CDSCO Requirements for In Vitro Diagnostic (IVD) Devices

Introduction

Diagnostic tests (IVDs) — which comprise reagents, kits, instruments and software that allow for sample processing and results interpretation outside of a living organism — play an essential role in caring for patients, monitoring community health, supporting clinical decisions and supporting patient outcomes. IVDs are considered a medical device and regulated as such in India through the Medical Device Rules, 2017 (under the Drugs & amp; Cosmetics Act of India). The CDSCO serves as the central licensing authority in India for many of the regulatory functions associated with IVDs. In the past few years, the CDSCO has strengthened its oversight of IVDs through updated classifications, new performance evaluation requirements and updated guidance documents (including the guidance on stability and risk assessment released in 2023–2024). This article provides an overview of what manufacturing, importing and other stakeholders should know by the year 2025 to compliantly place IVDs onto the market in India.

What are IVD Devices?

CDSCO uses the definition and scope provided by the Medical Devices Rules, 2017, to define IVDs. IVDs include simple single-use test kits (rapid antigen tests), complex laboratory analysers, control and calibration materials, and any necessary software. Examples of specimens from the human body that can be examined using IVD include blood, serum, urine, swabs, and tissues. IVDs are intended to assist with diagnosis, monitoring, screening, and/or compatibility testing of a specimen collected from a human.

Are IVD Devices Regulated by CDSCO?

Defining IVDs as medical devices as defined by their statute applying for Medical Device Registration and/or Approval under Medical Device Rules/2017. All IVD manufacturers should submit a Medical Device Registration Application to CDSCO and receive approval or registration certification from CDSCO before their sale, distribution, and/or use in India. CDSCO is the central authority responsible for the registration/approval of many IVD devices, especially Class II and Class III devices, and for issuing/importing licenses for all Class II and Class III devices. However, State Licensing Authorities are also responsible for issuing/manufacturing licenses for Class II and Class III devices and are subject to CDSCO's oversight in matters related to registration/approval of IVD devices. CDSCO provides continual guidance and updates on classification, guidance documents for performance evaluation guidance, stability testing, port inspection, and post-market surveillance for all IVD manufacturers/importers.

Classification of IVD Devices Under CDSCO

IVDs in India are classified according to a risk-based system into Class A (low), Class B (low-moderate), Class C (moderate-high), and Class D (high). The Medical Disposable Devices (MDD) Regulations guide the classification of IVDs by specifying what criteria will be used in determining which of these categories an IVD falls within. The Central Drugs Standard Control Organisation (CDSCO) is responsible for maintaining the current list of all IVDs that fall within each of these categories and is periodically updated. The classification of an IVD directly impacts its regulatory requirements, such as whether an IVD requires registration, clinical and/or performance evaluation or whether it needs to obtain a license. Please refer to the most recent published classification list maintained by the CDSCO, since classification lists are updated regularly.

CDSCO Approval Requirements for IVD Devices

Regulatory submissions are based on both regulatory authorities' device classifications (A–D) and the current classification status of the device in any foreign jurisdiction. Typically, the following items will appear on a regulatory submission:

• Device Class Confirmation

Initial registration or product registration for importers usually involves the submission of Forms MD-14 or MD-15 through the CDSCO (Sugam or CDSCO Online) website during the application process. In addition, when a manufacturer wants to begin selling their products in India, they are required to file for permission to manufacture/import and/or conduct clinical performance testing by submitting Forms MD-28 and MD-29 specifically for these purposes.

• Conformity Evidence

The documentation submitted to demonstrate the device's compliance with the regulatory requirements consists of a technical file/device master file along with documentation demonstrating that the device conforms to accepted standards through the provision of analytical/clinical performance data and ISO/IEC testing certification (where applicable). For many of the higher-risk devices, such as Class B/C/D IVDs, the CDSCO has developed a Performance Evaluation Report (PER) that must demonstrate the device's compliance through an industry-conducted performance evaluation of the device in India by CDSCO-accredited laboratories or Clinical Performance Evaluation Sites.

• Quality Management System (QMS)

Evidence must also be provided to demonstrate that a QMS is in place, which consists generally of an ISO 13485 certification and Site Audit Reports for each of the manufacturer's production sites based on the risk classification of each site. As part of its regulatory review of a manufacturer's device, the CDSCO may conduct an audit of the manufacturer's facility to evaluate the manufacturer's QMS.

• Labelling and Claims

Labelling must be in English, Hindi, or the local language where required, include a  clear Intended Use Statement (including storage and expiration conditions), and Instructions For Use. Instructions for Use must be consistent with submitted claims and evidence. 

As the requirements for labelling, advertising, marketing/or sale vary, with respect to both device class and to novelty of a device, all applicants are advised that they should review the related CDSCO IVD webpage and FAQ’s as well as the specific guidance documents applicable to their device.

Post-Licence Compliance Requirements

Licensing does not mark the end of a company's obligations. In India, additional post-license obligations consist of the following 4 components:

1. Reporting Adverse Events and Materiovigilance. Manufacturers/importers must keep a record of all adverse event reports and device incidents that occur after the product hits the market via the CDCSO's Medical Device Adverse Event Reporting System and online Reporting Forms to the CDCSO. Timely reporting ensures corrective action to prevent future occurrences, as well as subsequent regulatory follow-up.

2. Post Market Surveillance (PMS) and Vigilance. The CDCSO requires all license holders to establish PMS Systems to monitor device performance against standards. PMS also includes technologies for capturing Customer Complaints and performing trending of Customer Complaints to establish a process for Post Market Surveillance. The CDCSO has developed additional guidance on PMS (2023-2024) and will conduct periodic stakeholder seminars to enhance compliance efforts with applicable legislation.

3. Change Control and Post-Approval Changes. Any changes in the product, including design, intended purpose, Manufacturing Sites, Suppliers, or performance that may impact the manufacturer's ability to perform safely/effectively must be reported immediately to the CDCSO. In some instances, a Supplementary Submission or Fresh Evaluation may be required. The CDCSO publishes new procedures for Post Approval Changes for IVDs.

4. Compliance with CDCSO guidance or requirements related to labelling and packaging and Stability. By law, companies must follow CDCSO guidance in terms of Stability Studies and Labelling. The CDCSO published a Guideline Document on Stability Studies for IVDMD in 2024.

Step-by-Step CDSCO Approval Process for IVD Devices

The following is a sequential plan that can easily be modified to fit your specific device type and its requirements:

1. Verify the classification of your IVD product through the latest IVD classification list provided by CDSCO. Determine if the product is in Class A, B, C or D.

2. Determine if the device is newly introduced into India or has been previously marketed in other countries, and then whether it will require a clinical performance evaluation performed in India (usually required for Class B through D IVDs).

3. Create your technical documentation, which includes the following: Description of device, stated use, Information on how and where the device was manufactured, Master file of each manufacturing facility, Evidence showing device's performance through analytical studies and clinical evaluation, Stability testing, Risk analysis, Labels and instructions for use. The supporting documentation must support the guidelines set forth by CDSCO and conform to ISO 15189/20916 standards where appropriate.

4. Ensure the manufacturing site has been certified to ISO 13485 and is ready for inspection. If the device is being manufactured in India, contact the "State Licensing Authority" for information regarding requirements for obtaining permission to manufacture in the respective State.

5. Complete the required application on the Sugam/CDSCO web portal. Please be sure to include the reference forms as well: MD-24/MD-25 for application to conduct clinical performance evaluations, and MD-28/MD-29 for application to manufacture/import new IVDs, MD-14/MD-15 checklists used for verification of registration/import licensing. Be sure to pay associated fees, provide power of attorney/name of your local agent (importers) and attach copies of clinical performance evaluation reports.

6. Evaluation in India. Where necessary, submit a Written Performance Evaluation Report (PERR) and conduct performance evaluation within the CDSCO-notified lab(s) or through sites that have been approved for Clinical Studies. Additionally, have an understanding that obtaining approval in another country does not automatically exempt the requirements for conducting the performance evaluation for products intended for marketing in India, nor does it substitute for any requirements of Indian product performance evaluation requests. 

7. Answer Queries/Answering Questions: The CDSCO will respond to the queries of the Indian CDSCO. In addition to responding, submit all clarifications or data that are requested. Also, the CDSCO needs to review the entire dossier for the purposes of approving certain diagnostic products. 

8. Registering/Issuance of Licence. On satisfactory completion of the review of the product, the CDSCO will issue either the Import Licence (for imported products) or the Manufacturing Licence (for locally manufactured products) as described in the Indian Regulations for Medical Devices. At this point, you must abide by all post-marketing surveillance, vigilance and change control obligations.

Key Documents Required for CDSCO IVD Approval

While specific document types differ depending on the device/class involved, the following types of documents are typically needed for medical device applications:

• Cover letter and completed CDSCO online application form(s) (MD-14/24/28 and/or other appropriate application form(s)).

• Fee receipt/payment receipt (Challan) for payment.

• Power of Attorney or Authorised Agent for imported products (must be signed, notarised/attested).

• Device Technical File/Device Master File including description, intended purpose, manufacturing process, bill of materials/parts list, sterilisation (if applicable), and shelf life information.

• Analytical and clinical Performance Data (or PER), validation/verification and/or peer-reviewed documentation that support claims made regarding clinical performance. Submit findings/results of the Clinical Performance evaluation (with documentation of claim approval—MD-25).

• Quality Management System certificate/documentation (ISO13485) and documentation demonstrating readiness to undergo a site inspection.

• Stability Study Report(s) (CDSCO 2024 Guidance) and documentation of Labels/Instructions for Use (IFUs).

• Copies of all Marketing Authorisation documents provided by Regulatory Authorities of EU countries and/or the United Kingdom, the United States, Australia, Canada, and Japan and/or any relevant Authorised Body and/or any complaints received. Provide comparability tables and translation where applicable. CDSCO reserves the right to consider the possibility of accepting foreign Regulatory Authority approvals, but remains the final authority on the availability of local clinical and/or performance data.

Conclusion

IVD regulatory compliance in India is now established as an evolved risk-based framework based on the Medical Devices Rules; the IVD Classification List; and an increasing number of guidance documents published by CDSCO (e.g. Performance Evaluation; Stability; Port-Monitoring; PMS).

Action Steps to Establish Regulatory and Compliance Strategy:

• Verify your classification on the CDSCO website and build your Dossier content around the anticipated requirements for that classification. 

• If you are developing a Class B-D IVD or a Novel IVD, budget time and money to conduct Performance Evaluation/s in India (or in CDSCO-approved laboratories). This is typically a requirement for CDSCO. 

• Have a well-developed Quality Management System (QMS), documented Post-Market Surveillance/Vigilance process and Change Control Policy in place; these are essential elements for initial Regulatory Approval and Life-Cycle Compliance. 

• Utilise the CDSCO Guidance Documents (including the 2024 Stability Guidance Document and Performance Evaluation Guidance Document); these, as well as the FAQ section, contain practical information, checklists and laboratory resources.

Author:

ANANYA AGGARWAL
Delhi, India
KCC Institute of legal and higher education, Guru Gobind Singh Indraprastha University