List of participants
MEMBERS
Dr. T.B. Barragry, Prof. J.M. Boeynaems, Prof. J.R. Claude, Dr. W.H. De Jong, Prof. J.G. Descotes, Dr. R. Dobbelaer, Prof. J.A. Guimarães Morais, Dr. K.H. Jones, Dr. J. Löwer, Prof. Dr. H.W.J. Marquardt, Prof. P. Preziosi, Dr. E. Rodriguez Farré, Prof. M. Silbermann, Prof. K. Turnheim, Prof. D.F. Williams
APOLOGIES
Prof. F. Sjöqvist
COMMISSION
Ms. M. de Solà, Mr. W. De Klerck, Mr. C. Deckart, Mr. P. Daskaleros, Mr. P. Deboyser, Mr. N. Anselmann, Mr. A. Martin, Ms. S. Van Impe, Dr. A. Sanabria Tienza
EMEA
Mr. F. Sauer, Mr. N. Gates
1. Adoption of the Agenda
The agenda was adopted as follows:
1. Approval of the Agenda.
2. Approval of the Draft Summary Report of the first meeting of the SCMP&MD held on 10.11.97. (Doc. XXIV/SCMPMD/001/97).
3. Update by the chairman on the general functioning of the Scientific Steering Committee and the latest developments on "Tallow and Gelatine".
4. Information by the Commission of the legislation concerning Medicinal Products.
5. GMP for starting materials: list of excipients to be considered. (Doc. SCMPMD/0001/98, Doc. SCMPMD/0002/98)
6. Orphan medicinal products: guidance on the notion of "same medicinal product" for the purpose of marketing exclusivity.
7. Orphan medicinal products: guidance on the notion of "clinical superiority" for the purpose of marketing exclusivity.
8. Permitted colouring matters for use in medicinal products.
9. Draft guidelines on the use of specified risk materials for the manufacture of implantable medical devices. (Doc. CEN/TC 316/NO82, Doc. CEN/TC 316/NO83, Doc. CEN/TC 316/NO84, Doc. MEDDEV 2.5/5, Doc D(98)-III.D.2-NA/mt)
10. Equivalency of alternative products for the use of intestine of animal origin for surgical sutures.
11. Discussion on the transmission of CJD by blood and its derivatives.
12. Presentation of new electronic mail exchange system : EM4AC
13. Internal rules for the Scientific Committees (Doc . CSTEE/98/2).
14. Review of CPMP and CVMP guidelines
15. Miscellaneous.
2. Approval of the Draft Summary Report of the first meeting of the SCMP&MD held on 10.11.97. (Doc. XXIV/SCMPMD/001/97).
The Draft Summary Report was approved.
3. Update by the chairman on the general functioning of the Scientific Steering Committee and the latest developments on "Tallow and Gelatine".
The Chairman explained the general functioning of the Scientific Steering Committee (SSC).
Concerning the latest developments on "Tallow and Gelatine" the Chairman presented several documents in discussion on the SSC. These documents were sent by the secretary several days earlier to all members of the Committee.
A large discussion took place on the document " The safety of gelatine" of the SSC (Doc. SSC meeting 19-20.02.98/TSE/Gelatine/rev.05). The majority of members of the Committee made observations on the content of the document but agree with the main thrust of the document. Only one member disagreed, particularly with the classification made in the document of the use of gelatine.
The Chairman promised that he would relate the observations made by the Committee to the Plenary of the SSC of 19 and 20 February 1998.
4. Information by the Commission of the legislation concerning Medicinal Products.
M. Deboyser explained the subject and presented the working program of DG-III concerning the legislation on Medicinal Products for 1998.
He wished that the work of the SCMPMD be profitable for the Commission and that a link with the work of DG III be permanently maintained.
He also offered the possibility for the members of the Committee to connect with the Telematic information created by DG III. At a future meeting he could explain details about the connection.
Before the end of this year DG III will edit a CD on their activities.
Finally he informed the Committee about the relation between the European Agency for the Evaluation of Medicinal Products (EMEA) and DG III.
M. Sauer, Executive Director of EMEA (European Agency for the Evaluation of Medicinal Products) explained the mandate of the Agency, and exposed the work of the working-groups and Committee included in the organigrame of the EMEA.
He said that about 50 medicinal products were evaluated by the Agency in the last years in the central procedure to put these types of products on the market.
He wished that a good collaboration be established between the Committee and the Agency.
The Chairman said that for the benefit of consumer health, these good collaborations will continue.
5. GMP for starting materials: list of excipients to be considered. (Doc. SCMPMD/0001/98, Doc. SCMPMD/0002/98).
Recent developments, for example the risk of bovine spongiform encephalopathy contamination of some starting materials, have highlighted the need to 'built quality into' medicinal products by ensuring that good manufacturing practice is adhered to, throughout the manufacture of starting material as well as the active medicinal product.
The Commission has prepared a preliminary draft of a legislative proposal on GMP for starting material. This text provides a legislative basis for requiring, inspection and certification, to ensure that the starting materials used to manufacture medicinal products, are themselves manufactured in accordance with GMP. It is recognised that this legislative proposal should require a GMP requirement to be laid down and enforced, for the active ingredients in medicinal products. However, the excipients (inactive ingredients), if any, for which GMP should be laid down and enforced will be selected based on individual risk assessment.
Based on this background the Committee is asked the following:
"Are there any excipients, used in human and veterinary medicinal products, for which there is a consumer health/safety concern which needs to be addressed by laying down and enforcing a GMP requirement? If so which are these excipients?"
The Committee agreed to establish a Working-Group formed by Dr. Dobbelaer, Dr. Löwer and Prof. Claude. The raporteur will be Dr. Dobbelaer.
6. Orphan medicinal products: guidance on the notion of "same medicinal product" for the purpose of marketing exclusivity.
The Services of the Commission are finalising a Proposal for a Parliament and Council Regulation on orphan medicinal products. The aim of this proposal is to establish a Community procedure for designating orphan medicinal products and to introduce incentives for orphan medicinal products research, development and marketing, in particular by granting exclusive marketing rights for a ten year period. The protection thus granted would prevent the Community or a Member State from subsequently issuing a marketing authorisation for the same therapeutic indication, in respect of a similar medicinal products.
In addition, it will be indicated that the Commission shall, in consultation with the Member States, the Agency and interested parties, draw up detailed guidance for the application of this provision.
The Scientific Committee on Medicinal Products and Medical Devices is requested to provide:
"Guidance on the "similarity" test for the purpose of the application of the provision on market exclusivity for orphan medicinal products."
The Committee agreed to create a Working-Group to study this matter made up of Prof. Preziosi, Dr. Rodriguez Farré, Prof. Marquardt and Prof. Guimarães. Prof. Preziosi will act as raporteur.
7. Orphan medicinal products: guidance on the notion of "clinical superiority" for the purpose of marketing exclusivity.
With the background explained in the point 6, the Scientific Committee on Medicinal Products and Medical Devices is requested to provide:
"Guidance on the notion of "clinical superiority" for the purpose of the application of the provisions on designation and on market exclusivity for orphan medicinal products."
The Committee agreed that the Working-Group appointed for the previous point will work on this subject.
8. Permitted colouring matters for use in medicinal products.
According to the interpretation given by the Commission Services, only those colouring matters that are now listed in Annex I (positive list) to the "Directive 94/36 on colours for use in foodstuffs" but are not also listed in Annex IV (negative list of "colours permitted for certain uses only") are allowed for use in medicinal products.
Annex IV currently covers 10 colorants. The pharmaceutical industry is questioning the scientific justification for excluding the use of Annex IV colorants in medicinal products. According to industry, the most relevant of these "colours permitted for certain uses only" for the manufacture of medicinal products are: E 123 Amaranth, E 127 Erythrosin, E 161g Canthaxatin, E 173 Aluminium, E 174 Silver and E 175 Gold.
The Committee is asked the following:
"Is there a consumer health/safety concern to exclude the use of the "colours permitted for certain uses only" listed in Annex IV of Directive 94/36 (in particular: E 123 Amaranth, E 127 Erythrosin, E 161g Canthaxatin, E 173 Aluminium, E 174 Silver and E 175 Gold) in medicinal products?"
The Committee agreed that Prof. Preziosi would make a report on the information given by members of the Scientific Committee on Food and members of the Commission, on the situation concerning this matter.
9. Draft guidelines on the use of specified risk materials for the manufacture of implantable medical devices. (Doc. CEN/TC 316/NO82, Doc. CEN/TC 316/NO83, Doc. CEN/TC 316/NO84, Doc. MEDDEV 2.5/5, Doc D(98)-III.D.2-NA/mt).
The current situation for the marketing of CE marked devices is that the pertinent essential requirements are contained in annex 1 of directive 93/42/EEC and that these products are class III. This implies an examination of the product design or of type testing together with an appropriate quality system by an certification body. In the aforementioned case the certification body evaluates the risk/benefit ratio taking into account the current state of the art. Guidance is currently under development on the assessment of medical devices incorporating materials of animal origin with respect to viruses and transmissible agents.
The Committee is asked the following:
"In relation to the use of specified risk materials for the manufacture of implantable medical devices or those devices which come into contact with internal tissues during medical treatment, what are the factors to be taken into account when evaluating the risk/benefit analysis?"
The Committee agreed to establish a Working-Group integrated by Prof. Williams, Prof. Silbermann and Dr. W.H. De Jong. The raporteur will be Prof. Williams.
10. Equivalency of alternative products for the use of intestine of animal origin for surgical sutures.
The Committed is requested by the Commission to give response to these questions:
- "In the specific case of surgical sutures manufactured using intestine of animal origin (bovine and ovine) do the alternate products present an equivalent and/or satisfactory alternative in relation to safety and performance?
- "Under which conditions would it be acceptable to use such materials for the manufacture of sutures taking into account that currently available deactivation procedures for viral and non-conventional transmissible agents may not be used as they adversely affect the mechanical characteristics and functionality of the suture?"
The Committee agreed to establish a Working Group integrated by the same experts and raporteur of point 9.
11. Discussion on the transmission of CJD by blood and its derivatives.
The Chairman requested Dr. Löwer to explain the subject because Dr. Löwer has followed the discussion in different fora.
Dr Löwer said that he participated in a Working-Group meeting held on January 15th 1998 at the EMEA with experts of several nationalities, including experts from USA and Edinburg, but that no definitive conclusions were adopted.
The representative of the EMEA said that this subject will be further considered in a meeting of the Agency next week. For this purpose a document will be submitted to the competent Group for discussion.
No more information was available at this occasion.
The Committee agreed that Prof. Löwer will follow the matter and make reports to the Committee on the subject.
12. Presentation of new electronic mail exchange system : EM4AC.
M. Merlini made the presentation of new mail exchange system, and said that a electronic mailbox for the use of the Committee will be installed in the near future.
13. Internal rules for the Scientific Committees (Doc . CSTEE/98/2).
The internal rules were approved as figure in Doc. XXIV/SCMPMD - 98.002.
14. Review of CPMP and CVMP guidelines.
The Chairman said that at the next meeting a Working-Group would be established to study this matter.
15. Miscellaneous.
Ms. De Solà informed the Committee that a new system to accelerate the reimbursement of expenses of experts is under discussion.
No other points.
MEMBERS
Dr. T.B. Barragry, Prof. J.M. Boeynaems, Prof. J.R. Claude, Dr. W.H. De Jong, Prof. J.G. Descotes, Dr. R. Dobbelaer, Prof. J.A. Guimarães Morais, Dr. K.H. Jones, Dr. J. Löwer, Prof. Dr. H.W.J. Marquardt, Prof. P. Preziosi, Dr. E. Rodriguez Farré, Prof. M. Silbermann, Prof. K. Turnheim, Prof. D.F. Williams
APOLOGIES
Prof. F. Sjöqvist
COMMISSION
Ms. M. de Solà, Mr. W. De Klerck, Mr. C. Deckart, Mr. P. Daskaleros, Mr. P. Deboyser, Mr. N. Anselmann, Mr. A. Martin, Ms. S. Van Impe, Dr. A. Sanabria Tienza
EMEA
Mr. F. Sauer, Mr. N. Gates
1. Adoption of the Agenda
The agenda was adopted as follows:
1. Approval of the Agenda.
2. Approval of the Draft Summary Report of the first meeting of the SCMP&MD held on 10.11.97. (Doc. XXIV/SCMPMD/001/97).
3. Update by the chairman on the general functioning of the Scientific Steering Committee and the latest developments on "Tallow and Gelatine".
4. Information by the Commission of the legislation concerning Medicinal Products.
5. GMP for starting materials: list of excipients to be considered. (Doc. SCMPMD/0001/98, Doc. SCMPMD/0002/98)
6. Orphan medicinal products: guidance on the notion of "same medicinal product" for the purpose of marketing exclusivity.
7. Orphan medicinal products: guidance on the notion of "clinical superiority" for the purpose of marketing exclusivity.
8. Permitted colouring matters for use in medicinal products.
9. Draft guidelines on the use of specified risk materials for the manufacture of implantable medical devices. (Doc. CEN/TC 316/NO82, Doc. CEN/TC 316/NO83, Doc. CEN/TC 316/NO84, Doc. MEDDEV 2.5/5, Doc D(98)-III.D.2-NA/mt)
10. Equivalency of alternative products for the use of intestine of animal origin for surgical sutures.
11. Discussion on the transmission of CJD by blood and its derivatives.
12. Presentation of new electronic mail exchange system : EM4AC
13. Internal rules for the Scientific Committees (Doc . CSTEE/98/2).
14. Review of CPMP and CVMP guidelines
15. Miscellaneous.
2. Approval of the Draft Summary Report of the first meeting of the SCMP&MD held on 10.11.97. (Doc. XXIV/SCMPMD/001/97).
The Draft Summary Report was approved.
3. Update by the chairman on the general functioning of the Scientific Steering Committee and the latest developments on "Tallow and Gelatine".
The Chairman explained the general functioning of the Scientific Steering Committee (SSC).
Concerning the latest developments on "Tallow and Gelatine" the Chairman presented several documents in discussion on the SSC. These documents were sent by the secretary several days earlier to all members of the Committee.
A large discussion took place on the document " The safety of gelatine" of the SSC (Doc. SSC meeting 19-20.02.98/TSE/Gelatine/rev.05). The majority of members of the Committee made observations on the content of the document but agree with the main thrust of the document. Only one member disagreed, particularly with the classification made in the document of the use of gelatine.
The Chairman promised that he would relate the observations made by the Committee to the Plenary of the SSC of 19 and 20 February 1998.
4. Information by the Commission of the legislation concerning Medicinal Products.
M. Deboyser explained the subject and presented the working program of DG-III concerning the legislation on Medicinal Products for 1998.
He wished that the work of the SCMPMD be profitable for the Commission and that a link with the work of DG III be permanently maintained.
He also offered the possibility for the members of the Committee to connect with the Telematic information created by DG III. At a future meeting he could explain details about the connection.
Before the end of this year DG III will edit a CD on their activities.
Finally he informed the Committee about the relation between the European Agency for the Evaluation of Medicinal Products (EMEA) and DG III.
M. Sauer, Executive Director of EMEA (European Agency for the Evaluation of Medicinal Products) explained the mandate of the Agency, and exposed the work of the working-groups and Committee included in the organigrame of the EMEA.
He said that about 50 medicinal products were evaluated by the Agency in the last years in the central procedure to put these types of products on the market.
He wished that a good collaboration be established between the Committee and the Agency.
The Chairman said that for the benefit of consumer health, these good collaborations will continue.
5. GMP for starting materials: list of excipients to be considered. (Doc. SCMPMD/0001/98, Doc. SCMPMD/0002/98).
Recent developments, for example the risk of bovine spongiform encephalopathy contamination of some starting materials, have highlighted the need to 'built quality into' medicinal products by ensuring that good manufacturing practice is adhered to, throughout the manufacture of starting material as well as the active medicinal product.
The Commission has prepared a preliminary draft of a legislative proposal on GMP for starting material. This text provides a legislative basis for requiring, inspection and certification, to ensure that the starting materials used to manufacture medicinal products, are themselves manufactured in accordance with GMP. It is recognised that this legislative proposal should require a GMP requirement to be laid down and enforced, for the active ingredients in medicinal products. However, the excipients (inactive ingredients), if any, for which GMP should be laid down and enforced will be selected based on individual risk assessment.
Based on this background the Committee is asked the following:
"Are there any excipients, used in human and veterinary medicinal products, for which there is a consumer health/safety concern which needs to be addressed by laying down and enforcing a GMP requirement? If so which are these excipients?"
The Committee agreed to establish a Working-Group formed by Dr. Dobbelaer, Dr. Löwer and Prof. Claude. The raporteur will be Dr. Dobbelaer.
6. Orphan medicinal products: guidance on the notion of "same medicinal product" for the purpose of marketing exclusivity.
The Services of the Commission are finalising a Proposal for a Parliament and Council Regulation on orphan medicinal products. The aim of this proposal is to establish a Community procedure for designating orphan medicinal products and to introduce incentives for orphan medicinal products research, development and marketing, in particular by granting exclusive marketing rights for a ten year period. The protection thus granted would prevent the Community or a Member State from subsequently issuing a marketing authorisation for the same therapeutic indication, in respect of a similar medicinal products.
In addition, it will be indicated that the Commission shall, in consultation with the Member States, the Agency and interested parties, draw up detailed guidance for the application of this provision.
The Scientific Committee on Medicinal Products and Medical Devices is requested to provide:
"Guidance on the "similarity" test for the purpose of the application of the provision on market exclusivity for orphan medicinal products."
The Committee agreed to create a Working-Group to study this matter made up of Prof. Preziosi, Dr. Rodriguez Farré, Prof. Marquardt and Prof. Guimarães. Prof. Preziosi will act as raporteur.
7. Orphan medicinal products: guidance on the notion of "clinical superiority" for the purpose of marketing exclusivity.
With the background explained in the point 6, the Scientific Committee on Medicinal Products and Medical Devices is requested to provide:
"Guidance on the notion of "clinical superiority" for the purpose of the application of the provisions on designation and on market exclusivity for orphan medicinal products."
The Committee agreed that the Working-Group appointed for the previous point will work on this subject.
8. Permitted colouring matters for use in medicinal products.
According to the interpretation given by the Commission Services, only those colouring matters that are now listed in Annex I (positive list) to the "Directive 94/36 on colours for use in foodstuffs" but are not also listed in Annex IV (negative list of "colours permitted for certain uses only") are allowed for use in medicinal products.
Annex IV currently covers 10 colorants. The pharmaceutical industry is questioning the scientific justification for excluding the use of Annex IV colorants in medicinal products. According to industry, the most relevant of these "colours permitted for certain uses only" for the manufacture of medicinal products are: E 123 Amaranth, E 127 Erythrosin, E 161g Canthaxatin, E 173 Aluminium, E 174 Silver and E 175 Gold.
The Committee is asked the following:
"Is there a consumer health/safety concern to exclude the use of the "colours permitted for certain uses only" listed in Annex IV of Directive 94/36 (in particular: E 123 Amaranth, E 127 Erythrosin, E 161g Canthaxatin, E 173 Aluminium, E 174 Silver and E 175 Gold) in medicinal products?"
The Committee agreed that Prof. Preziosi would make a report on the information given by members of the Scientific Committee on Food and members of the Commission, on the situation concerning this matter.
9. Draft guidelines on the use of specified risk materials for the manufacture of implantable medical devices. (Doc. CEN/TC 316/NO82, Doc. CEN/TC 316/NO83, Doc. CEN/TC 316/NO84, Doc. MEDDEV 2.5/5, Doc D(98)-III.D.2-NA/mt).
The current situation for the marketing of CE marked devices is that the pertinent essential requirements are contained in annex 1 of directive 93/42/EEC and that these products are class III. This implies an examination of the product design or of type testing together with an appropriate quality system by an certification body. In the aforementioned case the certification body evaluates the risk/benefit ratio taking into account the current state of the art. Guidance is currently under development on the assessment of medical devices incorporating materials of animal origin with respect to viruses and transmissible agents.
The Committee is asked the following:
"In relation to the use of specified risk materials for the manufacture of implantable medical devices or those devices which come into contact with internal tissues during medical treatment, what are the factors to be taken into account when evaluating the risk/benefit analysis?"
The Committee agreed to establish a Working-Group integrated by Prof. Williams, Prof. Silbermann and Dr. W.H. De Jong. The raporteur will be Prof. Williams.
10. Equivalency of alternative products for the use of intestine of animal origin for surgical sutures.
The Committed is requested by the Commission to give response to these questions:
- "In the specific case of surgical sutures manufactured using intestine of animal origin (bovine and ovine) do the alternate products present an equivalent and/or satisfactory alternative in relation to safety and performance?
- "Under which conditions would it be acceptable to use such materials for the manufacture of sutures taking into account that currently available deactivation procedures for viral and non-conventional transmissible agents may not be used as they adversely affect the mechanical characteristics and functionality of the suture?"
The Committee agreed to establish a Working Group integrated by the same experts and raporteur of point 9.
11. Discussion on the transmission of CJD by blood and its derivatives.
The Chairman requested Dr. Löwer to explain the subject because Dr. Löwer has followed the discussion in different fora.
Dr Löwer said that he participated in a Working-Group meeting held on January 15th 1998 at the EMEA with experts of several nationalities, including experts from USA and Edinburg, but that no definitive conclusions were adopted.
The representative of the EMEA said that this subject will be further considered in a meeting of the Agency next week. For this purpose a document will be submitted to the competent Group for discussion.
No more information was available at this occasion.
The Committee agreed that Prof. Löwer will follow the matter and make reports to the Committee on the subject.
12. Presentation of new electronic mail exchange system : EM4AC.
M. Merlini made the presentation of new mail exchange system, and said that a electronic mailbox for the use of the Committee will be installed in the near future.
13. Internal rules for the Scientific Committees (Doc . CSTEE/98/2).
The internal rules were approved as figure in Doc. XXIV/SCMPMD - 98.002.
14. Review of CPMP and CVMP guidelines.
The Chairman said that at the next meeting a Working-Group would be established to study this matter.
15. Miscellaneous.
Ms. De Solà informed the Committee that a new system to accelerate the reimbursement of expenses of experts is under discussion.
No other points.