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Regulatory News Update - January 2012

The following regulatory information is provided as a service to our visitors. Whilst every effort has been taken to ensure its accuracy, it is for guidance only and TMQA cannot accept any responsibility for the consequences of its use.

Concerns over India's draft rules on Clinical Trials
Scientific Misconduct in Dutch Research Community
Formation of Asian CRO Alliance

MHRA Launches Consultation on Draft Regulations Transposing EU Directive 2010/84/EU

The Medicines and Healthcare products Regulatory Agency (MHRA) launched a public consultation (MLX 374) on 06 Dec 2011 to seek views on the draft regulations transposing the EU Directive 2010/84/EU on pharmacovigilance. This EU Directive was issued in Dec 2010 following a review by the European Commission of the European system of safety monitoring which began in 2005. The legislation was adopted by the European Parliament in Dec 2010 and must be transposed to UK law by 21 Jul 2012. It is accompanied by EU Regulation 1235/2010/EU on pharmacovigilance which must be transposed by 02 Jul 2012. Comments on this consultation are invited by 28 Feb 2012. This consultation is being performed in parallel with the consultation on the consolidated medicines regulations (MLX375) which were issued for consultation by the MHRA in Oct 2011.

Introduction of Requirement to Perform Technical Validation of eCTD

On 23 Dec 2011 the MHRA announced that from January 2012 there will be a requirement on all EU member states acting as Reference Member State (RMS) for new Marketing Authorisation (MA) applications to perform a technical validation of electronic Clinical Trial Dossier (eCTD) submissions. This RMS validation will be accepted by all concerned Member States – it is not envisaged that concerned Member States carry out their own independent eCTD validation. The RMS is the Member State which evaluates the marketing authorisation application dossier and prepares the assessment report on behalf of the concerned Member States. To comply with this regulation, from 03 Jan 2012 the MHRA will be technically validating all new MAA eCTD submissions for both National procedures and where the UK is the RMS. The MHRA will not perform technical validation on submissions from concerned Member States and will only upload these submissions if they are accompanied by a Technical Validation Report from the RMS.

Results of MHRA GCP Inspection Questionnaire

In May 2011 the MHRA sent out questionnaires to 40 organisations that had undergone GCP inspection by the MHRA between July and December 2010. Of the 40 questionnaires, ten were sent to non-commercial sites, 14 to commercial sites, 11 to investigators, three to phase I units and two for triggered inspections. Out of the 40 questionnaires sent 19 responses were received. The questions covered six main topics including: pre-inspection activities, opening meeting, conduct of the inspection, closing meeting, the inspection report and general observations relating to the inspection. Results from the questionnaires indicated that inspected organisations were generally satisfied with the GCP inspection process; the overall customer satisfaction rate was 82%. Negative comments included the following: completion of the Summary of Clinical Trial Systems (SCTS) took many hours and was of no use or benefit to the organisation and the information required on the list of clinical trials seemed excessive; there was a lack of opportunity to discuss/clarify deficiencies during the inspection or closing meeting; it was difficult to locate the correct information from the MHRA website. As a result of feedback from the questionnaires and the GCP Consultative Committee the following actions will be implemented: current guidance on completion of the SCTS has been revised to clarify the level of information that is required and feedback will be given to organisations on the content of their dossiers during the inspection preparation process.

FDA encourages Industry to Submit Draft Guidance Documents

The FDA is encouraging industry to submit draft guidance documents for consideration if they believe such guidance would advance understanding of a particular issue. This initiative is intended to further the push for transparency and to streamline new regulation. Currently, it is more common for industry to informally identify topics in need of the agency’s attention but teams at the FDA are now encouraging industry to submit draft guidance at industry events and online. It is hoped that this initiative will speed up the development of guidance documents. The agency has found that clarification of the annual guidance agenda is needed to give industry an idea of planned guidance documents and stimulate industry input.

FDA Publishes Guidance for Industry - Q8, Q9 and Q10 Questions and Answers

Following the finalisation of the ICH guidances Q8 (Pharmaceutical Development), Q9 (Quality Risk Management) and Q10 (Pharmaceutical Quality System), experiences implementing these guidances in the ICH regions have given rise to requests for clarifications. Thus the FDA released a guidance document in Nov 2011 titled: Guidance for Industry Q8, Q9 and Q10 Questions and Answers (R4). The FDA guidance is intended to clarify key issues and it reflects the current working procedure of the ICH Quality Implementation Working Group (Q-IWG) for implementing the Q8, Q9 and Q10 guidances. This guidance is a revision of the ICH guidance titled: Q8, Q9 and Q10 Questions and Answers (May 2010). In Nov 2010 the May 2010 guidance was revised to Q& A9 to section II.B.1 (Design Space (2.1)).

PPS Admits Falsifying Patient Records in Boehringer Trial

The US CRO, PPS Clinical Research, pleaded guilty to a charge of corruptly influencing, obstructing and impeding an inspection by the FDA in May 2010 by providing false patient records. PPS Clinical Research was contracted by Boehringer Ingelheim to run clinical trials of Flibanserin, a supposed ‘female viagra’, which was ultimately rejected by the FDA in 2010 due to lack of efficacy compared to placebo. Whistleblowers at PPS reported falsification of patient visits to Boehringer in 2009 and FDA investigators were subsequently called in by the company. FDA inspectors found falsified records about multiple patient exams that never occurred as well as other discrepancies. The investigation determined that a former PPS Study Coordinator had doctored the patient records. A lawyer for PPS stated that the Study Coordinator suffered from serious health issues that led her not to perform here job effectively. Prosecutors stated that PPS failed to have a trained investigator conduct some exams, backdated and falsified records and failed to properly oversee patient selection into the trial. PPS has agreed to a $68,000 fine, to forfeit $7,000 and to pay $206,000 in a civil settlement.

Concerns over India's Draft Rules on Clinical Trials

The Indian Ministry of Health and Family Welfare published draft rules on 18 Nov 2011 regarding compensation for clinical trial injury or death. These draft rules form part of the amended Drugs and Cosmetic Rules 1945. However, the US-based Association of Clinical Research Organisations (ACRO) has expressed its concerns to the Indian Ministry of Health and Family Welfare about the latest new draft rules on clinical trials in India which would see ethics committees take sole responsibility for determining serious adverse event (SAE) causality and compensation. ACRO argue that ethics committees are not best placed to make such determinations particularly if the institution with which they are affiliated could be impacted by their decisions. ACRO are concerned the ethics committees lack the scientific and medical knowhow to accurately identify SAE causality and, hence, the appropriate level of compensation. ACROs comments come at a time when the CRO sector in India faces considerable media and political criticism about how clinical trials are conducted in India. On 02 Jan 2012, the BBC reported that 12 doctors had been fined by the Madhya Pradesh state government for failing to gain patient consent during trials in the city of Indore. However, authorities in the state of Madhya Predesh have been criticised for the low fines handed out to the 12 doctors (5000 rupees (£60)). Activists and opposition parties have described the fine as a ‘joke’ and called for an investigation by the federal police.

Scientific Misconduct in Dutch Research Community

The Dutch research community has been left shocked after disciplinary action was taken against a third professor in as many weeks. Erasmus Medical Centre in Rotterdam recently dismissed Professor Don Poldermans, a prominent professor in perioperative cardiovascular care, for ‘serious violations of scientific integrity’ in his research. Professor Poldermans published over 600 scientific papers in a career lasting several decades. He was suspended in the summer of 2010 after a confidential tip-off from a junior researcher. His research was halted and an investigation committee looked into studies he had led dating back 10 years. The investigation revealed ‘serious shortcomings’ in the informed consent process, ‘serious protocol violations’ and ‘data fabrication’. Professor Poldermans dismissal came just weeks after the publication of a report by the University of Tilburg, Amsterdam and Groningen which found Professor Dietrich Stapel, professor of cognitive social psychology, guilty of unprecedented fraud. In addition, Radboud University has reprimanded Professor Roos Vonk for unprofessional conduct. Though not guilty of fraud, the design of a study in which she collaborated with Professor Dietrich Stapel, did not meet scientific standards.

Formation of Asian CRO Alliance

Six independent Asian CROs representing six Asian counties (China, India, Japan, Korea, Malaysia and Taiwan) have formed the Asian CRO Alliance (ACA) whose primary goal is to promote quality drug development in Asia. In the case of Asian parts of global clinical trials conducted by affiliates of multinational CROs with headquarters in Western countries, sponsors are generally concerned about the quality and convenience of one-stop service provided by multinational CROs. According to the Chairman of the ACA, most local Asian CROs and ACA members are better prepared to work with sponsors than affiliates of multinational CROs. He commented that ACA member CROs are more knowledgeable about local situations and more familiar with local idiosyncrasies than affiliates.