Questions & Answers

• At present, there is no consensus among regulators and industry on what the most relevant animal model is or if an animal model is deemed to be required. This is decided on a case by case basis.
• Mimic clinical scenario as closely as possible. This will dictate the animal model used.
• Use cells that are intended for clinical therapeutic use, or analogous cells.
• Cell viability, concentration/formulation, volume, rate of delivery, implant site, number of implants/ injections, etc. are all factors to consider for the number of animals and route of administration.
• Appropriate route of administration will be dictated by the delivery system chosen, timing of cell delivery, dosing regimen, etc.
• Anatomical location/extent of the diseased/injured area will further impact this decision.

Minutes 2017-12-07, p. 9

All classification decisions are made based on the best available information at the time. So it remains possible that classification decisions may change if the product changes, or if the understanding of the product changes. For this reason it is in the sponsor’s best interest to provide the most accurate information about the product, and not (for example) information to obtain the desired classification decision. This will help to avoid the negative impacts of re-classification.

Minutes 2016-02-23, p.3

Autologous cell therapy products meet the definition of “drug” and persons who prepare (manufacture) and administer (distribute) them must comply with sections 8 and 11 of the Food and Drugs Act.
Autologous cell therapy products, except lymphohematopoietic cells which have been minimally manipulated and are intended for homologous use in transplantation, like other new drugs, are regulated under the Food and Drug Regulations and must be authorized by Health Canada. As new drugs, they are subject to Division 8 of Part C of the Food and Drug Regulations, and as investigational drugs they are subject to clinical trial requirements under Division 5 of the Food and Drug Regulations. Clinical trials authorized by Health Canada are the mechanism through which patients can have access to investigational products where much remains to be known about safety and efficacy.”

Consolidated Policy Statement 2 (end of document)

No. Cell therapy products meet the definition of drug under the Food and Drugs Act (Position Paper) and, with limited exceptions, the Food and Drug Regulations (FDR) authorization requirements apply to stem cell based therapies.
Health Canada’s regulatory framework for drug products does not make separate provisions for therapies prepared “at the bedside”. Should a product be proven to be safe and efficacious through authorized clinical trials, Health Canada will take steps where needed to support access for patients in Canada, should clear regulatory barriers be identified. It is important to note that no such exemptions exist in Canada.

Minutes 2018-04-24 p. 2

• There is no ‘default’ for the use of nonhuman primates, rodent and non-rodent species, or multiple species.
• Scientific justification should be provided for the animal species/model(s) used.
• The limitations of the species/ model(s) used must be well understood and described.

Minutes 2017-12-07, p. 9

There is no predefined amount of preclinical data needed in order for a pre-CTA meeting to occur. It is dependent on the questions and needs of the sponsor. Some inquiries are best handled in a face to face meeting, while others can be done as a teleconference. The sooner the meeting occurs, the more general the advice will be. However, at minimum a hypothesis must be formed before the pre-CTA meeting. Health Canada recommends meeting:

• Early in the development stage: for general advice, recommend guidance documents.
• Close to starting the development or when a clinical trial design exists for more specific advice.

Minutes 2017-12-07, p. 8

No. Health canada will review ONLY the contents of your CTA. Your pre-meeting interaction with Health Canada is to help you conform to regulations and will not be held against you. Health Canada encourages and offers as many pre-submission meetings as required, without charge. This may shorten the time to the issuance of an NOL as long as you already have a hypothesis formed. 

Minutes: 2017-12-07, p. 3

• Published data can be accepted if the studies are done with the same product.
• The product is considered the same when the cells are processed the same way, not only when they are the same type of cells.

Minutes: 2017-12-07, p. 9

• Lack of proof-of-concept studies.
• Inclusion of pre-clinical data from a similar, but different products.
• No pre-clinical studies.

Minutes: 2017-12-07, p. 9

Cell therapies intented for treatment in humans, including unmodified cells and those that are genetically modified using non- replicating viral vectors, trigger an Environmental Assessment under the NSNR (Organisms) when they are manufactured or imported in any amount. When you apply for a clinical trial application (CTA), if you are importing or manufacturing a new living organism that is not listed on the Domestic Substances List (DSL), you should also file a NSN under the NSNR(O). While options are being explored by Health Canada at this time, the use of these products must be communicated to HECSB, including at the CTA stage of development.

Minutes: 2017-12-07, p. 4

Additional Information:

Living organism
A substance that is an animate product of biotechnology.

(Section 104, CEPA 1999)

Micro-organism
A microscopic living organism that is:
a) classified in the Bacteria, the Archaea, the Protista, which includes protozoa and algae, or the Fungi, which includes yeasts;
b) a virus, virus-like particle, or sub-viral particle;
c) a cultured cell of an organism not referred to in paragraphs (a) and (b),other
than a cell used to propagate such organism; or
d) any culture other than a pure culture.

(Subsection 1(1) of NSNR(O))

Substance
Any distinguishable kind of organic or inorganic matter, whether animate or inanimate.
Exclusions:

• Mixture (Any mixture that is a combination of substances and does not itself produce a substance that is different from the substances that were combined).

• Manufactured item formed into a specific physical shape necessary to its final function (i.e. the structural framework of a biofilter would not be considered a notifiable substance, although the micro-organisms used in the biofilter may be).

• Waste, effluents and emissions.

(Section 3, CEPA 1999)

Few exceptions may apply and the HECSB should be contacted for clarification. Subsection 106(6) of CEPA 1999 establishes criteria for living organisms that do not require notification.

• This is assessed on a case-by-case basis.
• The expectations from pre-clinical data are; 1) To support a rationale for the first-in-human or subsequent clinical trial or 2) To make recommendations regarding clinical trial design.
• If there are changes in the manufacturing process additional non-clinical data may be required.
• The results of the early phase trial may trigger the need for additional non-clinical studies.

Minutes: 2017-12-07, p.9

In general, if medical equipment is used in cell manufacturing it does not require separate certification, as long as it is used correctly and for its intended purpose. Equipment does not need to be licensed as a medical device to be used for manufacturing a drug in accordance with marketing or clinical trial authorization.

There are three scenarios:
1) Use of a device that is approved and used correctly - this requires no further information.
2) Use of a device that is licensed as a medical device but used for different purposes – in this case, information supporting its use for the associated manufacturing steps must be provided.
3) Use of a device that is not approved nor used for its intended purpose – in this case HC would need information to evaluate the equipment and the associated manufacturing steps.

There is often confusion on what types of claims can be made by device manufacturers. Health Canada is following up with manufacturers, as there have been some recent unsubstantiated claims. Medical devices are only approved for sale in Canada for their intended purpose. It is important for users to know that when manufacturing a drug they can use medical devices for purposes other than those for which they are licensed, as long as there is data to support such a protocol and it is submitted to the BGTD. The BGTD may contact MDB to consult on a case-by-case basis but a separate review by MDB may not be required.

Minutes: 2018-12-04 p. 1