News bulletin for small and
medium-sized enterprises
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This news bulletin is published four times a year by the
SME Office of the European Medicines Agency.
IN THIS ISSUE:
Veterinary medicines
1
Clinical trials
2
Advanced therapies
2
Pharmaceutical
and GMP guidance
3
(Pre)Clinical
guidance
3
Special ‘presubmission’ assistance for SMEs
3
eCTD, ‘MEDDEV’
and paediatric
medicines
4
Meetings
4
SME companies
registered with
the EMA
5
Contact
5
The news bulletin aims to bring to the attention of
SMEs, and their stakeholders, documents and activities
related to the European regulatory environment.
Veterinary medicines
A report from the Committee for Medicinal Products for Veterinary Use (CVMP) on the
functioning of veterinary legislation was released on 19 July 2010 (EMA/
CVMP/463298/2010). It details the CVMP contribution to the European Commission
initiative ‘Better regulation for Veterinary Pharmaceuticals’. The key areas identified by
the CVMP in the review of the veterinary legislation relate to:
•
•
Procedural aspects: simplification of marketing authorisation procedures, role
and functioning of the CVMP and referrals
Specific areas: availability of medicines, pharmacovigilance, antimicrobial resistance, environmental risk assessment, advanced therapies, medicinal products
containing biologically active substances, considerations arising from climate
change and new vaccines for emerging diseases.
The veterinary dictionary for drug regulatory activities (‘VeDDRA’) terminology, the list
of species and breeds, and the additional controlled terminology list are an integral part
of the European Union (EU) system for electronic reporting of adverse events to veterinary medicines into EudraVigilance Veterinary. It allows a systematic coding and analysis of reported adverse events to veterinary medicines (‘VeDDRA’ guidance EMEA/
CVMP/PhVWP/288284/2007-Rev.3). The update of the terminology is undertaken annually by the CVMP (EMA/123352/2004 – Rev.5) and the following revised documents will
come into effect in December 2010:
•
•
Combined VeDDRA list of clinical terms for reporting suspected adverse reactions
in animals and humans to veterinary medicinal products (EMEA/
CVMP/10418/2009); List of changes to the CVMP combined VeDDRA list of clinical terms for reporting suspected adverse reactions in animals and humans to
veterinary medicinal products for 2010 (EMEA/CVMP/PhVWP/344712/2010)
List of species and breeds for electronic reporting of suspected adverse reactions
in veterinary pharmacovigilance (EMEA/CVMP/553/03); List of changes to the list
of species and breeds for 2010 (EMEA/CVMP/PhVWP/346373/2010)
A ‘Questions and answers’ document on the implementation of CVMP guideline on environmental impact assessment for veterinary medicinal products in support of the VICH
guidelines GL6 (Ecotoxicity Phase I) and GL38 (Ecotoxicity Phase II) was released on
19 July 2010 (EMEA/CVMP/ERA/172074/2008-Rev.2).
A draft guideline on the conduct of bioequivalence studies for veterinary medicinal
products containing chemical entities was released on 19 July 2010 (EMEA/
CVMP/016/00-Rev.2). It specifies the requirements for the design, conduct, and
evaluation of bioequivalence studies for pharmaceutical forms with systemic action. In
addition, guidance is given on how in-vitro data may be used in specific cases to allow
bridging of safety and efficacy data. It is released for consultation until 31 October
2010.
© European Medicines Agency, 2010. Reproduction is authorised provided the source is acknowledged.
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Clinical trials
A reflection paper on ‘Expectations for electronic source data and data
transcribed to electronic data collection tools in clinical trials’ was
released on 12 August 2010 (EMA/INS/GCP/454280/2010). Collection of
accurate clinical trial data is essential for compliance with Good Clinical
Practice (GCP). With increasing use of information technology in
pharmaceutical development there is a need to have clear guidance on
the creation and capture of electronic clinical data in clinical trials in the
EU or in third countries. The paper outlines the current expectations of
regulators in the field in case the trial reports are submitted as part of
marketing authorisation applications to EU regulatory authorities.
EudraCT is the European Clinical Trials Database of all clinical trials which
started in the European Union from May 2004. EudraCT Version 8.0 will
go into production on 7 September 2010. Applicants are reminded that
EudraCT Version 8.0 will use a revised Clinical Trials Application Form
(Link).
A draft ‘Detailed guidance on the collection, verification and presentation
of adverse reaction reports arising from clinical trials on medicinal
products for human use’ was released on 17 June 2010 (Link). It was
prepared in response to calls from stakeholders during the public
consultation on the functioning of the Clinical Trials Directive to provide
short-term improvements of the detailed rules for safety reporting. Once
finalised, it will replace the following documents included in ‘Chapter II:
Monitoring and Pharmacovigilance’ of EudraLex - Volume 10 Clinical trials
guidelines:
•
•
•
Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from
clinical trials on medicinal products for human use;
Detailed guidance on the European database of Suspected Unexpected Serious Adverse Reactions
(Eudravigilance - Clinical Trial Module); and
Questions & Answers specific to adverse reaction reporting in clinical trials.
Advanced therapies
A draft guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified
cells was released on 18 June 2010 (EMA/CHMP/GTWP/671639/2008). It covers cases of genetically modified cells
intended for use in humans irrespective of the cell’s origin (human autologous or allogeneic, xenogeneic) or whether
the genetic modification has been carried out for clinical purposes or not (e.g. for manufacturing). The requirements
described in the guidance relate to market authorisation applications, but its principles may apply to development
stages. It is released for consultation until 30 November 2010.
A reflection paper on quality, non-clinical and clinical issues for the development of recombinant adeno-associated
viral vectors was released on 8 July 2010 (EMEA/CHMP/GTWP/587488/2007 Rev. 1). It elaborates on the points that
should be considered during the development of medicinal products derived from AAV and indicates requirements
that might be expected at the time of a market authorisation application.
A guideline on ‘quality, non-clinical and clinical aspects of live recombinant viral vectored vaccines’ was released on
10 July 2010 (EMA/CHMP/VWP/141697/2009). The document applies to live viruses that express a heterologous
antigen intended for the prevention and treatment of infectious diseases. Live viral vaccines that have been
genetically modified but do not express a heterologous antigen, plasmid DNA vaccines, recombinant protein
vaccines, vaccines against non-infectious indications based upon bacterial vectors such as salmonella and Bacillus
Calmette-Guérin (BCG) are outside the scope of the guideline. The document provides additional guidance to the
‘Note for guidance on gene transfer medicinal products’ (CPMP/BWP/3088/99). It will come into effect 1 January
2011.
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Pharmaceutical and GMP guidance
A draft ICH guidance ‘Topic Q3C (R4) Impurities: Guideline for residual solvents PDE Cumene (Human Medicines)’
was released on 14 July 2010 (EMA/CHMP/ICH/404855/2010). It is released for comments until 30 September
2010.
A draft guideline on ‘Setting specifications for related impurities in antibiotics that are fermentation or semisynthetic derived substances (Human and Veterinary Medicines)’ was released on 30 July 2010
(EMA/CHMP/CVMP/QWP/199250/2009). Antibiotics active substances are produced by fermentation processes,
chemical synthesis or both (semi-synthetic substances). Fermentation processes are more variable than synthetic
ones and have therefore more impact on the impurity profile. ICH Q3 (Impurities in new drug substances-Human
medicines) and VICH 10/11 guidelines (Impurities in new drug substances-Veterinary medicines) apply to
impurities of active substances manufactured by chemical synthesis only. The draft guidance is released for
consultation until 31 January 2011.
An updated ‘Questions and answers on Good Manufacturing Practice (GMP) webpage’ was released on 5 July 2010.
It includes new information on the traceability of manufacturing and distribution operations of medicinal products
batches and documentation requirements for active substance manufacturers who perform sterilisation of active
substances (Link).
(Pre)Clinical guidance
A ‘Questions and Answers’ document on the environmental risk assessment
guideline for medicinal products for human use was published on 19 July 2010
(EMA/CHMP/SWP/44609/2010). It is released for consultation until 30 September
2010.
A ‘Questions and answers’ document on the withdrawal of the ‘Note for guidance on
single dose toxicity’ was released on 19 July 2010 (EMA/CHMP/SWP/81714/2010).
In June 2008, the CHMP issued a concept paper which recommended the revision
of the guideline on single dose toxicity. It was thereafter agreed to remove the
guideline on single dose toxicity as the data obtained in traditional single dose
toxicity studies are of limited value and acute toxicity data can be obtained in other
types of toxicity studies e.g. dose-escalation studies or short-duration dose-ranging
studies.
A ‘Questions and answers’ document on the ‘Note for guidance on photosafety
testing’ was released on 19 July 2010 (EMA/CHMP/SWP/336670/2010). The CHMP
highlighted in 2008 the need to revise the guideline on photosafety testing. As the
International Conference on Harmonisation decided meanwhile to include
photosafety testing as a new topic, the plans for revising the guideline were
cancelled. As a result, interim guidance clarifying specific aspects of photosafety
testing has been drafted until the ICH guideline is finalised. The ‘Questions and
answers’ document is released for consultation until 30 September 2010.
A ‘Questions and answers’ document on the ICH guidance E7 Studies in support of special populations-Geriatrics
was released on 27 July 2010 (EMA/CHMP/ICH/604661/2009).
Special ‘pre-submission’ assistance for SMEs
Registered SMEs are reminded that meetings can be arranged with the SME Office to discuss a planned regulatory
strategy (i.e. ‘SME briefing meetings’). Ahead of formal pre-submission interactions, companies planning their
marketing authorisation application may wish to benefit from earlier interaction with regulators to discuss
administrative and regulatory aspects of their future dossier. For further information please contact directly the
SME Office at smeoffice@ema.europa.eu.
Special support for SMEs preparing the submission of Paediatric investigational plans (PIP) has recently been
introduced. The incentive allows companies to discuss their draft Paediatric investigational plan (PIP) before its
formal submission. Further information is available under Link.
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eCTD, ‘MEDDEV’ and paediatric medicines
Revised priority lists for studies of ‘off-patent’ paediatric medicines for the 7th Framework Programme of the
European Commission (5th call 2011; 6th call 2012) were released on 2 August 2010. The priority lists provide the
basis for the 2011 and 2012 calls of the 7th Framework Programme of the European Commission. It ensures that
funds are directed into research of medicines with the highest needs in children. One of the provisions of Paediatric
Regulation (EC) No 1901/2006 is the funding of studies into off-patent medicinal products. The funding currently
provided through the EU Framework Programme should stimulate the development and marketing of off-patent
medicinal products.
Applicants are advised that as of 1 July 2010, the EU M1 v1.4 must be used for all eCTD submissions for all
European procedures. Any eCTD submissions from this date using previous versions of the EU M1 specification
(v1.0. v1.1, v1.2.1 or v1.3) will not be accepted. The changes introduced relate to Commission Regulation (EC)
No. 1234/2008 on variations, and specifically the ‘grouping’ and ‘worksharing’ of variations. Further details are
available under link.
A revised guidance MEDDEV 2.4/1 on the classification of medical devices guideline has been published in June
2010 (Link). The ‘MEDDEV’ guidelines aim at promoting a common approach in the conformity assessment
procedures according to the relevant annexes of the EU Directives on medical devices. Its revision includes
information relating to devices containing human blood derivatives and medical devices manufactured using tissues
of animal origin.
Meetings
Reports and presentations from the following meetings were published:
•
•
The presentations of the SME workshop which took place on 28 May 2010 are available in the following link.
A report on the EMA workshop on stem cell based therapies was released on 1 July 2010
(EMA/319294/2010).
The following meetings which might be of interest to SMEs have been announced:
•
SME Day organised by TOPRA in collaboration with the SME office on 4 October 2010 (link)
SME companies registered with the Agency
488 companies currently have SME status assigned by the Agency. The list of companies is published on the
Agency’s website at: http://www.emea.europa.eu/pdfs/SME/registeredcompanies.pdf
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Contact the SME Office
The SME Office has been set up within the Agency to
address the particular needs of smaller companies. The
Office aims to facilitate communication with SMEs through
dedicated personnel who will respond to practical or
procedural enquiries, monitor applications, and organise
workshops and training sessions for SMEs. Any comments
on this news bulletin can be forwarded to the SME Office:
E-mail: smeoffice@ema.europa.eu
Direct telephone: +44 (0)20 7418 8575/8463
Fax: +44 (0)20 7523 7040
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