Ensuring patient health and safety

Patient safety is fundamental to our purpose: We cannot improve and extend people’s lives if we do not deliver safe, high-quality medicines. The importance of patient safety was highlighted in our 2021 materiality assessment, with both internal and external stakeholders identifying it as the most material topic.

Patient safety cuts across several strategic priorities for Novartis, including operational excellence and building trust with society. Our activities are focused on three areas that span the life cycle of our medicines and cover both our own operations and activities outside our walls: product quality, pharmacovigilance and combating falsified medicines.

Patient health and safety performance indicators

 

2021

2020

2019

GxP audits

 

 

 

Total audits executed

1 419

903

1 607

Internal1

125

111

162

External2

1 294

792

1 445

Regulatory authorities

 

 

 

Total inspections

126

126

187

Inspections found to be acceptable (%)

99.2

99.2

96.8

US FDA

 

 

 

FDA inspections

10

6

19

FDA warning letters

0

0

0

FDA Form 483

5

1

11

US FDA sponsor inspections

 

 

 

Inspections related to clinical trial management and pharmacovigilance

3

1

2

Number of FDA VAI (voluntary action indicated) classifications

0

0

1

Number of FDA OAI (official action indicated) classifications

0

0

0

Recalls

 

 

 

Total recalls

27

27

29

Class I recalls

3

1

3

Class II recalls

20

21

21

US FDA

 

 

 

FDA recalls

1

0

2

1

Total number of audits that are performed on facilities owned by Novartis

2

Total number of audits that are performed on GxP suppliers to Novartis

Product quality

We maintain a robust quality management system for the production of marketed products and investigational medicines, in full compliance with requirements from health authorities and other regulators around the world.

We hold relevant manufacturing licenses and Good Manufacturing Practice (GMP) certificates for 100% of our manufacturing, supply and distribution operations. These are issued after inspections by external health authorities such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), the World Health Organization (WHO) and Swissmedic. We hold relevant ISO certifications for the manufacture of medical devices.

99.2%

Regulatory inspections

of our facilities worldwide found to be acceptable

Of 126 inspections of our facilities by health authorities around the world in 2021, all but one (99.2%) were found to be acceptable without major findings. For the one inspection that required further improvement, a corrective action plan was deemed acceptable by the relevant health authority (EMA). Of the 126 inspections, 31 were performed remotely, and one FDA inspection relied on a prior inspection conducted by the Austrian healthcare authorities under a mutual recognition agreement.

We also have a strong auditing program covering both our own operations and those of our suppliers. Despite COVID-19-related challenges such as travel restrictions, we conducted 1 419 audits in 2021, including 1 294 audits of suppliers, with 690 audits conducted remotely. All but six audits were found to be acceptable (99.1%). One of the audits that required further improvement was at our own site due to unretrievable source data from a legacy system that is set to be decommissioned and replaced by the end of 2021. The other audits with opportunities for improvement were at external suppliers with corrective actions in progress.

We conduct thorough investigations when any deviations from current GMPs or other relevant regulations occur, or when we detect out-of-specification results or any other failures in our manufacturing processes. Incidents are assessed by subject matter experts and conclusions are provided to the appropriate health authorities with relevant documentation. Actions such as recalls are executed in agreement with the relevant authorities. Novartis initiated 27 recalls in 2021.

We also monitor our medicines for the possible presence of nitrosamines and completed all necessary nitrosamine assessments in 2021, closely following the recently agreed EMA/FDA implementation plan for the pharmaceutical industry.

We have a robust quality and safety training process for employees and third parties. We require all employees involved in manufacturing, supply and distribution to undergo at least two annual training sessions on quality standards. Employees can take additional training relevant to their role or worksite. We are regularly audited on our training procedures.

All third parties providing services or products manufactured to good practice standards are required to have their own quality assurance department and a formal training process. Novartis routinely assesses the capability and effectiveness of third-party training programs during audits to confirm suitability for the provided service or product. Despite the ongoing disruptions created by the COVID-19 pandemic, we maintained our quality and safety training process in 2021.

We look for ways to strengthen and streamline our quality processes to improve efficiency and bring our medicines to patients faster. This includes the use of digital technology and remote work across our quality operations, a trend that has been accelerated by the COVID-19 pandemic. For example, in 2021 we rolled out paperless quality control at three sites, including in Torre Annunziata, Italy, and in Ljubljana, Slovenia.

For more on this topic, please see the Novartis quality management system section of our corporate website.

Pharmacovigilance

Novartis continues its efforts to boost pharmacovigilance capabilities to support patient safety worldwide.

While clinical trials provide important information on a medicine’s safety during development, it is only after its use in greater numbers of patients in real-world settings that some adverse events become known. Effective pharmacovigilance requires activities to educate patients, providers and pharmacists, and strengthen reporting of adverse events to the company. Our pharmacovigilance and falsified medicines teams also work closely together, for example in cases where a disproportionate number of adverse events may indicate the presence of suspected falsified medicines.

We maintain a high level of compliance to regulatory requirements for both individual case safety reports and periodic benefit-risk assessments. In addition, in 2021 an internal audit confirmed the strength of the Novartis integrated pharmacovigilance governance model after it obtained ISO 9001 certification in the previous year.

With a growing number of medical devices in the Novartis portfolio, we have also built a robust system to monitor adverse events associated with medical devices worldwide. Novartis was the first company certified for compliance with the European Medical Devices Regulation, which came into force in 2021.

As a complement to traditional pharmacovigilance methods, we increasingly use technologies such as process automation, machine learning and natural language processing to analyze multiple data sources for adverse events.

Novartis collaborates with pharmacovigilance associations and authorities in multiple countries, including Italy, the Scandinavian countries, Switzerland, China and India, to support the implementation of local and international guidelines as well as the implementation of new adverse event reporting submission methods.

Further examples of our capacity-building initiatives in 2021 included training for clinical trial investigators in Mexico and China, as well as support for the creation of a local organization for pharmacovigilance professionals in the Philippines. In Asia, Novartis participated in regional forums where we presented our pharmacovigilance approach for advanced technology platforms, such as cell and gene therapies, while in Latin America we worked with partners to support them in reporting adverse events under different scenarios of the COVID-19 pandemic.

Examples of our capacity-building initiatives in 2021 included training for clinical trial investigators in Mexico and China

In response to the COVID-19 pandemic, we set up a task force to ensure the continuity of our pharmacovigilance system while providing support to healthcare professionals. We applied a pragmatic approach that created efficiencies across some of our processes such as the Individual Case Safety Report (ICSR) follow-up. We estimate that the ICSR efficiency gain translated into 2 500 saved hours for healthcare professionals at a critical time.

Worldwide patient safety offices contributed with safety data collection on COVID-19 investigator-initiated trials to support assessments about the impact of the new virus.

Falsified medicines

Falsified medicines are a growing global problem. The Pharmaceutical Security Institute reported a 38% increase in incidents of falsified medicines from 2016 to 2020, a trend that has been exacerbated by increased demand for medicines amid the COVID-19 pandemic.

At Novartis, our priority is to protect patient health and safety through quick authentication and reporting of falsified medicines to health authorities and the WHO. Since 2017, our efforts have helped prevent falsified medicines from reaching and harming more than 1.6 million patients.

In 2021, close collaboration with local law enforcement led to the investigation of 318 incidents in 41 countries, 66 successful enforcement actions, and the seizure of 1 million units of falsified medicines as well as the removal of more than 10 100 illicit advertisements from online platforms.

Digital technology is a critical part of our efforts to quickly authenticate falsified medicines. In 2021, we made significant progress on three interconnected digital solutions.

Authentifield by Novartis is a cost-effective mobile spectrometric sensor that can reduce the time needed to authenticate suspect medicines from several weeks to a maximum of five days. By early 2023, we aim to train 1 000 end users and deploy 500 sensors in 96 countries across 100 high-risk products in our portfolio.

Another project is MoVe, a mobile platform that enables Novartis employees to quickly verify the authenticity of secondary packaging for any product. The solution was in use in 24 countries by the end of 2021.

Finally, Novartis continued to lead an initiative with the Innovative Medicines Initiative and 12 major pharmaceutical companies to develop a use case for blockchain technology in the pharmaceutical supply chain. The aim is to empower patients to check their own medicines for authenticity while generating data – backed by robust privacy controls – on trends in falsified medicines.

10 days

Our policy

to report all confirmed incidents of falsified medicines to the WHO within 10 days was recognized as a best practice by the Access to Medicine Foundation

Fast authentication needs to be supported by timely reporting. Novartis has a policy to report all confirmed incidents of falsified medicines to the WHO within 10 days. Our efforts have been recognized as a best practice by the Access to Medicine Foundation. In 2021, Novartis was among the first pharmaceutical companies to join the WHO’s new online reporting platform for falsified medicines incidents.

We also engage with public and private stakeholders, such as the WHO and the Organization for Economic Co-operation and Development, to encourage coordinated action and promote effective policymaking on falsified medicines. In 2021, we delivered over 150 engagements and reached over 7 200 stakeholders in 14 countries.