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Regulation of stem cell lines FAQs

Following the transposition of the European Union Tissue and Cells Directives (EUTCD) into UK law on 5 July 2007 (via the Human Tissue (Quality and Safety) Regulations 2007 – ‘the Regulations’), the remit of the HTA extended to cover the regulation of cell lines grown outside the human body for human application.

Background

Before the transposition of the EUTCD, cell lines derived from human embryos were subject to regulation by two regulatory bodies: the Human Fertilisation and Embryology Authority (HFEA) and the Medicines and Healthcare products Regulatory Agency (MHRA). The HFEA regulates the creation and use of embryos prior to the derivation of human embryonic stem (hES) cell lines for research. The MHRA regulates the use of investigational medicinal products (IMPs) in clinical trials in the UK – this would include the use of cell lines as a component of an IMP. Eventual authorisation of a medicinal product in the UK falls under the remit of the MHRA or the European Medicines Agency (EMEA).

It is widely acknowledged that the intention underlying the creation of cell lines is that they will eventually be used as a medicinal product. However, at the point of creation of any particular cell line it is not possible to predict whether it will eventually result in being used for human application in a medicinal product or whether it will remain purely as a resource for research.

Since the 5 July 2007, any human tissue that is used in human application must comply with all the requirements of the EUTCD. In view of this it is imperative that a cell line created with the intention that it will at some point in the future be used in human application, can be shown to comply with the EUTCD. Failure to comply with the EUTCD requirements could in the future adversely affect an application for authorisation of a medicinal product.

I have an HFEA licence for research – will I also require an HTA Licence?

The HFEA regulates the use of gametes and embryos for use in fertility treatments and research. An HFEA research licence is required for any activity involving the use of an embryo for research, therefore an HFEA research licence must be in place before an embryo can be used for the purpose of creating cell lines. Once a cell line has been created it is a condition of an HFEA research licence that a sample line is deposited in the UK Stem Cell Bank. At this point the HFEA’s regulatory remit ceases.

The HTA’s regulatory authority commences at the point the embryo is disorganised and cells are grown to create cell lines with the intention that the lines may at some future time be used in human application. Therefore any organisation processing, testing, storing and distributing cell lines with the intention that they may be used in human application may (since July 5 2007), only do so under the authority of an HTA licence.

Under the Regulations, the HTA is responsible for ensuring that any tissues or cells intended for human application conform to the requirements of the EUTCD. A consequence of this is that the HTA will require evidence to show that a cell line intended for human application was procured in accordance with the Directives, and that the environment in which the source materials (i.e. the gametes and resultant embryo) were processed complied with the technical requirements of the Directives.

What evidence will the HTA require to prove compliance with the Directives
regarding procurement?

At the time of procurement the primary intention is to procure gametes to create viable embryos for use in fertility treatment. However, if a cell line from a donated embryo is created with the intention that it will at some future point be used in human application, the HTA requires evidence that the procurement of the source materials (i.e. the gametes) complied with the requirements of the Directives. Therefore the consent, donor selection criteria and traceability requirements of the Directives will have to be complied with to ensure that procurement has taken place in accordance with the Directives. A failure to comply with the procurement requirements of the Directives may prevent the future use of the cells in human application.

What environment will the gametes/embryo need to be processed in, in order to
comply with the Directives?

The EUTCD has set very specific standards regarding the environment within which human tissues and cells must be processed if they are to meet the standards of quality and safety required for use in human application. These standards apply to any processing carried out on a cell line created from an embryo and also to the source materials from which the cell line was created i.e. the gametes and embryo.

In particular, your attention is drawn to the fact that, from 5 July 2007, tissues or cells that are exposed to the environment during processing must be processed in an air quality environment where the particle counts and microbial colony counts are equivalent to those of Grade A with a background environment at least equivalent to Grade D (see HTA Directions 002/2007 paragraph 40).Tissues or cells not processed in a Grade A against D background must be stored separately and a risk assessment carried out to ensure that they meet suitable standards of quality and safety for use in human application.

Will cell lines stored and used for research be regulated by the HTA?

The HT Act 2004 licences (amongst other activities) the storage of relevant material for use for a scheduled purpose. One of the scheduled purposes is storage of relevant material for research. The Act excludes from the definition of relevant material the following categories of human material

(a) embryos outside the human body, and
(b) hair and nails from the body of a living person.

The HT Act also explicitly excludes from its remit the licensing of material if it is created outside the human body. Therefore the regulation of cell lines for research falls outside of the HTA’s remit, nor is such research captured within any other regulator’s remit.

However, the Regulations widen the scope of the HTA’s regulatory remit to include licensing the procurement, testing, processing, distribution and import/export of tissues and cells created and developed outside the human body for use for human application.

What should I do if some of the cell lines created are EUTCD compliant and others
are not?

Cell lines that are EUTCD compliant should be stored separately from those that are not to avoid any potential contamination issues.

What activities will the HTA licence with respect to cell lines for human application?

Since 5 July 2007, any establishment that carries out the following activities in relation to cell lines for human application requires either a licence from the HTA under the Regulations or have a third party agreement in place with an establishment that is licensed by the HTA under the 2007 Regulations.

• Testing
• Processing
• Import / export
• Distribution

Since 5 July 2007 any establishment storing cell lines for human application may only lawfully carry out this activity if licensed to do so by the HTA under the Regulations. Storage, unlike the above activities cannot be carried out under a third party agreement.

How do I find out further information on applying for a licence under the Regulations?

Any applicants should contact the Head of Regulation with responsibility for the geographical area in which activity is carried out.

Scotland, East of England, North East of England and South East of England.


Caroline Browne
020 7211 3408
caroline.browne@hta.gov.uk


Northern Ireland, Central England, South West England and South East England.

Imogen Swann
020 7211 3411
imogen.swann@hta.gov.uk

Wales, North West England and South East England.

Kristi Collins
020 7211 3413
kristi.collins@hta.gov.uk

Regulation of stem cell lines FAQs

Following the transposition of the European Union Tissue and Cells Directives (EUTCD) into UK law on 5 July 2007 (via the Human Tissue (Quality and Safety) Regulations 2007 – ‘the Regulations’), the remit of the HTA extended to cover the regulation of cell lines grown outside the human body for human application.

Background

Before the transposition of the EUTCD, cell lines derived from human embryos were subject to regulation by two regulatory bodies: the Human Fertilisation and Embryology Authority (HFEA) and the Medicines and Healthcare products Regulatory Agency (MHRA). The HFEA regulates the creation and use of embryos prior to the derivation of human embryonic stem (hES) cell lines for research. The MHRA regulates the use of investigational medicinal products (IMPs) in clinical trials in the UK – this would include the use of cell lines as a component of an IMP. Eventual authorisation of a medicinal product in the UK falls under the remit of the MHRA or the European Medicines Agency (EMEA).

It is widely acknowledged that the intention underlying the creation of cell lines is that they will eventually be used as a medicinal product. However, at the point of creation of any particular cell line it is not possible to predict whether it will eventually result in being used for human application in a medicinal product or whether it will remain purely as a resource for research.

Since the 5 July 2007, any human tissue that is used in human application must comply with all the requirements of the EUTCD. In view of this it is imperative that a cell line created with the intention that it will at some point in the future be used in human application, can be shown to comply with the EUTCD. Failure to comply with the EUTCD requirements could in the future adversely affect an application for authorisation of a medicinal product.

I have an HFEA licence for research – will I also require an HTA Licence?

The HFEA regulates the use of gametes and embryos for use in fertility treatments and research. An HFEA research licence is required for any activity involving the use of an embryo for research, therefore an HFEA research licence must be in place before an embryo can be used for the purpose of creating cell lines. Once a cell line has been created it is a condition of an HFEA research licence that a sample line is deposited in the UK Stem Cell Bank. At this point the HFEA’s regulatory remit ceases.

The HTA’s regulatory authority commences at the point the embryo is disorganised and cells are grown to create cell lines with the intention that the lines may at some future time be used in human application. Therefore any organisation processing, testing, storing and distributing cell lines with the intention that they may be used in human application may (since July 5 2007), only do so under the authority of an HTA licence.

Under the Regulations, the HTA is responsible for ensuring that any tissues or cells intended for human application conform to the requirements of the EUTCD. A consequence of this is that the HTA will require evidence to show that a cell line intended for human application was procured in accordance with the Directives, and that the environment in which the source materials (i.e. the gametes and resultant embryo) were processed complied with the technical requirements of the Directives.

What evidence will the HTA require to prove compliance with the Directives
regarding procurement?

At the time of procurement the primary intention is to procure gametes to create viable embryos for use in fertility treatment. However, if a cell line from a donated embryo is created with the intention that it will at some future point be used in human application, the HTA requires evidence that the procurement of the source materials (i.e. the gametes) complied with the requirements of the Directives. Therefore the consent, donor selection criteria and traceability requirements of the Directives will have to be complied with to ensure that procurement has taken place in accordance with the Directives. A failure to comply with the procurement requirements of the Directives may prevent the future use of the cells in human application.

What environment will the gametes/embryo need to be processed in, in order to
comply with the Directives?

The EUTCD has set very specific standards regarding the environment within which human tissues and cells must be processed if they are to meet the standards of quality and safety required for use in human application. These standards apply to any processing carried out on a cell line created from an embryo and also to the source materials from which the cell line was created i.e. the gametes and embryo.

In particular, your attention is drawn to the fact that, from 5 July 2007, tissues or cells that are exposed to the environment during processing must be processed in an air quality environment where the particle counts and microbial colony counts are equivalent to those of Grade A with a background environment at least equivalent to Grade D (see HTA Directions 002/2007 paragraph 40).Tissues or cells not processed in a Grade A against D background must be stored separately and a risk assessment carried out to ensure that they meet suitable standards of quality and safety for use in human application.

Will cell lines stored and used for research be regulated by the HTA?

The HT Act 2004 licences (amongst other activities) the storage of relevant material for use for a scheduled purpose. One of the scheduled purposes is storage of relevant material for research. The Act excludes from the definition of relevant material the following categories of human material

(a) embryos outside the human body, and
(b) hair and nails from the body of a living person.

The HT Act also explicitly excludes from its remit the licensing of material if it is created outside the human body. Therefore the regulation of cell lines for research falls outside of the HTA’s remit, nor is such research captured within any other regulator’s remit.

However, the Regulations widen the scope of the HTA’s regulatory remit to include licensing the procurement, testing, processing, distribution and import/export of tissues and cells created and developed outside the human body for use for human application.

What should I do if some of the cell lines created are EUTCD compliant and others
are not?

Cell lines that are EUTCD compliant should be stored separately from those that are not to avoid any potential contamination issues.

What activities will the HTA licence with respect to cell lines for human application?

Since 5 July 2007, any establishment that carries out the following activities in relation to cell lines for human application requires either a licence from the HTA under the Regulations or have a third party agreement in place with an establishment that is licensed by the HTA under the 2007 Regulations.

• Testing
• Processing
• Import / export
• Distribution

Since 5 July 2007 any establishment storing cell lines for human application may only lawfully carry out this activity if licensed to do so by the HTA under the Regulations. Storage, unlike the above activities cannot be carried out under a third party agreement.

How do I find out further information on applying for a licence under the Regulations?

Any applicants should contact the Head of Regulation with responsibility for the geographical area in which activity is carried out.

Scotland, East of England, North East of England and South East of England.


Caroline Browne
020 7211 3408
caroline.browne@hta.gov.uk


Northern Ireland, Central England, South West England and South East England.

Imogen Swann
020 7211 3411
imogen.swann@hta.gov.uk

Wales, North West England and South East England.

Kristi Collins
020 7211 3413
kristi.collins@hta.gov.uk