Good Manufacturing Practices (GMP) and Establishment Licences (EL) Issues

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.

Health Products and Food Branch Inspectorate
2nd Floor, Graham Spry Building
250 Lanark Avenue
A.L. 2002A
Ottawa, Ontario
K1A 0K9

July 1^st, 2010

To: Establishment Licence Holders

Re: Good Manufacturing Practices (GMP) and Establishment Licences (EL) Issues

This letter is intended to clarify Health Canada's position on the regulatory requirements for companies conducting certain activities on raw materials and a reminder for companies conducting sterilization (eg. gamma radiation, Ethylene Oxide (EtO)) of primary packaging materials used in the manufacture of aseptically filled sterile drug products which do not undergo terminal sterilization.

Activities related to raw materials

As per section C.02.009 (1) of the Food and Drug Regulations, testing of raw materials, including active pharmaceutical ingredients (API) is required under Division 2 - GMP. Any building conducting the final release testing of non-sterile APIs prior to their use in the fabrication of the finished product, as outlined in Division 2, must be GMP compliant and must have a valid EL or be listed on the foreign site annex of the importer's EL. Additionally, any building fabricating, packaging/labelling and testing sterile raw materials, including APIs and excipients, used in drug products that do not undergo terminal sterilization must be GMP compliant and must have a valid EL or be listed on the foreign site annex of the importer's establishment licence.

Activities related to sterilization of primary packaging materials

All current EL holders authorized to fabricate, package/label, import and distribute sterile drug products are reminded to ensure that third-party companies who perform the activity of sterilizing packaging materials used in the preparation of aseptically filled sterile products do so in accordance with Division 1A, and Division 2 (in particular, section C.02.029) of the Food and Drug Regulations. As stated in our letter dated 2009 (attached), all establishments are expected to comply, by September 1^st , 2010, with the requirement for companies conducting sterilization (eg. gamma radiation, Ethylene Oxide (EtO)) of primary packaging materials used in the manufacture of aseptically filled sterile drug.

For guidance regarding the information required for foreign sites please refer to sections 3.1 and 3.2 of the guidance document "Guidance on Evidence to Demonstrate Drug GMP Compliance of Foreign Sites (GUI-0080) ", which is fully implemented as of June 1^st, 2010.

Please be reminded that, for foreign sites located in a country with which Canada has a Mutual Recognition Agreement (MRA), if the activities or dosage forms are not covered by the MRA (e.g. products not considered a drug in the country of origin), the importer must submit GMP evidence in accordance with the abovementioned guidance document.

Failure to comply with the Food and Drug Act and its associated Regulations will necessitate compliance and enforcement action in accordance with Health Canada's "Compliance and Enforcement Policy (POL-0001) " as well as the "Good Manufacturing Practices and EL Enforcement Directive (POL-0004) " which are available on the Health Canada website.

Should you have any questions regarding EL renewal and GMP, please do not hesitate to contact us at the DEL_questions_LEPPP@hc-sc.gc.ca and GMP_Questions_BPF@hc-sc.gc.ca, respectively. We thank you for your cooperation.

Original signed by

Diana Dowthwaite
Director General
Health Products and Food Branch Inspectorate