Merck & Co, Inc

Evaluated: medicine & vaccine pipelines for priority** bacteria & fungi

A.1 Investments in R&D
MSD does not disclose publicly, or to the Benchmark, its R&D investments during 2019 and 2020 in antibacterial and antifungal medicines and/or vaccines for pathogens in scope. MSD has pledged USD 100 mn to the AMR Action Fund over the next ten years. 
 
A.2.1 Medium-sized pipeline
The company has 13 projects targeting pathogens in scope: 10 medicines and three vaccines, all targeting bacterial pathogens. Out of the 13 projects, two are in discovery stage, five are in preclinical development, two are in clinical development and four received marketing approval.  

A.2.2 MSD extending indications for their antibacterials
MSD’s clinical-stage medicine pipeline consists of both innovative and adaptive R&D projects. Relebactam/imipenem/cilastatin (Recarbrio™) received first marketing approval in July 2019 from the FDA for the treatment of complicated urinary tract (cUTI) and intra-abdominal infections (IAI). Recarbrio™ does not meet any of WHO’s innovativeness criteria. MSD has three adaptive projects aiming, respectively, to extend the indications of fidaxomicin (Dificid®), relebactam/imipenem/cilastatin (Recarbrio™) and tedizolid (Sivextro®).

A.2.3 Three vaccine candidates
MSD reports three vaccine projects in its pipeline. It includes one innovative candidate in preclinical development targeting Shigella spp. and two adaptive vaccine candidates targeting S. pneumoniae: V114 and V116.

A.2.4 Two candidates targeting critical and/or urgent priorities 
MSD has two medicines in its R&D pipeline targeting pathogens defined as ‘critical’ by WHO’s list of priority pathogens and/or characterised as ‘urgent’ threats by the US Centers for Disease Control and Prevention (CDC). Relebactam/imipenem/cilastatin (Recarbrio™) targets carbapenem-resistant Enterobacteriaceae, and fidaxomicin (Dificid®) targets C. difficile.

A.3 General commitments towards expanding access and affordability practices 
MSD does not report any specific access or stewardship plans for any of its six late-stage medicine and vaccine projects targeting pathogens in scope. Four out of six projects have ongoing clinical trials in access countries.‡ The company has made a general commitment about registering its products in LMICs, expanding access through broad registration and improving affordability. MSD supports the appropriate and responsible use of its antibacterial and antifungal medicines by supporting hospitals globally to strengthen their AMS programmes.

Evaluated: antibacterials manufacturing (APIs and drug products)

B.1 Environmental risk-management for own sites and suppliers; sets limits at own sites and suppliers
MSD reports a strategy to minimise the environmental impact of wastewaters and solid waste from antibacterial manufacturing at its sites, including audits at least every 1-2 years. It reports setting discharge limits in the receiving environment for all antibacterials manufactured at its sites, based on PNECs to limit AMR, as recommended the AMR Industry Alliance. It also reports quantifying discharge levels but there is no information on the methods used and compliance with set limits.

MSD requires third-party suppliers of antibacterials to follow similar standards, including on-site audits and limits based on PNECs. There is limited information whether it requests and reviews the discharge levels of its suppliers. 

MSD expects external private waste-treatment plants to comply with its general environmental standards. It reports auditing external private and public waste-treatment plants but no details on audit parameters are provided. It also does not report whether conservative measures for effluents sent to external public wastewater plants are employed.

B.2 Publicly discloses some information on environmental risk management and commitment to setting limits
MSD publishes some components of its environmental risk-management strategy. It is a member of the AMR Industry Alliance, which publishes a list of recommended antibacterial discharge targets. MSD publishes its commitment to setting these targets. It does not publish: (1) the results of environmental audits, whether conducted at its own sites, the sites of suppliers or external private and public waste-treatment plants; (2) a list of these suppliers and plants; or (3) the levels of antibacterial discharge from its own or suppliers’ sites.

B.3 System in place to maintain production quality for own and suppliers’ sites; no requests for official corrective action
MSD reports that its own sites and suppliers have a system to maintain high-quality antibacterial production, consistent with international GMP standards. This includes risk-based internal audits and tracking of corrective and preventive actions. It also requires its suppliers to audit their own suppliers. The Benchmark found no requests for official corrective action from the FDA or EMA related to non-conformities with cGMP at MSD’s own sites or any subsidiaries that manufacture antibacterials.

Evaluated: access activities relating to antibacterial & antifungal medicines & vaccines in 102 access countries‡

C.1.1 Limited information on registration filings for on-patent medicines
MSD performs below average as it does not disclose where it has filed five of its six relevant on-patent medicines for registration. However, it publicly reports that its on-patent medicine, ceftolozane/tazobactam (Zerbaxa®), a reserve antibiotic used to treat intra-abdominal infections, acute pyelonephritis, cUTIs and hospital-acquired pneumonia, was filed for registration in 25 LMICs.

C.1.2 Limited information on registration filings for off-patent/generic medicines
MSD’s performance is low. It reports no evidence of filing its seven relevant off-patent/generic medicines for registration in access countries. 

C.1.3 No information on registration filings for on-patent vaccines
MSD reports no evidence of filing its three relevant on-patent vaccines for registration in access countries.

C.2.1 Limited information on strategies to expand access to on-patent medicines
MSD performs below average. It expands access to its on-patent medicines in access countries through differential pricing and public or private partnerships and publicly commits not to enforce patents in low-income countries. MSD does not provide evidence of patient reach and geographic reach in low- and middle-income countries.

C.2.2 Limited information on strategies to expand access to off-patent/generic medicines
MSD’s performance is low as it discloses limited information on how it expands access to its seven relevant off-patent/generic medicines. It publicly reports to expand access through differential pricing and public or private partnerships with governments, NGOs and distribution channels. MSD does not provide evidence of patient reach and geographic reach.

C.2.3 Limited information on strategies to expand access to on-patent vaccines
MSD performs below average as it discloses limited information on how its expands access to its on-patent vaccines in access countries. It publicly discloses having differential pricing and intellectual property policies, and participating in public or private partnerships. To set the price of its vaccines, MSD takes into account the level of economic development, the channel of distribution and the public health needs. It has inter- and intra-country pricing strategies to allow for price flexibility. MSD publicly commits not to enforce patents in low-income countries. MSD does not provide evidence of patient reach and geographic reach for its strategies.

C.3 Limited information on strategies to ensure continuous supply
MSD has an average performance. It publicly reports to ensure accurate demand planning and commits to maintaining a reliable supply of its medicines and vaccines. MSD has supply agreements with local manufacturing partners to allow for local production of its vaccine. To mitigate against substandard and falsified products, MSD uses security features, has a dedicated anti-counterfeiting team in place, and raises public awareness.

Evaluated: stewardship activities relating to antibacterial & antifungal medicines globally 

C.4 Broad COI mitigation strategies in place for its educational programmes
MSD performs well in the analysis of its top five AMR-related educational programmes for healthcare professionals in conflict of interest (COI) mitigation. To mitigate COI for three programmes, it provides financial resources to independent third parties (CIDEIM, BSAC and the University of Dundee) to develop the programme. One programme (developed by the company) has all three COI mitigation strategies looked for by the Benchmark: (1) content is developed by a third party independent from the company’s own marketing department; (2) participants are not provided financial or material incentives (as it is a website); and (3) it does not use branded materials. The remaining programme has one COI mitigation strategy: it is unclear whether content is developed independently from its marketing department or whether it uses branded materials.

C.5 Engages in sales and marketing practices to address appropriate use
MSD performs above average in sales practices. It started a pilot in 2019 where it does not reward its sales agents based on antibacterial volumes sold in UK hospitals. However, outside of this pilot MSD does not report whether it decouples incentives for sales agents from sales volumes to help prevent the inappropriate use of its antibacterial and/or antifungal medicines.

MSD engages in marketing practices that aim to address the appropriate use of its antibacterial and/or antifungal medicines. Its marketing materials reflect emerging resistance trends and/or include treatment guidelines for healthcare professionals: it has developed its Star of Stewardship principles in which all marketing materials must include, e.g. specific indications, treatment duration and dose.

C.6 Does not report adapting brochures and/or packaging to facilitate appropriate use by patients
MSD does not report adapting brochures and/or packaging to facilitate the appropriate use of its antibacterial and/or antifungal medicines by patients.

C.7 Active in multiple AMR surveillance programmes; openly publishes aggregated results
MSD is active in multiple AMR surveillance programmes. It runs the multinational SMART programme, which is focused on respiratory infections and complicated intra-abdominal and urinary tract infections in 63 countries and has been running since 2002. MSD only shares the aggregated results through peer-reviewed open-access journal articles as well as on the online SMART database, a restricted data platform. Additionally, it is planning to make anonymised source data available for researchers upon request through the SMART database. For the remaining programmes, only the aggregated results are shared through peer-reviewed open-access journal articles, as well as on an open-access data platform for the CANWARD programme (a national programme managed by the Canadian Antimicrobial Resistance Alliance).