Benefit Risk Assessment on the Use of CMR and ED Phthalates

The world of medicine has transformed a lot and is still in the transformation process as conventional methods are being replaced by sophisticated devices. Surgeons and doctors are being replaced by robots, and the dependence on machines is increasing with the passage of time. The use of medical devices is becoming very common. From miniature implants to giant scanning machines, every device is helping the medical personnel in diagnosing and solving the illnesses.

These medical devices are made up of several parts and components. Although the main objective of these medical devices is to enhance and prolong the life of a person, the products and materials used in their production can put the life of the patient or a medical personnel in danger, given the fact that most of them possess hazardous properties.

The Molecular Structure of Phthalates

Phthalates are also such class of chemical compounds that are widely used in the production of the medical devices and are associated with certain life-threatening properties.

What Are Phthalates?

Phthalates are a class of chemical compounds that are the esters of 1,2-benzenedicarboxylic acid, also known as o-phthalic acid.

Structure of Phthalates

The chemical structure of phthalates comprises of one benzene ring and two ester functional groups that are linked with two consecutive carbons on the ring. The hydrocarbon chains present on the group can be straight or branching and are the reason why phthalates differ among their properties.

Classification of Phthalates

Phthalates [phthalate esters (PE)] are classified in three distinct groups depending upon the length of their carbon chains:

  • High Molecular Weight Phthalates (HMWs)

High Molecular Weight Phthalates have 7-13 carbon atoms in their carbon chain.

  • Low Molecular Weight Phthalates (LMWs)

Low Molecular Weight Phthalates have 3-6 carbon atoms in their carbon chain. DEHP or Di (2-ethylhexyl) phthalate is an example of the LMW phthalates and is commonly used as a plasticizer.

  • DMP and DEP

Dimethyl Phthalate and Diethyl Phthalate are the groups that make up the third group of the phthalates.

Uses of Phthalates

Phthalates serve various important functions in the industries, the most important of which is working as a plasticizing agent for polymers, of which Polyvinyl Chloride (PVC) is a prime example.

  • Use of HMW phthalates

HMW phthalates are used in coated fabrics, roofing membranes, wall coverings, food containers, and medical devices.

  • Uses of LMW phthalates

LMW phthalates are used in adhesives, paints, inks, enteric-coated tablets, varnishes, personal care products, and medical devices. DEHP is the LMW phthalate most commonly used in medical devices.

  • Uses of DMP and DEP

Instead of using those as plasticizing agents, industries usually use them as additives in cosmetics, household products, and medical devices.

The medical devices which are manufactured must be safe enough for both the patients and the handlers of the medical devices. Yet many potential mishaps can happen and can inflict serious damage to the parts of the body from which they come in contact.

EU MDR and Requirements Regarding Phthalates

The phthalates widely used in the production process are of two types. The CMR phthalates which have the Carcinogenic, Mutagenic, and toxic to Reproduction properties (hence named CMR) while the second type of phthalates are known as Endocrine-Disrupting or ED phthalates.

These phthalates can get disbanded and released into the human body easily as their relation with their polymers is weak. Once they get inside the human body, they can pose serious ill-effects on it.

The EU guidelines have stated that medical devices or any of its part with a composition of greater than 0.1% w/w of phthalates (possessing CMR or ED properties) will needs benefit risk analysis.

Benefit-Risk Analysis for CMR/ED PHTHALATES

The risk-benefit analysis is a comparison between the benefits and risks associated with an object or a situation. Systematic and step-wise design of BRA is given below:


The components and parts making up medical devices should be described. The presence of CMR or ED phthalates or both should be determined in weight by weight percentage (%w/w).


Description regarding the use and function of CMR/ED phthalate that has been used in the medical device.

2(a). Description of the function the phthalate is serving or the performance it is showing in the medical device.

2(b). Any medical or clinical benefit associated with the CMR/ED phthalate in the medical device.


Assessing the risks of the CMR/ED phthalate.

3 (a). Determine the exposure of the CMR/ED phthalate on the patient.

3 (b). Identify biocompatibility, toxicology, and CMR/ED hazards associated with the phthalate.

3 (c). Determine how much exposure the patient can bear based on the available pre-clinical and clinical information.

3 (d). Determine the risks for different intended use scenarios and patient groups.

Assessing Possible Alternatives to be used in Manufacturing of Medical Devices in place of CMR/ED Phthalates


The possible alternatives can comprise:

4 (a). Substances

4 (b). Materials

4 (c). Designs and/or Medical treatments.


The potential alternatives to be used in the place of CMR/ED phthalates should be identified for assessment. A justification should be provided regarding the inclusion or exclusion of any of the alternatives. This also includes the assessment for the availability of any potential alternatives. 


Describing identified potential alternatives.

6 (a). Describing the functionality and performance of the upper mentioned potential alternatives.

6 (b).  Describing the material and/or clinical benefits of the upper mentioned potential alternatives.


Determining the risks associated with identified potential alternatives.

7 (a). Based on a realistic worst-case scenario in the intended use, the patient’s exposure to the alternative should be determined.

7 (b). Any toxicological, CMR/ED hazards, and availability of biocompatibility should be identified where applicable.

7 (c). Determining the extent to which the effects of identified alternatives are tolerable to the patient.

7 (d). Determining the risks of these potential identified alternatives for different use scenarios and patient groups.

Comparing Assessing Potential Relevant Alternatives with CMR/ED Phthalates


Comparing the functionality and performance of CMR/ED phthalate versus functionality and performance of identified potential alternative(s).


Comparing between hazards associated with a CMR/ED phthalate used in a medical device against those of identified potential alternatives.


Comparing the benefits and risks associated with CMR/ED phthalate used in a medical device against those of identified potential alternatives.

TS Q & E can assist in BRA for CMR/ED Phthalates

In most of medical devices companies, doing the BRA is a challenging job for your medical device. You need professionals who understand regulatory guidelines on that as well those who know how such studies can be performed. TS Q & E can help in the entire process of the analysis. Check our service page on BRA for medical devices phthalates having CMR/ED properties and request more information directly from there.

About the Author

Waqas Imam

S. M. Waqas Imam is associated with TS Quality as a Regional Partner. He is also an ambassador of Medical Device Community. He is an Industrial Engineer by qualification and served the manufacturing industry since 2011. He is also IRCA CQI Lead Auditor of ISO 9001 and other management system standards. He had served as Quality Assurance and Regulatory Affairs Manager in QSA Surgical Pvt. Ltd. and Ultimate Medical Products. He managed requirements of ISO 13485:2003, EU directives, CE marking and FDA. He also served as Expert Blog Writer for 13485Academy and wrote expert articles on various topics of ISO 13485:2016.