The Global Aspect of Essential Principles for Medical Device Regulation

By Evangeline Loh

EP, ER, GSPR, ESER, EPSP…. It’s alphabet soup on the same concept advanced by the former Global Harmonization Task Force (GHTF), now International Medical Device Regulators Forum (IMDRF), as Essential Principles of Safety and Performance. For this Insight, we use the term “Principles” or “requirement” to refer collectively to these requirements.

To some extent, the adoption of principles reflects the structure and the basis of the legislation (another topic on which we could wax philosophical). For regulatory regimes modeled after the former GHTF guidance or European Medical Devices Directive MDD 93/42/EEC, particularly for example the legislation from members of the Association of South East Asia (ASEAN), it is more likely that there be principles.

Primary legislative references: Essential Principles (Therapeutic Goods (Medical Devices) Regulations 2002, Schedule 1), Essential Requirements (Medical Devices Directive MDD 93/42/EEC, Annex I), General Safety and Performance Requirements (Medical Devices Regulation (EU) 2017/745, Annex I), Requisitos essenciais de segurança  e eficácia (RDC 546/2021), Essential Principles of Safety and Performance (IMDRF/GRRP WG/N47 FINAL:2018).

We recently pondered over this topic when the Australian Therapeutic Goods Administration (TGA) announced a small change to their template for the Essential Principles (EP) in Schedule 1. The TGA posts an EP Checklist table template to their website.

As a global consultancy, we’re often asked questions related to this.

1. What are these principles/requirements?
2. What is the best method to address this, from the compliance perspective?
3. What is the best method to address this, from the documentation perspective.?
4. Is this document interchangeable between legislation?

What are these principles/requirements?

These principles are a series of general expectations for medical devices and medical device manufacturers. It is a basic tenat that medical devices are safe and effective/perform as intended throughout the entire life cycle. And, manufacturers must design and manufacture these devices accordingly. In their guidance (ARGMD), the TGA describes: “Manufacturers are responsible for generating, collating, assessing, and maintaining scientific and engineering evidence.”

For example, the first principle advances that devices need to perform as intended and be designed to perform as intended. The benefits need to outweigh the risks of the device.

The principles are generally organized into sections or chapters. The first section are general requirements and expected to be applicable to all medical devices. 

The IMDRF has issued guidance on these Essential Principles of Safety and Performance. There is also content in the IMDRF proposed Edition 4 of the guidance on the medical device submission Table of Contents. And, the GHTF had similar guidance.

In many cases, these principles are promulgated in the legislation. These were first Essential Requirements (ER) in 1990 from the European Active Implantable Medical Devices Directive AIMDD 90/385/EEC, 1993 for the Medical Devices Directive MDD 93/42/EEC, and then 1998 for IVDs. Modeling the European legislative system, the Australian legislation renamed these as EP (Therapeutic Goods (Medical Devices) Regulations 2002, Schedule 1). In Brazil, Resolution RDC 56/2001 introduced the Requisitos essenciais de segurança  e eficácia.

Subsequently, the European legislation has been revised in 2017 (Medical Devices Regulation (EU) 2017/745), and  Annex I requirements have been renamed General Safety and Performance Requirements (GSPR). And, the resolution has been revoked by RDC 546/2021. In Singapore, there has been guidance (GN-16) on the Essential Principles for Safety and Performance since 2008, and a template table available.

What is the best method to address this, from the compliance perspective?

One fundamental concept is while the principles are compulsory when published in legislation, the method the manufacturer selects to address compliance to that expectation is flexible. The manufacturer is expected to review these principles, determine which principle is relevant, and if so, describe plans to address compliance of the device to the requirement.  

The methods the manufacturer can use to demonstrate compliance depend on the regulatory system. In general, standards are voluntary. In Brazil, there are certain types of devices (generally, electrical medical devices) which the National Health Surveillance Agency (ANVISA) requires be certified by the Brazilian National Institute of Metrology, Standardization and Industrial Quality (INMETRO).

In Europe, the regulation advances voluntary harmonized standards (MDR Article 8), standards which have been harmonized to the MDR and published in the Official Journal of European Union (OJEU), as well as Common Specifications (CS, MDR Article 9). Similarly, in Australia, standards are voluntary as  medical device standards orders (MDSO) and conformity assessment standards orders (CASO).

If one were to present a hierarchical approach, this might be:

• Standards harmonized and published (OJEU, CS, MDSO, and CASO) or required (INMETRO)
• International (ISO) standards, standards from organizations within country
• Other technical standards (AAMI, ANSI), monographs, pharmacopeias
• Guidance, codes of practice
• Manufacturer’s internal standards
• All others

The evidence of compliance can constitute any document the manufacturer possesses to demonstrate how the device addresses the requirement: a certificate issued by another organization or the manufacturer, a test report, a protocol or a document. In addition, compliance can also be complete or partial.

What is the best method to address this, from the documentation perspective?

There are currently instructions on documenting compliance to the GSPR in the European legislation (Annex II, Section 4 of the MDR). It is also expected that if a principle is not applicable, the manufacturer document why an expectation is not relevant. This often results in rephrasing the expectation and indicating it is a null value (e.g., the device is not sterile nor is it intended to be sterilized by the user). The IMDRF guidance and TGA ARGMD include extensive guidance on this issue.

Unequivocally, regulators utilize tables which include the principles in one column and has other columns: applicable or not applicable, methods used to demonstrate compliance, applied standards, CS, or other, and evidence of compliance or reason not applicable. The MDR expects “cross-reference to the location” of the “precise identity of the controlled documents.” Explicit guidance about the columns is part of the Team-NB Position Paper on Best Practice Guidance of Technical Documentation under the MDR. The TGA template is a table. Similarly, a table is used for RDC 546/2021 in Brazil.

Is this document interchangeable between legislation?

Yes, manufacturers have exploited a global principles checklist. Provided the table includes all the principles from the salient legislation, one global table can be referenced. In addition, our colleagues in Brazil have been submitting the principles checklist from the EU or Australia in support of RDC 546/2021 for some time. We have been submitting these principles in English, even before RDC 751/2022 permitted English in the regulatory submissions to ANVISA. In Singapore, manufacturers can submit the principles checklist from the EU or Australia, or submit the Singapore principles.

Concluding remarks

Manufacturers can benefit from one global principles checklist. To some extent, this can serve as the table of contents to structure the design and development and regulatory documentation for their medical devices. 

Emergo by UL has often advised that every document referenced in a technical documentation file could conceivably be cited in the principles checklist. And, there should not be a document mentioned in the technical documentation file which is not referenced in the principles checklist and vice versa. Last, the principles are general, and the section which truly is a checklist and should be reviewed as such, is the section on labeling/information supplied by the manufacturer.