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: 4.1.2 Quality assurance where there is no national drug regulatory authority or no operational drug registration system

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

4.1.2 Quality assurance where there is no national drug regulatory authority or no operational drug registration system

Where there is no DRA, or there is a DRA but no operational drug registration system, the responsibility to ensure that the FDC products used are manufactured in accordance with GMP requirements and that the products are safe, efficacious and of good quality, will be that of the national TB programme. To do this, the NTP has to create a QA system of its own. This will consist of recruiting a qualified pharmacist to be responsible for QA of procured drugs and for requesting from the supplier a WHO- type certificate issued in accordance with the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce, which provides licensure status of the product and inspection status of the manufacturer (see section 4.4). Two types of certificate are to be requested within the scheme⁹:

• A Certificate of a Pharmaceutical Product (product certificate) issued by the DRA in the exporting country. This certificate contains the name and dosage form of the product, the INN and amount of active ingredient(s) per unit dose, name and address of product holder and/or manufacturing facility, the product formula (complete composition including all excipients), and product information for health professionals and for the public as approved in the exporting country.

• A Batch Certificate of a Pharmaceutical Product to confirm that individual batches conform to quality and other specifications (normally issued by the manufacturer). This document is a vital instrument in drug procurement and usually a mandatory element of the tender document.

⁹ Further information: Marketing Authorization of Pharmaceutical Products with Special Reference to Multisource (Generic) Products. A Manual for a Drug Regulatory Authority. Geneva, World Health Organization, 1998 (Regulatory Support Series, No.5, WHO/DMP/RGS/98.5). Also available at URL: http://www.who.int/medicines/library/qsm/manual-on-marketing/multisource-contents.html

In addition to requesting the information above, the NTP QA officer should:

• Carry out physical inspections - post-shipment inspections - every time consignments arrive, to verify that the goods meet the specifications (i.e. compare the supplier's invoice with the original purchase order/contract).

• Conduct quality surveillance during distribution, e.g. make sure the drugs are appropriately stored.

• Establish a defects reporting system.

• Create a product recall system.

Where creating a QA system is not applicable, the NTP should procure anti-TB medicines from pre-qualified sources that guarantee quality, safety and efficacy of the products and comply with GMP. Wherever possible, the NTP and its qualified pharmacist should conduct a site inspection to ensure that the manufacturer complies with current GMP requirements. The WHO guidelines on GMP can be applied.