Teva Uses AWS to Manage Digital Inhaler Data for Patients and Healthcare Providers

Teva used a group of Amazon Web Services (AWS) services—including AWS Lambda and Amazon Simple Storage Service (Amazon S3)—and worked alongside AWS Premier Consulting Partner Onica, a Rackspace Technology company, to construct its serverless architecture for the Digihaler® family of inhalers. This FDA-approved family of digital, breath-actuated inhalers uses built-in sensors to track how often and how well the inhaler is used as measured by inspiratory flow rates. Inhaler use is recorded as an event when the cap is opened or the patient inhales.^2–4 The inhaler records events and sends data directly to the Digihaler® app through Bluetooth wireless technology, and the app can then display data and reports that patients can choose to share with their healthcare providers. Using AWS services, Teva was able to establish a digital health platform (DHP) for the Digihaler® family of inhalers in less than a year—a cloud system that meets regulatory, privacy, and security requirements.

With a portfolio of over 3,500 products, Teva supplies thousands of drugs around the world. It’s also one of the largest manufacturers of inhalers. In 2013 the company imagined a way to enhance its product portfolio for patients around the world. “We saw a huge opportunity to go into the digital health space and progress existing inhaler technology into a digital inhaler,” says Mark Maalouf, vice president of Global Digital Health at Teva. “We imagined an inhaler that could track how often the inhaler is used and also measure inspiratory flow, which may help HCPs assess if inhaler technique needs improvement.” Research reveals that one of the biggest challenges in respiratory care is healthcare providers’ ability to accurately assess how often patients are using their inhalers,⁵ especially once they leave the healthcare provider’s office. This is where objective inhaler-use data could be beneficial, allowing for more informed discussions around the disease and treatment.

The Digihaler® family of inhalers, however, presented a range of technical challenges. Teva needed to add Bluetooth technology and built-in sensors to measure inspiratory flow rates and save data into the firmware. The company also needed to develop mobile applications that could securely communicate with the inhaler, store data, and give patients the ability to view and share that data. The data would travel to a cloud database—the DHP—which would permit both patient-specific data analysis and aggregated analysis of the information coming from the inhalers and applications.

One major consideration was security and privacy. “Because the system holds both protected health information and personally identifiable information, we needed to give the patient control over who can access their data, such as their physician,” says Yaron Nir, head of the DHP. These privacy issues were also important from a legal and regulatory standpoint: Teva wanted the digital inhaler system to be compliant with HIPAA and global health regulations.

The development of this system faced an extremely tight deadline: Teva had set an internal target of 1 year to develop the production version of the DHP, and it needed a tested, trustworthy cloud provider as a foundation. “The maturity of AWS infrastructure and the level of security audits that AWS performs on its data centers and services gave us peace of mind,” says Maalouf. “We knew that the privacy and security of patient and customer data would be the top priority.” Teva decided to engage AWS Partner Onica to develop a custom system that Teva would be able to adapt and expand as needed.

Once Onica and Teva got to work, the main challenge was time. Implementing a serverless architecture using AWS solutions empowered Teva to scale, control costs, and experience fast development cycles. “We needed to put it into production about 7.5 months after our project kickoff,” says Matt Puccio, practice manager of cloud-native development with Onica. “So we used a lot of cloud-native technologies to build in an expedited fashion. Using AWS was the major reason why we could meet this timeline.”

To build the DHP, Onica used AWS Lambda so that it could run code without having to provision or manage servers. “AWS Lambda lets you use the service as needed,” says Nir. “It’s not always alive and kicking. Once it’s needed, it wakes up and starts to engage.” The database component of the DHP would be crucial to allow for both analysis of an individual patient’s usage of the inhaler and big data analytics across all users. The system relies on Amazon S3—an object storage service that offers industry-leading scalability, data availability, security, and performance—as a long-term database. It pairs Amazon S3 and Amazon DynamoDB, a key-value and document database that delivers single-digit millisecond performance at any scale and uses the latter as a mobile snapshot database. For the system to comply with regulations, Teva needed to be able to both store all records indefinitely and access quick snapshots of its data. “That’s one of the things we found beneficial about AWS,” Nir explains. “Using Amazon DynamoDB allowed us to create a very fast-paced and simple-to-scale database.”

To address the security needs that were a critical part of Teva’s requirements for the system, Teva harnessed Amazon Cognito to provide secure user sign-up, sign-in, and access control. Nir appreciates that Amazon Cognito is “very, very secure,” and it helped Teva build a robust authentication mechanism that would help the company safeguard user data.

Using AWS services, Teva and Onica were able to build the DHP on a tight schedule without sacrificing security, speed, or analytical capability. Teva and Onica worked together to automate a once long, tedious, manual verification and validation process in every deployment. Automating this process extends compliance early into the development cycle, bridging the gap between engineering and quality control. This process automation is part of Teva’s long-term success, which depends on the ability to stay compliant while developing at a rapid pace. “Teva’s speed of innovation and its ability to quickly ship products to its platform demonstrates the company’s commitment to the end user, because the company prioritized operating in such an automated and controlled way,” says Puccio.

Teva is now commercializing the Digihaler® family of inhalers in the United States. “In less than a year,” Nir says, “we were able to develop and deploy a digital health platform.” Teva has big plans for the franchise and its potential. In the long-term, it is evaluating ways to expand digital devices like the Digihaler® family of inhalers and data analysis tools like those Teva has built on AWS, so patients, caregivers, and healthcare providers can have more informed conversations thanks to an increased understanding of patients’ inhaler use. “By continuing to make strides in the digital health space, backed by innovative AWS technology, we are able to develop and build a digital offering in-house—from the device to the software—allowing us to expand our capabilities beyond respiratory in the future,” Maalouf says.

To learn more, visit aws.amazon.com/health/biotech-pharma.

• Deterioration of Asthma: Need for more doses of ProAir Digihaler than usual may be a marker of acute or chronic deterioration of asthma and requires reevaluation of treatment, such as possible need for anti-inflammatory treatment, e.g., corticosteroids
• Use of Anti-Inflammatory Agents: ProAir Digihaler alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids
• Cardiovascular Effects: ProAir Digihaler, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by heart rate, blood pressure, and/or symptoms. If such effects occur, the drug may need to be discontinued. ProAir Digihaler, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension
• Do Not Exceed Recommended Dose: Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma
• Hypersensitivity Reactions including Anaphylaxis: Immediate hypersensitivity reactions may occur after administration of albuterol sulfate, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Hypersensitivity reactions including anaphylaxis, angioedema, pruritus, and rash have been reported with the use of therapies containing lactose, an inactive ingredient in ProAir Digihaler
• Coexisting Conditions: ProAir Digihaler, like all sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines
• Hypokalemia: As with other beta-agonists, ProAir Digihaler may produce significant hypokalemia in some patients. The decrease is usually transient, not requiring supplementation
• Most common adverse reactions (≥1% and >placebo) are back pain, pain, gastroenteritis viral, sinus headache, urinary tract infection, nasopharyngitis, oropharyngeal pain and vomiting
• Drug Interactions: Other short-acting sympathomimetic bronchodilators should not be used concomitantly with ProAir Digihaler
  • Beta-Blockers: Beta-adrenergic-receptor blocking agents not only block the pulmonary effect of beta-agonists, such as ProAir Digihaler, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers
  • Diuretics: Caution is advised in the coadministration of beta-agonists with non-potassium sparing diuretics (such as loop or thiazide diuretics). Consider monitoring potassium levels
  • Digoxin: Carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and ProAir Digihaler
  • Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: ProAir Digihaler should be administered with extreme caution to patients being treated with these agents, or within 2 weeks of discontinuation of these agents, because the action of albuterol on the cardiovascular system may be potentiated. Consider alternative therapy
    

Please read the full Prescribing Information.

• Deterioration of Disease and Acute Episodes: AirDuo Digihaler should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma. ArmonAir Digihaler and AirDuo Digihaler are not indicated for the relief of acute bronchospasm. An inhaled, short-acting beta2-agonist, not ArmonAir Digihaler or AirDuo Digihaler, should be used to relieve acute symptoms such as shortness of breath
• Excessive Use and Use with Other Long acting Beta2-Agonists: AirDuo Digihaler should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
• Patients using AirDuo Digihaler should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason
• Oropharyngeal Candidiasis has occurred in patients treated with ArmonAir Digihaler or AirDuo Digihaler. Advise patients to rinse the mouth with water without swallowing following inhalation
  
• Immunosuppression and Risks of Infections: Patients who use corticosteroids, such as found in AirDuo Digihaler and ArmonAir Digihaler are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients. Use with caution in patients with the above because of the potential for worsening of these infections
• Transferring Patients from Systemic Corticosteroid Therapy: Particular care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available ICS. Taper patients slowly from systemic corticosteroids if transferring to ArmonAir Digihaler or AirDuo Digihaler
• Hypercorticism and Adrenal Suppression may occur with high doses of ICS, including fluticasone propionate, or at the recommended dose in susceptible individuals. If such changes occur, discontinue ArmonAir Digihaler or AirDuo Digihaler slowly
• Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors: The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, ketoconazole) with ArmonAir Digihaler or AirDuo Digihaler is not recommended because increased systemic corticosteroid adverse effects may occur; increased cardiovascular adverse effects may also occur with AirDuo Digihaler
• Paradoxical Bronchospasm and Upper Airway Symptoms: Paradoxical bronchospasm may occur. if bronchospasm occurs treat immediately with an inhaled, short-acting bronchodilator discontinue AirDuo Digihaler or ArmonAir Digihaler and institute alternative therapy
  
• Hypersensitivity Reactions, Including Anaphylaxis: Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of ArmonAir Digihaler or AirDuo Digihaler. Discontinue ArmonAir Digihaler or AirDuo Digihaler if such reactions occur
• Cardiovascular and Central Nervous System Effects: The salmeterol component of AirDuo Digihaler, can be associated with excessive beta-adrenergic stimulation which could present as the following symptoms: seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Use with caution in patients with cardiac arrhythmias, hypertension, coronary insufficiency. Drug may need to be discontinued in certain patients.
• Reduction in Bone Mineral Density (BMD): Decreases in BMD have been observed with long-term administration of products containing ICS. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care when using ArmonAir Digihaler or AirDuo Digihaler
• Effect on Growth: ICS may cause a reduction in growth velocity, Patients should be maintained on the lowest dose of inhaled corticosteroid that effectively controls their asthma. Monitor growth of pediatric patients receiving ArmonAir Digihaler and AirDuo Digihaler.
• Glaucoma and Cataracts: Long-term use of ICS, including fluticasone propionate, a component of ArmonAir Digihaler and AirDuo Digihaler, may increase the risk for cataracts or glaucoma. Regular eye exams should be considered
• Eosinophilic Conditions and Churg-Strauss Syndrome: Systemic eosinophilic conditions, such as Churg- Strauss syndrome, may occur when using ArmonAir Digihaler or AirDuo Digihaler. Be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy
• Coexisting Conditions: Use AirDuo Digihaler with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines
• Hypokalemia and Hyperglycemia: Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. Decrease in serum potassium are usually transient, not requiring supplementation. Be alert to hypokalemia and hyperglycemia in patients using AirDuo Digihaler
• Adverse Reactions with ArmonAir Digihaler: Most common adverse reactions (greater than or equal to 3%) are: upper respiratory tract infection, nasopharyngitis, oral candidiasis, headache, and cough
• Adverse Reactions with AirDuo Digihaler: Most common adverse reactions (greater than or equal to 3%) include nasopharyngitis, oral candidiasis, headache, cough and back pain

Please see full Prescribing Information for AirDuo Digihaler and ArmonAir Digihaler. To learn more, visit www.Digihaler.com.