How much do you know about active pharmaceutical ingredient?
What is an active ingredient? What is the difference between an active ingredient, an active pharmaceutical ingredient, and a bulk process intermediate?
Active ingredients are the substances in drugs that are responsible for the beneficial health effects experienced by consumers. The active ingredient in a pharmaceutical drug is called an active pharmaceutical ingredient (API). An example of an API is the acetaminophen contained in a pain relief tablet. The active ingredient in a biological drug is called a bulk process intermediate (BPI). An example of a BPI is the insulin contained in an insulin pen cartridge, for use by diabetics.
Why regulate active ingredients?
The quality of active ingredients in a drug has a direct effect on the safety and efficacy of that drug. Poorly manufactured and contaminated active ingredients have been associated with negative health outcomes, including death, in a number of incidents over the past decades. For this reason, most countries around the world are now regulating active ingredients.
Regulating active ingredients in Canada will help increase the quality and safety of drugs for consumers, will strengthen the pharmaceutical drug supply system in Canada, and will bring Canada into line with its international regulatory partners.
When will the amended Food and Drug Regulations come into effect?
The Food and Drug Regulations (Regulations) were amended by extending the requirements of Establishment Licensing and Good Manufacturing Practices to the manufacturing and importation of active pharmaceutical ingredients. The amended Regulations were published in part II of the Canada Gazette on May 8, 2013, and came into force on November 8, 2013.
As of November 8, 2013, all establishments in Canada that are conducting the licensable activities of fabrication, packaging/labelling, testing and importing of APIs, including finished dosage form fabricators that import APIs for use in manufacturing their own products, are subject to the applicable GMP requirements and are required to submit an Establishment Licence (EL) application form (FRM-0033), and if applicable, signing the attestation to the GMP compliance status of the foreign buildings where fabrication, packaging/labelling and/or testing of APIs occur (Part B, section 5.1 of FRM-0033) and completing the Foreign Building Information Table referenced in Part B Section 5.1 of FRM-0033 before February 08, 2014.
Importers of finished dosage forms (who are not conducting any API activities in Canada) are subject to the applicable GMP requirements and are required to submit an amendment to their existing EL by signing the attestation to the GMP compliance status of the foreign buildings where fabrication, packaging/labelling and/or testing of APIs occur (Part B, section 5.1 of FRM-0033) and completing the Foreign Building Information Table referenced in Part B Section 5.1 of FRM-0033 to Health Canada before February 8, 2014.
Importers of finished dosage forms that also import APIs will be required to submit an EL application to Health Canada in order to include the API importation activity on their EL before February 8, 2014.
Distributors and Wholesalers of APIs in Canada that source APIs within Canada and that perform no other licensable activities are subject to the applicable GMP requirements but are not required to hold an EL for these activities.
Establishments in Canada that begin to conduct licensable activities related to APIs on or after November 8, 2013 are required to:
meet the applicable GMP requirements;
submit an EL application form (FRM-0033) and, if applicable, the attestation as well as the completed API Foreign Building Information Table;
be inspected and found to be compliant with the applicable Division 2 requirements of the Regulations; and
have a EL issued by Health Canada prior to starting licensable activities.
Finished Dosage Form Fabricators that source APIs within Canada (i.e., do not conduct API licensable activities in Canada) are subject to the applicable GMP requirements but are not required to amend their existing EL. Finished Dosage form fabricator can only use APIs that were fabricated, packaged/labelled and tested by a Canadian or foreign building that met GMP requirements. Furthermore, the finished dosage form fabricator can only source APIs from a Canadian company that meets GMP requirements for importing APIs.
For additional information please refer to the Notice to Stakeholders – Amended Food and Drugs Regulations for Active Ingredients – Coming into force on November 8, 2013 available on the Health Canada website.
Do the amended Food and Drug Regulations apply to active ingredients used in pharmaceutical drugs? in biological drugs? in over-the-counter drugs? in veterinary drugs? in natural health products? in disinfectants?
The decision to modify the Food and Drug Regulations was made after a number of consultations with different industries.
The amended Food and Drug Regulations apply to active ingredients in pharmaceutical drugs for human use. Pharmaceutical drugs include both prescription and over-the-counter drugs.
The amended Food and Drug Regulations do not apply to active ingredients used solely in drugs for veterinary use or in natural health products.
The active ingredients in biological drugs (also known as bulk process intermediates) were subject to the establishment licensing and Good Manufacturing Practices requirements of the Food and Drug Regulations prior to the amendment which came into force on November 8, 2013. The amended Food and Drug Regulations continue to apply to the active ingredients in biological drugs.
Until the new Blood Regulations are made, existing requirements, as they read immediately before the coming into force of the Regulations Amending the Food and Drug Regulations (1475 — Good Manufacturing Practices), will continue to apply to whole blood and blood components.
Active ingredients used in the fabrication of hard surface disinfectants (also known as antimicrobial agents) that are exempt from the requirements of Division 1A (Establishment licences) and Division 2 (Good Manufacturing Practices) of Part C of the Food and Drug Regulations are not covered under the API regulatory framework. Active ingredients used in the manufacture of disinfectant products, which are not considered as antimicrobial agents (such as antiseptic hand soaps), will be covered by the new Regulations.
Do the amended Food and Drug Regulations apply to excipients?
Excipients are drug ingredients other than the active ingredient that produces health benefits for patients. The amendment does not affect the existing requirements for excipients.
Do the amended Food and Drug Regulations apply to medical gases?
The amendment does not affect the existing requirements for medical gases.
Will finished dosage form importers be affected by the amended Food and Drug Regulations for active ingredients?
Finished dosage form importers will be subject to Establishment Licensing and Good Manufacturing Practices (GMP) requirements for the active ingredients used in the finished dosage form drugs they import, and will be required to demonstrate their compliance with the new requirements during their regular inspection. For additional information please refer to the Notice to Stakeholders – Amended Food and Drugs Regulations for Active Ingredients – Coming into force on November 8, 2013 available on the Health Canada website.