Research Licence Renewal Inspection Report

Transcription

1 Research Licence Renewal Inspection Report Project Title Derivation of Pluripotent Human Embryo Cell Lines Research Licence Number R a Person Responsible Nominal Licensee Inspection type Professor Austin Smith Professor Tom Blundell Renewal Licence expiry date 30 November 2009 Centre Number 0252 Centre Name Wellcome Trust Centre for Stem Cell Research, University of Cambridge Centre Address Treatment centres donating to these research projects Inspection date 10 June 2009 Wellcome Trust Centre for Stem Cell Research University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR Bourn Hall (Centre 0100) Licence Fee paid? Invoiced for a renewal on 31/03/09 and paid on 28/04/09. Licence Committee Date 16 September 2009 Inspector(s) Mrs Sarah Brain Mrs Gill Walsh Miss Jenny McLaughlin Page 1 of 22

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. This report covers the period between 29 th August 2008 and 10 th June Brief Description of the Project The title of project R0178 is Derivation of Pluripotent Human Embryo Cell Lines. This is a University-based research only centre and the current licence is due to expire on the 30th November Lay summary The lay summary of the research project is: The pre-implantation embryo develops two distinct cell populations, an outer layer called trophectoderm that is destined to form the placenta, and an inner group of pluripotent cells that will be responsible for subsequent growth, differentiation and development of the foetus. In mice it has proven possible to isolate both types of cell and to propagate them in the laboratory as so-called trophoblast stem cells and embryonic stem cells respectively. The purpose of the proposed research is to establish similar stem cell lines from human embryos. Such cells would undergo prolonged multiplication whist remaining capable of differentiation. The interests in this are several fold. The process of isolating and characterising stem cells will improve understanding of the requirements for growth and survival of pre-implantation human embryos. This would be anticipated to lead to direct benefits for programmes for the treatment of infertility involving in vitro fertilisation and for pre-implantation genetic diagnosis. The differentiation of human pluripotent stem cells provides a model for early postimplantation embryogenesis and initiation of human foetal development. Characterisation of stem cell differentiation can be anticipated to yield new knowledge of normal development of human embryos and congenital disease. Pluripotent embryonic stem cells are closely related to the cancerous stem cells of a type of tumour known as teratocarcinoma. Their study will therefore constitute an important resource for developing a better understanding of, and treatment for, this kind of cancer. Human pluripotent stem cells should constitute a continuous and expandable source of differentiated cells. Resultant availability of normal human cell types would provide powerful screening tools for discovery of new Pharmaceuticals and for toxicological determinations. Page 2 of 22

3 Pluripotent stem cells are expected to give rise to functional adult types of cell, for example nerve cells and heart cells. This creates the potential for developing cell replacement and tissue repair therapies for a range of serious human illnesses and injuries such as Parkinson's disease, diabetes and cardiac infarction. Growth and differentiation of trophoblast stem cells would provide a model for human placental development and a normal reference for malignant trophoblast known as choriocarcinoma. Each of the above goals can only be met by study of human embryos and derivative stem cells. Research licence purposes and activities The licence was granted for the following purposes: Increasing knowledge about the causes of congenital disease Sch 2 3(2)(b) Human Fertilisation and Embryology Act 1990 Increasing knowledge about the development of embryos Purposes) Regulations 2001 s2(a) Human Fertilisation and Embryology (Research Increasing knowledge about serious disease 2001 s2(b) Human Fertilisation and Embryology (Research Purposes) Regulations Enabling any such knowledge to be applied in developing treatments for serious disease Human Fertilisation and Embryology (Research Purposes) Regulations 2001 s2(c) Research activities Use of donated embryos for research Storage of licensed material Creation of embryos for research Derivation of human embryonic stem cells Cell nuclear replacement X X X Changes/ improvements since last inspection No changes to premises, equipment or licensed staff since the last inspection Page 3 of 22

4 Additional licence conditions and recommendations and actions taken by centre since last inspection Condition N/A A Complied Y/N Changes/Improvements made since last inspection Recommendations Action Taken The audit of donor records indicated that on one occasion embryos have been used in research without the consent of one of the gamete providers (egg donor).schedule 3 6- (3) of the HFE Act 1990 requires that An embryo the creation of which was bought about in vitro must not be used for any purpose unless there is effective consent by each person whose gametes were used to bring about the creation of the embryo to the use for that purpose of the embryo and the embryo is used in accordance with those consents. This breach is to be reported to the HFEA as an incident. Procedure to be put in place to ensure that in the future no embryos are used in research without the consent of both gamete providers. The system to ensure that embryos do not develop after 14 days or (if earlier) the appearance of the primitive streak does not specify provision for illness or incapacity of the primary investigator by involvement of a second individual to ensure compliance with Code of Practice Standard It is recommended that the protocol be amended to incorporate this safeguard. Procedure to be documented It is recommended that the PR communicates with the supplying centres on a frequent basis to ensure that members of staff consenting Page 4 of 22 The breach was reported to the HFEA as an incident on the 28 th August 2008 and was duly investigated by the HFEA clinical Governance team. The PR informed the HFEA that he had reminded the clinical coordinators at the centre involved that embryos generated using donated gametes would not normally be considered for this research. The paperwork for transferring embryos to the research was amended to require affirmation that consent had been obtained from both gamete providers. This form was supplied to the HFEA. The centre supplying embryos to this project has changed from centre 0070 to centre 0100 since the last inspection and the PR stated that they now avoid using embryos created with donor gametes within the research project. The protocol has been amended as recommended. A copy of this protocol was sent to the HFEA shortly after the interim inspection in The PR stated that following the inspection he supplied centre 0070 with a copy of the annual report.

5 patients for donation to research are kept informed about the project and are able to answer questions about the research. The PR stated that they have only recently received embryos from this centre and that he is planning to send them a copy of the progress report to update them on the results from the project so far. It is recommended that the PR reviews the service records and ensures that all equipment is monitored and maintained. It is recommended that the PR discusses the consenting processes with staff at centre 0070 and ensures that he is familiar with the processes and assured that the material used in the research project has been donated in an ethical manner. In particular, the PR must ensure compliance with Code of Practice Standard The PR must also satisfy himself that the information provided to potential donors is in accordance with Code of Practice Guidance G It was also recommended that the PR obtains and reviews a copy of centre 0070 s protocol for obtaining patient consent to research to ensure that the consent process is in accordance with the requirements of the Code of Practice. The patient information states that patient identifying information will remain confidential and will not be disclosed to researchers at centre This is not actually the case as consent forms sent to the research centre include patient identifying information, and the straws/amps containing the embryos are labelled with patient identifying information. The PR should review this and must ensure that the patient information reflects practice. The centre supplying embryos to this project has changed from centre 0070 to centre 0100 since the last inspection. Evidence of communication between the research team and the new supplying centre, centre 0100, was provided during the inspection. Staff were able to confirm that equipment is subject to annual servicing. Records to support this were provided during the inspection. The centre supplying embryos to this project has changed from centre 0070 to centre 0100 since the last inspection. The PR explained that the research team had spent two days at the new supplying centre so that they understood consenting and laboratory practices that take place there. The PR explained that the research team had spent two days at the new supplying centre so that they understood consenting and laboratory practices that take place there. The centre supplying embryos to this project has changed from centre 0070 to centre 0100 since the last inspection. The PR has obtained a copy of centre 0100 s protocol for obtaining patient consent to ensure that the consent process is in accordance with the requirements of the Code of Practice. Patient information still states that patient identifying information will remain confidential and will not be disclosed to researchers at centre Whilst the consent forms and laboratory sheets which are sent to the research centre with the donated embryos were seen to be redacted so that patient identifying information remains confidential, the straws containing embryos are labelled with patient identifying information. The PR has stated that there is no straightforward way for Bourn to remove identifiers from the straws Page 5 of 22

6 The patient information referred to date of expiry when referring to fresh embryos. This was discussed with the PR who confirmed that this was a mistake, copied from the frozen embryo information, which will be amended. and that since they do not keep the straws and don't record anything written on them, the embryos remain for all practical purposes anonymous to the research team. The PR informed the HFEA that the patient information for fresh embryos has been amended to delete reference to date. The patient information supplied to the HFEA during the inspection still included this reference but was of a generic nature used for all patients. Summary for Licence Committee Inspection findings Overall the inspectorate was satisfied that the centre demonstrated compliance with regulatory requirements for organisation, premises and equipment, donation of material, patient information and consents and scientific practice. However, the Committee are asked to note the following: Progress reports not submitted in line with requirements of General Direction D2006/4. The PR has been reminded of the requirements for submission of progress reports. The written patient information does not outline all of the tests that may be performed as part of the licensed research project on embryos. It is recommended that the information be reviewed to ensure that it reflects the research undertaken. Renewal application The PR has applied for the licence to be renewed for a period of three years and has proposed that the licence be renewed under the following purposes: -Promoting advances in the treatment of infertility Human Fertilisation and Embryology Act 1990 Sch 2 3(2)(a) -Increasing knowledge about the causes of congenital disease Human Fertilisation and Embryology Act 1990 Sch 2 3(2)(b) -Increasing knowledge about the development of embryos Human Fertilisation and Embryology(Research Purposes) Regulations 2001 s2(a) - Increasing knowledge about serious disease Human Fertilisation and Embryology (Research Purposes)Regulations 2001 s2(b) - Enabling any such knowledge to be applied in developing treatments for serious disease Human Fertilisation and Embryology (Research Purposes) Regulations 2001 s2(c) The peer reviewer considering the application agreed that the research would be necessary or desirable under those purposes and although the reviewer initially raised concerns about Page 6 of 22

7 the methodology employed by the research team he/she has since agreed that the application is appropriate. The Executive support this application and recommend that the licence be renewed without additional conditions for a period of three years. Breaches of the Act, Standard Licence Conditions or Code of Practice: The table below sets out matters which the Inspection Team considers may constitute breaches of the Act, Standard Licence Conditions and/or the Code of Practice, and their recommended improvement actions and timescales. The weight to be attached to any breach of the Act, Standard Licence Conditions or Code of Practice is a matter for the Licence Committee;- Breach Action required Time scale Progress reports have not been submitted at 6 monthly intervals. Standard Licence Condition 19.5 requires that the centre shall provide the Authority with a progress report as specified in Directions. The relevant General Direction, D2006/4, requires that progress reports be submitted on a 6 monthly basis. Timely submission of progress reports. 1 st December A copy of the certificate of the licence is not displayed at the research unit. Standard Licence Condition 19.3 requires that A copy of the Certificate of Licence (first page of the licence) describing the activities authorised by the licence must be displayed at the licensed premises in a position or positions in which it can easily be read by persons who are receiving treatment services or providing gametes or embryos for use for the purpose of activities governed by the Act, or who may wish to do so. It should be noted, however, that this centre is a stand alone research centre which patients do not visit. The written patient information that is currently in use does not explain that donated embryos may be used subject to immunostaining and used to help characterise cells present in the inner cell mass. Standard Licence Condition Display of certificate of the licence. Patient information, provided in written and oral form, to be reviewed to ensure that it accurately reflects the tests Page 7 of 22 The PR has notified the HFEA Executive that action has been taken in response to this breach: at 16:38 on the day of inspection, after the inspection team had left the premises, the PR ed to confirm that the licence was now displayed. 1 st September 2009.

8 A19.6 requires that before donors give consent to donation of their embryos for use in the research project, they must be given oral information supported by relevant written information which confirms the specific research project and any tests that may be performed as part of the licensed research project on embryos. performed. Non-Compliance Area for improvement Action required Time scale N/A Recommendations Area for improvement Action required Time scale The patient information states that patient identifying information will remain confidential and will not be disclosed to researchers at centre This is not actually the case as the straws/amps containing the embryos are labelled with patient identifying information. The PR to ensure that the patient information reflects practice. With immediate effect. Proposed licence variations None Page 8 of 22

9 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 Principal investigator 1 Scientists 2 Laboratory technicians 0 Support staff (receptionists, record managers, 0 quality and risk managers etc) Highlighted areas of firm compliance The PR has completed the PR entry programme and his responses were considered to be satisfactory by the Executive. The project is funded by research grants from the Medical Research Council. This information is provided to patients within the written research information. The project has been approved by a properly constituted ethics committee. An organisational chart has been developed which clearly outlines the reporting relationships within the research team. Since the last inspection, the centre supplying embryos to this project has changed from centre 0070 (The Bridge Centre) to centre 0100 (Bourn Hall Clinic). The research team explained that their main contact at Bourn Hall Clinic is Bourn Hall s senior scientist and that they communicate frequently with her, either via or by phone. Evidence of communication between the two groups was provided during the inspection. Issues for consideration Although a written adverse incident handling policy is in place it was noted that this did not include information on the HFEA reporting requirements. Although there is no Code of Practice requirement that this information be included the inspectorate suggested that the protocol be updated to reflect that all adverse incidents must be reported to the HFEA, by Page 9 of 22

10 telephone within 12 working hours of the identification of the adverse incident and submit an adverse incident report form within 24 working hours, as this would assist future compliance with Code of Practice Standard Since the inspection the protocol has been updated and a copy was sent to the HFEA Executive on the 11 th June Progress reports have not been submitted in accordance with the timelines outlined in General Direction D2006/4. Since the licence was awarded in December 2006 the HFEA Executive received progress reports in July 2007, November 2007, July 2008 and information on progress was also provided as part of this renewal application which was received in May A progress report was not received in December The PR is reminded of Standard Licence Condition 19.5 which requires that the centre shall provide the Authority with a progress report as specified in Directions. The General Direction which is currently in force and relates to progress reports, D2006/4, requires that the PR shall submit a progress report to the HFEA every six months from the date the licence was granted. The next progress report will therefore be due on the 1 st December Executive recommendations for Licence Committee Note potential breach of General Direction D2006/4. Areas not covered in by this inspection None Page 10 of 22

11 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 There have been no changes to premises or equipment since the last HFEA visit. Staff reported that they have all necessary pieces of equipment to meet their objectives. Embryos donated to research are stored in a research dewar which is kept in the cryostore in the basement of the building. This store is secured with a swipe card mechanism. The area can be accessed by university staff who are not on the centre s licence but the dewar was seen to be locked. Staff confirmed that the key is held by two licensed researchers only. A low oxygen monitor is in place within the cryostore and a personal low oxygen alarm is also available for staff to use. The protocol for response to the low oxygen alarm was seen to be displayed outside the door to the cryostore. The research laboratory is secured using a key pad lock. On the day of the inspection this lock was not set but the principal investigator explained that this is because there were no embryos in the laboratory. A sample of the research equipment was seen to have evidence of recent servicing. Research staff reported that equipment is subjected to service on an annual basis. Records were also supplied as evidence of this. Issues for consideration During the inspection it was noted that a copy of the certificate of the licence was not displayed at the research unit. The PR was reminded that he should ensure compliance with Standard Licence Condition 19.3 which requires that a copy of the Certificate of Licence (first page of the licence) describing the activities authorised by the licence must be displayed at the licensed premises in a position or positions in which it can easily be read by persons who are receiving treatment services or providing gametes or embryos for use for the purpose of activities governed by the Act, or who may wish to do so. It should be noted, however, that this centre is a stand alone research centre which is not visited by patients. The Committee are asked to note that the HFEA Executive inspectorate were informed shortly after leaving the centre that action had been taken in response to this breach and that, according to the PR, the licence is now on display. Executive recommendations for Licence Committee None Areas not covered in by this inspection None Page 11 of 22

12 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 Highlighted areas of firm compliance Roles between treatment and research are separated as this centre is a research only centre (S.8.4.1). Since the last inspection, the centre supplying embryos to this project has changed from centre 0070 (The Bridge Centre) to centre 0100 (Bourn Hall Clinic). The PR explained that his team visited Centre 0100 for two days in August 2008 so that they could meet the embryologists, observe the techniques used at Bourn Hall Clinic for thawing and fixing embryos and so that they could understand the process of obtaining consent from possible donors. This outcome of this visit was seen to be documented in a file note which was provided to the inspection team. The PR has also obtained a copy of Bourn Hall Clinic s protocol for obtaining consent. Patients have access to discuss the implications of donating material to research with an individual independent of the research project. Contact details for this individual are provided within the written patient information. The senior scientist at Bourn Hall Clinic informs the research team when embryos have been donated for research and is responsible for transporting them, along with the relevant paperwork to centre The inspection team were informed that this individual is also responsible for ensuring that the staff at Bourn Hall Clinic are kept up to date with research activities and the implications for patients of donating to research. Researchers receive clear information on the statutory storage period expiry date. Laboratory forms provided by the supplying centre were seen to include this information. Copies of the specific research consent forms are also supplied to the researchers. It was noted that all patient identifying information on these documents had been redacted and the PR explained that they no longer receive confidential information about the embryo donors. On arrival at the centre, the researchers aim to use the embryos as soon as possible. For those embryos which will remain in storage, a bring forward system is in place. The spreadsheet used to support this system was provided at the inspection, this clearly defined the statutory storage expiry dates and when embryos had arrived and been used at the centre. There is a procedure in place regarding the withdrawal of material from use in research if a donor withdraws consent before material is used in the project. This is supported by a written protocol. Page 12 of 22

13 Issues for consideration None Executive recommendations for Licence Committee None Areas not covered in by this inspection Prevention of coercion of prospective donors Page 13 of 22

14 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 Summary of audit of patient records Five sets of records from patients who donated embryos to this project were reviewed and were seen to contain valid consent forms. The audit of donor records also revealed that in one case embryos created using donated eggs had been used within the research but that staff had checked that the egg donor had consented to use of eggs in research and provided the research team with evidence to that effect. Highlighted areas of firm compliance Written patient information was considered by the inspectorate to be clear and lay intelligible. Issues for consideration Overall the patient information sheet and the consent form were seen to comply with the requirements for documented information as outlined in the Code of Practice (7th Edition) and Licence Conditions. However, the written patient information that is currently in use does not explain that donated embryos may be used subject to immunostaining and used to help characterise cells present in the inner cell mass. Standard Licence Condition A19.6 requires that before donors give consent to donation of their embryos for use in the research project, they must be given oral information supported by relevant written information which confirms the specific research project and any tests that may be performed as part of the licensed research project on embryos. It is therefore recommended that the PR reviews the patient information, provided in written and oral form, to ensure that it accurately reflects the tests performed. At the previous inspection it was noted that although the patient information stated that patient identifying information will remain confidential and will not be disclosed to researchers at centre 0252 the consent forms sent to the research centre included patient identifying information, and the straws/amps containing the embryos were labelled with patient identifying information. This issue was reviewed on this inspection and during an audit of research records it was seen that the consent forms and laboratory sheets that are now sent to the research centre with the donated embryos are redacted so that patient identifying information remains confidential. However, the straws containing embryos which have been donated for research remain labelled with patient identifying information. The PR has stated that there is no straightforward way for Bourn Hall to remove identifiers from the straws and that since they do not keep the straws and don't record anything written on them, the embryos Page 14 of 22

15 remain for all practical purposes anonymous to the research team. Whilst the Executive acknowledge the difficulties associated with redacting information on the embryo straws it is recommended that that the PR ensures that the patient information reflects practice, i.e. that the research team do have access to patient identifying information, albeit briefly. Executive recommendations for Licence Committee Note that patients are informed that their information will not be shared with researchers but that some identifying information is disclosed. Areas not covered in by this inspection None Page 15 of 22

16 5. Scientific practice Desired outcome: Research is carried out in accordance with licence conditions and makes progress towards achieving stated aims Summary of: Standard operating procedures Minimisation of material loss and wastage Ability to achieve set aims and objectives Summary The PR reported that there has been no change to the methods used within the project since the research licence was granted although they have introduced immunostaining as a technique for characterising the candidate pluripotent cell compartment in embryos developed to blastocyst in different culture conditions. The centre received 157 frozen embryos from centre 0100 between 1 August 2008 and 31 May 2009 and 141 of these had been used within the project at the time of the renewal application. In the original proposal, the PR had expected to use 100 frozen embryos and 25 fresh embryos within the project each year. The PR explained that not all embryos that were donated to the project could be used for stem cell derivation, as they did not have the necessary consent. Approximately fifty percent of the embryos were donated with a general consent to early embryo development research work. These embryos were used for the immunostaining part of this project. The remaining embryos were donated with consent to stem cell derivation. In the next 12 month period the PR expects to use 300 frozen embryos. The PR anticipates that these embryos will continue to be supplied by centre 0100 but that more of the embryos will have been donated for the stem cell derivation work. Summary of audit of stored and biopsied material The inspectorate were provided with a record of the embryos that are currently held in storage. This report stated that there are 28 embryos in store awaiting use and that all are being stored in accordance with the statutory storage consent period. Review of the log and the file indicated that no embryos are being stored outside the statutory storage period and the next embryos to reach their expiry date will do so on the 16 th December A spot check of embryos stored took place during the inspection. One set of embryos were chosen from the tank and the identification code shared with the inspectorate. The embryos were being stored in accordance with the statutory storage consent period. Renewed project objectives No changes to project aims and objectives. These objectives were: (i) To derive and characterise continuous stem cell lines from human embryos. Our focus is on pluripotent embryonic stem (ES) cells and secondarily on trophoblast stem (TS) cells, but it is also recognised that tissue stem cells may arise via spontaneous Page 16 of 22

17 (ii) (iii) (iv) (v) commitment of pluripotent cells during the derivation culture and that such tissue stem cells would be a valuable resource for biomedical research into tissue-specific diseases. To optimise the culture conditions for derivation and propagation of human pluripotent embryonic stem cells. In particular to develop serum-free and, if possible, feeder-free conditions. To establish a panel of between 10 and 20 phenotypically and karyotypically characterised human pluripotent stem cell lines and to deposit these lines in the UK Stem Cell Bank. To derive human embryonic stem cells carrying monogenic disease genes from embryos identified by pre-implantation genetic diagnosis. To investigate derivation of trophoblast stem cell lines from human embryos and, if derived, to deposit these in the UK Stem Cell Bank. Lay summary of research undertaken In the mouse, laboratory culture of embryos before implantation into the uterus can result in the generation of stem cells that can be multiplied for prolonged periods. One such stem cell is the embryonic stem (ES) cell. ES cells in the laboratory retain characteristic properties of early embryo cells, including most importantly the ability to make all types of cell found in the developing foetus and later in the adult. This property is called pluripotency. Mouse ES cells have been used to generate heart, nerve and blood cells in the laboratory that have been successfully transplanted into adult rodents. In the last few years it has been shown by several research groups, including our own, that similar pluripotent embryonic stem cells can be derived from human embryos that are left over from infertility treatment. Research on human ES cells has the potential to increase understanding of many serious human diseases, to contribute to the discovery and testing of new drugs to combat these diseases, and possibly to provide cells that can be transplanted to replace the damaged or dead cells in conditions such as Parkinson s diseases or Type I diabetes. In this project we aim to produce new human ES cell lines from donated embryos left over after infertility treatment. The embryos are maintained in the laboratory for a few days until they form a structure called the blastocyst. At that point the embryo is separated into its constituent cells which are then treated to attempt to promote formation of stem cells. We will use new conditions we have developed that allow propagation of stem cells without use of animal products. These defined conditions are important for future research and for eventual pharmaceutical and clinical applications. We will study the development of the pluripotent cell population in the embryo in these chemically defined conditions and then attempt to derive stem cells after dissociation using procedures we have developed for mouse and rat stem cell derivation. Once stem cells are multiplying stably they are called a cell line. We will compare the human ES cell lines developed in the defined conditions to determine how much their properties vary according to their individual genetic composition. This is currently unknown because available human ES cell lines have been obtained and propagated using a variety of different methods which are likely to influence their behaviour. It is also possible that other types of stem cell may develop spontaneously from separated embryo cells. While not the primary aim of this project, if such tissue stem cells do arise we will attempt to maintain them because they would be a valuable resource for biomedical research into tissue development and disease. All the stem cell lines derived in this project will be deposited in the UK Stem Cell Bank to Page 17 of 22

18 make them available to the research community. Peer review comments (if applicable) This renewal application has been considered by a peer reviewer. The peer reviewer agreed that the research is necessary or desirable for the following purposes: Promoting advances in the treatment of infertility Human Fertilisation and Embryology Act 1990 Sch 2 3(2)(a) Increasing knowledge about the causes of congenital disease Human Fertilisation and Embryology Act 1990 Sch 2 3(2)(b) Increasing knowledge about the development of embryos Human Fertilisation and Embryology(Research Purposes) Regulations 2001 s2(a) Increasing knowledge about serious disease Human Fertilisation and Embryology (Research Purposes)Regulations 2001 s2(b) Enabling any such knowledge to be applied in developing treatments for serious disease Human Fertilisation and Embryology (Research Purposes) Regulations 2001 s2(c) The peer reviewer initially raised issues about the application and recommended that the application be reviewed and resubmitted by the applicant. The peer reviewer s concerns have been addressed by the PR and the peer reviewer has since confirmed that he/she found the response to be appropriate. Issues for consideration None Highlighted areas of firm compliance Laboratory activities, including the procedure for disposal of material, are supported by documented standard operating procedures. These documents were provided during the inspection and were seen to have been subject to recent review. There is a procedure in place to ensure that embryos are not cultured for longer than 14 days or after the appearance of the primitive streak. This procedure has been documented in a protocol and the procedure seen to be followed in the sample of research records audited by the inspection team. Executive recommendations for Licence Committee None Areas not covered on this inspection None Page 18 of 22

19 Report compiled by: Name Designation Sarah Brain HFEA inspector Date 11 th June 2009 Page 19 of 22

20 Appendix A: Centre Staff interviewed PR and 2 members of the research team. Appendix B: Licence history Licence Status Type Active From Expiry Date R0178/1/a Active Research Project 01/12/ /11/2009 R0252/1/a Never Issued/Amended before offered to centre Research Project 01/12/ /11/2009 No additional conditions are on the current licence. Prior to 2006, a licence was held for this project but the premises were in Edinburgh University. The current licence was granted on the 1 st December 2006 following the move from Edinburgh to new premises at Cambridge University. Page 20 of 22

21 Appendix C: Response of Person Responsible to the inspection report Centre Number Name of PR Austin G. Smith. Date of Inspection 10 th June Date of Response 17 th July 2009 I have read the inspection report and agree to meet the requirements of the report. Signed.. Name Austin G. Smith. Date 17 th July Correction of factual inaccuracies Please let us know of any factual corrections that you believe need to be made. We will make alterations to the report where there are factual inaccuracies. A revised Patient Information sheet has been submitted to MREC for approval. The revisions are: (i) a statement that some embryos may be stained to detect markers of stem cells rather than used directly to make stem cell lines. (ii) a statement that patient names may briefly be visible to members of the research team, but will not be recorded. 2. Please use the space below to document any comments or additional information that you would like to be considered by a Licence Committee. Page 4, recommendation 1: Centre 0100 has now changed their policy regarding embryos created with donor gametes and are consenting them for this research. The Bourn SOP ensures that consent is obtained from the gamete provider. Page 21 of 22

22 3. Please state any actions you have taken or are planning to take following the inspection with time scales We welcome comments about the inspection on the inspection feedback form, a copy of which should have been provided at the inspection. If you require a copy of the feedback form, please let us know. Please return Appendix C of the report electronically to your inspector or in hard copy to: Regulation Department Human Fertilisation & Embryology Authority 21 Bloomsbury Street London WC1B 3HF Page 22 of 22

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