Backgrounder 3 Novolizer®: significant advance in inhalation therapy for improved asthma management
Following a symposium at last year’s European Respiratory Society congress
Professor Peter Barnes (Imperial College, London) concluded that “Inhaled
therapy is likely to remain predominant in the future and the type of inhaler is
just as important as the class of drug in the long-term management of asthma
Backgrounder 2 in this pack (The need for the ideal inhaler) described the
drawbacks of many of the current inhaler systems and includes a list of
requirements for an ‘ideal inhaler’. There is an urgent need to improve the
delivery of asthma drugs to provide improved control of symptoms in this vast
and growing global disease (see backgrounder 1). This backgrounder
describes an innovative, new delivery device, NOVOLIZER® (MEDA), which
has been specifically developed to meet the criteria for a significantly easier-
to-use, easy-to-introduce and consistently effective inhaler (Figure 1). The
new device uses a clear understanding of the modern physics of particle
deagglomeration to deliver drug accurately and consistently to the lungs.
[Figure 1 – Photograph of NOVOLIZER as in O’Connor B paper, page S14 “The ideal inhaler” Resp Med 2004 (suppl A): S10-16.” highlighting features of the devices with their benefits to patients and doctors] What are the key problems in inhaler design that NOVOLIZER® is designed to overcome?
Current inhalers suffer from a number of limitations including:
• Poor drug deposition in the lungs• Inconsistent drug delivery both between doses and between devices• Lack of feedback mechanisms to reassure patients• Complex instructions and procedures• Need for high inspiration rates• Poor compliance rates
The engineers and physicians who designed NOVOLIZER® aimed to address
each of these significant limitations. What is different about the design of NOVOLIZER®?
The device incorporates elegant design and engineering to deliver correct
doses of drug time-after-time. Based on a clear understanding of the physical
properties required for effective dry powder inhalation, NOVOLIZER® uses its
unique, patented cyclone technology to separate the fine and coarse particles
of the powdered drug. Actuation is made easy by selecting a low to medium
level of inspiratory flow resistance – unlike other devices which require higher
NOVOLIZER® incorporates an innovative flow trigger valve system which
releases drug only if the inspiratory flow sufficient for correct lung deposition is
achieved. The device has a minimum inspiratory flow rate threshold of only
35-50 L/min allowing use by a wide variety of patients.2 This mechanism
overcomes the problems of poor patient inhalation technique and ensures
Is the device reliable with consistent drug delivery?
The Viatris team worked in close co-operation with European academic
centres to engineer an inhaler which effectively delivers the drug to the large
and small airways – consistently, time-after-time. Within milliseconds of
inhalation the flow of drug is evenly delivered in a clean stream of air into the
large and small airways with minimal deposition in the mouth. The innovative
refill system delivers up to 200 metered doses of drug from a replaceable
cartridge. The refill system keeps costs down.
In vitro studies comparing budesonide fine particle doses have shown that
compared with the Turbuhaler®, and at equal mean fine particle dose, there is
more consistency of dose deposition with the NOVOLIZER®.3
The device has been extensively tested in real life clinical situations and the
dose emitted. Handling of the device is not affected by temperature, humidity,
long-term use (6 months with twice daily administration) or storage for up to 3
years. 3,4,5 These studies also compared inhalers from different batches and
found no significant difference in performance. How does the NOVOLIZER® compare with other inhalation devices?
Data from a randomised, cross-over study in which single doses of
radiolabelled budesonide 200 µg were administered to healthy volunteers, showed low flow rate dependency for peripheral lung deposition with the
NOVOLIZER®.6 When used optimally, there was greater drug deposition in the
lungs as well as reduced deposition in the mouth with NOVOLIZER®
In a number of randomised, controlled clinical trials designed to show
equivalence, the efficacy of drugs delivered by NOVOLIZER® has been shown
to be at least as good as other leading inhaler devices in terms of increasing
FEV1, improvements in clinical symptoms and decline in albuterol use.7,8,9
Interestingly, patients preferred NOVOLIZER® to either the MDI or DPI
(Turbuhaler®) used in these studies. How does the patient know the dose has been delivered correctly?
Unlike other devices, NOVOLIZER® provides multiple, simple, feedback
signals when correct inhalation has been achieved.2,10 Patients are able to
see, hear and taste that they have received the accurate dose of asthma
medication. For example, only when the correct inhalation has been achieved
will an indicator on the unit change colour (the coloured window changes from
red to green). At the same time the patient will hear a “click” if correct
inhalation takes place. If you breathe inappropriately there is no colour
change and no audible “click”. In addition, lactose added to the active
ingredient provides a sweet taste to let patients know when the dose has
been taken correctly. Meanwhile, a dose counter only moves forward when
• Provide reassurance for patients that they have taken their dose
• Aid compliance and allow compliance to be monitored by healthcare
• Avoid the risk of accidental overdose or under-dosing.
Is the NOVOLIZER® easy to use correctly?
The NOVOLIZER® has low-to-medium airflow resistance making it available
for use by most asthma patients including children, older adults and other
patients who make have limited inspiratory flow.2 Patients normally learn to
use the device in less than five minutes and therefore it has high patient
acceptance.7 Three simple steps allow consistent delivery of drug time-after-
3. Inhale deeply and hold breath for a few seconds (Figure 2)
[Figure 2. Include series of 3 photographs from detail aid titled “simple, breath-actuated inhalation”]
Many manufacturers claim that their device is easy to use, but NOVOLIZER®
is proven to be easy to use correctly. A post-marketing surveillance study in
3057 patients showed that NOVOLIZER® delivered budesonide therapy
effectively to significantly improve asthma symptoms (median total symptom
score decreased from 8 to 2 on a 15 point scale) and improve lung function
(PEFR increased from 5 l/s to 6.3 l/s, median FEV1 increased from 2250 ml to
2700 ml).11 An overwhelming majority of patients were satisfied with the new
control features of the device and 90% of those who had used other devices
before rated the feedback mechanisms of NOVOLIZER® as better or much
better. Compliance in the study was assessed by physicians as good or
Is NOVOLIZER® really suitable for children?
The simple instructions for use and low inspiratory flow requirement mean that
NOVOLIZER® is ideal for use in children with asthma. In a study of 137
children with asthma, all of those over the age of six were able to perform
correct inhalation manoeuvres with the NOVOLIZER® significantly in excess of
the peak inspiratory flow required for actuation.12 The study also showed that
84% of children under six were able to generate sufficient peak inspiratory
flow to operate the device. The feedback mechanisms incorporated in the
NOVOLIZER® are of particular value in children as they allow accurate
identification of successful and unsuccessful attempts. The innovative design
of NOVOLIZER® means that under-dosing or over-dosing are virtually
1. Barnes PJ. Decision making in asthma therapy – what is important in
clinical practice? (Editorial overview). Respiratory Med 2004; 98:S1-3.
2. Kohler D. The Novolizer: overcoming inherent problems of other dry
powder inhalers. Respir Med 2004;98 (Suppl A): S17-21.
3. Munzel U, Marschall K, Fyryns B, Wedel M. Variability of budesonide
fine particle dose emitted through two multidose dry powder inhalers.
Poster presented at the European Respiratory Society Annual
4. Mueller S, Fyrnys B. Development of formoterol fumarate dehydrate
powder for inhalation delivered through a multidose dry powder inhaler.
Eur Respir J 2004; Suppl 45: 582S (abstract P3575).
5. Mueller S, Fyrnys B. In use performance of formoterol fumarate
dehydrate for inhalation delivered through a multidose dry powder
inhaler. Eur Respir J 2003; Suppl 45: 473S (abstract P2985).
6. Newman SP, Pitcairn GR, Hirst PH et al. Scintigraphic comparison of
budesonide deposition from two dry powder inhalers. Eur Respir J
7. Chuchalin AG, Kremer HJ, Metzenauer P et al. Clinical equivalence
trial on budesonide delivered either by the Novalizer multidose dry
powder inhaler or the Turbuhaler in asthmatic patients. Respiration
8. Kunkel G, Metzenauer P, Hoesch S et al. Comparison of a formoterol
multiple dose dry powder inhaler with a formoterol single dose dry
powder inhaler in patients with moderate to severe asthma. Eur Respir J 2004; 24 (Suppl 48): 260s (abstract P1708).
9. Kunkel G, Chuchalin AG. Therapeutic equivalence of the Sofotec
Novolizer to established standard devices in COPD and asthma. Curr Opin Pulm Med 2001; 7 (Suppl 1): S15-17.
10. Virchow JC. Guidelines versus clinical practice: which therapy and
which device? Respir Med 2004; 98 (Suppl B): S28-34.
11. Möller M, Fritsche D, Rivera D, Libertus H. Improvement of asthma
therapy by a novel budesonide multidose dry powder inhaler. Arzneim-Forsch/Drug Res 2003; 53 (8): 562-7.
12. Vogelberg C, Kremer H-J, Ellers-Lenz B et al. Clinical evaluation of the
peak inspiratory flow generated by asthmatic children through the
Novolizer. Respir Med 2004; 98 (10): 924-31.
Read "FDA Violation of the Rule of Law" FDA VIOLATION OF THE RULE OF LAW  By Jonathan W. Emord Many thanks to the Richmond Health Freedom Expo for inviting me to speak and to the TalkStar Radio Network for broadcasting and webcasting this presentation live over that network. Today we discuss the Food and Drug Administration's violations of the rule of law. The FDA is an executive bra