Vol. 147, No. 11 — May 22, 2013
Registration
SOR/2013-90 May 2, 2013
FOOD AND DRUGS ACT
Regulations Amending the Food and Drug Regulations (1663 — Schedule F)
P.C. 2013-525 May 2, 2013
His Excellency the Governor General in Council, on the recommendation of the Minister of Health, pursuant to subsection 30(1) (see footnote a) of the Food and Drugs Act (see footnote b), makes the annexed Regulations Amending the Food and Drug Regulations (1663 — Schedule F).
REGULATIONS AMENDING THE FOOD AND DRUG REGULATIONS (1663 — SCHEDULE F)
AMENDMENT
1. Part I of Schedule F to the Food and Drug Regulations (see footnote 1) is amended by adding the following in alphabetical order:
Pancreatic extracts, when sold in a dosage form that provides more than 20 000 USP units of lipase activity per dosage unit or indicated for the treatment of pancreatic exocrine insufficiency
Extraits pancréatiques, lorsque vendus sous forme posologique fournissant plus de 20 000 unités USP d’activité lipasique par unité posologique ou indiqués pour le traitement de l’insuffisance pancréatique exocrine
Pancreatin, when sold in a dosage form that provides more than 20 000 USP units of lipase activity per dosage unit or indicated for the treatment of pancreatic exocrine insufficiency
Pancréatine, lorsque vendue sous forme posologique fournissant plus de 20 000 unités USP d’activité lipasique par unité posologique ou indiquée pour le traitement de l’insuffisance pancréatique exocrine
Pancrelipase, when sold in a dosage form that provides more than 20 000 USP units of lipase activity per dosage unit or indicated for the treatment of pancreatic exocrine insufficiency
Pancrélipase, lorsque vendue sous forme posologique fournissant plus de 20 000 unités USP d’activité lipasique par unité posologique ou indiquée pour le traitement de l’insuffisance pancréatique exocrine
COMING INTO FORCE
2. These Regulations come into force six months after the day on which they are registered.
REGULATORY IMPACT ANALYSIS STATEMENT
(This statement is not part of the Regulations.)
Background
Before a drug can be sold in Canada, Health Canada assesses its safety, efficacy and quality as required by the Food and Drugs Act and associated regulations. Sections C.01.041 to C.01.049 of the Food and Drug Regulations control the sale of medicinal ingredients that are listed in Schedule F. Schedule F designates prescription drug status, and contains two Parts: Part I of Schedule F lists medicinal ingredients that require a prescription for human and veterinary use, and Part II of Schedule F lists medicinal ingredients that require a prescription for human use.
Determining the prescription status of a medicinal ingredient (or classes of drugs) depends upon the risk factors associated with their use; any revisions to prescription status listings are also based on the risk factors and a scientific assessment. Health Canada’s Drug Schedule Status Committee (DSSC) makes recommendations for prescription status and bases the scientific assessment of each medicinal ingredient against established and publicly available risk factors, such as the need for direct practitioner supervision, the toxicity profile, the pharmacological properties and therapeutic uses of the medicinal ingredients. A complete list of the factors may be accessed at www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/pol/schf_annf_fact_pol-eng.php.
Pancreatic enzymes are important for the adequate absorption of fat, proteins, and, to a lesser extent, carbohydrates from the diet. Failure of the pancreas to secrete and deliver an adequate level of enzymes to the digestive tract results in the inability to properly digest food, otherwise known as pancreatic exocrine insufficiency (PEI). Several medical conditions can cause this lack of enzymes, including cystic fibrosis, chronic inflammation of the pancreas, or blockage of the pancreatic duct(s).
Currently, pancreatic enzyme products are available without a prescription as natural health products under the Natural Health Products Regulations; however, certain pancreatic enzymes (i.e. pancrelipase, pancreatin and pancreatic extracts) for the treatment of established pancreatic insufficiency have been regulated provincially as prescription drugs since 1999. Health Canada’s DSSC recommends prescription status for this medicinal ingredient with qualifications as to strength and indication. At certain levels or when used to treat certain medical conditions, oversight by a practitioner is necessary to ensure that appropriate risk/benefit information is considered before drugs containing this medicinal ingredient are administered and that the drug therapy is properly monitored.
In the United States, pancrelipase products for oral administration for the treatment of PEI are registered as prescription drugs. In Australia, all pancreatic enzymes are considered to be “prescription only medicines” for the treatment of any condition unless they are contained in a preparation containing 20 000 British Pharmacopoeia (BP (see footnote 2)) units or less of lipase activity per dosage unit. In the United Kingdom, pancreatin (pancrelipase is not defined as a separate drug) is regulated as a “prescription only medicine” unless the product has a maximum strength of 25 000 European Pharmacopoeia (Ph. Eur.) units of lipase per gram of powder.
Issues and objectives
When used in the treatment of cystic fibrosis or PEI, pancreatic enzyme products are designated prescription status provincially, as they are associated with a number of risk factors which support the need for direct practitioner supervision. However, at a federal level, the Food and Drug Regulations currently permit pancreatic enzymes to be sold without a prescription regardless of level or indication for use. This broad permission does not reflect the DSSC recommendation for prescription status at certain dosages or when used to treat a serious medical condition.
The objective of this proposal is to add pancreatic enzymes to Schedule F at a specific strength threshold to enable those products that fall under the limit to be licensed as natural health products (NHPs) and not require a prescription. This level has been assessed to be an appropriate margin of safety and practitioner intervention is not required to allow products under this safe limit to be available without a prescription (e.g. when used as a digestive aid).
Any potential safety concerns associated with these products when used as an NHP would be mitigated by the threshold limit of less than 20 000 USP (see footnote 3) units of lipase activity. All other aspects related to safety, efficacy and quality would be considered during the premarket review process under the Natural Health Products Regulations. This amendment also ensures that any risks associated with higher dosages or when used in the treatment of a serious medical condition would have consistent requirements for practitioner oversight through prescription status.
Description
This regulatory amendment adds pancrelipase, pancreatin and pancreatic extracts where the strength per dosage unit exceeds 20 000 USP units of lipase activity, or when indicated for the treatment of pancreatic exocrine insufficiencyto Part I of Schedule F to the Food and Drug Regulations to designate its prescription status.
Products for the treatment of PEI or above this strength threshold will require a prescription for their sale, and the sale of products under this threshold or for other indications will still be regulated as natural health products under the Natural Health Products Regulations.
“One-for-One” Rule
The “One-for-One” Rule does not apply to this proposal as there is no change in administrative costs on business.
Small business lens
The small business lens does not apply to this proposal, as there are no costs on small business.
Consultation
Advance notice of this regulatory proposal was communicated to provincial and territorial ministries of health, medical and pharmacy licensing bodies, and industry, consumer and professional associations through a Notice of Intent (NOI). The NOI was published in the Canada Gazette, Part I, on February 11, 2012, and sent directly to stakeholders on February 15, 2012, followed by a 75-day comment period. This initiative was also posted on the Health Canada and Consulting with Canadians Web sites on February 13, 2012.
This advance notice, plus a six-month coming into force, is intended to provide manufacturers of affected products with sufficient time to transition and obtain approval of their Drug Identification Number for biologics (DIN-B) submission. In addition, guidance and draft labelling information has been sent (August 27, 2012) to manufacturers of products affected by this regulatory amendment to assist in preparing the required prescription labelling.
Comments were received from 10 respondents: 3 associations of health professionals; 3 individuals; and 4 companies associated with the manufacturing and marketing of health products.
Six respondents expressed support for this amendment to Schedule F, noting thatpancrelipase, pancreatin and pancreatic extracts for the treatment of established pancreatic insufficiency have already been regulated provincially as prescription drugs since 1999. Four respondents did not support the amendment, noting that these products have been available for decades without serious adverse effects.
In response to concerns and for increased transparency, an electronic copy of Health Canada’s science assessment was sent to all stakeholders (April 13, 2012), and no changes have been made to the dosage threshold originally proposed and no reference to “per kilogram body weight per day or meal” has been added since each patient is unique and their health professional will determine the correct balance between a dose per day or per meal, adjusted for body weight. The issues and concerns raised by respondents are summarized below with Health Canada’s responses.
Comment
Three respondents questioned the need for this amendment or risks posed to users, and noted that these products have been available for decades without serious adverse effects and that Health Canada’s current monograph for pancreatic enzymes allows 5 000–10 000 USP units of lipase activity per dosage unit (e.g. per capsule), one to four times per day.
Response
As noted above and as further explained in Health Canada’s science assessment that was sent to stakeholders, the risk factors associated with the use of these products, at or above the established dosage threshold and for the serious health conditions identified, justify its prescription status. They align with the existing provincial requirement for a prescription, and with their prescription status in other countries. When used to treat a serious condition (such as PEI) patients typically receive 25 000 to 40 000 USP units of lipase activity for each meal or snack, or 700 000 USP units per day. At these levels, the safe use of these products requires direct practitioner supervision and routine laboratory monitoring. For example, there are potential or known undesirable or severe side effects, such as scarring of the large intestine, at excessive or even normal PEI therapeutic dosage levels that would need to be managed by a practitioner, to determine and maintain the optimum dose, as the response to these ingredients varies greatly from one patient to another. Testing is needed to determine the level at which these ingredients are effective as the risk of the potential serious adverse effects increases if the dose is excessive.
Comment
One respondent expressed concern that this amendment would limit Canadians’ access to digestive enzymes.
Response
To clarify the respondents’ misunderstanding, the regulatory proposal pertains to medicinal ingredients that are already regulated as prescription drugs provincially, and access to digestive enzymes in general will not be affected as lower doses for non-prescription purposes, such as digestive aids, will continue to be available as authorized natural health products.
Rationale
This amendment to add certain pancreatic enzyme products with qualifiers to Schedule F listing is based on Health Canada’s scientific assessment and recommendation, given the potential benefits, harms and uncertainties related to its use at different strengths and dosages. Stakeholders have been provided extensive notification and opportunity to comment, and have received guidance on how to transition any affected products. This proposal will permit the sale of these products while ensuring that appropriate safety measures are in place.
The impacts in terms of expected benefits and costs are as follows.
Public
Accessing these medicinal ingredients under these conditions through a prescription from a practitioner will benefit Canadians by decreasing the risks of improper use, and by ensuring the guidance and care of a health professional. The addition of the threshold limit provides an appropriate margin of safety whereby products under this limit would be available to Canadians without a prescription as natural health products. In addition, medicinal ingredients listed in Schedule F may be covered by both provincial and private health care plans.
Health insurance plans
The cost of drug products for human use containing medicinal ingredients listed in Schedule F may be cost covered by both provincial and private health care plans.
Provincial health care services
Potential additional costs for health care services should be minimal since it is already current practice for pharmacists to dispense only upon receipt of a prescription.
Manufacturers
Going forward, pancrelipase, pancreatin and pancreatic extracts where the strength per dosage unit exceeds 20 000 USP units of lipase activity, or when indicated for the treatment of pancreatic exocrine insufficiencywill require a valid Drug Identification Number (DIN) and prescription labelling. Notice of the impending change in regulatory status was communicated to the pharmaceutical industry through the Notice of Intent, and additional guidance has been provided to assist in meeting the requirements for this transition. The advanced notice, in addition to a delayed coming into force, is intended to provide manufacturers of affected products with sufficient time for the transition.
Implementation, enforcement and service standards
This amendment will come into force six months after publication in the Canada Gazette, Part II.
This amendment does not alter existing compliance mechanisms under the provisions of the Food and Drugs Act, the Food and Drug Regulations and the Natural Health Products Regulations enforced by the Health Products and Food Branch Inspectorate.
Contact
Brian Fuerst
Refer to Project Number: 1663
Office of Legislative and Regulatory Modernization
Policy, Planning and International Affairs Directorate
Health Canada
Holland Cross, Tower B, 5th Floor
1600 Scott Street
Address Locator: 3105A
Telephone: 613-946-7268
Fax: 613-941-7104
Email: lrm-mlr@hc-sc.gc.ca
- Footnote a
S.C. 2012, c. 19, s. 414(2) - Footnote b
R.S., c. F-27 - Footnote 1
C.R.C., c. 870 - Footnote 2
A unit used in Britain to measure the potency of a vitamin or drug, that is, its expected biological effects. For each substance to which this unit applies, the British Pharmacopoeia Commission has determined the biological effect associated with a dose of 1 BP unit. Other quantities of the substance can then be expressed in terms of this standard unit. In many cases, the BP unit is equal to the international unit (IU). Since the British Pharmacopoeia includes the standards of the European Pharmacopoeia, BP units are equivalent to the “Ph. Eur.” units for those substances covered by both sets of standards. - Footnote 3
Pharmacopoeia is a book issued by an officially recognized authority to serve as a standard for describing drugs, chemicals, and medicinal preparations. Examples include the United States Pharmacopoeia (USP), Chinese Pharmacopoeia (ChP), BP, and Ph. Eur.