Update on the Medical Device Regulations in India

With a population of 1.2 billion, a growing middle class and a booming economy, India is experiencing increasing demand for medical devices.  The Indian medical device market is thriving and currently has a total worth of about $3 billion (US), with growth anticipated at 12% to 16% over the next five years India is an important destination for foreign medical devices:  imported products represent more than 70% of the market.  As a huge growth opportunity, regulatory professionals need to closely follow the evolving Indian medical device regulations.
This article discusses both current medical device regulations as well as proposed medical device regulations.

The Indian Medical Device Regulatory Landscape Today 

Regulated Medical Devices
Only certain products require medical device registration in India. Over the years, there have been three announcements outlining the medical device products that must be registered.
Prior to 2005, medical devices such as disposable hypodermic syringes, tubal rings, condoms, metered dose inhalers, etc., were required to be registered in India.  Beginning 1 March 2006, items such as cardiac stents, drug eluting stents, catheters, intraocular lenses and bone cement, were required to be registered for import, manufacture and sale.  And on 20 March 2009, the Central Drugs Standard Control Organization (CDSCO) clarified that sterile medical devices such as spinal needles, insulin syringes, endotracheal tubes, cardiac patches, and extension tubes were also required to be registered.

Current Product Registration Process 
Under CDSCO’s current system, products requiring medical device registration in Indianeed approval from the Drugs Controller General of India (DCGI).  After receipt of the application with fees, evaluation begins. DCGI may require clinical testing in India or request information on clinical trials performed abroad. Before a medical device can be sold in India, both a Registration Certificate and an Import License are required.

Current Product Registration Submission Documents
On 4 August 2010 CDSCO released new guidelines for document submission for medical device registration in India. Documents required to be submitted for medical device registration in India include:
1.  Cover letter that specifies whether the registration application is being submitted for the first time or for re-registration.
2.  Authorization Letter listing the name and designation of the person authorized to sign all legal documents on behalf of the manufacturer.
3.  Form 40 for the issuance of the Registration Certificate.  Form 40 can be submitted by the manufacturer or through an authorized agent in India.
4. Power of attorney provided by a manufacturer to its agent in India, authenticated either in India or in the country of origin.
5.  Schedule D (I) and D (II).  Schedule D(1) outlines the particulars of the manufacturer and manufacturing premises such as the name and the address of the manufacturing premises.  Schedule D(II) or the Device Master File is an executive summary of the medical device to be registered and contains information on the device, its sterilization requirements, etc.
6.  Plant Master File contains information about the product and control of the manufacturing process at the manufacturing site.
7.  Wholesale license along with a Free Sale Certificate or Certificate of Marketability for each device issued by any of the Global Harmonization Task Force (GHTF) member countries, e.g., the US, Canada or Japan.
8.  Manufacturing License or Plant Registration Certificate issued by the National Drug Regulatory Authority or equivalent.

Import License Application Process
After obtaining the Registration Certificate, a medical device importer can apply for an Import License from DCGI.  On 25 August 2010, CDSCO released new guidelines for document submission to obtain a medical device Import License.
Currently, required documentation includes a cover letter, Authorization Letter and Wholesale License (for sale and distribution) with the same content requirements as the documents for medical device registration in India.  In addition, a completed Application for Import License (Form 8 and Form 9), by the manufacturer and confirms the applicant as an importer, is required.  Other requirements include the Registration Certificate issued by CDSCO and applicable fees.  For renewal, a copy of the existing Import License is also necessary.
If a single manufacturer is importing medical devices that are made in two or more factories located in different places (though manufacturing the same device), a separate Import License is required for each factory location.

Inspections of Foreign Manufacturing Facilities
CDSCO has recently begun inspections of manufacturing facilities in foreign countries, such as Italy, to help ensure the quality of drugs and medical devices imported into India.  Once initial pilot projects are successful, the CDSCO will introduce auditing and inspection of manufacturing in more countries in the near future.

New Proposed Medical Devices Regulation Bill
In 2006, the Medical Devices Regulation Bill (MDRB) was proposed by the Ministry of Science and Technology.  The MDRB was designed to consolidate laws related to medical devices and establish the Medical Device Regulatory Authority of India (MDRA).
This proposal was aimed at establishing and maintaining a national system of controls for the quality, safety and availability of medical devices in India.  The bill was intended to be fully implemented by 31 December 2009 as a Parliament Act.   However, it was not passed by India’s Council of States and was subsequently abolished.  Recently though, there has been talk of reintroducing the MDRB in late 2011 or early 2012.

If enacted, the MDRB will govern all medical devices throughout India.  Companies wishing to import devices into India or manufacture products locally will have to comply with the design, manufacturing, packaging, labeling, import, sale, use, and disposal requirements of the MDRB. Also the bill will expand the list of products requiring medical device registration in India.

Proposed Penalties
The proposed MDRB also lays out penalties for offenses relating to medical devices, including fees for misconduct.
For example, misbranding a medical device will incur a fee of up to 300,000 rupees (about $6,700), or imprisonment of up to six months, or both. Failure to comply with the direction of MDRA will incur a fine of up to 500,000 rupees (about $11,100), or imprisonment of up to one year, or both.  Providing false information will incur a fine of up to 100,000 rupees (about $2,200) or imprisonment of up to three months.  Lastly, carrying out a medical device business without medical device registration in Indiawill incur a fine of up to 100,000 rupees (about $2,200) or imprisonment of up to six months.  The calculations are based on an exchange rate of 45 rupees to the US dollar.

Additionally, the Indian government issued a set of draft guidelines for the regulators to assess medical device manufacturers.  These guidelines will eventually form a part of the MDRB.  The guidelines are to be adopted by representatives of the Indian regulatory body for use in evaluating an application for registration of a medical device, granting a Manufacturing License and auditing a medical device manufacturer.

Proposed New Clinical Trial Regulations 
Additionally, the MDRB discusses clinical trials and Clinical Research Organizations (CROs) in India.  If the bill is approved, some high-risk medical devices will require local clinical trials in India in addition to foreign clinical data.  In general, more-stringent regulations will apply to CROs and clinical trials.

Indian CROs are required to register with the Licensing Authority (CLAA) in order to conduct clinical trials. Once permission by DCGI is granted for clinical trials, companies are required to register them in the Indian Council of Medical Research (ICMR) clinical trial registry before the initiation of the trial.

In January 2011, the Ministry of Health and Family Welfare issued a notification to amend the Drugs and Cosmetic Rules with some minor proposals (draft rules) on clinical trial establishments. Now, the registration of the CRO is to be valid for five years from the date of issue, unless suspended or cancelled earlier.  Additionally, CROs whose registration has been suspended or cancelled by the Licensing Authority may, within 90 days of receiving the suspension/cancellation order, appeal to the Central Government to reverse or modify the order.

There are also proposed additions that stress the quality of clinical trials, the need for proper procedures and requirements for skilled CRO staff.  They state that the CRO shall implement quality assurance and quality control measures and have well-documented Standard Operative Procedures (SOPs).  Second, CROs are required to maintain complete and accurate data and documentation on the conduct of clinical trials and related investigations.  Third, all documentation and communication records are required to be dated, filed and preserved for five years after the completion of the study.  Strict confidentiality is to be maintained when accessing and retrieving clinical trial information.  And lastly, CROs shall implement education programs to assist investigators in carrying out research studies according to the Indian clinical trial guidelines and regulations. Training should include protocol adherence, GCP guidelines, etc.

Overall, CRO responsibilities regarding clinical trials are becoming better defined in India in an effort to lessen corruption and increase accuracy.  This way, they can be used in global clinical trials and for medical device registration in India.

Proposed Establishment of MDRA
If enacted, the new bill will establish MDRA as the regulatory and enforcement body for medical devices.  It will be an autonomous committee under the Ministry of Science and Technology or Ministry of Health.  The proposal also calls for another new entity called the Central Drug Authority (CDA).  See Figure 2 for the proposed organization.  The roles and responsibilities of MDRA and CDA are still being worked out.

MDRA is expected to be headquartered in New Delhi.  There may also be other regional offices established in India.  The chief executive officer of MDRA and other members of the organization shall be appointed by the Central Government.  The CEO shall be responsible for the day-to-day administration of the MDRA, implementing the work and decisions adopted by the MDRA and ensuring that the MDRA carries out its tasks effectively.

MDRA shall consist of nine members appointed by the Central Government, including:  two eminent medical device technologists or scientists,  the secretary general of the Quality Council of India, the CEO of  MDRA and two eminent medical practitioners.

In addition, the proposed agency may also establish an advisory committee to help with MDRA implementation consisting of: the chairperson of MDRA, the CEO of the advisory committee, two representatives from the medical device industry, one representative from the Indian Medical Association, two biomaterial scientists, etc.

Responsibilities of MDRA will include issuing regulations regarding the safety and performance, design and manufacturing of medical devices in India; providing a risk-based classification system for medical devices; and providing scientific advice and technical support to the Central Government and the state governments regarding policies that affect medical devices.  In addition, MDRA may also carry out necessary inspections on medical device manufacturers, specify an appropriate system for enforcing standards for medical devices and stipulate the procedures and guidelines for testing laboratories.

The proposed MDRA may serve as a support mechanism for DCGI.  It is also possible that MDRA will fall under the Ministry of Health as an office of CDA (see Figure 3 for the CDA organization). However, the agency’s specific responsibilities in regards to licensing and medical device registration in India are still under deliberation.

In addition, the Central Government will also establish one or more tribunals, known as the Medical Device Safety Appellate Tribunals (MDSAs), to hear the appeals by medical device companies regarding MDRA decisions.

If approved, CDA’s proposed structure will replace the current structure of CDSCO.

Proposed Classification System for Medical Devices
If the MDRB is implemented, a risk classification system for medical devices will be set up comprising Classes A, B, C and D.  This classification is consistent with the definition and guidance from the Global Harmonization Task Force (GHTF), as well as the EU medical device directives.

Class Risk Level Device Examples
A Low Risk Thermometers / Tongue Depressors
B Low Moderate Risk Hypodermic Needles / Suction Equipment
C Moderate High Risk Lung Ventilators / Bone Fixation Plates
D High Risk Heart Valves / Implantable Defibrillators

If a medical device manufacturer wants to reclassify a device to a lower-risk class, it needs to submit justification to the Central Licensing Approval Authority (CLAA) for evaluation.

If a medical device manufacturer wants to reclassify a device to a lower-risk class, it needs to submit justification to the Central Licensing Approval Authority (CLAA) for evaluation.

Other Updates:  Draft Guidelines on Reporting Serious Adverse Events 
On 11 May 2011, CDSCO released draft guidelines on reporting serious adverse events (SAEs) for medical devices in clinical trials.  At present, CROs and medical companies are using multiple different formats to report SAEs.  CDSCO is trying to standardize the reporting procedure.

All SAEs occurring in clinical trials should be reported within 14 calendar days to DCGI.  The medical device company/sponsor/CRO is responsible for reporting the SAEs.  A brief narrative (not exceeding 10 lines) describing what happened should be enclosed along with a statement of whether the outcome was fatal.  Reporting SAEs requires a cover letter detailing the incident and initial and follow-up reports regarding the SAE. If some information is unavailable at the time of the report, such as causality assessment by the CRO or compensation provided for the study-related injury/death, a follow-up report must be provided.

The cover letter should include the DCGI clinical trial file number, the complete address and contact details of sponsor and CRO (if any), the phase of clinical trial, the category of clinical trial and the adverse event and its diagnosis.

In the future, due to the huge market opportunity in India, more and more foreign medical device companies are expected to try to import their products.  With an evolving situation on regulation and medical device registration in India, companies will need to stay up-to-date in order to achieve success in India.