Regulatory Editor

India's Central Drugs Standard Control Organization (CDSCO) has finalized its regulatory framework for medical devices and diagnostics, with several important changes compared to the draft. Among these is that the agency will not require that device makers obtain a new license for currently approved devices within 180 days of the effective date, but will instead have until Jan. 1, 2018 to renew their licenses and otherwise bring their operations into compliance.

The government of India had reviewed some proposed legislation in 2013 that would have amended the Drugs and Cosmetics Act of 1940 to provide for regulation of devices, but formally abandoned the effort last year. In a statement dated June 22, 2016, the Union Cabinet said it would "not be appropriate to carry out further amendments" of the statute in its then-existing form, given the pace of technological change in devices and in other life sciences not then directly regulated by the CDSCO's regulatory framework.

The statement also pointed to a desire to attract investors and to ensure that India will become "an international hub for manufacturing" of medical devices and in vitro diagnostics, making note also of an interest in efforts designed to "facilitate the ease of doing business" in India.

The draft rule had proposed a grandfathering of devices already available for sale, although the sponsor would have to apply for a marketing license within 180 days of the effective date. The draft rule reiterated this provision for both devices already marketed and those already notified, in both cases under Section 3 (clause b, sub-clause iv) of the Act. The draft had stipulated that the same provisions applied to diagnostics.

In contrast, the final rule omits this entire discussion and instead notes that its provisions go into effect Jan. 1, 2018, giving sponsors the last 11 months of 2017 to get their filings in order. Chapter 1 of the final rule has little more to say about the period of implementation, however.

One feature of the draft that did not change in the final is that both therapeutic and in vitro diagnostic devices will still be subject to a four-tier, risk-based classification system using alphabetic characters rather than the numeric system seen in other nations. Class A devices make up the low-risk items, while high-risk devices are class D. The two intermediate classes are low-moderate risk (class B) and moderate-high risk (class C).

Both the draft and final rules stated that the Drugs Controller General (DCG) of India would be responsible for licensing and enforcement for class C and D devices, whereas the related state agencies would handle these functions for class A and B devices. Should a manufacturing site produce class C and/or D devices along with class A and/or B devices, the central government would – apparently by default – handle compliance and licensing for that site rather than subject the site to split federal-state regulation. However, the federal authority can delegate its tasks to state authorities, thus seemingly ensuring the one-regulator scenario regardless of the regulator and the inventory produced at a site.

LIMITS OF 'CUSTOM DEVICE' NOT SPECIFIED

The draft and final documents said that a custom device is one that is made in accordance with a prescription, but which "does not include a mass production" of the device. Neither document offers any specific limits as to the number of custom devices beyond which such an offering becomes a mass-produced device. Manufacturers must hew to Section 3 of the Bureau of Indian Standards Act of 1985 in terms of device production, and any processes or other standards not addressed therein would have to comply with related ISO and IEC standards.

Notified bodies (NBs) operating in India will have to undergo certification by a national accreditation body, which will in turn be charged with periodic audits of the NBs it licenses. NBs will also be limited to inspections of manufacturing of class A and B devices unless that NB can demonstrate it has at least two years experience. CDSCO said interested parties can file applications for NB status starting July 1, 2017.

Sites that manufacture class C and D devices must be inspected within 60 days of the filing of an application for site licensing, 45 days after which the federal licensing agency must determine whether to grant a license. Applicants have 60 days to appeal an adverse decision. Under the section dealing with labeling, CDSCO said it will enforce unique device identification mandates starting in January 2022. However, this section does not directly address changes made to labeling intended to deal with new safety and/or efficacy information.

QUALITY SYSTEM REVIEW AT 'PLANNED INTERVALS'

The quality management systems section applies to therapeutic and IVD devices, but to contraceptive devices as well. Companies must appoint a management representative responsible for oversight of the quality system, and the quality system must be reviewed "at planned intervals." The document spells out requirements for design inputs and outputs as well as design verification/validation, along with requirements for device history records and corrective and preventive actions. CDSCO will also require installation and operation qualification for manufacturing equipment.

Non-class A medical devices without predicates will typically require a clinical study, albeit with several exceptions, including instances in which the government declares an urgent need and for diseases with no treatment. A device that is deemed investigational in India may be able to obtain a license if that device has been on the market for at least two years in any one of the U.S., the U.K., Australia, Canada and Japan.

The bulk of the document's remaining information on predicate devices, and the meaning of the term "substantial equivalence," is in the section on clinical investigations. This section said that substantial equivalence requires the same intended use and technological characteristics, while different technological characteristics are acceptable so long as the sponsor can demonstrate that "the device is as safe and effective as the predicate." However, this passage also suggested that these definitions apply only to the section dealing with clinical investigations of therapeutic and diagnostic devices, and no alternative definitions of those terms appear in the rule.

The rule allows for post-market studies for purposes other than surveillance, such as for "optimizing the intended use" of the device. Devices that are subject to clinical study requirements will also be subject to general postmarket surveillance reports at each six-month interval for the first 24 months after approval. Annual reports will be required for the two following years, and all reports are due within 30 days of the end of the reporting period. CDSCO said it would extend these reporting requirements should it deem such an extension necessary.

Medical Device Daily will cover the final guidance in more detail in a subsequent issue.

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