Research Licence Inspection Report

Transcription

1 Research Licence Inspection Report Project Title Research licence Number Person Responsible Nominal Licensee Inspection type Date application fee paid A novel approach for extracting cells during embryo biopsy without the use of acid tyrode s (expires 28 th Feb 2009) R0177 Lucy Jenner Louise Kellam Renewal research inspection; request for a 3 year renewal 14 th August 2008 Centre Name and number CARE Nottingham, Centre 0101 Centre Address Treatment centres donating to these research projects John Webster House 6 Lawrence Drive Nottingham Business Park, Nottingham, NG8 6PZ CARE Manchester, centre 0185 On application in 2006 CARE Sheffield, centre 0061 On application in 2006 CARE Northampton, centre 0016 On application in 2006 Inspection date 04 November 2008 Licence Committee Date 15 th January 2009 Only CARE Nottingham, 0101, in last year Inspector(s) Andy Leonard; Sarah Hopper Page 1 of 17

2 About the Inspection: The purpose of the inspection is to ensure that research is carried out in compliance with the HF&E Act 1990, Code of Practice, licence conditions and directions and that progress is made towards achieving the stated aims of the project. The report is used to summarise the findings of the inspection highlighting areas of firm compliance and good practice, as well as areas where improvement may be required to meet regulatory standards. It is primarily written for the Licence Committee who makes the decision about the centre s licence renewal application. The report is also available to patients and the public following the Licence Committee meeting. Brief Description of the Project R0177, A novel approach for extracting cells during embryo biopsy without the use of acid tyrode s Licence granted for the purpose of: developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation Human Fertilisation and Embryology Act 1990 Sch 2 3(2)(e) A. Lay summary (unchanged): An alternative method of embryo biopsy that does not involve the use of chemicals to breach the zona pellucida is desirable. The proposed method also needs less specialised equipment (i.e.: the double tool holder and the Acid Tyrode's pipette). Therefore making the procedure possible for clinics without access to this equipment. Acid Tyrode's is a highly acidic solution (ph ) and the human zona pellucida and blastomeres react with variable sensitivity to it. It is difficult to gauge the amount of acid Tyrode's that is needed and too much can result in an unacceptably large hole or even the zona dissolving completely. In the former, blastomeres may prematurely hatch out of the zona. Therefore a procedure that does not involve acid Tyrode's must be less invasive to the embryo. One alternative is mechanical zonal breaching (Roudebush et al (1990) Am J Obstet Gynecol 162(4): and Tarin et al (1993) Fertility and Sterility 59(5):943-52), but the method being researched in this project is significantly simpler than that approach. An alternative approach to embryo biopsy is the use of a laser to breach the zona pellucida. This method avoids the use of acid Tyrode s on the embryo, thus reducing some of the risk of damage. However, this method does require expensive specialised equipment and so is not available to all clinics. It is important that all maternal cumulus cells are removed from the embryo before zona drilling by either of the methods, as the presence of any of these cells in the diagnosis would make the results, at best, unreliable and at worst, incorrect. The same applies to any sperm lodged in the zona pellucida during IVF and therefore ICSI must be applied to fertilise the eggs. It is predicted that these factors will not be an issue with the novel method. Page 2 of 17

3 Research activities Research on human embryos Storage of licensed material Creation of embryos for research Derivation of human embryonic stem cells Cell nuclear replacement Summary for Licence Committee This renewal inspection was of project R0177 A novel approach for extracting cells during embryo biopsy without the use of acid Tyrode s. Project R0177 investigates alternative methods of embryo biopsy at day 3, that do not involve the use of chemicals to breach the zona pellucida. It compares embryo survival to the blastocyst stage and blastomere/nucleus recovery after embryo biopsy using Acid Tyrode s, laser biopsy or blastomere enucleation. The applicants have considerable appropriate experience and are well qualified to continue the programme of research. The premises and equipment are appropriate. Embryo usage in project R0177 this year was reported in the pre-inspection questionnaire. In summary, the project has used 41 embryos (all fresh) in the last year (25 biopsied by laser, 16 by enucleation). Survival to blastocyst stage was seen in 24% of laser dissected embryos and 68.7% of enucleation biopsied embryos. When the total data set of 88 embryos biopsied since March 2007 is considered (23 embryos biopsied by acid tyrode s; 40 by laser; 25 by enucleation), blastocysts survival rates of 35%, 22% and 44% were observed in the acid tyrode s, the laser and the enucleation arms, respectively. The PR said that progress has been impeded this year because fewer frozen embryos have been donated to the project than anticipated. In addition, the PR has previously stated that in treatment cycles at the centre, a large proportion of embryos are cultured to the blastocyst stage for transfer and/or freezing. This has impacted on the provision of fresh day 3 embryos suitable for the project. The PR predicts that the project will use 60 fresh embryos and 20 frozen embryos next year. The application for R0177 was considered by an external reviewer who supported renewal of the project research licence for 3 years The points for consideration by Licence Committee regard: The PR should complete the PR Entry Programme to comply with General Direction D2008/1a outlined in CH(08)01a. Review of 6 sets of patient records indicated that consent for research donation was obtained on the day of embryo transfer in four recent cases. While the inspectorate were assured that written research information was provided to the patients some time before the consent was taken, there was no record in the patient notes of the date on which that information was provided in either of the four cases. Thus, compliance with Standards S (c) (the Centre shall ensure that..the person donating gametes Page 3 of 17

4 and/or embryos to research should be given sufficient time to consider the implications of their donations before the donated material is used in any research programme) could not be evidenced. It is recommended that information provided to the patient is logged in the patient record. It is also recommended that the research consenting procedure is updated to include the stage of treatment at which written research information should be provided and that the provision of research information should be logged in patient records. These recommendations should be acted on by January 31 st The PR should also review the practice of consenting patients on the day of embryo transfer. The inspectorate suggests this practice is discontinued as it would appear to be contrary to the Centre s recruitment procedure, as described by the PR. If it is continued, the PR should ensure compliance with Standard S ( Where embryos are used in research, the Centre shall ensure that clinical and research roles are separated, so that individuals involved in advising patients regarding clinical decisions about their licensed treatment, are not involved in the research project to which patients are considering donating embryos ). Treatment and research embryology is performed within the same laboratory, by the same personnel. The separation of treatment and research activities was not absolute but the inspectorate concur with the PR s assessment that it is unlikely that research goals impact on treatment plans. To ensure compliance with Standard S.8.4.1, the PR should review laboratory procedures to ensure effective, demonstrable, separation of research and treatment activities is achieved. The inspectorate recommend renewal of the research licence for project R0177 for 3 years. Page 4 of 17

5 Report of Inspection findings 1. Organisation Desired Outcome: The research is well-organised and managed and complies with the requirements of the HFE Act. Summary of findings from inspection Evidence of: Leadership and management Staffing Funding Organisation of the centre Resource management Research governance Staff R0177 Principal investigator Dr Lucy Jenner Scientists 6 Support staff None on licence; all support activities performed by licensed staff Highlighted areas of firm compliance The PR has demonstrated knowledge of the regulatory requirements of the HFEA and is the Laboratory Manager but not the PR under the Treatment and Storage Licence. The PR has a research PhD, has published research papers and has been a member of the Society of Reproduction and Fertility since Inspection of the centre and discussion with staff indicated that the centre and its laboratory are well organized and all activities there are governed by an extensive quality manual. The project is led by the Person Responsible (PR) and supervised on a day to day basis by the PR, the Nominal Licensee (NL) and another embryologist, who focuses on recruitment. Other scientists involved in the project are members of the embryology team. Their CVs were provided with the research licence application and their experience and suitability were considered appropriate. Discussion with a junior embryologist indicated that induction is detailed and involves signing off of items over a probation period. Appropriate training opportunities (e.g. health and safety, use of liquid nitrogen) are also provided. The embryologists at the Centre meet regularly and the research project and HFEA letters and Alerts can be discussed. The study requires further work to improve the significance level of the putative differences and has not been published or presented at open conferences yet. Results are however discussed at internal meetings of CARE embryologists and may be presented at the next annual CARE group meeting. Funding for the project comes from the CARE organisation and is secure for the term of the research licence application. The research project utilises the general laboratory facilities at the centre which are secure and well supplied and maintained. Research activities are controlled by written procedures, supplied prior to inspection, which ensure a consistent approach. The research programme is steered by the PR, the NL and one embryologist, who have regular meetings to discuss results. Page 5 of 17

6 Issues for consideration The PR has yet to complete the Research PR Entry Programme. This is a breach of General Direction D2008/1a outlined in CH(08)01a. The PR is now working through the PREP and expects to have it completed by the end of Executive recommendations for Licence Committee That the PR should complete the PR Entry Programme. Areas not covered in by this inspection All areas covered Page 6 of 17

7 2. Premises and equipment Desired Outcome: The premises and equipment are safe, secure and suitable for their purpose. Summary of findings from inspection: Suitability of premises Storage facilities Safety of equipment Servicing and maintenance of equipment Highlighted areas of firm compliance Manipulation of embryos for research is carried out in the laboratories used for the treatment and storage licence. These laboratories are well equipped and maintained and access is restricted to licensed personnel only. Embryos are stored in a designated security area with controlled access, either in incubators or in dewars. In the majority of cases, day 3 embryos are sourced fresh from couples undergoing treatment when they are excess to requirements, because the couple do not want to freeze them or because they are of too poor a quality to freeze. Stored frozen embryos are occasionally obtained for research from patients who no longer wish to use them in treatment. They remain in their storage dewar until used in research, though patient records are marked to indicate research consent has been provided and the embryos are logged as being consented for research use. Researchers are advised of the date of expiry of consent to storage and procedures are in place to ensure embryos are used prior to this time. Laboratory equipment at the centre is, including that used in research, on a database which ensures regular servicing and maintenance. Equipment is used according to manufacturer recommended protocols and is electrically tested annually. Servicing records were present though the PR committed to tidy them up in the near future to allow easier searching for specific documentation. The cryostore is fitted with a low oxygen level alarm and the centre has a written protocol outlining the appropriate response to the alarm. The cryostore is locked though the dewars within are not. The level of security was considered appropriate by the inspectorate as the cryostore is within a secure laboratory, within a secure dedicated building. Issues for consideration None Executive recommendations for Licence Committee None Areas not covered in by this inspection All areas covered Page 7 of 17

8 3. Donation of material Desired outcome: Donors are recruited appropriately and any research carried out on their embryos is in accordance with their consent. Summary of findings from inspection: Recruitment of donors Ensuring prospective donors have access to further guidance Ensuring prospective donors have time to consider donation properly Ensuring patient consent is not breached Donor and patient records Prevention of coercion of prospective donors Highlighted areas of firm compliance The recruitment of donors is covered by a written procedure and includes a checklist on the patient laboratory sheet to verify documentation and consents are appropriate for research donation and that written information has been provided. According to standard practice, as defined by the PR and NL, patients are provided with written information regarding the research project by the nursing staff before the start of treatment, along with other treatment information. Written research information is retained by the patients and the nurses have been briefed regarding the research projects by the PR and NL at clinical meetings. Patients are advised verbally and in written information that they can discuss research donation with nurses or members of the embryology staff. Research consent forms are usually signed at the same time as HFEA and local treatment consent forms, if patients wish to consent to research donation. This process is usually performed in the presence of nursing staff who can either answer patient questions or guide the patient to an embryologist. According to this recruitment procedure, research donors were considered by the inspectorate to be provided enough time to consider their donation and no complaints regarding this, or coercion, have been received by the HFEA or the centre. Donors receive no benefits. Donated material is marked with the patient s CARE identification number and embryo number. This allows tracking from research records to patient records. A robust system is in place for the identification of cryopreserved material reaching the end of the consented storage period Issues for consideration Review of 6 sets of patient records indicated that consent for research donation was obtained on the day of embryo transfer in four cases between 5 th May 2008 and 26 th September This is contrary to the recruitment practice outlined by the PR and NL. When questioned about this contradiction, the PR accepted consenting occurs occasionally on the day of embryo transfer, but emphasised that research information would have been provided to the patient by the nurses long before the consent was taken, and thus informed consent would have been taken. Unfortunately there was no record in the patient notes of the date on which Page 8 of 17

9 written research information was provided to the patient in either of the four cases, thus compliance with Standards S (c) (the Centre shall ensure that..the person donating gametes and/or embryos to research should be given sufficient time to consider the implications of their donations before the donated material is used in any research programme) could not be evidenced. The PR should also review the practice of consenting patients on the day of embryo transfer. The inspectorate suggests this practice is discontinued as it is contrary to the Centre s recruitment procedure, as described by the PR. If it is continued, the PR should ensure compliance with Standards S ( Where embryos are used in research, the Centre shall ensure that clinical and research roles are separated, so that individuals involved in advising patients regarding clinical decisions about their licensed treatment, are not involved in the research project to which patients are considering donating embryos ). Executive recommendations for Licence Committee The PR should ensure that records are kept in patient notes of when research information is provided to patients. The research consenting procedure needs to be updated to include the stage of treatment at which written research information should be provided and that the provision of research information should be logged in patient records. It is suggested that the Centre stop consenting patients for research on the day of embryo transfer, and if it continues, the PR ensures compliance with Standards S Areas not covered in by this inspection All areas covered Page 9 of 17

10 4. Patient information and consents Desired outcome: Patients are provided with appropriate information which allows them to give informed consent. Summary of findings from inspection: Patient information Consent forms Patient information for projects deriving embryonic stem cells Consent forms for projects deriving embryonic stem cells Highlighted areas of firm compliance During the inspection, the PR informed the inspectorate that the project would be attempting to confirm whether useful genetic material was present in biopsied material. The nature of the testing was discussed, as was the possibility of a change being needed to patient information. The PR has decided to use a DNA staining protocol to test for nucleic acids in the biopsied material, rather than a genetic information providing test. Patient information has been modified to reflect this and submitted to the HFEA Executive. It is noted that this test does not constitute a test providing genetic information, so the requirements related to secondary genetic testing and patient information do not apply. The revised patient information and consent forms were reviewed by the inspectorate and were found to be compliant with the Code of Practice, 7 th edition. They were considered well prepared and informative. The consent for research is checked by an embryologist at least three times during the treatment cycle before embryos are donated into the research pathway, and a checklist in the patient record ensures the consent is checked at the time of donation. If a patient were to withdraw consent, an embryologist (usually the NL or PR) would be notified and the patient record immediately modified to note the withdrawal. Issues for consideration None Executive recommendations for Licence Committee None Areas not covered in by this inspection All areas covered Page 10 of 17

11 5. Scientific practice R A novel approach for extracting cells during embryo biopsy without the use of acid tyrode s Desired outcome: Research is carried out in accordance with licence conditions and makes progress towards achieving stated aims Summary of: Peer review Summary The PR stated on inspection in November 2007 that between 01/03/2007 and 22/11/2007, 47 embryos were used. On this inspection, the PR stated that 41 embryos were used between the last inspection on 22/11/2007 and 29/09/2008. Thus the project has used a total of 88 embryos. Across the whole project, blastocyst survival rates of 35%, 22% and 44% were observed in the acid tyrode s, the laser and the enucleation arms, respectively. The PR said that progress has been impeded this year because fewer frozen embryos have been donated to the project than anticipated. In addition, the PR has previously stated that in treatment cycles at the centre, a large proportion of embryos are cultured to the blastocyst stage for transfer and/or freezing. This has impacted on the provision of fresh day 3 embryos suitable for the project. The PR predicts that the project will use 60 fresh embryos and 20 frozen embryos next year. The Centre has clear procedures and practices to prevent the maintenance of an embryo in culture beyond 14 days or the appearance of the primitive streak, if earlier. The Centre has recently rationalised the recording of embryos used in research into a single log book. This is an advance on the previous method which involved several logs being maintained. Summary of audit of stored and biopsied material Frozen embryos for research may be stored in a locked dewar storage facility, however there was only one set of frozen embryos in storage on the day of inspection, so a dewar spot check was not performed. An audit of stored material is performed annually which also verifies all embryos have been used when stated. Renewed project objectives The PR stated in the progress report: Future objectives i) To continue to collect data in the 2 current investigation arms ii) To even up the numbers between the 2 arms. iii) To investigate the possibility of testing the biopsied nuclear material. Methods These do not differ from the previous year for the biopsy methods and the assessment of continued development of the embryos. We intend to discuss and investigate the most appropriate way to confirm the presence of nuclear material in the biopsies. In the first Page 11 of 17

12 instance this will be a simple staining method. During inspection, the possibility of genetic testing of biopsied material was discussed. Subsequently the PR has decided to confirm the presence of genetic material using nuclear staining as opposed to a molecular biological method which would provide genetic sequence information Discussion It would appear from the figures presented that the embryos being biopsied by the novel method have a high potential for continued development. As the numbers are still low in both groups it is essential to expand the data by carrying out more procedures In order to remove the possibility that this group benefited from a potentially advantaged set of embryos. As the laser is the routine method use in our clinic for treatment PGD cases we have replaced the control group (acid tyrode s) with a laser biopsy method in this reporting period. Although the results presented seem to indicate that the development of these embryos is lower than the acid tyrode s group it should be noted that within clinical cases this is not the case. It is possible that the embryos used in the research group were of lower grades that those allocated to the novel method and for this reason it is important that both of the groups are added to in order to remove any possible skew. We intend to consider the most appropriate way to confirm the presence of nuclear material in the biopsies. In the first instance this will be a simple staining method. In discussion with the genetics lab we will decide on the most appropriate way to store the material for amplification and testing of DNA. Summary of research undertaken The PR stated in the progress report: The data thus far indicates the embryos have an improved chance of developing to the blastocyst stage following the novel method of biopsy (enucleation) compared to using the laser. More numbers are needed in both groups to test significance. Also, it is yet to be established how easy it would be to analyse the DNA removed in the biopsy in order to test for genetic diseases. To this end some recently derived biopsies have been stored frozen ready for testing. From now on all biopsied material will be frozen and stored in the laboratory for later analysis. The acid tyrode s arm of the investigation was discontinued in November Embryo usage In this period ( ), 41 embryos; 25 using laser, 16 the novel method In total ( ), 88 embryos; 23 using acid tyrode s, 40 laser, 25 the novel method Results In this period ( ) Laser biopsy 6 embryos survived to blastocyst stage out of 25 biopsied, i.e. 24% Enucleation 11 blastocysts out of 16 biopsied, i.e. 68.7% Page 12 of 17

13 In total ( ): Biopsy method Number biopsied at day 3 Number reaching blastocyst stage % blastocyst formation Acid tyrode s Laser EN Totals Peer review comments (if applicable) The original application for R0177 was considered by an external reviewer who supported renewal of the research licence. The reviewer noted that the use of human embryos in the project is justified and that all work completed appeared to be covered by the original application. Progress appeared satisfactory taking into account that the progress report covers only a part year (7 months) and that the number of available embryos has been lower than originally estimated. The reviewer considered the numbers of embryos used were in line with original predictions making allowance for supply issues mentioned by the PR. The reviewer noted a predicted use of 60 fresh embryos is in line with the 41 embryos used so far in the project, but 20 frozen embryos may be more difficult to achieve considering the failure to obtain any frozen embryos for the study so far. The reviewer also noted small arithmetic errors in embryo usage calculations and the reviewer had some confusion regarding which period of work data was derived from. The reviewer questioned whether decisive results could be obtained within the twelve month extension of the project applied for. The peer review was discussed with the PR on inspection. As a result the PR submitted a revised application post-inspection which: 1. Applied for a licence for 3 years (the PR had thought they could only apply for one year). 2. Corrected the embryo usage data. 3. Emphasised which period data was derived from in the discussion of results. 4. Included the testing of biopsied material using a staining method. 5. Revised the licensed activities to remove those activities performed under the treatment and storage licence. Patient information was also modified to include that biopsied material would be investigated using a staining method and was also submitted for review The revised application was sent to the peer reviewer who replied (14/11/2008): In my initial peer review of this application (dated 03/11/08) my recommendation was for acceptance but I did raise some issues concerning apparent discrepancies in some of the data presented and some incomplete sections of the application. It was also my opinion that a one year licence was likely to be insufficient to complete the project. Page 13 of 17

14 In the light of my comments and following discussion of the project with an HFEA inspector the applicants have made some amendments to their original application. In the revised application data concerning embryo numbers have been corrected and it is now clear how many embryos have been used in each phase of the project. Further details of the proposed experimental procedure under the new licence have been given. The applicants have also now applied for a three year licence which I believe is more realistic in terms of obtaining a clear and definitive answer to their research questions. My recommendation is therefore to accept the application in this revised form. Issues for consideration Treatment and research embryology is performed within the same laboratory, by the same personnel. The embryos donated to research also remain labelled with patient details. The separation of treatment and research activities was discussed with the PR. The PR outlined that the project uses fresh embryos considered unfit for treatment and/or freezing, and that fitness/unfitness is defined by criteria clearly stated within laboratory procedures. She noted that embryo grading for transfer was normally performed in the morning by a different embryologist from that who would actually perform embryo transfer and/or freezing later in the day. It was accepted by the PR that the second embryologist may sometimes re-grade the embryos, dictating treatment or research use, and could also perform the research work. The PR added however that this was rare, that the selection of embryos for treatment/freezing is reviewed with the patient and the clinician, and that the embryologists tended to promote embryo freezing over research, hence the low rate of embryo donation to the project and the low grade of those donated. The PR considered there was little possibility of research goals impacting on treatment plans. The inspectorate accept this assessment, however they request the PR to review laboratory procedures to ensure effective, demonstrable, separation of research and treatment activities. Executive recommendations for Licence Committee None Areas not covered in this inspection All areas covered Report compiled by: Name Andrew Leonard Designation HFEA inspector Date 20 th November 2008 Page 14 of 17

15 Appendix A: Centre Staff interviewed PR, NL 1 embryologist Appendix B: Licence history The centre has held a number of research licenses as detailed below: R A novel approach for extracting cells during embryo biopsy without the use of acid Tyrode s active from March 2008 Feb 2009 R A novel approach for extracting cells during embryo biopsy without the use of acid Tyrode s active from March 2007 Feb 2008 R Evaluation of blastocoele collapse versus expanded blastocysts for successful cryopreservation using vitrification active from March 2007 Feb 2008 R A Novel Protocol For Extracting Cells During Embryo Biopsy Without The Use Of Acid Tyrode s - active from September 2002 to 2004 R Assessment Of Human Spermatid Chromosomes After Injection Into Hamster Oocytes active from January 1999 to 2000 R Evaluation On The Use Of Spermatids For Achieving Conception In Vitro active from February to May 1998 R Diagnosis Of The Common Aneuploidies In Human Pre-Implantation Embryos Using Fluorescent In Situ Hybridisation active from April 1999 to March 1996 R In-Vitro Maturation And Cryopreservation Of Human Oocytes active from July 1994 to 1995 None of the licenses had conditions or recommendations attached Page 15 of 17

16 Appendix C: RESPONSE OF PERSON RESPONSIBLE TO INSPECTION REPORT Centre Number 0101 Name of PR Dr Lucy Jenner Date of Inspection 4th November 2008 Date of Response By , 23 rd December 2009 Please state any comments regarding the inspection and actions you have taken or are planning to take following the inspection with time scales I agree with the main points raised in the inspection report, and am pleased with the decision to consider licensing the project for 3 years. Since the inspection I have raised the question of the timing of information giving and consent taking. The arrangement is now that the Clinical Secretaries enclose the Research Patient Information Document in the pack sent out to patients prior to treatment commencement. This pack contains the patients treatment protocol as well as all the treatment consent and information documents. The secretaries have agreed to document the enclosure of the research PI document in the patients records. The Clinical SOP has been altered to reflect this change and is attached with this response. I am considering the request to separate treatment from research activity and need to discuss with the team. This will either be achieved by a rota, or by documenting the embryologists involved at both stages. The PR subsequently added by on 5 th January 2009: All the embryologists are aware that consent is not to be taken on the day of embryo transfer. The separation of treatment and research activities is something I will make the team aware of when we have a lab meeting (due to Christmas and ACE I haven't had the chance to discuss this yet). I indicated to you on the day of inspection and in my response that I am aware of the standard, but that I feel that no-one in my team would be influenced in this way. As the team here is essentially a clinical team it is possible that there could be an overlap, but what I intend to do is make everyone aware that the person using the embryos for research should not be the one who has the discussion with the patient prior to the embryo transfer regarding the fate of the embryos. Page 16 of 17

17 2. Correction of factual inaccuracies Please let us know of any factual corrections that you believe need to be made (NB we will make any alterations to the report where there are factual inaccuracies. Any other comments about the inspection report will be appended to the report). Page 17 of 17

18 Research Licence Committee Meeting 15 January Bloomsbury Street London WC1B 3HF MINUTES Item 1 Research Project RO177: A novel approach for extracting cells during embryo biopsy based at CARE Nottingham (0101) Licence Renewal Members of the Committee: Emily Jackson, Lay Member Chair Richard Harries, Lay Member David Archard, Lay Member Neva Haites, Professor of Medical Genetics, University of Aberdeen In Attendance: Chris O Toole, Head of Research Regulation Claudia Lally, Committee Secretary Providing Legal Advice to the Committee: Mary Timms, FFW Solicitors Declarations of Interest: members of the Committee declared that they had no conflicts of interest in relation to this item. The following papers were considered by the Committee: papers for Licence Committee (40 pages) no papers were tabled. 1. The papers for this item were presented by Andrew Leonard, HFEA Inspector. Dr Leonard informed the Committee that this project is comparing three methods of embryo biopsy and looking at survival rates for the embryos up to blastocyst stage. The research project has been licensed for two years and the team are experienced and well qualified. Dr Leonard reported that the Person Responsible has applied to renew the licence for three years since more data needs to be collected in order to make significant comparisons of the three techniques. The application estimates the use of 60 fresh and 20 frozen embryos in the next year of the research. Dr Leonard affirmed that the Person Responsible has now submitted a satisfactorily completed Person Responsible Entry Programme (PREP) assessment. 2. Dr Leonard informed the Committee that the inspection found that four donors had consented to donate embryos to the project on the day of egg collection. He

19 added that the Person Responsible has now stated that from now on consent will be sought from potential donors well before the onset of treatment. Dr Leonard informed the Committee that he had previously understood that measures had already been put in place to ensure that consent takes place well before treatment commences and will therefore be closely monitoring this issue to ensure that it has finally been addressed. 3. Another issue Dr Leonard brought to the Committee s attention is that the Person Responsible should do more to ensure effective and demonstrable separation of research and treatment at the centre. Dr Leonard added that during discussions on this point with the Person Responsible he has been satisfied that processes are now in place to ensure this separation. The Committee s Decision 4. The Committee noted that the Person Responsible had now submitted a satisfactorily completed PREP. The Committee also noted that steps have been put in place to ensure that there is a sufficient period of time between the consent process and egg collection. Furthermore, the Committee noted that the Person Responsible had reassured Dr Leonard that there are now procedures in place to ensure the separation of clinical practice and research. 5. The Committee agreed that the activity to be licensed is use of embryos in research and storage of embryos for use in research. The Committee noted that this activity is not prohibited under the Human Fertilisation and Embryology Act The Committee agreed that this activity appears to be necessary or desirable for the following specified purpose: developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation Human Fertilisation and Embryology Act 1990 Schedule 2, paragraph 3(2)(e) 7. The Committee agreed that they were satisfied that the proposed use of human embryos is necessary for the purpose of the research, since it would not be possible to test biopsy methods for use on human embryos on anything other than human embryos. 8. The Committee noted that the patient information and consent forms are satisfactory, as they have previously been seen and approved by the Committee. 9. The Committee were satisfied that the requirements for granting a licence under section 16 of the Human Fertilisation and Embryology Act 1990 were

20 fulfilled. They decided to renew the licence for the research for a period of three years. Signed. Date.. Emily Jackson (Chair)