Combination Products
Introduction and Requirement
A Combination Product is one that consists of more than one component part, commonly known as a “kit product”. It is presented as a single product and is licensed for a single set of indications.
There are two types of Combination Products within the CCDD:
1) Products where each component contains at least one active ingredient:
Combination Product with multiple active components, each described by a unique combination of substance-strength set, single dose form and (if not continuous) a unit of presentation (whether explicitly stated or implicit); for example:
CANESTEN COMBI 1 DAY COMFORTAB + EXTERNAL CREAM BAYER INC
clotrimazole 1 % cutaneous cream
substance-strength set = clotrimazole 1%
dose form = cutaneous cream
unit of presentation = N/A (continuous)
clotrimazole 500 mg vaginal tablet
substance-strength set = clotrimazole 500 mg
dose form = vaginal tablet
unit of presentation = implicit – “per tablet”
HP-PAC TAKEDA PHARMACEUTICALS AMERICA INC
amoxicillin 500 mg oral capsule
substance-strength set = amoxicillin 500 mg
dose form = oral capsule
unit of presentation = implicit – “per capsule”
clarithromycin 500 mg oral tablet
substance-strength set = clarithromycin 500 mg
dose form = oral tablet
unit of presentation = implicit – “per tablet”
lansoprazole 30 mg gastro-resistant capsule
substance-strength set = lansoprazole 30 mg
dose form = gastro-resistant capsule
unit of presentation = implicit – “per capsule”
2) Products where one or more components may be inactive and act as a diluent or placebo.
Combination Product with an active and an inactive component, where the component containing active ingredient substance is described by a substance-strength set, a single dose form and a unit of presentation (whether explicitly stated or implicit) but the inactive presentation is described minimally; for example:
BREVICON 0.5/35 TABLETS (28-DAY PACK) PFIZER CANADA ULC
ethinyl estradiol 35 mcg and norethindrone 0.5 mg oral tablet with lactose oral tablet
substance-strength set = ethinyl estradiol 35 mcg and norethindrone 0.5 mg
dose form = oral tablet
unit of presentation = implicit – “per tablet”
lactose oral tablet
GLUCAGEN HYPOKIT NOVO NORDISK CANADA INC
glucagon (glucagon hydrochloride) 1 mg per vial powder for solution for injection with diluent solution syringe
substance-strength set = glucagon (glucagon hydrochloride) 1 mg per vial
dose form = powder for solution for injection
unit of presentation = explicit – “per vial”
diluent solution syringe
Why Combination Products are Needed in the CCDD
In order to generate the CCDD from the Health Canada Drug Product Database, a mechanism is required to describe combination products that differentiates them from multi-ingredient products and makes them easier for stakeholders to identify.
Limitations
It is possible to describe the dose form(s) and ingredient substance-strength set(s) information for a combination product, but it is not currently possible in the available structures to describe the quantity (either explicitly or by proportion) of each component present in the combination product. For example: it is not possible to describe that there are 21 “ethinyl estradiol 35 mcg and norethindrone 500 mcg oral tablets” with 7 “lactose oral tablets” in the Brevicon 28-day product.
NTP_type Attribute
To indicate that combination products are a different type of medicinal product within the CCDD, rather than use an additional qualifier (such as “combination product”) in the NTP formal name or French description, combination products will be indicated using a “ntp_type” attribute in the NTP class.
The COMB ntp_type attribute will be used to indicate only those combination products that contain two or more components that contain active ingredient substance(s), even if a therapeutically inactive component is also present (as for example 9009392 below). The ntp_type attribute will not be used on combination products where the second manufactured item is:
a therapeutically inactive diluent
a therapeutically inactive “placebo” (as in the Brevicon 28-day product)
Examples of combination products explicitly identified by having "COMB" in the NTP_type attribute:
NTP Code | NTP Formal Name | NTP French Description |
|---|---|---|
9006481 | clotrimazole 1 % cutaneous cream with clotrimazole 500 mg vaginal tablet | clotrimazole 1 % crème cutanée avec clotrimazole 500 mg comprimé vaginal |
9009392 | ethinyl estradiol 35 mcg and norethindrone 0.5 mg oral tablet with ethinyl estradiol 35 mcg and norethindrone 0.75 mg oral tablet with ethinyl estradiol 35 mcg and norethindrone 1 mg oral tablet with lactose oral tablet | éthinylestradiol 35 mcg et noréthindrone 0.5 mg comprimé oral avec éthinylestradiol 35 mcg et noréthindrone 0.75 mg comprimé oral avec éthinylestradiol 35 mcg et noréthindrone 1 mg comprimé oral avec lactose comprimé oral |
9012653 | amoxicillin 500 mg oral capsule with clarithromycin 500 mg oral tablet with lansoprazole 30 mg gastro-resistant capsule | amoxicilline 500 mg capsule orale avec clarithromycine 500 mg comprimé oral avec lansoprazole 30 mg capsule gastrorésistante |
Examples of the combination products shown below would NOT have the "Comb" type but would have the usual “NA”:
NTP Code | NTP Formal Name | NTP French Description |
|---|---|---|
9009393 | ethinyl estradiol 35 mcg and norethindrone 0.5 mg oral tablet with lactose oral tablet | éthinylestradiol 35 mcg et noréthindrone 0.5 mg comprimé oral avec lactose comprimé oral |
9012981 | glucagon 1 mg per vial powder for solution for injection with diluent solution | glucagon 1 mg par fiole poudre pour solution injectable avec solution diluante |
Combination Product NTP Formal Name Pattern
The Formal Name pattern to describe a combination NTP will respect that the product is described by either:
Multiple sets of unique “substance-strength set, dose form and, when required, unit of presentation”.
One or more sets of unique “substance-strength set, dose form and, when required, unit of presentation” PLUS a minimal description of an inactive component (diluent or placebo).
The phraseology that will clearly differentiate a combination product from a multi-ingredient product will be to use “with” as the conjunction between each manufactured item component.
The order of active ingredient substances will be alphabetic, both within each substance-strength set and between the different components, with the exception of inactive components such as lactose tablets, which will be described at the end of the formal name. For those components that have the same active ingredient substances (the clotrimazole example) the alphabetic order of dose form will be used. If the active ingredient substance(s) and dose forms are both the same, the components will be in ascending order of strength (as in some benzoyl peroxide products).
Examples:
NTP Code | NTP Formal Name | NTP French Description |
|---|---|---|
9006481 | clotrimazole 1 % cutaneous cream with clotrimazole 500 mg vaginal tablet | clotrimazole 1 % crème cutanée avec clotrimazole 500 mg comprimé vaginal |
9009397 | ethinyl estradiol 35 mcg and norethindrone 1 mg oral tablet with lactose oral tablet | éthinylestradiol 35 mcg et noréthindrone 1 mg comprimé oral avec lactose comprimé oral |
9012653 | amoxicillin 500 mg oral capsule with clarithromycin 500 mg oral tablet with lansoprazole 30 mg gastro-resistant capsule | amoxicilline 500 mg capsule orale avec clarithromycine 500 mg comprimé oral avec lansoprazole 30 mg capsule gastrorésistante |
9012981 | glucagon 1 mg per vial powder for solution for injection with diluent solution | glucagon (chlorhydrate de glucagon) 1 mg par fiole poudre pour solution injectable avec solution diluante seringue |
For products that are supplied with a diluent (often referred to as “kits”) the diluent should be only briefly described (e.g., as “diluent solution”) rather than in detail (e.g., “bacteriostatic water for injection”), and no volume stated. Similarly, for products with an effectively inert component (as in the every-day oral contraceptive products), the inert component will also be minimally described without any requirement for strength information (e.g., “lactose oral tablet”).