Mutual Recognition Agreement (MRA) between

Australia and European Union (EU)

Medicinal Products Annex

A Guide for
Australian Manufacturers and Exporters of
Medicinal Products

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 Mutual Recognition Agreement (MRA) between
Australia and European Union (EU)

Medicinal Products Annex

A Guide for Australian Manufacturers and Exporters of

Medicinal Products

What is the MRA?

The MRA allows EU member countries to recognise certificates of conformity issued by Australia
using Australian conformity assessment or inspection rules and regulations, and vice versa. That is,
the MRA provides for conformity assessment to be carried out in the country of manufacture.

The MRA became operative on 1 January 1999 and covers various other industry sectors
including medical devices, machinery, pressure equipment, low voltage equipment,
telecommunication terminal equipment, electromagnetic compatibility and automotive parts.

In recognition that different legislative and regulatory requirements apply between MRA
partners, the MRA does not create a direct equivalence between Australia and EU regulations.
Rather, it allows for mutual recognition of test results and other conformity assessment
documentation including certification.

Scope of the Medicinal Products Annex:

The full title of the Medicinal Products Annex is “Medicinal Products GMP Inspection and
Batch Certification”.

The Medicinal Products Annex covers all those medicinal products for human and veterinary use
that are manufactured in Australia and EU, and to which GMP requirements apply, including
chemical and biological pharmaceuticals, immunologicals, radiopharmaceuticals, and products
derived from human blood/plasma. The MRA has the provision to be applied to medicinal
products covered by the legislation of one party but not the other, eg. vitamin and herbal
products, active pharmaceutical ingredients, manufacture of products for clinical trials, and pre-
marketing inspections.
It is important to note that the MRA only applies to GMP inspections of manufacturers of
medicinal products, and subsequent certification of the manufacturer. It does not apply to the
mutual recognition of marketing authorisation of medicinal products. Australian manufacturers
and/or sponsors wishing to market medicinal products in Europe will still need to lodge an
application for product marketing authorisation with an individual EU member country (“de-
centralised” procedure) or EMEA (“centralised” procedure).

For further information on the procedures for lodging applications for product marketing
authorisation, refer to “The rules governing medicinal products in the European Union”,
particularly Volumes 2A and 2B on “Notice to applicants – Medicinal products for human use”
(this publication can be obtained from the Office for Official Publications of the European
Communities, L-2985 Luxembourg).

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The need to have quality, safety and efficacy data assessed in Europe for medicinal products proposed to
be exported to Europe makes the Medicinal Products Annex different to other Annexes of the MRA. That
is, other Annexes provide for all aspects of conformity assessment of products for export to Europe to be
done in Australia, and vice versa.

Certification of Manufacturer:
The main thrust of the Medicinal Products Annex is the recognition of GMP inspections
conducted by the other party. This is facilitated by the exchange of a "Certificate of GMP
Compliance of a Manufacturer" certifying that the manufacturer has been inspected and found to
comply with GMP for the manufacture of a specific medicinal product or group of medicinal
products.

The "Certificate of GMP Compliance of a Manufacturer" may be requested by the exporter,

importer or competent authority. It is usual for a competent authority to request a "Certificate of
GMP Compliance of a Manufacturer" during the assessment/evaluation of an application for
marketing approval of a drug product. The benefit of an exporter or importer requesting these
certificates is that the certificate can be lodged as part of an application for European marketing
approval before assessment commences. The contact details for the competent authority of each
country of EU from whom GMP certificates may be requested is attached at Annex C.

A standardised "Certificate of Compliance of a Manufacturer" has been developed between the

competent authorities of Australia and EU. The current version of this standardised certificate is
attached at Annex A.

The Therapeutic Goods Administration (TGA) is nominated in the MRA as the Official
Inspection Service for Australia. Any request for a "Certificate of Compliance of a
Manufacturer" pertaining to an Australian manufacturer of a medicinal product for human use
should be made to: The Chief GMP Auditor, TGA, PO Box 100, Woden, ACT, 2606. The TGA
fee relevant to GMP certification will apply for requests received from importers and exporters;
the fee will not apply when the request comes from a European competent authority.

Batch Certification:
EU legislation requires that each batch of medicinal product imported into Europe must be
accompanied by a batch certificate. This certificate must:
• show agreed testing specification of the product
• show reference of analytical methods and test results
• contain a statement like “batch records reviewed and found to be in conformity with GMP”
• be signed by the person in the company responsible for releasing the batch of medicinal
product for sale/supply.

The batch certificate must be held by the European importer and be available upon request by the
relevant authority in Europe. The need for a batch certificate is a specific requirement of Europe;
there is no similar Australian requirement.

An internationally harmonised batch certificate has been developed for use by all MRA partners.
The current version of this certificate is attached at Annex B.

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Unlike the MRAs that Europe has arranged with USA and Canada, the MRA with Australia has
no transitional period (or confidence building period) for medicinal products. This is because
equivalence has already been established between Australia and Europe through Australia’s
membership of the Pharmaceutical Inspection Convention. Because of this, Australian
manufactured medicinal products need not be re-analysed in Europe provided a batch certificate
accompanies each batch sent to Europe and this certificate is retained by the European importer.

Official Batch Release:

Official batch release relates to the testing by competent authorities of batches of immunological
medicinal products (vaccines) and blood products. Whilst the MRA does not encompass the
mutual recognition of official batch release, it does allow for the exchange of such certification to
take place if required.

Veterinary Medicines:
A two-year transition period was applicable initially to Australian-made veterinary medicines
exported to Europe. Following an assessment by EC of Australia’s system of regulatory
controls for veterinary medicines the transition period was removed on 1 July 2001. That is,
the MRA became fully operational for veterinary products on 1 July 2001.

Whilst TGA is nominated in the MRA as the Official Inspection Service for all medicinal
products, including veterinary medicines, any request for a Certificate of Manufacturer relating to
an Australian veterinary manufacturer should be made to: GMP Licensing Scheme Manager,
National Registration Authority (NRA), PO Box E240, Parkes, ACT 2600.

Country of Origin:
The MRA applies to goods undergoing the final significant manufacturing step in Australia, and
vice versa. That is, the MRA cannot be applied to manufacturers located outside EU or Australia.
It is possible that the country of origin provision may be removed from the MRA sometime in
the future in order to make it consistent with the MRA’s that Europe has arranged with USA and
Canada.

Further Information:
A copy of the MRA, including the Medicinal Products Annex, can be obtained from the web site:
http://www.ecdel.org.au Further information on the Medicinal Products Annex can be obtained
from Mr Bob Tribe of TGA (Ph. (02) 62328629 Fax (02) 62328426) in relation to medicines for
use in humans, and from Mr Graham Savage of NRA (Ph. (02) 62723418 Fax (02) 62724753 )
in relation to veterinary medicines.

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 Annex A

(LETTERHEAD OF COMPETENT AUTHORITY)

Certificate No: _ _ _/_ _ _/_ _

CERTIFICATE OF GMP COMPLIANCE OF A MANUFACTURER

ISSUED UNDER THE PROVISIONS OF THE MUTUAL RECOGNITION
AGREEMENT BETWEEN THE EC AND AUSTRALIA

As requested by ............................................................................................…… on ....../....../....... (date),

the Competent Authority of.............................................……. (Country) confirms the following:

The company ..........................................................,

whose legally registered address is: ...........................................................................................................
...........................................................................................................
...........................................................................................................
...........................................................................................................

has been authorised, in accordance to the [Agricultural and Veterinary Chemicals Codes; the Therapeutic
Goods Act 1989; Directive 75/319/EEC, Article 16, and/or Directive 81/851/EEC, Article 24, or Directive
92/25/EEC article 3, transposed in the following national legislation: .
.........................................................................................................(*).]

under the authorisation reference number ........................................,

covering the following sites of manufacture:

1.........................................................................................................

2.........................................................................................................

to carry out the following operations:

• total manufacture(*) or
• partial manufacture(*)
• import of medicinal products from third countries (applicable only for the EC)(*)

of the following medicinal product or group of products for human use / use in animals(*):

....................................................................................................................................................................

in the following dosage forms / product types: (see overleaf).

....................................................................................................................................................................

(*): Delete that which does not apply

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From the knowledge gained during inspection of this manufacturer, the latest of which was conducted on
…../...…/...… (date), it is considered that the company complies with the Good Manufacturing Practice
requirements referred to in the Agreement of Mutual Recognition between the European Community and
Australia.

This certificate remains valid for 3 years from the date of last inspection.

…../...…/.....… (date) Name and signature of the authorised person of the Competent
Authority of (country)

…………………………………………….

(name)
(title)
(Competent Authority)
(phone & fax numbers)

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Dosage forms / product types of which manufacture is authorized (*):
(Suggested categories for inclusion on the first page of the certificate)

Sterile products:
Liquid dosage forms (Large Volume Parenterals)
- aseptically prepared
- terminally sterilized
Liquid dosage forms (Small Volume Parenterals)
- aseptically prepared
- terminally sterilized
- eye drops
Semi-solid dosage forms
Solid dosage forms - solid fill
- freeze-dried
Non-sterile products:
Liquid dosage forms
Semi-solid dosage forms
Solid dosage forms
- unit dose form (tablets, capsules,
suppositories, pessaries)
- multi dose form (powders, granules)
Biological products:
Vaccines
Sera
Blood products
Allergens
Other (describe: e.g. hormones, enzymes of human or animal origin,
genetically engineered products)
Packaging only:
Liquid dosage form
Semi-solid dosage form
Solid dosage form

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Coding System for Numbering the Certificate of GMP compliance for a Manufacturer

αα/001β/yyyy

αα = Country code (see below)

β = H (medicine for human use) or V (veterinary medicine)
001 = sequential number, commencing with 001 for each new year
yyyy = year

For example, certificate number AT/001H/2000 would be the 1st certificate issued in 2000 by Austria
for a medicinal product for human use.

Country Codes:

AU = Australia
AT = Austria
BE = Belgium
DK = Denmark
FI = Finland
FR = France
DE = Germany
GR = Greece
IE = Ireland
IT = Italy
LU = Luxembourg
NL = Netherlands
PT = Portugal
ES = Spain
SE = Sweden
UK = United Kingdom

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 Annex B

Internationally Harmonised Requirements for Batch Certification

Explanatory Note

In the framework of Mutual Recognition Agreements, the Sectoral Annex on Good Manufacturing
Practices (GMP) requires a batch certification scheme for drug/medicinal products covered by the
pharmaceutical Annex. The internationally harmonised requirements for the content of the batch certificate
of a drug/medicinal product is attached. The importer of the batch is to receive and maintain the batch
certificate issued by the fabricator/manufacturer. Upon request, it has to be readily available to the staff
of the Regulatory Authority of the importing country. This certification by the manufacturer on the
conformity of each batch is essential to exempt the importer from re-control (re-analysis).

Each batch transferred between countries having an MRA in force, must be accompanied by a batch
certificate issued by the fabricator/manufacturer in the exporting country. This certificate will be issued
further to a full qualitative and quantitative analysis of all active and other relevant constituents to ensure
that the quality of the products complies with the requirements of the Marketing Authorisation of the
importing country. This certificate will attest that the batch meets the specifications and has been
manufactured in accordance with the Marketing Authorisation of the importing country, detailing the
specifications of the product, the analytical methods referenced, the analytical results obtained, and
containing a statement that the batch processing and packaging quality control records were reviewed and
found in conformity with GMP. The batch certificate will be signed by the person responsible for releasing
the batch for sale or supply/export at the fabrication/manufacturing site.

These harmonised requirements have been agreed by the Regulatory Authorities of the following
parties/countries: Australia, Canada, European Community, New Zealand and Switzerland.

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 Content of the Fabricator’s/Manufacturer’s Batch Certificate
for
Drug/Medicinal Products Exported to Countries
under the Scope of a
Mutual Recognition Agreement (MRA)

[ LETTER HEAD OF EXPORTING MANUFACTURER]

1. Name of product.

Proprietary, brand or trade name in the importing country.

2. Importing Country.

3. Marketing Authorization Number.

The marketing authorisation number of the product in the importing country should be
provided.

4. Strength/Potency.

Identity (name) and amount per unit dose required for all active ingredients/constituents.

5. Dosage form (pharmaceutical form).

6. Package size (contents of container) and type (e.g. vials, bottles, blisters).

7. Lot/batch number.

As related to the product.

8. Date of fabrication/manufacture.

In accordance with national (local) requirements.

9. Expiry date.

10. Name and address of fabricator(s)/manufacturer(s) - manufacturing site(s).

All sites involved in the manufacture including packaging and quality control of the batch
should be listed with name and address. The name and address must correspond to the
information provided on the Manufacturing Authorisation/Establishment Licence.

11. Number of Manufacturing Authorisation / Licence or Certificate of GMP Compliance

of a manufacturer/fabricator.

Number should be given for each site listed under item 10.

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12. Results of analysis.

Should include the authorized specifications, all results obtained and refer to the methods
used (may refer to a separate certificate of analysis which must be dated, signed and
attached).

13. Comments/remarks.

Any additional information that can be of value to the importer and/or inspector verifying the
compliance of the batch certificate (e.g. specific storage or transportation conditions).

14. Certification statement.

This statement should cover the fabrication/manufacturing, including packaging and quality
control. The following text should be used: ”I hereby certify that the above information is
authentic and accurate. This batch of product has been fabricated/manufactured, including
packaging and quality control at the above mentioned site(s) in full compliance with the
GMP requirements of the local Regulatory Authority and with the specifications in the
Marketing Authorisation of the importing country. The batch processing, packaging and
analysis records were reviewed and found to be in compliance with GMP”.

15. Name and position/title of person authorizing the batch release.

Including its company/site name and address, if more than one company is mentioned under
item 10.

16. Signature of person authorizing the batch release.

17. Date of Signature

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 Annex C

The European Agency for the Evaluation of Medicinal Products

Inspection Sector

London, 6 July 2001

Doc. Ref: EMEA/MRA/

Mutual Recognition Agreements, Sectoral Annex on GMP

Contact details in European Member States for requests of GMP certificates

Country H/V Contact person phone & fax & email

Mr Robert Bodmann Phone: +43 1 711 72 46 95

Bundesministerium für soziale Sicherheit und Fax: +43 1 714 92 22
Austria H+V Generationen E-mail:
Radetzkystraße 2 robert.bodmann@bmsg.gv.at
A - 1031 Vienna
Mr Robert Delattin Phone: + 32 2 210 49 29
Algemene Farmaceutische Inspectie Fax: + 32 2 210 48 80
Belgium H+V
Rac Vesalius 307 E-mail:
B - 1010 Bruxelles robert delattin@health.fgov.be
Ms Anne Marie Vangsted Phone: + 45 44 88 91 11
Denmark H+V Lægemiddelstyrelsen Fax: + 45 44 88 91 95
Frederikssundsvej 378 E-mail: amv@dkma.dk
DK - 2700 Brønshøj
Ms Eija Pelkonen Phone: + 358 9 473 34 205
Finland H+V National Agency for Medicines Fax: + 358 9 473 34 267
P.O. Box 55 E-mail: eija.pelkonen@nam.fi
FIN - 00301 Helsinki
Mr Jacques Morénas Phone: + 33 1 55 87 39 17
Agence Française de Sécurité Sanitaire des Produits de Fax: + 33 1 55 87 39 12
H Santé E-mail:
143-147 Boulevard Anatole France jmorenas.afssaps@nomade.fr
France F – 93285 Saint-Denis CEDEX
Mr Dominique Mourot Phone: + 33 2 99 94 78 60
V Agence Française de Sécurité Sanitaire des Aliments Fax: + 33 2 99 94 78 64
La Haute Marche Javané E-mail: d.mourot@anmv.afssa.fr
F - 35133 Fougères
Ms Sabine Atzor
Zentralstelle der Länder für Gesundheitsschutz bei Phone: +49 228 977 94 31
Germany H+V Arzneimitteln und Medizinprodukten Fax: +49 228 977 94 44
Sebastianstrasse 189 E-mail: zlg@zlg.nrw.de
D -53155 Bonn
Ms Vassiliki Revithi Phone: + 30 1 650 72 04
National Organisation for Medicines Fax: + 30 1 654 95 91
Greece H+V Mesogion 284 E-mail: reg@eof.gr and
155 62 Holargos inspec1@eof.gr
Athens
Ms Muireann Lydon
Irish Medicines Board Phone: + 353 1 676 4971
Ireland H+V The Earlsfort Centre Fax: + 353 1 676 4061
Earlsfort Terrace E-mail: muireann.lydon@imb.ie
IRL - 2 Dublin

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 Mr Carmine Guarino
Ministry of Health Phone: +39 06 5994 3424
Department for medicines evaluation and Fax: +39 06 5994 3684
H
pharmacovigilance E-mail:
Viale della Civiltà Romana, 7 c.guarino@sanita.it
I 00144 Rome
Italy
Mr Virgilio Donini Phone: +39 06 5994 3591
Ministry of Health Phone: +39 06 5994 3590
V Dipartimento Alimenti e Nutrizione e Sanità Pubblica Fax: +39 06 5994 6949
Veterinaria Ufficio XI E-mail:
Piazzale Marconi, 25 (Palazzo Italia) v.donini@sanita.it
I – 00144 Rome
Ms Jacqueline Genoux-Hames
Ministère de la Santé Phone: +352 478 55 93
Luxembourg H+V Division de la Pharmacie et des Médicaments Fax: +352 22 44 58
Villa Louvigny E-mail: dpmlux@pt.lu
Allée Marconi
L – 2120 Luxembourg
Mr A J Smallenbroek
The Inspectorate of Health Care of the Public Health Phone: + 31 70 340 63 25
H Supervisory Service of the Netherlands Fax: + 31 70 340 71 59
P.O. Box 16119 E-mail: aj.smallenbroek@igz.nl
NL – 2500 BC The Hague
Netherlands
Mr R H L M Maassen
The Inspectorate of Health Care of the Public Health Phone: + 31 70 340 55 64
V Supervisory Service of the Netherlands Fax: + 31 70 340 71 59
P.O. Box 16119 E-mail: rh.maassen@igz.nl
NL – 2500 BC The Hague
Ms Lina Mendes
Instituto Nacional da Farmácia e do Medicamento Phone: + 351 21 798 71 00
Portugal H+V Parque de Saudé de Lisboa Fax: + 351 21 798 73 16
Av do Brasil 53 E-mail: lina.mendes@infarmed.pt
P - 1700 Lisboa
Ms Estrella Sintas Ponte Phone: + 34 91 596 14 72
H Agencia española del medicamento Fax: + 34 91 596 14 55
C/ Huertas, 75 E-mail: esintas@agemed.es
E - 28014 Madrid
Spain
Ms Cristina Gómez-Chacón Phone: + 34 91 596 41 56
V Agencia española del medicamento Fax: + 34 91 596 14 55
C/ Huertas, 75 E-mail: cgomez@agemed.es
E - 28014 Madrid
Mr Lennart Ernerot Phone: + 46 18 17 46 76
Sweden H+V Läkemedelsverket Fax: + 46 18 54 85 66
Box 26 E-mail: lennart.ernerot@mpa.se
S - 751 03 Uppsala
Mr Chris Brown
Medicines Control Agency Phone: + 44 20 7273 06 01
United Room 17-143
H+V Fax: + 44 20 7273 06 76
Kingdom Market Towers E-mail: chris.brown@mca.gov.uk
1 Nine Elms Lane
UK - London SW8 5NQ
Public 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK
Tel: (44 20) 7418 8400 Fax: (44 20) 7418 8595
E-mail: mra@emea.eudra.org http://www.eudra.org/emea.html

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