Operational Guide for National Tuberculosis Control Programmes on the Introduction and Use of Fixed-Dose Combination Drugs: 4. ENSURING THE QUALITY OF FDC DRUGS: 4.1 Building a quality assurance system for the national TB programme: 4.1.1 Quality assurance where there is an operational drug regulatory authority

Operational Guide for National Tuberculosis Control Programmes on the Introduction and Use of Fixed-Dose Combination Drugs
(2002; 81 pages)

Table of Contents

ACKNOWLEDGEMENTS
LIST OF ACRONYMS AND ABBREVIATIONS
PREFACE
KEY POINTS
1. INTRODUCTION
	1.1 Aim and objectives
	1.2 What you can find in this guide
	1.3 Background and rationale
2. PROGRAMMATIC AND MANAGERIAL REQUIREMENTS FOR FDCS
	2.1 DOTS strategy
		2.1.1 Challenges in TB control
		2.1.2 Why switch to FDCs?
		2.1.3 FDCs and adverse effects
		2.1.4 Directly observed treatment and FDCs
	2.2 FDC formulations in the WHO Model List of Essential Medicines
	2.3 Treatment regimens using FDCs
	2.4 Justification for dosage forms and dosage schedules
3. FDC DRUG MANAGEMENT
	3.1 Product selection
	3.2 Procurement
		3.2.1 Quantification of drug needs
		3.2.2 Procurement methods and selection of suppliers
		3.2.3 Procurement and quality assurance
		3.2.4 Minimum product specifications, packaging and labelling requirements to be specified in the contract
	3.3 Distribution and storage
	3.4 Rational use of anti-TB medicines
	3.5 Drug problem reporting system
	3.6 Monitoring and evaluation
	3.7 Summary checklist for good anti-TB drug management
4. ENSURING THE QUALITY OF FDC DRUGS
	4.1 Building a quality assurance system for the national TB programme
		4.1.1 Quality assurance where there is an operational drug regulatory authority
		4.1.2 Quality assurance where there is no national drug regulatory authority or no operational drug registration system
	4.2 Bio-availability and bio-equivalence (interchangeability) data
	4.3 Laboratory testing
	4.4 The WHO Certification Scheme
	4.5 Facilitating the drug registration process
5. HOW TO INTRODUCE AND CHANGE OVER TO A REGIMEN WITH 4-DRUG FDCS/2-DRUG FDCS: PLANNING AND IMPLEMENTING A "SCENARIO"
	5.1 The challenge
	5.2 Planning
	5.3 The process
		5.3.1 Decision-making phase
		5.3.2 Preparation
		5.3.3 Initial implementation
		5.3.4 Full implementation
Annex 1. Glossary and use of terms
Annex 2. WHO Certification Scheme - Model Certificate of a Pharmaceutical Product¹
Annex 3. WHO Certification Scheme - Model Batch Certificate of a Pharmaceutical Product
Annex 4. Example of an order form for anti-TB drugs for treatment facilities
Annex 5. Steps in the quantification of anti-TB drugs using consumption-based information
Annex 6. Suggested reading
Request for feedback on the guide

4.1.1 Quality assurance where there is an operational drug regulatory authority

Where there is an operational DRA, the NTP has to follow the directives of the DRAand work closely with it. The programme has to procure and use only those FDC drugs approved by the DRA. In addition, the NTP has to:

• Request the supplier to submit a copy of the marketing authorization (certificate of registration) issued by the DRA to ensure that the product has been officially registered for use in the exporting country.

• Check with DRA if product is registered in your own country.

• Request the supplier to submit a WHO-type batch certificate (see Annex 3) issued by the manufacturer of the product. AWHO-type Batch Certificate differs from the normal certificate of analysis in that it also provides information on: 1) the specification of the product at the time of batch release and the results of full analysis on the batch in question; 2) whether the product has been registered in the country of manufacturer; 3) the product licence number (registration number); 4) the name and address of the product licence holder etc.

• Make a physical inspection on arrival of the shipment - to verify adherence to contract specifications and spot any gross deficiencies. Also, random samples may be taken from each batch for laboratory testing to confirm the quality of the batch.

• Conduct quality surveillance during distribution - quality surveillance should be carried out once the FDC drugs are in the distribution chain. This involves ensuring that personnel involved are qualified, that storage facilities and transport conditions are appropriate, and that drugs have not expired. If necessary, samples should be taken and tested to confirm that product quality has been maintained.

• Establish a product defects reporting system - a product defects reporting system should be developed for prescribers/health workers, dispensers, store managers, etc., to report suspected or confirmed quality defects. There should be established written procedures and forms for reporting defective FDC drugs. All reports must be carefully reviewed using laboratory testing as required, and the appropriate action taken, including product recalls. The national drug regulatory authority should be informed about the situation.

• Create a recall receiving system - there should be a system to recall defective FDC products from health facilities and distribution outlets promptly. There should be written procedures. Distribution records should be kept complete and up to date to permit an effective recall. Recalls should be initiated promptly. All health facilities and distribution outlets to which FDC drugs have been distributed should be informed promptly of any intention to recall. Recalled products should be kept in a separate place. The quantities recalled should be reconciled with the quantities distributed and a report prepared for submission to the DRA.