Product wastage from modern human growth hormone administration devices: a laboratory and computer simulation analysis

Figures & data

Table 1 Characteristics of devices and growth hormone formulations included in the analysis

Device	Total device content (mg)	Maximum single dose (mg)	Dosing increment (mg)	Stable at room temperature after first use
FlexPro®	5.0	2.00	0.025	Yes (up to 3 weeks at <25°C)
NordiFlex®	5.0	1.50	0.025	Yes (up to 3 weeks at <25°C)
NordiPen®/SimpleXx®	5.0	1.25	0.050	Yes (up to 3 weeks at <25°C)
NordiLet®	5.0	1.91	0.067	Yes (up to 3 weeks at <25°C)
Omnitrope® Pen-5	5.0	2.70	0.050	No

Table 2 Example procedure for measuring growth hormone wastage with NordiPen®/SimpleXx® 5 mg or Omnitrope® Pen-5

Step	Description
1.	Store all pens at standard conditions (18°C–28°C and 25%–75% humidity) for 30 minutes
2.	Use a trial pen to ensure that the 500 mm G 22 tubing and needle (NovoFine® G 31 × 6 mm needle for Norditropin® devices, or Micro-Fine™ BD 31 G × 5 mm for Omnitrope® Pen-5) are filled with test liquid
	• Mount the trial pen with a NovoFine G 31 × 6 mm needle for Norditropin devices or Micro-Fine BD 31 G × 5 mm for Omnitrope Pen-5
	• Perform an air shot of one increment until liquid appears at the needle tip
	• Replace the needle with the 500 mm G 22 tubing (connected to the scale)
	• Manually zero the scale
	• Perform air shot of one increment until the weighing shows around 7.5 mg
3.	Select fixed time test in METDose with a preset period of 6 seconds for Norditropin devices or 5 seconds for Omnitrope Pen-5
4.	Zero the scale
5.	Replace the trial pen with a test pen
6.	Press “Start” (records GH dripping with needle on prior to injection)
7.	Zero the scale
8.	Make an air shot
9.	Press “Start” (records GH waste during air shot)
10.	Zero the scale
11.	Dial the pen to 25 increments (1.25 mg) for NordiPen/SimpleXx or 54 increments (2.7 mg) for Omnitrope Pen-5
12.	Press “Start” (records GH dripping while setting dose)
13.	Repeat steps 4–12 with the rest of the test pens

Notes: NordiPen/SimpleXx manufactured by Novo Nordisk A/S, Bagsværd, Denmark; Omnitrope Pen-5 manufactured by Sandoz International GmbH, Holzkirchen, Germany.

Abbreviations: GH, growth hormone; METDose, dose measurement software.

Table 3 Laboratory analysis findings for 5 mg devices including dripping with the needle attached and when setting the GH dose, reported in mg of active GH (converted from mass of GH solution)

Analysis	FlexPro®	NordiFlex®	NordiPen®/SimpleXx®	NordiLet®	Omnitrope® Pen-5
Wastage with the needle on prior to injection (mg)
Mean*	−0.00212	−0.00678	−0.00257	−0.00922	0.09781
SD	0.00119	0.00160	0.00312	0.00145	0.01655
P	<0.05	<0.05	<0.05	<0.05	–
Wastage during dose setting (mg)
Mean	0.00231	0.00018	0.00191	0.00000	0.00087
SD	0.00134	0.00021	0.00165	0.00000	0.00058
P	<0.05	<0.05	<0.05	<0.05	–

Notes:P-values are presented relative to Omnitrope Pen-5. FlexPro, NordiFlex, NordiPen/SimpleXx and NordiLet are manufactured by Novo Nordisk A/S, Bagsværd, Denmark. Omnitrope Pen-5 is manufactured by Sandoz International GmbH, Holzkirchen, Germany. *Negative values arose due to capillary phenomena when changing devices. Owing to the comparative nature of the study, these effects were left uncompensated.

Abbreviations: GH, growth hormone; SD, standard deviation.

Figure 1 Modeled growth hormone wastage per patient per year for 5 mg administration devices in US, European, and Japanese settings.

Notes: FlexPro, NordiFlex, NordiPen/SimpleXx and NordiLet are manufactured by Novo Nordisk A/S, Bagsværd, Denmark. Omnitrope Pen-5 is manufactured by Sandoz International GmbH, Holzkirchen, Germany.
Abbreviation: GH, growth hormone.

Table 4 Modeled annual GH wastage per patient with 5 mg and 10 mg devices in simulated US, European, and Japanese cohorts of pediatric patients on GH treatment

Analysis	FlexPro®	NordiFlex®	NordiPen®/SimpleXx®	NordiLet®	Omnitrope® Pen-5
US 5 mg
Increment wastage (mg)	4.63	4.63	7.60	11.98	7.60
Wastage with needle on prior to injection (mg)	0.00	0.00	0.00	0.00	35.69
Wastage during dose dialing (mg)	0.84	0.07	0.70	0.00	0.32
Europe 5 mg
Increment wastage (mg)	3.80	3.80	9.74	9.37	9.74
Wastage with needle on prior to injection (mg)	0.00	0.00	0.00	0.00	35.69
Wastage during dose dialing (mg)	0.84	0.07	0.70	0.00	0.32
Japan 5 mg
Increment wastage (mg)	3.96	3.96	7.92	10.93	7.92
Wastage with needle on prior to injection (mg)	0.00	0.00	0.00	0.00	35.69
Wastage during dose dialing (mg)	0.84	0.07	0.70	0.00	0.32
US 10 mg
Increment wastage (mg)	7.60	7.60	16.64	23.70	16.64
Wastage with needle on prior to injection (mg)	0.00	0.00	0.00	0.00	71.67
Wastage during dose dialing (mg)	1.69	0.13	1.39	0.00	0.64
Europe 10 mg
Increment wastage (mg)	9.74	9.74	15.83	21.53	15.83
Wastage with needle on prior to injection (mg)	0.00	0.00	0.00	0.00	71.67
Wastage during dose dialing (mg)	1.69	0.13	1.39	0.00	0.64
Japan 10 mg
Increment wastage (mg)	7.92	7.92	18.26	25.30	18.26
Wastage with needle on prior to injection (mg)	0.00	0.00	0.00	0.00	71.67
Wastage during dose dialing (mg)	1.69	0.13	1.39	0.00	0.64

Notes: FlexPro, NordiFlex, NordiPen/SimpleXx and NordiLet are manufactured by Novo Nordisk A/S, Bagsværd, Denmark. Omnitrope Pen-5 is manufactured by Sandoz International GmbH, Holzkirchen, Germany.

Abbreviation: GH, growth hormone.

Figure 2 Growth hormone wastage per patient per year for 10 mg administration devices in US, European, and Japanese settings.

Notes: FlexPro, NordiFlex, NordiPen/SimpleXx and NordiLet are manufactured by Novo Nordisk A/S, Bagsværd, Denmark. Omnitrope Pen-5 is manufactured by Sandoz International GmbH, Holzkirchen, Germany.
Abbreviation: GH, growth hormone.