Connected drug delivery

The need for connected drug delivery devices

Most people would agree that drug delivery devices have improved in recent years, particularly with the increased focus on usability (or ‘human factors’).  However, adherence remains a challenge and payers are looking for ways to increase the cost-effectiveness of healthcare.  One strategy for managing both issues is connecting drug delivery devices to the internet.

The potential benefits of connected drug delivery devices have been much discussed and can be summarised for stakeholders as follows:

  • Patient
    • Reminders
    • Training
    • Evidence for incentives
    • Hawthorne effect
    • Peer support
  • Carer
    • Reminders
    • Training
  • Payer
    • (Non)adherence data
    • Reduced costs (50% of patients suffering chronic illness do not take their medication as prescribed, costing US $100 billion to $300 billion annually in avoidable direct healthcare costs in the US alone [1])
  • Healthcare professional
    • (Non)adherence data
    • Additional support for least adherent
    • Adverse events
  • Healthcare provider, or regulatory authority
    • (Non)adherence data
    • Adverse events
    • Clinical trial data (pre and post market)
    • Population trends
  • Pharma
    • Adverse events
    • (Non)adherence data
    • Clinical trial data (pre and post market)
    • Reimbursement evidence
    • Market understanding
    • Product and training improvements
    • Increased sales by increased adherence. (Non-adherence causes US $637 billion lost pharma revenue annually [2])

The disadvantages of connecting drug delivery devices to the internet are:

  • Increased cost of devices and infrastructure.
  • Potential increase in usability risks.
  • Reliability risks due to technical complexity.
  • Concerns over data privacy and robustness against hacking and malware.
  • Unclear regulatory landscape due to the unfamiliarity of the technologies in the regulatory context.
  • Environmental concerns for disposal of electronic waste.

Nevertheless, for some drugs and indications the advantages are compelling, so we should look at how connectivity might be implemented in a drug delivery device.

Device strategies

There are 3 main strategies for implementing connectivity in a drug delivery device:

  1. An add-on, typically to an existing design.
  2. An upgrade, which is integrated but does not change the core functionality or use case.
  3. Built-in, which can change the core functionality and use case.

Many pharmaceutical companies and drug delivery device manufacturers already have devices either on the market or in late stage development.

An industry survey of inhalers, for example, shows various companies using one or more of the three strategies.  Note that we see the same trends in the injector industry.

Add-ons

Add-ons have the advantages that:

  • They can be added to existing devices, in most cases without interfering with the existing device function.
  • They could be reusable even if the existing device is disposable.
  • Patients could pay for the add-on themselves, whereas the existing drug delivery device might be paid for by an insurer or national health service.
  • There is less development risk due to limited revalidation of the existing device.

Propeller and Adherium are notable because they support a wide range of existing inhalers.

Propeller Health

Propeller Health’s smart phone app, and inhaler add-on

Adherium

Adherium’s add-ons fitted to various commercial inhalers, and Adherium’s smart phone app

Cohero provides a spirometer so patients can measure their lung function.  This combination of drug delivery device and diagnostic device is powerful because it can provide direct disease management results to help patients and clinicians assess progress and can enable payment-by-results rather than pay-per-dose.  Linking delivery devices with diagnostics was pioneered by the insulin pens (and to a greater degree, insulin pumps) and blood glucose meters used for diabetes.  The obvious benefit is that the drug delivery device can respond to changes in the biomarker in real-time.  In addition, it gives much better insight than measuring only the quantity and time of dose taken because the patient and healthcare professional can see how the body responds to the drug. Perhaps the diagnostics could be used to identify more subtle problems.  For example, if outcomes were poor in a certain area, an investigation might reveal poor training by the local healthcare facility.

Cohero's add-on

Cohero Health’s BreatheSmart™ app, HeroTracker™ sensors, and spirometer.

Inspair measures inspiratory flowrate so can determine both if the patient’s breathing profile is correct, and if they actuated the inhaler at the right point in their inspiration. Devices which provide feedback like this can be used for ‘continuous improvement’ training, which is more interactive and personalised than a static training video or patient instruction leaflet.  It helps with the ‘learn-ability’ of the device, which was identified as a major challenge in recent industry-wide research performed by Springboard.

Biocorp Inspair

Biocorp Inspair

However, it is important to consider that add-ons have the obvious disadvantage that the existing geometry is not modified so:

  • Add-ons cannot be integrated into the existing device, and thus add bulk to the device, and there are additional use steps to attach them.
  • Technical possibilities are limited. For example, it is more difficult to sample the air flow.

Upgrades

A strategy to overcome the limitations of the add-ons is to upgrade an existing design.  Novartis is supporting the Propeller add-on [3], but is also upgrading the Breezhaler to the cloudhaler and adding built-in connectivity by working with Qualcomm Life. [4, 5]

Novartis Cloudhaler

Novartis Cloudhaler

H&T Presspart is working with Cohero to upgrade standard Metered Dose Inhaler actuators with connectivity. [6]  A notable feature of the Presspart strategy is that the connected functionality is optional.  That is, the drug delivery and dose counter functions are still entirely mechanical, so the patient can, in principle, use the device safely and effectively even if the electronic functions fail.

Presspart eMDI

H&T Presspart eMDI

An alert reader will notice that the upgraded devices do not change the use steps or core functionality of the devices.  If we want to use electronics and connectivity to change fundamentally the way the patients (and carers, trainers etc.) interact with their device, we need to build the electronics and connectivity into the device from the ground up.

Built-in connectivity

Devices which have connectivity built into them from the beginning can make significant changes in user interaction.  The design being built-in also allows more substantial changes to the device, such as advanced features and sensing options. For example, the 3M Intelligent Control Inhaler actively adapts the flowrate to suit the patient and delivers the dose automatically at the right point in the inspiration. A similar example is Opko’s Inspiromatic active dry powder inhaler, and Aptar is partnering with Propeller to develop a new connected metered dose inhaler. [7]

3M Intelligent Control Inhaler

3M Intelligent Control Inhaler

The disadvantages of built-in connectivity mirror substantially the advantages of add-ons.  For example, a device with built-in connectivity could be more difficult to make reusable, which adds built-in cost and environmental impact.

Uptake and retention of connected devices

Public interest in connected drug delivery devices has not been measured on a wide scale yet, but we can draw inferences from health-related smartphone apps.  More than 50% of US smartphone users downloaded a health-related app in 2015.  Individuals more likely to use health-related apps tended to:

  • Be younger,
  • Have higher incomes,
  • Be more educated,
  • Be Latino/Hispanic, and
  • Have a body mass index (BMI) in the obese range (all P<0.05). [8]

However, weekly retention of apps is poor, even for apps which tend to be associated with hardware such as Fitbit, Garmin and Nike+.

Market Share of the Top 5 Fitness Apps

Market Share of the Top 5 Fitness Apps

The reasons for people stopping the use of health apps were primarily:

  • High data entry burden 45%
  • Loss of interest 41%
  • Hidden costs 36%

Out of 1604 people, 662 (41%) said they would not pay anything for a health app. [8]

In November 2017, an analyst from Ernst & Young identified the following hurdles to the widespread adoption of connectivity in drug delivery devices: [9]

  1. Devices and services.
  2. Evidence.
  3. Data infrastructure.
  4. Business model.

Let us assess the progress and challenges in each area in turn.

Devices and services

Merck Group launched easypod for human growth hormone in 2006, which gained connectivity in 2012, [10] and RebiSmart for multiple sclerosis, which was launched in 2007 and gained connectivity in 2011.  They use the easypod Connect [11] and MSdialog [12] web platforms, respectively, for uploading patient data from the device and adding supporting information manually.

One of the challenges is gaining regulatory approval of medical devices that connect to smartphones, but AliveCor has pioneered the way here by being the first to gain FDA approval for smartphone-based medical device software with its atrial fibrillation diagnostic app.

In diabetes, Roche has bought the mySugr web platform, whose Bolus Calculator has Class IIb approval in the EU, and the logbook has Class I approval in both the EU and USA.

So, we can see that connected drug delivery devices are breaking through onto the market, and the regulatory approval and services around them are entirely feasible.

Evidence

Payers and regulators (not to mention patients and healthcare professionals) will want to see clinical evidence for the efficacy of connectivity.  Fortunately, the evidence is mounting.  Data from Propeller Health, for example, shows reduced short-acting beta agonist use, [13] reduced hospitalisations and reduced emergency room visits. [14]  Adherium claims similar clinical evidence. [15]

If efficacy is proven for certain indications, we would still need evidence for preference and adherence.  Fortunately, several studies have been done in these areas too.  For example:

  • An observational study on the RebiSmart device found that 91% liked using the device, and 96% found it ‘easy or very easy to use’. [16]
  • An autoinjector preference patient survey found that 82% of BetaConnect patients were ‘highly satisfied’ compared to 67% of RebiSmart and 60% of ExtaviPro patients. [17] The first two devices have connectivity, but the latter does not.
  • A retrospective adherence study on patients with multiple sclerosis using RebiSmart found ‘greater than 95% adherence’ over a 140-week duration (N = 110). [18]

Unfortunately, evidence of malware and hacking has also appeared.  For example, remote hacking exploits have been demonstrated on some Medtronic insulin pumps, [19] Hospira infusion pumps, [20] and Animas OneTouch Ping insulin pumps. [21]

Data infrastructure

It is logical for companies to roll out their connectivity infrastructure using the following building blocks:

  1. Adding connectivity to the drug delivery device.
  2. Optionally connecting the drug delivery device to a ‘mobile medical app’. This can be an app running on a smart phone (such as AliveCor’s KardiaMobile app), or on a dedicated device (such as Abbot’s FreeStyle Libre device).
  3. Cloud storage and web apps that can be accessed through a web browser.
  4. Electronic Health Records.

The main cloud computing providers (Amazon Web Services, Google Cloud Platform and Microsoft Azure) have various offering that are HIPAA compliant, so can be used for some medical data in the United States, but HIPAA compliance is not regarded as strong enough protection for the data of EU citizens.  The  General Data Protection Regulation (in force from 25 May 2018) places further requirements on the controllers and processors of personal data.

Several companies and collaborations are creating cloud technologies to handle data from connected medical devices. For example, Salesforce.com (in the form of its force.com platform), Qualcomm Life and Philips HealthSuite are working on patient data platforms.  Roche bought Flatiron which developed the OncologyCloud, claimed by them to be the ‘industry-leading electronic medical record for oncology, advanced analytics, patient portal and integrated billing management’, [22] Medicom is handling the data services for Bayer’s BetaConnect device, and Redox is developing a way to share healthcare data between heterogenous technologies.  In effect, Redox can take data from any input, perform transformations and analytics on it, and convert it into a given Electronic Health Record format.

Business models

Payers are trying to reduce costs, so simply adding connectivity and expecting to be able to charge more is not a convincing strategy.  However, a holistic view of the health economics of a given indication can reveal compelling business models in some cases.

Example business models already in use include:

  • A collaboration between Amgen and Humana whereby Amgen analyses real-world evidence from Humana’s members with data from wearable devices, apps and smart drug delivery devices. [9]
  • A collaboration between Amgen and Harvard Pilgrim Healthcare whereby Amgen will fully refund the cost of Repatha if the patient is hospitalised by a stroke or myocardial infarction. Naturally, Harvard Pilgrim will need to show that the patient had adhered to the Repatha regimen and connectivity is a convincing way to do this.
  • Abbot did not get reimbursement initially when it developed the FreeStyle Libre flash glucose sensor, so sold it direct to patients. It has since been approved for purchasing by the UK National Health Service. [23]

Summary and final thought

From what Springboard sees in its day-to-day work, every company involved in drug delivery devices either has a connected technology or is developing one. Clinical evidence for improved adherence exists, and evidence for other clinical benefits is mounting.  The data infrastructure exists, although systems are not familiar to patients or healthcare professionals yet, and there are legal hurdles to overcome when transferring patient data between legal jurisdictions. Traditional business models have struggled, but innovative business models are progressing.

Connected drug delivery devices are already with us, and more are coming to market.  The idea that connectivity itself will solve the adherence problem is unrealistic.  However, for the first time, healthcare professionals will be able to identify who is adherent and who is not, which will allow them to refocus efforts on those who have the most difficulty adhering.

If you are from a pharmaceutical company or medical device manufacturer and wish to talk with us at Springboard about any medical device development questions, please get in touch.

References

[1] Iuga AO, McGuire MJ, “Adherence and health care costs”. Risk Manag Healthc Policy, 2014, Vol 7, pp 35–44.

[2] Forissier T, Firlik K, “Estimated Annual Pharmaceutical Revenue Loss Due to Medication Nonadherence”. Capgemini and HealthPrize white paper, 2016.

[3] Tyer D, “Novartis Signs ‘Connected Inhaler’ Deal with Propeller Health”. PMLive, Feb 2017.  Accessed May 2018

[4] “Network Connected Inhaler for COPD”. myAirCoach. (Accessed May 2018)

[5] Pai A, “Novartis, Qualcomm Life to Develop Connected Inahler for COPD”. MobiHealthNews, Jan 2016. (Accessed May 2018)

[6] H&T Presspart eMDI product webpage. (Accessed May 2018)

[7] Comstock J, “Propeller Health, Aptar Partner to Create Connected Metered Dose Inhalers”. MobiHealthNews, Feb 2016. (Accessed May 2018)

[8] Krebs P, Duncan DT, “Health App Use Among US Mobile Phone Owners: A National Survey”. JMIR mHealth uHealth, Nov 2015, Vol 3(4), epub.

[9] Handschuh T, “Smart Devices – How to Unlock Their Potential in the Real World.” Presentation at PDA Universe of Prefilled Syringes and Injection Devices, Vienna, Nov 2017.

[10] “Merck Serono Launches easypod™ Connect in Europe”. Merck Serono press release, Oct 2011. (Accessed May 2018)

[11] easypod® Connect product webpage. (Accessed May 2018)

[12] RebiSmart MSdialog product webpage. (Accessed May 2018)

[13] Merchant RK, Inamdar R, Quade RC, “Effectiveness of population health management using the Propeller Health Asthma Platform: A randomized clinical trial”. J Allergy Clin Immunol Pract, May-Jun 2016, Vol 4(3), pp 455–463.

[14] Merchant RK et al, “Interim results of the impact of a digital health intervention on asthma healthcare utilization”. J Allergy Clin Immunol, Feb 2017, Vol 139(2), p AB250.

[15] “The Medication Nonadherence Epidemic”. (Accessed May 2018)

[16] D’Arcy C et al, “Patient assessment of an electronic device for subcutaneous self-injection of interferon ß-1a for multiple sclerosis: an observational study in the UK and Ireland”. Patient Prefer Adherence, Jan 2012, Vol 6, pp 55–61.

[17] Limmroth V et al, “Autoinjector preference among patients with multiple sclerosis: results from a national survey”. Patient Prefer Adherence, Aug 2017, Vol 11, pp 1325–1334.

[18] Solsona E et al, “Impact of adherence on subcutaneous interferon beta-1a effectiveness administered by RebiSmart® in patients with multiple sclerosis”. Patient Prefer Adherence, Mar 2017, Vol 11, pp 415–421.

[19] Goodin D, “Insulin pump hack delivers fatal dosage over the air“.  The Register.  Accessed July 2018.

[20] Finkle J, “FDA warns of security flaw in Hospira infusion pumps.”  Reuters.  Accessed July 2018.

[21] Finkle J, “J&J warns diabetic patients: Insulin pump vulnerable to hacking.”  Reuters.  Accessed July 2018.

[22] Kewon A, “Drug Giant Roche Buys Former Google Execs’ Flatiron in $1.9B Deal”. BioSpace, Feb 2018. (Accessed May 2018)

[23] Woodfield J, “FreeStyle Libre to be available on the NHS from November”. Diabetes.co.uk, Sep 2017. (Accessed May 2018)

An introduction to needlestick protection and safety syringes

The need

Needlestick injuries are second only to back injuries as a cause of injury to healthcare workers (HCW), with up to 1,000,000 cases estimated annually in the EU [1]. The risk transmission of blood-borne viruses has been shown to be around 1 in 3 if the patient is Hepatitis B Virus positive, 1 in 30 if Hepatitis C Virus positive and 1 in 300 if HIV positive [2, 3]. Even when infections are not transmitted such an injury can cause considerable fear and stress [4].

In many cases, it is not feasible to eliminate injections or use another administration method as a substitute.  Therefore, the hazard is most effectively handled by engineering solutions which separate those at risk from the sharps (Figure 1). Research by the UK’s Health and Safety Executive has found that education and training related to safer sharps is only effective when combined with safer sharps devices [5] and the UK’s Health Protection Agency recommends that Primary Care Trusts and hospitals adopt safety devices in place of conventional devices [2].  In the US, the CDC estimated that up to 88% of sharps injuries in hospitals could be prevented by using safer medical devices [6].

Figure 1 – Hierarchy of hazard controls with increasing effectiveness (Source: National Institute for Occupational Safety and Health)

The legal requirements

Many regulators around the world require needlestick protection, and others are in the process of implementing it.  Examples are:

The international standard ISO 23908:2011 defines the requirements and test methods for sharps protection features on single-use hypodermic needles, introducers for catheters, and needles used for blood sampling.

‘Active’ and ‘passive’ solutions

Broadly, solutions can be classed as:

  • Active (the user must take some type of action to initiate the feature) or
  • Passive (the feature is activated automatically, without user intervention).

Active solutions rely on the HCW completing an extra step, which relies on training and changing existing behaviours. The UK National Health Service Employers organisation recommends that needle safety mechanisms should be an integral part of the device, require little change of technique and are preferably activated automatically or with a single hand [7].

A simple active solution is to cap the exposed needle with a shield after use, such as Smith Medical’s Point-Lok® needle protection device (Figure 2).  The device sits on a flat surface to accept and lock onto the exposed needle.

Figure 2 – Smith Medical’s Point-Lok® needle protection device

Active Sharps Injury Protection (sheath)

Syringes with integral sharps injury protection (SIP) often use a cover that shields the user from the needle after use.  This cover can be an extendable tube (Figure 3). The syringe is pulled back into the sheath, which clicks and locks into place. The sheath covers the outer surface of the barrel during the injection.  These syringes should be held by the flange, so the sheath is not displaced before the end of the injection. This may require a change in habit for HCWs. Example of this type of safety syringe include:

  • BD Safety-Lok™ Syringe (1, 3, 5 & 10 mL, takes luer Lok needles)
  • EasyTouch® ShealthLock™ Safety Syringe (fixed needle 1 & 3 mL, exchangeable needle 3, 5 & 10 mL)
  • Medtronic Monoject™ Safety Syringe (with needle, for insulin and tuberculin)
  • Sol-Millenium Sol-Guard™ Safety Syringe (with needle, for insulin and tuberculin)
  • UltiMed Ulticare® Safety Syringe (1, 1.5 & 3 mL permanently attached needle)
  • Vogt Medical VM® Safety syringe (1, 3, 5 & 10 mL)

Figure 3 – BD Safety-Lok™ Syringe, an example of a safety syringe with a tubular SIP feature

A similar solution is the Raumedic RauSafe, which uses a telescopic sheath that is manually extended and locked out over the needle after the injection.  This avoids covering the external surface of the barrel before and during the injection

Figure 4 – Raumedic RauSafe shown with the protective sheath extended

Active Sharps Injury Prevention (hinge)

The needle safety feature can also take the form of a hinged cover.  The cover can be pushed down with a finger or against a hard surface so only one hand is required. The cover can be incorporated into the syringe, such as:

  • EasyTouch® FlipLock™ Safety Syringe (fixed needle, 1 & 3 mL, exchangeable needle 3, 5 & 10 mL)
  • Medtronic Magellan™ Safety Syringe (fixed needle insulin & turerculin)
  • Vogt Medical VM® Safety syringe (1, 3, 5, 10 & 20 mL)

The same feature can be incorporated into attachable needles, such as:

  • BD Eclipse™ Safety Needle (18 – 30G)
  • EasyTouch® FlipLock™ Safety Syringe (18 – 31G)
  • Medtronic Monoject™ Safety Needle (18 – 30G)
  • Terumo SurGuard®3 Safety Needle (18 – 30G)
  • Smiths Medical Jelco® Needle-Pro® EDGE™ Safety Needle (18 – 30G)
  • Sol-Millenium Sol-Care™ Safety Needle (18 – 30G)
  • Vogt Medical VM® Safety needle (20 – 27G)

A potentially cost-effective and versatile solution is Schreiner MediPharm’s Needle-Trap, which incorporates the hinged cover into the syringe label.

Figure 5 – Hinged SIP covers (left: EasyTouch® FlipLock™ Safety Syringe, middle: Terumo SurGuard®3 Safety Needle, right: Schreiner MediPharm Needle-Trap)

There are some multi-hinged needle covers available that can facilitate easier one-handed application:

  • BD SafetyGlide™ Needle
  • Medtronic Magellan™ Safety Needle

Figure 6 – Left: BD SafetyGlide™ Needle, Right: Medtronic Magellan™ Safety Needle

Active Sharps Injury Prevention (needle retraction)

Instead of shielding the needle after use, the needle can be retracted into the syringe after the injection.  There are products available to do this manually, by pulling back on the plunger rod, such as:

  • EasyTouch® Retractable Safety Syringe
  • Nemedico ClickZip™ Needle Retractable Safety Syringe
  • Sol-Millennium SOL-CARE™ Safety Syringe

 

Figure 7 – EasyTouch® Retractable Safety Syringe instructions (adapted from http://mhcmed.com/products/easytouch-safety-products/safety-syringes/)

Similar retraction technology is available as a needle with luer lock connection, such as in the Retractable technologies EasyPoint® Needle.  The sharp is automatically captured in an adjacent chamber but an additional user step is required to activate this process.

Figure 8 – EasyPoint® retractable needle

Passive Sharps Injury Protection (needle retraction)

There are syringes available which retract the needle into the barrel automatically using a spring, eliminating any extra user steps. Examples include:

  • BD Intergra™ Syringe (3 mL, requires detachable BD Integra needles)
  • Retractable technologies VanishPoint® Syringe (attached needle, 0.5, 1, 3, 5, and 10 mL)
  • DMC Medical SureSafe™ Syringe (fixed needle 0.5 & 1 mL, changeable needle 3ml, 5ml & 10ml)

Figure 9 – BD Intergra™ Syringe retracting syringe

Passive Needle Safety devices

An alternative solution is to encompass the syringe in a safety device.

The BD Preventis™ allows a 0.5 ml or 1.0 ml pre-filled syringe to be packaged inside a casework that incorporates an automatic safety lock system. The safety device uses a spring to extend a protective sheath after injection.

Figure 10 – BD Preventis™ needle shielding system

Such single-use devices can be used with syringes and shift the act of shielding the needle from the user to the device.  Typically, a syringe is inserted inside such a device and the injection is performed by depressing a plunger rod, then after the injection is complete a spring acts to withdraw the syringe and shield the needle.

In the Biocorp Newguard, the user’s push on the plunger rod acts on a spring which causes a needle retraction and lockout after injection.  The Nemera Safe’n’Sound and the BD Ultrasafe™ does not require the user to work against a spring but uses an unclipping mechanism release the compressed spring at end of injection to activate the retraction.

The Owen Mumford Unisafe™ avoids using a spring altogether and retracts the syringe by transferring the plunger rod stroke through a threaded interface.  This can help the user see the syringe and its contents before and during the injection.

Figure 11 – Left: Nemera Safe’n’Sound, Middle: Biocorp New guard, Right: Owen Mumford Unisafe™

If you would like to know more about needle safety devices, or have a need to procure or develop one, please get in touch. Springboard develops injection technologies, and conducts technology scouting, technology procurement, due diligence and usability engineering projects for our clients.

References

[1] European Parliament. Preventing needle-stick injuries in the health sector, 11th February 2010.

[2] Health Protection Agency, Eye of the Needle – United Kingdom Surveillance of Significant Occupational Exposures to Bloodborne Viruses in Healthcare Workers,
November 2008

[3] UK Health Departments, Guidance for Clinical Health Workers: Protection Against Infection with Blood-borne Viruses, April 1998

[4] Royal College of Nursing, Sharps safety – RCN Guidance to support the implementation of The Health and Safety (Sharp Instruments in Healthcare
Regulations), 2013

[5] Health and Safety Executive, An evaluation of the efficacy of safer sharps devices, 2012

[6] U.S. Occupational Safety and Health Administration, Needlestick/Sharps Injuries, Accessed March 2018

[7] NHS Employers, Managing the risks of sharps injuries, December 2015

 

 

Consultancy or manufacturer?

Let us suppose you need a new product developed.  You have 3 choices:

  1. Develop the product entirely in-house.
  2. Contract a consultancy to develop the product for you.
  3. Contract a manufacturer to develop the product for you.

In the past, companies would develop products themselves, entirely in-house.  In recent years, that model has become less common as companies have reduced their internal R&D teams and looked for collaboration to bring new products to market.

In some markets, engineering and design consultancies have delivered development projects as a service.  More recently, manufacturing companies have hired development engineers and set up development labs.   This article discusses the pros and cons of each method.  If you would like to know more, or have any feedback, do not hesitate to get in touch.

Development strategy Pros Cons
In-house
  • Knowledge stays in-house.
  • Limited IP leakage (other than employees leaving, indiscretions etc.).
  • Lower cost if, and only if:
    • Team and facilities are already in place, and
    • Recruitment, training, site and maintenance costs are not in your budget, and
    • Your team is fully utilised on productive projects at all times.
  • Limited to the skillset of the existing team.
  • Psychological inertia due to historical products and constraints.
  • Large expense of keeping the team when they are not fully utilised.
Consultancy
  • Highly skilled people available. This can make all the difference between a device passing tests and getting to market on time, or languishing in endless cycles of fire-fighting modifications. Removing even one redesign-revalidate cycle can easily save far more money than using a low-fee-rate manufacturer.
  • Flexible team structures.
  • Best option for an impartial view of which technologies would work best.
  • Impartial as to which manufacturer to use: consultancies are the best option if you intend to have more than one manufacturing source for risk mitigation.
  • Some consultancies, particularly those that specialise in your industry, will have relevant up-to-date experience from other projects.
  • Can have high fee rates (particularly those with > 100 employees).
  • Might not have experience in manufacturing. You can ask who will be working on the project, and what their experience is.
  • Consultancies with internal projects might save the best ideas for themselves. Springboard does not have internal projects.
Manufacturer
  • Fee rate can appear lower than consultancies.
  • Sometimes, deep knowledge of a given manufacturing process.
  • Good at making incremental changes to existing products, but not at innovating new products.
  • It will be very difficult to transfer manufacture to another party because the design will be optimised
    for their processes, and there will be no documentation or data necessary for transfer to another company.
  • Manufacturing costs will be high because they will need to recover their costs and make more profit than otherwise to make up for Net Present Value, and their risk.
  • Most manufacturers are trying to build up their own IP portfolio. This might mean they save the best ideas for themselves, or put some of their IP into your product.
  • Limited to the skillset of the existing team.
  • Psychological inertia due to knowledge of their existing processes. For example, if the company is very experienced with aluminium tooling, can you guess what your tools will be made from, even if steel tooling would have been a better option?

How to find the best contract R&D partners

“Most of us understand that innovation is enormously important.  It’s the only insurance against irrelevance”

Gary Hamel

“Innovation requires the ability to collaborate and share ideas”

Bill Gates

Innovation is critical to all businesses. We live in a knowledge-driven economy and, especially in medical devices and drug delivery, giving patients the benefits of new and better products is clearly beneficial for all concerned: patients, payers, healthcare authorities, pharmaceutical companies, and medical device manufacturers.

Collaboration is more important than ever to manage technical risks and build on the best talent available throughout the development process.  But there are very few sources of good information on how to find the best companies to collaborate with.  This article gives an insight based on many years of experience in the field.

We hope that it is helpful and perhaps even interesting!

Working together

Step 1: Consider the pros and cons of working with external experts

Collaborating with external experts works best when you and the relevant stakeholders within your organisation (particularly the development team) see the value.

In some cases, there’s reluctance to collaborate, but it can lead to projects not working very well due to the limits of the skills, capability and equipment of your own development team.

In other cases, where you just want more people in your office or labs to work under your own supervision, a lone contractor may be more appropriate than an external R&D partner. Using contractors is a different mind set from working with external R&D companies because typically the latter will take on leadership to overcome hurdles in the way, and display a greater degree of autonomy on reaching a solution.

It is misleading to compare quotes to salaries. This is a common temptation, but when you consider the salary of yourself or your staff, you are not including pension, bonus, National Insurance, premises, training, recruitment costs, computers, software licences, under-utilisation, lab equipment, lab space, insurance, accounting and legal support and so on. If you add up those things for your internal team, you will find the market rate for R&D work. The quotes from potential partners should match this: they should be the market rate after all. When coupled with rapid and reliable progress on solving a valuable problem, the cost-effectiveness should be clear.

If you and your team do see the value in an external collaboration, move to Step 2…

Step 2: Think about what you’re asking for

What is it that you need?  This will inform what you’re looking for in an external partner.

When it comes to specifying the size and shape of a project, there are 3 competing factors:

  • Quality.
  • Time.
  • Cost.

Typically, you can optimise a project for any 2 of the above.

Step 3: Find out from peers who is good

Reputation is everything. A really good innovation partner will have a good reputation which others in your field will know about.  If you don’t know who to ask, maybe former colleagues at another company can help [Springboard has gained many clients this way].  You can always get in touch and ask us!

You may already know that a company’s name being well-known correlates strongly with its marketing budget, and not necessarily with the quality of its work.

It is about the people, not the brands.  We have found that the most important ingredient in successful development projects is the quality of the people.  Two qualities stand out as being vital:

  • Their technical and project management ability; and (no less)
  • Their ability to communicate and work with you (and you trust them).

Really good engineers and scientists will be able to use the right technique and equipment even if they have not used exactly the same things before.  On the other hand, it could be folly to expect mediocre engineers and scientists to develop market-leading high performance, usable and safe products, or fix non-trivial technical problems.  Perhaps ask yourself this provocative question: “How many opportunities do I have to get this project right?”

There is sometimes a downside to really capable people: they can be arrogant and therefore not so good to work with.  The best way to assess this is Step 4…

Step 4: Talk with the potential partners

It is worth spending the time to speak with potential partners because a website or word-of-mouth cannot give the full picture about the quality and attitude of the people actually working at the potential partner company.  By definition, case studies on websites will be very old because they have to be outside of confidentiality terms.  Therefore, the people that developed those devices might not be working at that company anyway.

Talking with the company can help you assess:

  1. Would I want to work with these people?  Are they listening to me?
  2. Are they capable people who I trust to deliver the project successfully?
  3. Do they understand the constraints of the project?

Here is a list of common pitfalls to watch for:

  1. Be aware of the A-team/B-team.  You might be talking to some experienced, capable people during the negotiation and planning, only to find that you get a completely different set of people working on the project once it starts.  You can minimise this risk by seeking assurances about who would be working on the project: the partner should be able to at least be sure of the project leader.
  2. Ensure the correct incentives.  If the potential partner has internal projects, it will be wanting to secure its own IP.  If it has experience in your field, it is probably going to want to secure its own IP in your field.  Development contracts can say that IP will belong to you, but perhaps you do not want an incentive for people working on your project to keep the best ideas for their company.  The best way around this is to use a partner which does not have internal projects at all.
  3. Location is almost irrelevant.  If you work for a leading multinational organisation, you probably want to find the best team in the world to deliver your projects – why not?  The probability of having an excellent team available down the road is slim.  If you do, that’s great!  If you do not, it does not tend to matter these days whether they are 500 miles away or 1,500.  Weekly web conferences cover most project updates, and regular face-to-face meetings are easy in this age of cheap and convenient air travel.
  4. Size is important, but maybe not how you think.  A partner who is too small (one or two people) might not have the breadth and depth of the skills that you need, and you would be at the mercy of any one person being sick or taking holiday when you need them most.  A large partner will prioritise their largest projects. If your project is many millions of dollars in each phase, great! if not, you might find you are not at the front of the queue for resources if you use large partners.
  5. Will the rest of your company treat your partner well?  You may have found the right partner who you trust and you’re really keen go get a great project going. It helps the relationship, and therefore chances of success, if your procurement department agrees to reasonable payment terms, and your accounts department fulfils its obligation to pay on time.

Step 5: Decide who you want to work with

This may be the hardest step.  There are any number of approaches to come to a decision…

Factors such as trust in the people, and your belief in their ability to deliver are hugely important.  Therefore, a spreadsheet of metrics (beloved by procurement departments) is probably not the best way to decide between potential partners.

Perhaps the best way is to think about which partner you would prefer to have a long-term business relationship with, and see if their match to the current project need is good enough.

 

We hope that you have found this post helpful!

If this post has teased any thoughts or questions, please either write a comment below, or get in touch.  We would love to hear from you.

 

Springboard moves into new premises

Fast-growing product and technology innovator Springboard has expanded into larger offices at St John’s Innovation Park in Cambridge, UK, having outgrown its space in the Innovation Centre itself.

A steady flow of new projects for international clients has required the scale-up and Springboard has built additional capacity into its new HQ.  Now, the labs and offices are under one roof in a 4,000 sq ft unit, which also has self-contained meeting rooms and reception area.

Springboard team

Springboard’s capabilities have been in strong demand, and its project portfolio has been international from day one, driven by recommendations (word of mouth) between major medical device and pharmaceutical companies, especially where they have run into problems with a medical device.  Its focus has already enabled a number of big-name clients to launch devices that they could not have otherwise, and in the process saved time and money in product development. Cul-de-sacs have been moulded into highways of success for a large number of satisfied clients.

The consultancy’s reputation for troubleshooting and technical excellence spread across Europe and the United States. We are proud to say that more than 80 per cent of Springboard’s work is repeat business.

Some problems with delivery devices – injectables for example – cannot be solved “simply by throwing man hours at it”; in-depth technical insight and world-class engineers are required. And that is exactly what Springboard has provided since opening its doors.

Springboard has put much time and effort into recruiting, mentoring and training the best team possible.  The diversity and depth of skills now far outstrips that of the founders and includes skills in physics, optics, thermodynamics, fluidics, materials science, biotech, mechanics, systems engineering, electronics and manufacture engineering. This means the company now takes on cross-disciplinary projects and creates teams that have the breadth of knowledge to ensure success.  Recruiting talented people is a time consuming challenge, but of even more importance is creating an environment in which they can flourish. The company’s focus on professional development means people have opportunities to take responsibility and grow their careers at the company.

This broad church of capability is exactly what the founders wanted to achieve – a turnkey capability in the segment, rather than being pigeon-holed simply for one area of expertise.

We believe another strength of Springboard is its open innovation culture. Springboard can provide a fully self-sufficient team to a project but welcomes input from clients either through brainstorming sessions or weekly updates.  This approach enables the client to retain control of the concept while giving Springboard full rein to suggest enhancements.  “They don’t have to hand-hold us but they get to contribute; we believe in a highly collaborative approach”.

Springboard is also renowned for its highly ethical approach to projects. Its mantra is to work on innovation that are technically challenging but also ethical and worthwhile.  Staff like to be able to say that they are working on a project that will certainly improve peoples’ lives and might, for example, lead to a cure for cancer.  This approach is helping the business recruit the highest calibre of engineers and scientists; the ongoing recruitment process is also enhanced by Springboard’s outreach activities with schools, colleges and Cambridge University.

If you would like to know more, please get in touch.

The rise of the bolus injector

Engineers and scientists are working hard to revolutionise the way patients take new and existing drugs.

Many of the new drugs under development are ‘biologics’, which tend to be unsuitable for taking orally (as a pill) because the liver metabolises them. A classic example of a widely-used biologic drug is insulin for diabetes mellitus.

Therefore injection is the most common way of taking biologics.

Some of the biologic drugs, particularly monoclonal antibodies, require large masses to be injected.  In order to inject a large drug mass, we have two choices: increase the injection volume, or increase the concentration of drug in the formulation.

Problems with increasing the injection volume

Injecting a large volume requires either:

  • A high flow rate, which can be painful and unsightly; or
  • A long duration of injection, which can be uncomfortable and difficult to maintain injector position.

In addition, many injection devices are limited to 1 mL volume because:

  • Historically many autoinjectors were based on the 1 mL BD Hypak; and
  • It is extremely expensive to refit the aseptic filling lines that have been built for 1 mL syringes.

Problems with increasing the drug concentration

Increasing the concentration of the drug in the liquid increases the formulation viscosity, which cannot become too great because:

  • Patients are demanding thinner and thinner needles, which strongly increases the resistance to flow and would increase injection duration to unacceptable periods for viscous drugs;
  • Injection devices contain typically a glass syringe, which breaks if too much force is used to drive the formulation through the needle; and
  • Many drugs, especially those based on proteins, aggregate (stick together) above a certain concentration.

Autoinjectors without glass syringes

There are various autoinjector technologies which do not contain a glass syringe, such as:

  • The Crystal Zenith range from West Pharmaceutical Services; and
  • The Oval Medical autoinjector.

These autoinjectors may be able to deliver viscous drugs, but still tend to be limited in injection volume due to the discomfort of injecting large volumes quickly and the difficulty in holding the autoinjector steady for long enough.

The bolus injector

The solution may be a different class of injection device: the bolus injector (sometimes called a ‘patch pump’, although this term is also used for ambulatory infusion pumps).

A bolus injector may be described as a device with performance and usage between current autoinjectors and infusion pumps:

  • A bolus injector is typically attached to the patient’s body for a few tens of seconds to a few hours, unlike an autoinjector which is held in the hand. Therefore a bolus injector may be able to deliver a larger volume than an autoinjector because it does not need to be manually held in position during injection, and could contain a larger drug reservoir. In addition, avoidance of a glass syringe may enable delivery of more viscous drugs.
  • A bolus injector is normally designed to deliver its payload promptly, unlike an infusion pump in which the duration of delivery is a key parameter in the therapy (such as a constant, low flow rate, basal dose of insulin 24 hours per day). The bolus injector is only attached to the patient for the few minutes or hours that it is delivering its dose.

Example bolus injectors

There too many bolus injectors in development to list here but some examples are:

BD is developing the Libertas bolus injector built around a pre-filled BD Neopak syringe.

BD Libertas bolus injector

BD Libertas

West has launched the Smart Dose injector for Amgen’s Repatha drug.  The device is based on the Crystal Zenith plastic cartridge.

West SmartDose

West SmartDose

Enable Injections is working hard on its eponymous device, which takes a different approach to the prefilled devices above:  the drug is supplied in a separate vial or syringe, then a filling pump fills the injector with the drug formulation shortly before attaching the injector to the body.  This means that the device avoids some of the regulatory hurdle of proving drug stability for many months before use.

Enable Injections

Enable Injections

SteadyMed is developing the ‘PatchPump’ platform which uses an expanding battery to force drug out of a flexible primary drug container.

SteadyMed PatchPump (R)

SteadyMed PatchPump (R)

Sensile Medical has various formats of pump based around its core micropump technology.

Sensile SenseTrial

Sensile SenseTrial

Ypsomed is promoting its YpsoDose concept based on 5 mL or 10 mL prefilled glass cartridges.

Ypsomed YpsoDose

Ypsomed YpsoDose

Bespak has created a prototype demonstrator of a HFA gas-powered bolus injector, called Lapas.

Bespak Lapas

Bespak Lapas

There are many other devices in development, such as the NeuroDerm continuous subcutaneous infusers.  Others have been mothballed or cancelled, or otherwise fallen by the wayside such as the Roche Single Injection Device (formerly MyDose), Ratio Drug Delivery’s NuPrivo, and Unilife’s Precision Therapy.

If your organisation is developing a bolus injector and you have recommendations for improving the list above, please get in touch.

Challenges for new bolus injectors

Many bolus injector designs use a novel primary pack, and pharmaceutical companies are very reluctant to risk their drug launch on new materials and designs. Device developers are trying to reduce the risk by using materials that have been used with drugs before.

The second challenge is that a new primary drug container is likely to be incompatible with the pharmaceutical companies’ aseptic filling lines, which are extremely expensive and time-consuming to build and validate.

In addition, some bolus injectors have advanced features such as automatic needle insertion and electronic control which increase development complexity.

Finally, new devices must meet the newly raised regulatory demands on usability (human factors).

The future

The drug delivery device industry is working hard to define the requirements and test methods for acceptable bolus injectors, which is likely to become ISO 11608 part 6.

We expect that bolus injectors will become a familiar part of the drug delivery device space, and that they could enable exciting new therapies such as regenerative medicine.

If you would like to know more about bolus injectors, or have a need to procure or develop one, please get in touch. Springboard develops injection technologies, and conducts technology scouting, technology procurement, due diligence and usability engineering projects for our clients.

Full disclosure: the author has worked on numerous injection device developments for pharmaceutical companies and device manufacturers, and has been asked to attend the meetings to draft ‘ISO 11608-6 Needle-based injection systems for medical use – Requirements and test methods – Part 6: Bolus Injectors’.

This post was originally posted on 19 September 2013 and has been updated since.

Latest news on wearable bolus (large volume) injectors

We have received a great number of enquiries for the latest information on wearable bolus (large volume) injectors, especially since our article “The Rise of the Bolus Injector” was published.

Therefore, Springboard’s Director of Drug Delivery Device Development, Tom Oakley has written a brand new article for OnDrugDelivery featuring the latest technical, commercial and regulatory developments in the world of bolus injectors.

Head over to OnDrugDelivery to read the latest news on bolus injectors, or read the whole edition devoted to large volume injectors.

Devices covered in the OnDrugDelivery magazine include:

  • Unilife Precision-Therapy
  • Sensile Medical SenseCore
  • West SmartDose
  • Enable Injections
  • BD Libertas
  • SteadyMed PatchPump

If you are from a pharmaceutical company or medical device developer and would like to find out more about bolus injectors and their development, please contact Tom Oakley on +44 (0) 1223 422 273.

Massive demand for top medical device developers

Springboard has been featured in a new article about the demand for top medical device developers.

As a leading technology consultancy, Springboard excels in the development of devices for safety-regulated industries such as medical devices. These span drug delivery devices, diagnostics, minimally-invasive surgical tools, wound care and more.

See the full article at Business Weekly or, if you would like to get in touch now, call Tom Oakley on +44 (0) 1223 422 273.