Regulatory Framework around Companion Diagnostics

INTRODUCTION

Companion Diagnostics (“CDx”) are In Vitro Medical Devices (“IVDs”), often used in combination with drugs to test their efficacy on a particular patient and to determine the patient’s eligibility for the recommended treatment with a specific drug. IVDs are substances intended to be used outside the body for the diagnosis of any disease or disorder. They can be used alone or in combination with therapeutic drugs or medical products to determine whether a particular drug is safe and suitable for a patient. When used in combination with such drugs, it is termed as CDx.  An example of a CDx is a genetic sequencer, which sequences DNA or RNA to identify specific genetic mutations or markers. 

Clinical practice today demands precise accuracy, due to which this practice relies on a variety of diagnostics tools and healthcare resources, including CDx, to guide treatment decisions. Thus, as CDx stands at the intersection of technology, medicine, and innovation, the prospects for CDx in India appear promising with an expansive future.

NATURE OF CDx

CDx are medical devices, usually IVDs, that provide relevant information necessary to select a patient’s most appropriate treatment option. By identifying specific genetic markers or mutations, CDx helps predict a patient’s response to a particular therapy before a clinical trial is conducted. This helps in developing tailored treatment plans to suit each patient’s individual needs, resulting in more effective and efficient clinical trials in the healthcare industry. These CDx are generally not sold separately and are mainly used for a drug trial.

REGULATORY FRAMEWORK OF CDx

Unlike the United States of America and the European Union, India has no legislation regulating CDx. However, in India, CDx are covered under the definition of ‘medical devices’, which are regulated by the Drugs and Cosmetics Act, 1940 (“Act”) and the Medical Device Rules, 2017 (“Rules”) framed thereunder. The Rules define ‘medical devices’ by including IVDs under its purview. These Rules cover various aspects such as classification, registration, manufacturing and import, labelling, sales, and post-market requirements of medical devices, including CDx, in the healthcare sector.
Earlier, medical devices were regulated by the Act and the Drugs and Cosmetics Rules, 1945 (“Drugs Rules”). However, the Rules now have an overriding effect on the Drugs Rules. As a result, the Rules regulate the renewal of licences or issuance of new licences for manufacture, import, the conduct of clinical performance evaluation, etc.,1 which are crucial steps in ensuring the safety and efficacy of healthcare products.

LIFE OF A CDx UNDER THE INDIAN REGULATORY FRAMEWORK

The procedure for approvals of the CDx starts with a CDx being a new IVD, i.e. a device which has not been approved for manufacture for sale or for import by the Central Licensing Authority (“CLA”) and is being tested to establish its performance for the relevant analyte or other parameter.2 A new IVD requires several permits and licences from the CLA and State Licensing Authority. A broad procedure for an approval of CDx is as follows: 

  1. Formation of ethics committee; 
  2. Permission to conduct clinical performance evaluation of CDx;  
  3. Test licence for import or manufacture of IVDs; 
  4. Permission to import or manufacture a new IVD; and 
  5. Procurement of manufacturing licence/import licence.

CLASSIFICATION OF CDx AS A CLASS C MEDICAL DEVICE

The Rules classify medical devices based on parameters such as the intended purpose of the devices, use of the device in combination with other devices, etc., as specified in Part II of the First Schedule of the Rules. Such classification is as follows: 

REGULATORY FRAMEWORK AROUND COMPANION DIAGNOSTICS

One of the parameters to classify medical devices under Part II of the First Schedule of the Rules is the intended purpose of the devices. Paragraph 2(b)(6) of Part II of the First Schedule of the Rules states that IVDs used for “screening for disease stages, for the selection of patients for selective therapy and management”, will be assigned as class C medical devices. Thus, CDx, which are IVDs used to predict a patient’s response to a particular therapy, are generally categorised under class C, i.e. moderately high-risk medical devices. 

PRODUCT STANDARDS FOR CDx

The Rules require CDx to conform to the standards laid down by the Bureau of Indian Standards.3 However, if relevant standards have not been laid for a specific CDx, then that CDx must conform to the standards laid down by the International Organisation for Standardisation, the International Electrotechnical Commission, or any other pharmacopoeia standards. If any of the above-mentioned specific standards are not available for a CDx, then that device shall conform to the validated manufacturer’s standards.4

CONSEQUENCES OF NON-COMPLIANCE OF THE RULES

Any person to whom permission has been granted under the Rules, fails to comply with any of the conditions of permission or any of the provisions of the Act or the Rules, the CLA may:5

  1. issue warning letter giving details of deficiency found; or
  2. debar the investigator or sponsor, including their employees, subsidiaries and branches, agents, contractors, and sub-contractors to conduct any clinical investigation for such period as it thinks fit; or
  3. suspend the permission for such period as it thinks fit or cancel either wholly or partly the permission.

Section 27 of the Act prescribes that if any person manufactures for sale or distribution, sells, stocks, exhibits or offers for sale or distributes any medical device without a valid licence as required under Section 18(c) of the Act, shall be punishable with imprisonment for three to five years and with a minimum fine of INR 1,00,000 or three times the value of the drugs confiscated, whichever is more. On the commission of subsequent offences, the term of imprisonment is seven to ten years, and a minimum fine of INR 2,00,000.6 The Rules also provide for medical management and compensation in case of injury to a participant in a clinical investigation.7

CONCLUSION

Considering that CDx deals with the safety of people, it is essential for India to have strict regulations in place and to balance it with the ease of doing business for the growth of domestic manufacturing of such devices rather than imports in the healthcare industry. The current regulatory regime under the Act and the Rules regulate these devices’ manufacturing, sale, or import as an IVD rather than providing for separate legislation that explicitly regulates the CDx, like in the United States of America.8 Therefore, considering the growth of the CDx market in India and the global regulatory regime, India needs to implement CDx specific regulations to ensure that people’s health and safety are not compromised.


[1] Medical Devices Rules, 2017, Rule 96.
[2] Medical Devices Rules, 2017, Rule 60.
[3] Medical Devices Rules, 2017, Rule 7.
[4] Medical Devices Rules, 2017, Rule 7.
[5] Medical Devices Rules, 2017, Rule 54 and Rule 61. 
[6] Drugs and Cosmetics Act, 1940, Section 27. 
[7] Medical Devices Rules, 2017, Rule 52.
[8] https://www.fda.gov/medical-devices/in-vitro-diagnostics/companion-diagnostics