Indian Regulatory Requirements

Indian Regulatory Requirements

Indian Regulatory Requirements: Indian pharmaceutical regulations are primarily governed by the Drugs and Cosmetics Act, of 1940, and the Drugs and Cosmetics Rules, of 1945. The CDSCO, under the Ministry of Health and Family Welfare, is the central regulatory authority responsible for drug control and regulation in India.

• Central Drug Standard Control Organization (CDSCO)
• State Licensing Authority – Organization, Responsibilities,
• Certificate of Pharmaceutical Product (COPP),
• Indian Regulatory requirements and approval procedures for New Drugs.

Central Drug Standard Control Organization (CDSCO)

• The Central Drugs Standard Control Organisation (CDSCO) under the Directorate General of Health Services, Ministry of Health & Family Welfare, and Government of India is the National Regulatory Authority (NRA) of India.
• Its headquarters is located in New Delhi and also has six zonal offices, four sub-zonal offices, thirteen Port offices, and seven laboratories spread across the country.
• The Drugs & Cosmetics Act, 1940 and Rules 1945 have entrusted various responsibilities to central & state regulators for the regulation of drugs & cosmetics
• It envisages uniform implementation of the provisions of the Act & Rules made there under for ensuring the safety, rights, and wellbeing of the patients by regulating the drugs and cosmetics
• CDSCO is constantly thriving to bring out transparency, accountability, and uniformity in services in order to ensure the safety, efficacy, and quality of medical products manufactured, imported, and distributed in India
• Under the D&C Act, CDSCO is responsible for the approval of New Drugs, Conduct of Clinical Trials, laying down standards for Drugs, control over the quality of imported Drugs & coordination of activities of State Drug Control Organizations by providing expert advice with a view to bring about uniformity in the enforcement of the D&C Act.
• Further CDSCO along with state regulators- is jointly responsible for the grant of licenses of certain specialized categories of critical Drugs such as blood, blood products, I. V. Fluids, Vaccine, and Sera.

Drugs Controller General of India [DCGI]

• He/she is responsible for the approval of New Drugs, Medical Devices, and Clinical Trials to be conducted in India.
• He is appointed by the central government under the DCGI the State drug control organization will be functioning.
• The DCGI is advised by the Drug Technical Advisory Board (DTAB) and the Drug Consultative Committee (DCC)

Vision:

To Protect and Promote Public Health in India.

Mission:

To safeguard and enhance public health by assuring the safety, efficacy, and quality of drugs, cosmetics, and medical devices.

Organization Chart

Zonal offices

• Mumbai
• Kolkata
• Chennai
• Ghaziabad
• Ahmedabad
• Hyderabad

These are involved in GMP audits and inspection of manufacturing units of large volume parental, sera, vaccine, and blood products.

Sub-zonal offices

• Chandigarh
• Jammu
• Bengaluru

These centers coordinate with state drug control authorities under their jurisdiction for uniform standards of inspection and enforcement.

Central Drugs Testing Laboratories

• Central Drug Laboratory, Kolkata
• Central Drug Testing Laboratory, Mumbai
• Central Drug Testing Laboratory, Chennai
• Central Drug Laboratory, Kasauli
• Regional Drug Testing Laboratory, Guwahati
• Regional Drug Testing Laboratory, Chandigarh

These laboratories are responsible for the quality control of drugs and cosmetics in the country.

Functions of CDSCO (At the Center)

• Approval of new drugs and clinical trials.
• Import Registration and Licensing
• Licensing of Blood Banks, LVPs, Vaccines, r-DNA products, and some Medical devices and Diagnostic agents.
• Amendment to D&C Act and Rules.
• Participation in WHO GMP certification schemes.
• Banning of drugs and cosmetics.
• Grant to test license, personal license, NOC’s for export.
• Testing of drugs by Central Labs.
• Publication of Indian Pharmacopoeia.
• Monitoring adverse drug reactions.
• Guidance on Technical matters.

Function of State Licensing Authorities

• Licensing of drug testing laboratories.
• Approval of drug formulation for manufacture.
• Monitoring of quality of Drugs and cosmetics, manufactured by the respective state and those marketed in the state.
• Investigation and prosecution in respect of contravention in respect of contravention of legal provisions.
• Administrative actions.

– Pre- and post-licensing inspection.

– Recall of sub-standard drugs.

Responsibilities of Central Authority

• Approval of new Drugs.
• Clinical trials in the country.
• Laying down the standards for drugs.
• Control over the quality of imported drugs.
• Coordination of the activities of state drug control organizations.
• Providing expert advice with a view of bringing about uniformity in the enforcement of the Drugs and Cosmetics Act.

Responsibilities of State authority

• Manufacturing, sales, distribution of drugs licensing drug testing laboratories.
• Approving drug formulation for manufacture.
• Carrying pre and post-licensing inspection.
• Overseeing the manufacturing process for drugs manufactured by respective state units and those marketed in the state.

State Drugs Control Organisation

Drug Approval Process

Approval for New Drugs

New drugs are permitted to be marketed in the country in accordance with the permission granted by DCGI after ensuring that these drugs are

• Safe
• Effective
• Comply with the requirement of Schedule Y of the Drug and Cosmetic rules.

Applicants are required to provide technical data with respect to safety and efficacy before these can be permitted to be marketed in the country

The definition of the new drug also includes fixed-dose combinations to be marketed for the first time in India

Clinical Trials

• Schedule Y of the Drugs and Cosmetics Act explains the guidelines for granting permission for conducting clinical trials in India.
• The protocol for such trials is examined by the office of DCGI before permission is granted.
• The office of DCGI also grants permission for conducting bioequivalence studies.
• Registration of clinical trials has been made mandatory with the centralized clinical trial registry of ICMR with effect from 15th 2009.
• Drug and Cosmetic rules are being amended to make mandatory the registration of clinical research organizations.
• Drug and Cosmetic Act is proposed to be amended to include a separate chapter on clinical trials.

Drug Approval Process

When a company in India wants to manufacture/import a new drug it has to apply to seek permission from the licensing authority by filing Form 55 and also submitting the data as given in Schedule Y of the Drug and Cosmetics Act 1940 and Rules 1945.

New drug substance discovered in India – start from phase I to phase III should involve 500 patients, 10-15 centers.

New drug substances discovered in other countries – Phase I data needs to be submitted along with the application to the licensing authority.

Phase III should involve 100 patients, in 3-4 centres.

Clinical Trial Process

Schedule Y of the Drugs and Cosmetics Act explains the guidelines for granting permission for conducting clinical trials in India.

The protocol for such trials is examined by the office of DCGI before permission is granted.

The Office of DCGI also grants permission for conducting bioequivalence studies.

In March 2011, the CDSCO office constituted 12 new drug advisory committees (NDACs).

Presently these committees are named “Subject expert committees” (SECs).

Three Tier Process

Feb 2013, a three-tier process has been implemented, where each clinical trial application is being referred for review to the technical and apex committee.

Step 1. Review in SEC meeting (if approved moves to step 2)

Step 2. Review by technical Committee (if approved moves to step 3)

Step 3. Review by APEX Committee (if approved, final approval granted by DCGI)

Cosmetics

The cosmetics division, the central drug standard control organization is responsible.

For the import of cosmetics in India, the imported cosmetic products are required to be registered with CDSCO by giving application in form 42 to obtain registration certificate form 43.

The manufacturer himself/ the authorized agents of the manufacturer / the subsidiary of the manufacturer/ any other importer can be applicants for the issuance of a registration certificate for the import of cosmetics into India.

The license will be granted within 6 months.

Fees of 250$ to be paid.

The following licences are required for cosmetic product manufacturing and marketing in India according to the Drug and Cosmetic Act, of 1940

License on form 32 is issued for manufacture/sale distribution of cosmetic

License on form 32-A is issued for lone license manufacturing/sale distribution of cosmetics.

SLA will give a license to manufacture cosmetics.

Fee of 2500 to be paid

Medical Devices

On 17, October 2016 the Union Health Ministry of India published the new medical device rules draft, which will be effective from January 1, 2018.

The risk-based classification for medical devices ranges from

1. Class A low risk (thermometer, tongue depressor)
2. Class B low moderate risk (suction equipment, hypodermic needle)
3. Class C high moderate risk (ventilator, bone fixation plate)
4. Class D high-risk (heart valves, AICD)

SUGAM-Online licensing portal

An online licensing portal of CDSCO was implemented in Jan. 2016 and has been named SUGAM to file applications for various services like application submission, processing, and grant of permission for quick delivery of services.

RECALLS

The recall is an action taken to withdraw/ remove the drugs from distribution or use including corrective action for which deficiencies are reported in quality, efficacy, and safety.

Class I

Class II

Class III

Types of Recall

Voluntary Recall

Statutory Recall

Certificate of Pharmaceutical Product (COPP)

• The Central Drugs Standard Control Organization (CDSCO), which is the national drugs regulatory authority, regulates the import and export of drugs in the country, through the port offices located in different parts of the country.
• The certificate of pharmaceutical product (CPP or CoPP) is a certificate issued in the format recommended by the World Health Organization (WHO).
• The WHO GMP certificate is mandatory in most global markets for pharmaceutical companies to be able to sell medicines.
• The manufacturer of an exporting country must be licensed by the regulatory authority of that country and comply with the WHO GMP guidelines
• The application for grant of WHO GMP Certificate of Pharmaceutical Product shall be made to respective zonal/sub zonal officers as per the requirement.
• The COPP will be issued by zonal/sub-zonal officers on behalf of the Drugs Controller General (India) after inspection and satisfactory clearance by CDSCO officers as per WHO – GMP guidelines.
• It is valid for 3 years from the date of issue and companies can apply for renewal after that.
• The certificate of a pharmaceutical product (COPP) is issued under WHO GMP based on guidelines laid down by the health agency and is aimed at diminishing the risks inherent in pharmaceutical production.
• The certificate helps the regulator ensure that drugs are consistently produced and are quality controlled before they leave the country.

Documents required for applying for granting or revalidation of COPPs:

• Application form Manufacturer
• Site Master file (as specified under WHO TRS 823)
• Copy of Manufacturing License
• List of Approved Products
• List of products applied for issuance of COPPs
• List of SOPs and STPs
• Stability Data (3 batches) Accelerated / Real Time
• List of equipment and Instruments
• List of Technical staff, their qualification, experience, and approval status
• Manufacturing Layout Plan
• Process validation for 3 batches of each product
• Schematic diagram of Water system specifying circulation loop and MOC (Material of Construction)
• Schematic diagram of HVAC system specifying terminal filter configuration
• Export data of the last 2 years in case of revalidation
• Product Summary sheet

Procedure for accepting the application for Issue of COPP

• Applications forwarded before 01‐10‐2009 will be considered provided they should resubmit the application in the revised format with forwarding letter, notarized product summary sheet, and other documents that were not submitted earlier as per requirement on a first come first serve basis.
• All applications received will be scrutinized by CDSCO Officials after receipt and a query letter will be sent to the applicant, if any or otherwise will be considered for inspection.
• Inspection will be carried out by CDSCO Officers as per WHO GMP guidelines of TRS 823/908 for non-sterile products,  TRS  822/902  for  Sterile  Products, and other relevant guidelines in  TRS937, TRS 929, TRS 863, etc. as applicable from time to time.
• The self-appraisal checklist should be filled out and submitted to the CDSCO officer before the inspection.
• The inspection team verify the checklist at the time of inspection.
• Inspectors brief the inspection findings at the exit meeting
• The report should clearly define deficiencies as per WHO GMP guidelines.
• Respective Zonal/Sub‐Zonal certifying authority prepares a “Review Report” based on a review of observations of the checklist and written inspection report as per WHO GMP guidelines.
• The firm may reapply, if required after proper compliance after 5 months from the date of rejection
• If the same firm applies after 5 months, scrutiny of such application should be asked for earlier compliance with documentary pieces of evidence in addition to the usual general requirements for submission of application for issue of COPP

Indian Regulatory Requirements FAQ

What is the role of the Central Drugs Standard Control Organization (CDSCO) in India’s pharmaceutical regulatory framework?

The CDSCO is the central regulatory authority responsible for controlling and regulating pharmaceuticals in India. It oversees drug approvals, clinical trials, and post-marketing surveillance to ensure safety, efficacy, and quality.

What is the Drugs and Cosmetics Act, of 1940, and how does it relate to pharmaceutical regulations in India?

The Drugs and Cosmetics Act, of 1940, is a key piece of legislation that governs pharmaceutical regulations in India. It outlines the legal framework for the manufacture, sale, and distribution of drugs and cosmetics.

How are drugs registered in India, and what is the registration process like?

Drugs are registered in India by submitting applications to the CDSCO. The registration process involves providing data on a drug’s safety, efficacy, and quality, followed by a review by the CDSCO.

What is the approval process for new drugs in India, and who oversees it?

New drugs in India go through a rigorous approval process overseen by the CDSCO’s New Drug Advisory Committees. The process includes pre-clinical and clinical trials to evaluate safety and efficacy.

How are clinical trials regulated in India, and what safeguards are in place for patient safety?

Clinical trials in India are regulated by the CDSCO and Institutional Ethics Committees (IECs). They ensure that clinical trials adhere to ethical standards and prioritize patient safety.

India is known for its generics industry. What are the regulatory requirements for generic drug approval in India?

Generics in India must demonstrate bioequivalence with reference drugs and meet stringent quality standards to gain approval from the CDSCO.

What role do State Licensing Authorities play in India’s pharmaceutical regulatory framework?

State Licensing Authorities work in collaboration with the CDSCO to implement regulatory requirements at the state level. They grant licenses, inspect manufacturing facilities, and ensure compliance with regulations.

Why is it essential for pharmaceutical companies to understand and adhere to Indian regulatory requirements?

Understanding and adhering to Indian regulatory requirements is crucial for pharmaceutical companies operating in the Indian market. Compliance ensures product quality, safety, and efficacy, and it is necessary for market entry and patient safety.

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