed. Drug assay development was, to a certain extent, covered by ICH Q2R1, which deals with analytical methods used for drug product characterization, but then one would need to interpret matrix as a biological matrix. Therefore, many companies claimed to follow the FDA's guidance even though the guidance is not formally applicable to Europe. But, for conduct of bioanalytical support to preclinical and clinical studies, there was no other guidance in place and so all European-based and global pharmaceutical companies with affiliates in Europe, as well as contract research organizations (CROs), cross-referenced the workshop papers and FDA guidance on bioanalytical method validation.Recently, the European Medicines Agency (EMEA) committee for medicinal products for human use (CHMP) efficacy working party (EWP) released a concept paper to close this gap [6]. In addition, a revision to the guidance for the evaluation of bioequivalence was released for comments that also required bioanalytical input [7]. Previously, bioanalytical input to EMEA guidance or investigations, if at all, was mainly channeled through the European Federation of Pharmaceutical Industries and Associations (EFPIA) to the individual pharmaceuticals companies and had to be consolidated in meetings before delivery back to the EMEA (e.g., guidance on drug in control samples [8]).For responding back to the EMEA on the recent bioequivalence and method validation guidance, all of the European Bioanalysis Forum (EBF) member companies decided to use the EBF organization to provide a single consolidated response to the EMEA. The EBF is an organization of bioanalysts from European or global R&D-based pharmaceutical companies that have affiliates with bioanalytical operations in Europe (27 members to date). The goal of this organization is to share and foster a common understanding of bioanalysis from a scientific as well as a regulatory perspective in the areas of both small and large molecules. This is currently accomplished by two 'members-only' meetings and one open symposium per year, discussing bioanalytical matters with other stakeholders from CROs, instrument and software suppliers, representatives from agencies and academia. When the EMEA request for comments on the draft method validation guidance came to the attention of the EBF in January this year, it was immediately decided to take on this task. EBF discussions and internal member company discussions on the different topics of this draft guidance were initiated with the goal to feed back one consolidated response to the EMEA. The challenging aspect of this was to combine and consolidate the individual company responses and to stay within the timelines regarding the delivery of the response to the EMEA. In preparing our comments on the concept paper, we took into account not only all aspects from the EMEA wishlist but also the relevant sections from: ▪ FDA/CDER 2001 Guidance for Industry, Bioanalytical Method Validation [3];▪ 2006 Crystal City 3 recommendations and workshop/conference report [5].Other related regulation or guidance: ▪ OECD GLP: 1–15 [101];▪ ICH – S3A, ICH E6, Q2 [102-104];▪ FDA 21 CFR 320.29, 21 CFR parts 58, 21 CFR part 11 [105-107];▪ EMEA CPMP/EWP/QWP/1401/98 [108].A major driver for us was to come to one consistent set of globally applicable bioanalytical guidelines. The response sent in before the 31 March 2009 deadline contained three major points: ▪ The European and global companies with affiliates in Europe and members of the EBF acknowledged that the EMEA is going to develop a guidance covering the important area of measurement of drug exposure during preclinical and clinical development;▪ FDA guidance and the 2006 Crystal City 3 White paper [5] are widely accepted as standards that mostly work well;▪ EBF companies would, however, prefer to work according to one global guidance that should be an ICH guidance resulting from the position of the FDA, EMEA and other stakeholders.A few other points in the concept paper were identified as issues requiring change, clarification or removal. The EBF asked for a clear definition on the applicability and relationship of the process of method validation and conduct of bioanalysis for clinical studies to GLP, since diffuse statements in the past have caused a lot of confusion. The guidance should also, according to the EBF's understanding, clearly distinguish which parameters must be assessed either for chromatography-based methods or ligand-binding based methods. Furthermore, it should preferably also be clear for which type of measurements the guidance will be valid because, in some instances, such as special and rare matrices, including tissue homogenates, it is nearly impossible or meaningless to assess all method parameters. Other aspects the EBF suggested were: refrain from using the term 'limit-of-detection' as it does not have any relevance for bioanalysis and to use the term 'selectivity' as a basic method parameter instead of specificity (selectivity is the IUPAC-preferred term). In addition, the EBF took this opportunity to incorporate its recommendations on incurred sample reanalysis, which in some aspects are different to the AAPS/FDA conclusions.The EBF Steering Committee is very proud of its members being able to organize a review of the EMEA concept paper within their own organizations and provide comments within only a few weeks. Furthermore, it was good to see that, on most of the items, there was very little disagreement. This eased the process of consolidation, but still, taking into account that this time-critical response was achieved by the EBF while at the same time preparing the response on the bioequivalence guidance and a White paper dealing with the EBF's position on ISR, it was a truly Herculean task.With all the enthusiasm and energy in the group, the EBF will continue to raise their voice to comment on bioanalytical matters via this and other journals and main conferences, as recently demonstrated.DisclaimerThe views expressed in this article are those of the EBF steering committee and do not necessarily reflect the respective company's position on the subject.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.Bibliography1 Shah VP, Midha KK, Dighe S et al. Analytical methods validation: bioavailability, bioequivalence and pharmacokinetic studies. Conference report. Eur. J. Drug Metab. Pharmacokinet.16,249–255 (1991).Crossref, Medline, CAS, Google Scholar2 Shah VP, Midha KK, Findlay JW et al. Bioanalytical method validation – a revisit with a decade of progress. Pharm. Res.17,1551–1557 (2000).Crossref, Medline, CAS, Google Scholar3 US FDA. Guidance for Industry: Bioanalytical Method Validation. Rockville, MD, US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research, USA (2001).Google Scholar4 DeSilva B, Smith W, Weiner R et al. Recommendations for the bioanalytical method validation of ligand-binding assays to support pharmacokinetic assessments of macromolecules. Pharm. Res.20,1885–1900 (2003).Crossref, Medline, CAS, Google Scholar5 Viswanathan CT, Bansal S, Booth B et al. Bioanalytical method validation and implementation: best practices for chromatographic and ligand binding assays. AAPS J.9(1),E30–E38 (2007).Crossref, Google Scholar6 EMEA. Concept paper/recommendations on the need for a (CHMP) guideline on the validation of bioanalytical methods. EMEA/CHMP/EWP/531305/2008 (2008).Google Scholar7 EMEA. Investigation of bioequivalence. CHMP/EWP/QWP/1401/98 (2008).Google Scholar8 EMEA. Guidance for the evaluation of control samples in non-clinical safety studies: checking for contamination with test substance. CPMP/SWP/1094/04 (2005).Google Scholar101 OECD principles on GLP, numbers 1 to 15 www.oecd.org/document/63/0,3343,en_2649_34381_2346175_1_1_1_1,00.htmlGoogle Scholar102 ICH S3A. 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CPMP/EWP/QWP/1401/98 www.emea.europa.eu/pdfs/human/qwp/140198enrev1.pdfGoogle ScholarFiguresReferencesRelatedDetailsCited ByValidation of bioanalytical chromatographic methods for the quantification of drugs in biological fluidsBioanalytical chromatographic method validation according to current regulations, with a special focus on the non-well defined parameters limit of quantification, robustness and matrix effectJournal of Chromatography A, Vol. 1353Bioanalytical method validation and bioanalysis in regulated settingsThe European Bioanalysis Forum community's evaluation, interpretation and implementation of the European Medicines Agency guideline on Bioanalytical Method ValidationPeter van Amsterdam, Arjen Companjen, Margarete Brudny-Kloeppel, Michaela Golob, Silke Luedtke & Philip Timmerman13 March 2013 | Bioanalysis, Vol. 5, No. 62012 White Paper on Recent Issues in Bioanalysis and Alignment of Multiple GuidelinesBinodh DeSilva, Fabio Garofolo, Mario Rocci, Suzanne Martinez, Isabelle Dumont, France Landry, Catherine Dicaire, Gabriella Szekely-Klepser, Russell Weiner, Mark Arnold, Surendra Bansal, Kevin Bateman, Ronald Bauer, Brian Booth, Scott Davis, Sherri Dudal, Dominique Gouty, John Grundy, Sam Haidar, Roger Hayes, Mohammed Jemal, Surinder Kaur, Marian Kelley, Magnus Knutsson, Olivier Le Blaye, Jean Lee, Steve Lowes, Mark Ma, Toshinari Mitsuoka, João Tavares Neto, Robert Nicholson, Eric Ormsby, Jeffrey Sailstad, Lauren Stevenson, Daniel Tang, Jan Welink, CT Viswanathan, Laixin Wang, Eric Woolf & Eric Yang9 October 2012 | Bioanalysis, Vol. 4, No. 18Leveraging Advances in HPLC and Sample Preparation to Maximize DMPK Data Quality15 May 2012Analytical Method Development and Validation in Accordance to the Regulatory Guidelines31 January 2012SQA opinion paper on global harmonization of the bioanalytical method validation guidancesChristopher Tudan, Stephen Rogenthien and Anthony Jones26 November 2010 | Bioanalysis, Vol. 2, No. 122010 White Paper on Recent Issues in Regulated Bioanalysis & Global Harmonization of Bioanalytical GuidanceNatasha Savoie, Fabio Garofolo, Peter van Amsterdam, Surendra Bansal, Chris Beaver, Patrick Bedford, Brian P Booth, Christopher Evans, Mohammed Jemal, Marc Lefebvre, Arthur Leonardo Lopes de Silva, Steve Lowes, Joseph C Marini, Robert Massé, Louise Mawer, Eric Ormsby, Mario L Rocci Jr, CT Viswanathan, Jason Wakelin-Smith, Jan Welink, Joleen T White, Eric Woolf26 November 2010 | Bioanalysis, Vol. 2, No. 12Formation of a Global Contract Research Organization Council for BioanalysisNoel Premkumar, Stephen Lowes, James Jersey, Fabio Garofolo, Isabelle Dumont, Robert Masse, Betty Stamatiou, Maria C Caturla, Ray Steffen, Michele Malone, Elliot Offman, Timothy Samuels, Phillip Oldfield, Lorella Di Donato, Douglas Fast, Daniel Tang, Marc Moussallie, John Doughty, Mario Rocci, Mike Buonarati, Dominique Gouty, Darioush Dadgar, John Stamatopoulos, Alan Breau, Bernard Ntsikoussalabongui, Mohammed Bouhajib, Bob Nicholson, Richard Tacey, Peter Ketelaar, Chad Briscoe, Shane Karnik, Jaap Wieling, Jon Kirk Smith, Michael J Reid, Richard LeLacheur, John Chapdelaine, Saadya Fatmi, Farhad Sayyarpour, Xinping Fang, Jeremy Cook & David Browne20 October 2010 | Bioanalysis, Vol. 2, No. 11Towards harmonized regulations for bioanalysis: moving forward!Peter van Amsterdam, Berthold Lausecker, Silke Luedtke, Philip Timmerman & Margarete Brudny-Kloeppel13 April 2010 | Bioanalysis, Vol. 2, No. 4 Vol. 1, No. 5 Follow us on social media for the latest updates Metrics History Published online 27 August 2009 Published in print August 2009 Information© Future Science LtdDisclaimerThe views expressed in this article are those of the EBF steering committee and do not necessarily reflect the respective company's position on the subject.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download
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