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______________________________________________________________________________ Laboratoire National de Contrôle des Produits Pharmaceutiques Date: 13-14.05.2005 1/4

World Health Organization Public Inspection Report

(WHOPIR) This report is the property of the organization responsible for performing the inspection.

1. General information

Name of laboratory Laboratoire National de Contrôle des

Produits Pharmaceutiques (LNCPP)

Address Polyclinique 8 Mai 1945, Bouzaréah 16035 Alger Algeria

Postal address Direction Générale Polyclinique Ahmed Aroua, Rond point Sidi Yahia, 16035 Alger Algérie

Email lncpp@santé.dz

Telephone number + 213 (0) 21 48 18 89

Fax number + 213 (0) 21 60 54 96

Summary of activities Algerian national control laboratory for medical drugs and devices. World Health Organization Collaborating Centre for Drug Conformity (CECOMED)

Date of inspection 13 and 14 June 2005

Programme Prequalification Programme: Quality-Control Laboratories.

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______________________________________________________________________________ Laboratoire National de Contrôle des Produits Pharmaceutiques Date: 13-14.05.2005 2/4

2. Inspection summary An inspection was carried out - as part of the prequalification of quality control laboratories in Africa - in order to assess compliance with Good Practices for National Pharmaceutical Control Laboratories as recommended by WHO. At the time of the inspection, the laboratory was under the control of the Ministry of Health and Population and of Hospital Reform, and was responsible for the control of medical drugs and devices. The laboratory had three main areas of activity: - Control of drugs within the framework of the Registration process, subsequent to an

application for a marketing authorization (manufacture or import). An authorization was granted or refused after examination of the MA file. The feasibility of control methods was evaluated at this stage and the product was analysed at the time of an initial application, if the registration was effective.

- Technical and regulatory control of each batch of drugs marketed in Algeria, whether

imported or locally manufactured, may entail, if required, a complete or partial analysis of the proprietary drug. The Agency also awarded approval to all local manufacturing units and issued certificates of compliance for export.

- As part of checks, controls may be carried out on proprietary drugs which quality and

compliance with the MA file needed to be confirmed. LNCPP had two different sites in Algiers (the Directorate-General and Laboratory) as well as two other laboratories located at Oran and Constantine. These two sites were not inspected. The laboratory in Algiers had five technical units: Chemistry, Pharmaceutical Techniques, Biology, Pharmaco-Toxicology, and Medical Devices. The inspection mainly focused on the Chemistry and Pharmaceutical Technique units. The overall organization, system of quality assurance and the equipment were inspected and source data were examined in detail in respect of several chemical and pharmaceutical techniques applied more particularly to antituberculosis and anti-infective drugs, as well as the overall documentation and procedures. Accreditation of LNCPP under ISO standard 17025 was pending. The quality assurance system and documentation associated with it were operational and in compliance with Good Practices, and as described in a quality manual. However, the system required further development in order to cover all areas of activity. LNCPP did not carry out control of antiretrovirals. This was subcontracted to the university laboratory or carried out at the manufacturing sites, in collaboration with the manufacturers.

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______________________________________________________________________________ Laboratoire National de Contrôle des Produits Pharmaceutiques Date: 13-14.05.2005 3/4

The laboratory's various activities were performed by qualified and motivated staff. Activities were shared among several operational units, in conformity with an efficient organizational structure. Some items of equipment, such as the HPLC, were not new and were being replaced. Some items of equipment were calibrated annually by an outside agency (dissolution apparatus), while others (HPLC) were being incorporated into an annual calibration programme. The laboratory was capable of performing the following activities in respect of finished products: - Physico-chemical tests (disintegration time, dissolution, friability and hardness pending

calibration of the new apparatus), - UV spectrophotometry, - Infra-red spectrometry (apparatus out-of-order on the day of the inspection), - HPLC with UV, diode array and refraction index detection, - Gas chromatography, - Atomic absorption spectrometry, - Potentiometry (equipment out-of-order on the day of the inspection). 2.1. Quality Assurance The quality assurance system was being developed and lacked detail in certain areas, such as out of specification investigation (reports did not clearly identify the origin of the problems or the corrective measures needed). There were no references in the notebooks describing the preparation of the different solutions and reagents and records for the preparation of the different reagents and volumetric solutions were not available at the time of the inspection. 2.2. Documentation Documentation control required attention as this activity was not under the full control of a Quality Assurance system. 2.3. Equipment Certain items of equipment, in particular the HPLC were not calibrated annually by a certified outside agency. The control over HPLC columns required attention as no performance test was carried out on the columns at the beginning and end of each analysis to check their performance. HPLC chromatograms (as raw data) did not reflect integration parameters such as retention times, peak areas, number of theoretical plates. Balances had been calibrated using certified weights. However, these were unsuitable to their sensitivity. 2.4. Materials The reference standards used for assay and related impurities were not systematically calibrated by comparing to a primary reference substance.

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3. Conclusion From the inspection of the premises, the interviews with staff and the documentation reviewed, the Algerian National Pharmaceutical Products Control Laboratory (LNCPP) located at Algiers, Algeria was considered capable of operating in compliance with the Good Practices for National Pharmaceutical Control Laboratories recommended by WHO for analysis of finished products (with the exception of those for antiretrovirals, which were not performed) as listed below:

Type of analyses Finished products Pharmaceutical techniques Disintegration and dissolution of tablets and capsules

Hardness, friability, disintegration of suppositories: New equipment pending calibration.

Physical and chemical tests pH, volumetric titration, Atomic absorption. Identification Thin-layer chromatography, visible UV

spectrophotometry and HPLC (Infra-red spectrometer out of order)

Dosage, impurities and similar substances.

HPLC, UV detection - DAD and refraction index detection), Gas chromatography and visible UV spectrophotometry (Potentiometers out-of-order) Determination of impurities and similar substances by comparison with a reference substance.

The numbered observations (non-compliances with the guidelines) listed in the full inspection report were addressed by the laboratory and verified by WHO by evaluation of the response to the inspection report with supportive documentation on the corrective actions (planned and implemented). However, as the laboratory's activities and the Quality Assurance systems were changing and being developed; testing of starting materials was being organized and there were plans to move to more suitable premises, a further inspection to assess these changes was recommended.