Merck

Regulatory

The Life Science industry operates in one of the world’s most regulated environments with an increase in regulatory requirements and complexity. As a global leader in the Life Science industry, we have a team of regulatory experts from around the world to help you to stay on top of current trends and future quality and regulatory opportunities as well as supporting with potential regulatory challenges.

Use this page to navigate over a wide range of specialities and access to dedicated regulatory expertise.

Our Life Science business supports the registration of APIs and excipients in the US, EU, ICH-region and emerging countries, including preparation and submission of: US Drug Master Files (DMF), EU-ASMF (Active Substance Master Files), CEP dossiers and other Master Files to competent authorities.

More information about Pharmaceutical & Biopharmaceutical Manufacturing

Chinese Regulations for Excipients and Active Pharmaceutical Ingredients (APIs)

China is a highly attractive market for pharmaceutical companies due to the growing population and an aging society. However, the outstanding market opportunities are accompanied by substantial challenges for companies who want to manufacture, import or sell drugs in China.

The latest reforms in Chinese regulations have increased regulatory efficiency and transparency, resulting in better alignment with international approaches. The latest revised China Drug Administration Law enforced the implementation of the Marketing Authorization Holder system, as well as the co-review regulation relevant for APIs, excipients and packaging.

According to Regulation No.146, issued by the former China Food and Drug Administration (CFDA) that is now known as the National Medical Products Administration (NMPA), an API or excipient manufacturer shall submit a technical dossier to the NMPA to obtain a registration number. The registration number will be officially published by the Center of Drug Evaluation (CDE, a department under NMPA responsible for technical evaluation) on the CDE website after acceptance.

Many of our excipients and APIs are already registered with the CDE. The registration numbers are available on the CDE website.

Download our current registration dossier list.

Customers who require a Letter of Access to refer to any of our registered excipients or APIs in their drug application should contact their local sales representative.

For more detailed information:
Related White Paper: About Chinese Registration
Related Webinar: Chinese Excipients Regulation Overview

Elemental Impurities

For our Life Science Emprove® products, we generate data on elemental impurities to support our customers in accordance with ICH guideline Q3D on elemental impurities. The EII (Elemental Impurity Information) dossier provides batch data and is also part of our new Emprove® "Operational Excellence Dossier."

The product specification and Certificate of Analysis include general information about elemental impurities.

Related webinar: Guideline on Elemental Impurities: Challenges and Approaches for Implementation

Learn more about the Emprove® Program

Nitrosamines

The presence of nitrosamines in pharmaceutical products has emerged as a public health concern, leading health authorities to provide guidance for Marketing Authorization holders and manufacturers alike to perform risk assessments and implement mitigation strategies in case of possible contamination. Our experts effectively and efficiently supported the risk assessment of APIs and Excipients and have made assessment statements available to be used by customers via the Emprove® Dossiers. Our team consists of active members of Agency working groups and industry associations, thus keeping us apprized on the topic and providing continuous support to our customers.

Related webinar:
Nitrosamines - New Requirements to Evaluate Contamination Risks
Risk-Based Approach to Evaluate Nitrosamines and Elemental Impurities from Single-Use Components

USP <665>: Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products and Biopharmaceutical Drug Substances and Products

Single-use technology (SUT) is well established in the biopharmaceutical industry. One of its major challenges is the timely evaluation of leachables derived from the variety of different plastic components. For any regulatory submission of a medicinal product, data and risk assessment of potential leachables are required when single-use systems (SUS) are used in the manufacturing process. The United States Pharmacopeia (USP) was driving the discussion to establish a standard procedure to qualify SUS and published the new general chapter <665> in 2021 to become official as of May 2026.

The <665> objective to ensure the SUS is suitable for its intended use includes a standard extraction protocol to assess an organic extractables profile as a baseline for drug manufacturer’s toxicological assessment. With our Emprove® Program, we support to fast-track extractables risk assessment by providing reliable extractables data based on USP <665> as well as the industry standards established by the BioPhorum Operations Group.

More information about: Emprove® Filters and Single-Use Components portfolio

Related webinar: Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and Tomorrow

Biological reactivity testing for Filters and Single-Use: Transitioning from In Vivo to an In Vitro method for evaluation

Aligned with the USP initiative referenced below, we are removing animal testing and will use only the In-Vitro method ISO 10993-5, Biological evaluation of medical devices-tests for in vitro cytotoxicity, for both filter and Single-Use Technology (SUT) plastic material qualification.

A recent United States Pharmacopoeia (USP) communication highlighted a strategy to eliminate animal testing of plastics. This strategy included the removal of the USP <88> Biological Reactivity Test, In Vivo classification system for animal testing and re-emphasize a cell-based alternative approach provided in USP <87> Biological Reactivity Test, In Vitro. These compendial standards for biological reactivity testing of elastomerics, plastics and other polymeric materials are focused on drug product packaging (i.e., primary container closures) and delivery systems (e.g., syringes, auto-injectors, inhalers, intravenous systems). Plastics used in pharmaceutical manufacturing systems, such as filters and SUT, are out of scope of the referenced bioreactivity testing standards. Because of a lack of any specific standards for manufacturing systems, the industry has historically implemented USP <88>, Class VI for both filters and SUT. Our company has made the decision to transition away from this animal testing approach and utilize in vitro testing for filters and SUT, based on recent collaborations with the USP and industry groups, along with an evaluation of the testing methods. Both the in vitro and in vivo methods demonstrate the reactivity of a plastic material, and it’s been demonstrated that the methods are comparable.

ISO 10993-5 is an international medical device standard for in vitro bioreactivity testing, which also meets the requirements of USP <87>.

Related reference: USP’s Approach for Future Revision of Biological Reactivity Chapters (87), (88), and (1031). (July 1, 2020) - https://online.usppf.com/usppf/document/GUID-DB0E469C-AD8F-41EE-A4B9-0A785A61E79B_10101_en-US

Related webinar: Regulatory Talks: Is USP 88, Class VI Animal Bioreactivity Testing Necessary for Plastics used in Manufacturing

Related webinar: Evaluating USP 665 for Extractables testing and reducing animal testing for Biological Reactivity

Related white paper: Industry Alignment to Eliminate USP <88> In Vivo Animal Bioreactivity Testing for Polymer Characterization in Pharma Manufacturing

Cell and gene therapies are novel modalities, so regulatory expectations are continuously evolving. Globally, regulatory agencies are publishing guidance to address various aspects of cell and gene therapy development.

Our Life Science business is actively developing various solutions across the therapy development and manufacturing processes. We offer several products as well as manufacturing and testing services to meet this market’s needs.

Recent relevant regulatory guidance includes:

  1. EudraLex: The Rules Governing Medicinal Products in the European Union, Volume 4, Good Manufacturing Practice;
    Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products
  2. This guidance details GMP requirements that should be applied in the manufacturing of ATMPs that have been granted marketing authorization and those used in a clinical trial setting. It promotes a risk-based approach and phase appropriate level of implementation. In addition, emphasis is placed on implementation of adequate systems to ensure traceability of the ATMPs and their starting and critical raw materials.
  3. US FDA 2020: Chemistry, Manufacturing and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs); Guidance for Industry
    https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-control-cmc-information-human-gene-therapy-investigational-new-drug
    This document lays out the regulatory expectations regarding raw and starting materials, drug substance and drug product identity, purity, potency and safety for early phase gene therapies.
  4. European Union 2021: Questions and answers on the principles of GMP for the manufacturing of starting materials of biological origin used to transfer genetic material for the manufacturing of ATMPs (europa.eu)

This guidance clarifies the applicability of GMPs to starting materials used in the manufacture of ATMPs at various phases during development. This is most relevant to vectors (viral/microbial) used in cell and gene therapy manufacturing.

Our products and services are designed to meet the requirements laid out in these and other relevant regulations.

Related webinars:
Navigating regulations - novel cell therapy platforms and their path to clinical manufacturing
Navigating the Regulatory Terrain during Cell & Gene Therapy Production

mRNA

Using RNA as an active ingredient in drug products has become increasingly important during recent years, despite it being unstable in body fluids and unable to integrate into the genome of human cells. Besides in vivo applications, ex vivo gene correction modalities are applied for therapeutic use.
More information

Related resources:
Webinar: Regulatory Considerations for mRNA
Virtual Symposium: How mRNA Technology Impacts our Future (on24.com)

A successful food and beverage industry is dependent on working with partners who understand and deliver products that meet regulatory needs. Our food and beverage team leverages their extensive knowledge of global regulations to help ensure our ingredients, filters and testing offers meet the needs of our customers.

Flavors & Fragrances

We provide extensive documentation for our flavors to support our customers’ needs, including:

  • Regulatory statements declaring compliance to US or EU regulations where appropriate
  • Nutritional Statements
  • Allergen declarations for food allergens of concern in the US, EU and Japan
  • GMO statements meeting EU 1829/2003 and 1830/2003 requirements as well as the USDA Bioengineered Food Disclosure (6 CFR 77) requirements
  • Vegan/Vegetarian declarations
  • US and EU Natural declarations for natural flavors
  • Kosher and Halal certificates for appropriate products

All our food products are managed in facilities that adhere to strict Hazard Analysis and Critical Control Points (HACCP) principles and meet all hygiene and GMP requirements. Find the flavor ingredients you need by searching or sorting for desired organoleptic properties on our Flavors & Fragrances page. Here, you can also find the latest white papers, regulatory information and product highlights.

Our flavors are thoroughly tested and managed to ensure they meet Flavor and Extract Manufacturers Association (FEMA) and EU flavouring information system FLAVIS requirements. FEMA and FLAVIS numbers are displayed on our product pages where appropriate.

Food Additives

Our food additives, offered through our Emprove® portofolio are thoroughly tested and managed to ensure they meet Food Chemical Codex (FCC) and E-number requirements. FCC and E-numbers are displayed on our product pages where appropriate.

Our material quality dossiers include:

  • Manufacturing flow diagram
  • TSE/BSE statement
  • Allergen certificate
  • GMO certificate
  • Melamine declaration
  • Halal certificate
  • Kosher certificate

FCC Food additives List

Food & Beverage Testing

Our food and beverage testing portfolio is rigorously reviewed and tested to ensure it meets the latest regulatory and ISO methods. A thorough review of our industry-wide regulations as well as testing by food group and country and region can be found on our food and beverage testing regulatory compliance page.

Food Contact Materials

The Certificate of Quality (CoQ) for our filters includes information on animal origin, non-fiber releasing compliance (per 21 CFR 210.3), USP <88> activity testing for toxicity as well as the technical details needed to choose the best filters for your beer, wine, water or other food and beverage manufacturing.

See our Filtration page to learn more about our filters for food and beverage and pharmaceutical manufacturing.

Cannabis Testing in Food & Beverage

North America has seen rapid growth of the cannabis industry in recent years. Canada legalized the sale of cannabis food and beverage products (with some restrictions) and, while still federally banned in the US, many state jurisdictions have legalized some form of recreational or medical edible cannabis containing THC levels above 0.3 percent.

State testing requirements for cannabis may target bacterial pathogens, contaminants like pesticides, heavy metals and mycotoxins in plant materials and derivatives. Potency and cannabinoid quantitation are also important as these factors often drive safety and compliance.

We work closely with trade organizations like AOAC’s Cannabis Analytical Science Program (CASP) to better fulfill testing needs and communicate regulatory expertise. Products like our Simplate® Yeast and Mold Color Indicator have undergone formal review by AOAC for testing some cannabis products.

Additionally, we offer a comprehensive portfolio of analytical standards and certified reference materials (CRMs). We also provide testing standards for terpenes, cannabinoids, pesticides, mycotoxins and heavy metals and potency testing.

More information on products that currently support cannabis testing

Cultured Meat

A recent UN report estimates that 14.5 percent of all anthropogenic global greenhouse gasses are a result of livestock. Raising livestock not only consumes considerable energy resources but also requires tremendous land use. Additionally, meat production is highly inefficient. It takes an estimated 7 kg of grain to produce 1 kg of meat, so the impact of livestock production must be added to the resources needed to grow, process and transport feed. In light of these concerns, there is a strong drive to find alternatives to current meat production to help meet the consumption needs of a growing population.

Cultured meat – meat grown in bioreactors from a few animal stem cells – offers the promise of healthy, nutritious meat without the environmental impact of raising livestock.

Our Cultured Meat Innovation Center works closely with cultured meat innovators and regulatory agencies to bring to market tools and ingredients needed for the rapidly growing field. With dedicated regulatory experts, we are your partner to help drive innovations from the lab to the dinner table. For example, we are working to bring Cell Culture Media to market that meets both the technical needs as well as food grade and regulatory requirements for growing cultured meat.

The certification and registrations of Medical Devices and In Vitro Diagnostics (IVDs) require Preparation and maintenance of technical documentation. After product launch, we support vigilance and post-marketing activities. In case of planned or unplanned inspections from Competent Authorities or Notified Bodies, global regulatory team works together with quality and other cross-functional teams to minimize non-compliance risks

EU Medical Devices and In Vitro Diagnostics Regulations, 2017

The EU Medical Devices and In Vitro Diagnostics Regulations from 2017 are the biggest change in European regulations related to medical devices and in vitro diagnostics (IVDs) since the introduction of the current EU CE marking directives.

The regulations have a number of new requirements and changes. Some of the major changes are listed below:

  • Changes in the classification of IVDs, will lead to a greater number of IVDs requiring notified body conformity assessments (ca. 80%)
  • New requirements for performance evaluation for IVDs, including performance evaluation reports
  • Person Responsible for Regulatory Compliance is a new functional role within an organization aimed to ensure safety and efficacy of devices through their entire lifecycle
  • Introduction of traceability provisions - Unique Device Identification number (EU UDI)
  • More strict control of the manufacturers from the site of Notified Bodies. Manufacturers should be ready to unannounced audits.

ISO 13485:2016

  • After more than ten years, the update to the global standard for medical device quality management systems (QMS) was adopted. ISO 13485:2016 replaced the previous version from 2003.
  • Up until March 2019, ISO 13485:2003 and ISO 13485:2016 coexisted, allowing manufacturers, accreditation/certification bodies and regulators time to transition to the new standard. The European harmonized version of the ISO 13485 standard is used to demonstrate QMS conformity for the CE marking of Medical Devices and IVDs under the current European Directives and new regulations. The 2016 standard will also be used as the basis for the inspections under MDSAP (Medical Device Single Audit Program).
  • In 2021, the amendment, EN ISO 13485:2016+A11:2021 was published. This amendment features new annexes that link the requirements of the Regulation (EU) 2017/745 and (EU) 2017/746 to specific clauses of the ISO 13485:2016 standard. Once the 2021 standard is officially harmonized, compliance with its clauses will grant a presumption of compliance to the corresponding requirements of the new regulations for the next five years.

Download our ISO 13485 certificates.

Electrical and Electronic Equipment, EEE products are defined as any equipment that requires electrical energy to complete their intended use or function. This can include single phase mains voltage, three phase mains voltage or battery-powered equipment. These products can incorporate everything from heaters to lasers, to UV lamps and high voltage electrical subsystems.

What type of products do we offer?

Each major global market has their own regulatory requirements, yet many global markets are harmonized in terms of what is required before sale. Most regulatory requirements can be grouped into the following categories:

  • Electromechanical Safety: These requirements look at spark, fire, shock, sharp edges, instructions for use and other similar hazards with an electrical product.
  • Electromagnetic Compatibility and Electromagnetic Interference: These requirements review the electrical radiation/noise a product gives off during normal operation and reviews if the product malfunctions while accepting outside electrical radiation/noise.
  • Environmental Compliance: These requirements take into consideration the environmental impact of the electrical device once its useable life has expired and it seemingly must be disposed of. This category includes requirements such as the Restriction of Hazardous Substances (ROHS) and the Waste of Electrical and Electronic Equipment (WEEE). (Note: although these are European directive references, nearly all major markets have similar requirements.)

Some regulations require third party testing and certification other requirements are met through self-certification. In both cases, before a product is released to market, said product must have proof of compliance with these regulations within the products Technical File. Proof of compliance can come in the form of Certified Body (CB) Test Reports, CB certificates, Nationally Recognized Testing Laboratory Listing Reports, Electromagnetic compatibility EMC and Federal Communications Commission (FCC) test reports, amongst other options. This technical file should be available to customers, authorities and auditors alike in order to quickly prove the device meets all applicable regulations.

To learn more about global regulatory requirements around Electrical and Electronic Equipment, check out our compliance partners at Intertek Testing Services

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