S.P. SHANITECHNICAL OFFICER (Drugs)

CENTRAL DRUGS STANDARD CONTROL ORGANIZATION(DIRECTORATE GENERAL OF HEALTH SERVICES)

MINISTRY OF HEALTH & FAMILY WELFARE,NEW DELHI

Structure of CDSCO

• DGHS

• DCG(I): NRA

• Zonal Offices: 4- DI

• Sub Zonal Offices: 3- DI

Surveillance of adverse event following immunization

( Regulatory Issues)

Definition of Drugs

• All medicines for internal or external use of human beings or animals and all substances intended to be used for or in the diagnosis, treatment, mitigation or prevention of any disease or disorder in human beings or animals, including preparations applied on human body for the purpose of repelling insects like mosquitoes.

• Including vaccines

Definition of Adverse Drug Reaction

• All reaction which is harmful and unintended and which occurs at doses normally used in man for the PROPHYLAXIS, diagnosis or treatment of disease or the modification of physiological function.

Types of Adverse Drug Reaction

- Fatal

- Life-threatening

- Results in persistent or significant disability, incapacity

- Results in or prolongs hospitalisation

- Congenital anomalies/birth defects

- Other: Medical judgment should be exercised in deciding

whether a reaction is serious in other situations. Important

adverse reactions that are not immediately life-threatening

or do not result in death or hospitalisation but may

jeopardise the patient should be considered as serious.

REGULATORY ISSUES

• Drugs & Cosmetics Acts and Rules thereunder

• Standards

• NCL/CDL

• Regulation of Vaccine

1. Administrative Issues

-Coordination

-Inspection/Investigation

-Approval by Central Govt.(CLAA)

-Logistics for sending samples

- Review of Quality Safety & Efficacy

-Suspension/Cancellation of License

DRUGS & COSMETICS ACT & RULES THEREUNDER

DRUGS & COSMETICS ACT & RULES THEREUNDER

2. Legal Issues- All vaccine is new drug ( Rule 122 E)

- Import of Vaccine is covered under Rule 122 A

- Manufacture of Vaccine is covered under Rule 122 B

- Registration/ Import License

- Manufacturing Permission is accorded in Form 28-D

- Testing of Vaccine is done at Statutory Lab CDL/NCL, Kasauli (Section-6 )

- Generation of PMS Data as a Post Licensure condition.

STANDARDS

• Indian Pharmacopoeia

• Recognition of other pharmacopoeia USP, EP, BP etc.

Approval of new vaccines

• Clinical trials as per GCP guidelines/Schedule ‘Y’

• Manufacturing facility inspected/verified

• Batch to batch testing

• PMS

• Involvement of expert bodies like NIB, NCL & ICMR, other experts

CDL is responsible for

Pre-release Certification

of Vaccine

in the Country

MAJOR PLAYER IN REPORTING ADVERSE EVENTS

• Patients

• Health Professionals

• Media

• Marketing Authorization Holders

• Manufacturers

• Local Health Authorities, Agencies

• NRA of Exporting Country

• WHO (World Health Organization)

COORDINATION ACTIVITIEWS AT THE LEVEL OF DCGI DURING REPORTING OF ADVERSE EVENTS

DCGI

Reporting of

Adverse Events

State Licensing Authority

Zonal Office

of CDSCO

STATE

EPI

CDL

Statutory

Action

Manufacturer

CASES REPORTED AT DCGIYear 2002 -2003- Death reported following immunization with DPT Vaccine , Batch No.

364 of Biological. E. Ltd., Hyderabad at Pimpri , Chinkwada Distt. Regulatory investigation was performed by Sub-Zonal office , Hyderabad. Death was not due to the faulty practice by the manufacturer.

- Death reported following immunization with DPT Vaccine of Serum Institute of India Ltd., Pune . Regulatory investigation was performed . Death was not due to the faulty practice by the manufacturer.

- Death reported following immunization with Measles Vaccine of Serum Institute of India Ltd. , Pune . Regulatory investigation was performed . Death was not due to the faulty practice by the manufacturer.

In all the cases , no causality analysis was reported to DCGI.

Year 2004- Death reported following immunization with imported Oral Polio

Vaccine of GSK, Belgium. The matter was referred back to Deptt. of Family Welfare for causality report.

• Year 2005– 5 cases of death – On investigation: Unrelated to vaccine– Other cases of minor AEFI: 14

MODUS OPERANDI ADOPTED AT THE TIME OF ADVERSE EVENTS

• Temporary suspension of Product

• Regulatory Investigation/Inspection

• CDL Testing

• Recall of batch: In case death linked with vaccine quality

• Statutory action proposed

• Review of quality

LIMITATIONS

• Inadequate sampling

• Cold Chain conditions

• Short expiry vaccine

• Delay in reporting

• Logistic problems in sending samples

• Inadequate information

SUGGESTIONS

• Time Frame for reporting different episodes of adverse events (Reference: National Child Vaccine Injury Act) e.g. In case of TT containing vaccine, anaphylaxis should be reported within 0-7 days and brachial neuritis within 0-28 days.

• Causality analysis be performed before statutory action is warranted

• Proper coordination and Faster Investigation• Instant reporting by CDL, Kasauli

Suggestions

• Validation of refrigerators for vaccine storage

• Telephone number of informer

• Recording of proper batch number of vaccine, diluents

• Prompt investigation/coordination