Position paper on risk assessment of the use of starting materials of ruminant origin in veterinary medicinal products intended for use in ruminant species (EMEA/CVMP/121/01 — February 2001) adopted by the Committee for Veterinary Medicinal Products (CVMP) — July 2001
Date: 2001-07-01
Institutions: European Commission
Subjects: animal product, bovine spongiform encephalopathy, cattle, health risk, pharmaceutical legislation, veterinary drug

C 286/10

EN

Official Journal of the European Communities

12.10.2001

Position paper on risk assessment of the use of starting materials of ruminant origin in veterinary
medicinal products intended for use in ruminant species

(EMEA/CVMP/121/01 (cid:151) February 2001)

adopted by the Committee for Veterinary Medicinal Products (CVMP)

July 2001

(2001/C 286/05)

Introduction

When assessing the risk of the use of veterinary medicinal
products intended for use in ruminant species, a number of
factors need to be taken into account which are additional to
those detailed in the (cid:145)Note for guidance for minimising the risk
of transmitting animal spongiform encephalopathy agents via
medicinal products(cid:146) (the joint CPMP/CVMP note for guidance).
Ruminants are susceptible to BSE by the oral route and the risk
of
transmission is greatest when animals are exposed to
infectious material derived from the same species. Transmission
of infectivity to food producing species represents a risk of
amplifying TSE infectivity in a form that is readily transmissible
to man. It therefore follows that manufacturers should demon-
strate that they have addressed the additional considerations
that relate to ruminant species when analysing, and mini-
mising,
transmission of TSEs by veterinary
medicinal products intended for use in ruminants.

the risk of

Although particular attention is paid in this position paper to
milk and milk products due to their exclusion from the note
it is important to note that the scope of this
for guidance,
position paper extends beyond milk to cover all substances
of
intended for
ruminants.

ruminant origin when used in products

Manufacturers of products intended for use in non-ruminant
species, whether food producing or not,
i.e. pigs, poultry,
horses, dogs,
fish, rabbits and cats, need only address the
factors detailed in the joint CPMP/CVMP note for guidance (1).

This position paper details under what circumstances an
additional risk assessment should be carried out, and the
factors that should be taken into account, when minimising
the risks of transmission of TSEs to ruminant species. Manu-
facturers have
the option of obtaining a certificate of
compliance from the EDQM to demonstrate compliance of
starting materials of animal origin that fall within the scope
risk
of
the
assessment
separate
requirement from the certification procedure. The additional
intended for
risk assessment
ruminant species, irrespective of whether or not a certificate
is available for one or more starting materials used in their
production and should be carried out by the marketing auth-
orisation holder or applicant.

referred to in this document

required for all products

joint CPMP/CVMP note

for guidance. The

is a

is

As indicated in the joint CPMP/CVMP note for guidance,
applicants for marketing authorisations should take account
of the latest available scientific information when preparing a
In the event of a change in the state of
risk assessment.
knowledge or the disease situation, the risk posed should be
reassessed. Likewise, this position paper will be updated in line
with future changes
to the joint CPMP/CVMP note for
guidance.

Scope

This document relates to the use of:

(i) substances of animal origin that

fall within the scope
the joint CPMP/CVMP note for guidance
(Section 2) of
when used in the manufacture of veterinary medicinal
products intended for administration to ruminant species,
i.e. cattle, sheep, goats and deer;

(ii) milk and milk derivatives under the following defined

circumstances:

Whereas milk and milk derivatives are specifically excluded
from the joint CPMP/CVMP note for guidance provided, the
milk is obtained from healthy cows and is fit for human
consumption, these materials fall within the scope of this
position paper when used under the following conditions,
both of which must apply:

(cid:151) the veterinary medicinal product

is
parenteral administration to a ruminant,

intended for

AND

substance,

(cid:151) the milk or milk derivative is used as a source of the
or
an
active
formulation (i.e. not when
component of
used as a component of a medium or solution used
during the production of one of the final ingredients).

as
the final

excipient,

stabiliser

(1) Cats and other felidae have also been shown to be susceptible to
TSEs when exposed to infectivity by the oral route. Although there
are no additional requirements for products intended for use in
these species, manufacturers should address, where relevant, any
particular issues related to the TSE risk for felidae.

Risk assessment

Manufacturers should perform a risk assessment and justifi-
cation for use of substances falling within the scope of this
document taking into account the following factors.

12.10.2001

EN

Official Journal of the European Communities

C 286/11

should use substances of
Where possible, manufacturers
non-ruminant origin for products
ruminant
species. Where this is not possible, a justification should be
provided for the use of ruminant-derived material.

intended for

controlled for freedom from TSEs. These requirements do not
therefore apply to substances such as lanolin that fall outside
the scope of the joint CPMP/CVMP note for guidance and this
position paper.

When milk and milk derivatives fall within the scope of this
document (see section (cid:145)Scope(cid:146), above),
full compliance with
joint CPMP/CVMP note for guidance should be demonstrated
in terms of the origin of the milk and, where relevant, the
treatment applied (such as removal of cells).

Use of specified risk materials (SRMs) as a starting material at
any stage of the production process will be unacceptable to
competent authorities in all but the most exceptional cases.
Only where a risk-benefit analysis clearly shows that it is in
the interests of public and animal health for a particular
veterinary medicinal product to be made available would use
of SRMs be permitted. In these circumstances, manufacturers
shall demonstrate that the use of all other possible sources of
starting materials has been explored and eliminated and that
every possible measure to minimise risk has been taken. Such
measures would include sourcing starting materials from a
country officially classified as being free from animal TSEs,
use of animals less than one year old, pre-mortem inspection
and, where relevant, testing for the presence of infectivity.

The presence of SRMs as contaminants of other starting
concern in
materials of animal origin is of particular
products intended for ruminants. Particular attention should
be given to ensuring, and describing,
that measures and
quality systems are in place to ensure that contamination
with SRMs does not occur.

The risk of transmission will be related both to the route of
administration and the quantity of risk material that might be
present in the final product.

scrapie by sourcing materials of

Attention must be paid to minimising the potential risk of
transmission of
small
ruminant origin that fall within the scope of
this position
paper from a country free from scrapie or by taking other
measures to ensure that the herds of origin from which the
source animals are derived are adequately monitored and

All of the factors listed above should be specifically addressed
when carrying out a risk assessment of seed materials for use
in a vaccine intended for ruminants, as described in the CVMP
position paper EMEA/CVMP/019/01.

Practical outcomes

The basis of demonstrating compliance of starting materials
used in the production of veterinary medicines should rely,
where possible, on the issue of a certificate of compliance by
the European Department
the Quality of Medicines,
for
following assessment of a data package submitted by the manu-
raw material
facturer of
the
the
requirements of
the joint CPMP/CVMP note for guidance
have been met.

to demonstrate

that

compliance of

When a marketing authorisation holder is seeking to demon-
strate
a veterinary medicinal product
intended for ruminant species for which EDQM certificates
are available for all relevant raw materials,
the certificates
that
should be presented together with a risk assessment
addresses the additional risk factors listed in this position
paper.

compliance of

When a marketing authorisation holder is seeking to demon-
strate
a veterinary medicinal product
intended for ruminant species for which EDQM certificates
are not available for all relevant substances, certificates could
be presented for those substances for which they are available.
For those raw materials (including milk derivatives, where
relevant) for which certificates are not available the applicant
should submit the data necessary to demonstrate compliance of
the raw materials with the joint CPMP/CVMP note for guidance
together with a risk assessment that addresses the additional
risk factors listed in this position paper for the veterinary
medicinal product as a whole.