Poor quality of medicines undermines health care and is unfortunately quite common in many countries. Accepted quality standards for testing drugs are published in various pharmacopoeias, for example the US, British, European or International Pharmacopoeias. Quality criteria are purity, potency, uniformity of dosage form, bioavailability and stability. All these aspects of quality may be affected by the manufacturing process, packaging, storage and other factors. Poor quality may result in lack of therapeutic effect, and cause adverse or toxic reactions; these in turn may result in harm to patients (through prolonged or drug-induced illness), as well as waste of limited resources.
Product quality is ensured through adherence to a quality assurance system. Brief definitions are given below (MSH 1997, chapter 18 on ‘Quality Assurance for Drug Procurement’ and chapter 24 on ‘Drug Management for Health Facilities’; WHO 1999a).
• Quality assurance is the sum of the activities and responsibilities intended to ensure that medicines reaching patients are safe, effective and acceptable to the patient.
• Good manufacturing practices (GMP) are part of quality assurance and should ensure that products are consistently produced and controlled to the quality standards appropriate to their intended use and required by drug regulatory authorities.
• Quality control is the part of GMP where drug samples are tested against specific quality standards. Laboratory testing of drug samples is done by the manufacturer during the process of manufacture (resulting in a certificate of analysis for each batch). Testing may be carried out during the licensing process by the national drug regulatory authority. Testing may also be done by the purchaser (or DTC) after receipt of medicines. Noncompliant, poor-quality samples found at this stage may result from a variety of causes such as poor manufacture, storage or handling.
Inadequate quality of medicines not only undermines health care in general, through lack of therapeutic effect and increased adverse reactions, but also other aspects of medicines policy. For example, a DTC may be unable to implement a generic substitution policy because it cannot distinguish between good-quality and poor-quality generic products and therefore prescribers believe all these products to be of poor quality. Many bodies are involved in drug quality assurance - drug licensing authorities, regulatory bodies, enforcement authorities and inspectorates, drug procurement offices, pharmacies and prescribers (by reporting on non-effectiveness). DTCs can help to ensure drug quality through coordination of all the various actors within health facilities and liaison with manufacturers and drug regulatory bodies.
Efficient management of the hospital medicine system will help to ensure the availability of medicines of adequate quality as well as containing costs. The DTC should work closely with the hospital pharmacy to provide guidance and promote recommended principles in procurement, storage and distribution. Where there are no existing policies and guidelines on supply management, the DTC should initiate action and give advice to the pharmacy. Pharmacists are vital in ensuring good drug quality and supply management; they are also the partners of prescribers in ensuring that patients receive safe and effective drug therapy. However, in many developing countries, pharmacists often have rather low status. It is therefore important that the image and status of the pharmacy and the pharmacist be raised when human resource development is considered.
5.3.1 Role of the DTC in procurement
Procurement practices can have a significant bearing on drug quality. The DTC should ensure that the practices followed by the responsible department will ensure adequate drug quality. The DTC should not spend committee time and meetings in deciding order lists, nor should DTC members generally be on tender committees assessing bids to supply drugs. However, a DTC should monitor and ensure implementation of good procurement procedures. In some hospitals this may mean the DTC has to reassess and identify the limits of its role. The DTC must be represented in the preparation of the annual hospital budget, including review and allocation of the drug budget. Criteria for good procurement practices have been agreed by WHO, UNICEF, UNFPA and the World Bank (WHO/UNICEF/ UNFPA/WB 1999) and are summarized in box 5.1 in the context of hospital practices.
5.3.2 Role of the DTC in medicine distribution and storage
The quality of medicines can be adversely affected by poor storage and distribution. The DTC has a role in ensuring that the practices followed by the responsible department are consistent with those that ensure the highest possible drug quality. In some situations this may mean that the DTC must be able to assist the pharmacy in initiating and monitoring an adequate system for drug storage and distribution. Good storage and distribution practices are summarized in box 5.2.
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BOX 5.1 GOOD PROCUREMENT PRACTICES
Efficient transparent management
• Divide procurement functions and responsibilities (selection, quantification, product specification, pre-selection from suppliers and adjudication of tenders), among different offices, committees and individuals to ensure that no one individual is dealing with all activities and thus susceptible to undue external influences. The DTC should be responsible for selection and product specification, and the procurement department for the other functions.
• Follow explicit documented procedures for adjudicating tenders and awarding procurement contracts. The procurement department should do this and should regularly report to the DTC and senior management, and undergo external audit annually.
Drug selection and quantification
• Base procurement on the formulary list, using generic or International Nonproprietary Names (INN). The DTC should decide the formulary list and approve purchase of non-formulary drugs.
• Select formulary drugs carefully to ensure safety and efficacy. This includes choosing appropriate dosage forms, preparations and packaging and defining the specifications of the products to be purchased; for example, theophylline elixirs for children should not contain alcohol.
• Use the method of quantification best suited to the available data - morbidity method if morbidity data are available and standard treatment guidelines (STGs) are followed, or consumption method if there are no morbidity data and STGs are not followed. Adjustments may have to be made cautiously if there is not enough budget to procure all the medicines needed (see point below).
• Use VEN analysis (see section 6.2.3) to identify the most essential medicines, especially if there is insufficient budget to finance all medicine needs. The DTC should assist the procurement group to do this once each department has submitted the yearly quantification of medicine needs.
Financing and competition
• Buy in bulk if possible. DTCs of small hospitals can collaborate with other hospitals and recommend that bulk procurement be done jointly to get good value for money.
• Agree a regular procurement schedule and decide criteria for emergency purchase in circumstances where it is absolutely indispensable to prevent immediate danger to life.
• Purchase only from the supplier who holds the current contract as decided through the competitive tender adjudication process to ensure the lowest possible purchase price.
Supplier selection and quality assurance
• Procure only registered products from reliable, licensed suppliers and manufacturers that comply with GMP and have good records of performance, to ensure that medicines procured meet the required standard of quality. The qualification of suppliers can be checked through networking with the national drug regulatory body and other agencies, obtaining all appropriate certification and, if necessary, laboratory testing of received products. Some purchasers have negotiated with manufacturers to pay for quality testing at a laboratory of the purchaser’s choice. Suppliers who do not have permanent addresses or who are not prepared for visits to their premises without prior notice are unlikely to be reliable.
• Only accept medicines with the appropriate documentation, including:
- a certificate of analysis issued by the manufacturer (batch certificate)
- for imported medicines, a WHO-type certificates issued by the drug regulatory authorities of the exporting country
- detailed product specifications.
• Ensure quality through the inclusion of certain pre-tendering criteria, for example specifying a minimum shelf-life, or insisting manufacturers have a minimum turnover or proof of GMP compliance.
• Find out from various sources (such as regulatory bodies) whether a generic product is bioequivalent to the brand product. If it is not, efficacy can only be established by a clinical trial. If possible, ask the manufacturers to produce evidence of bioequivalence.
Adapted from WHO/UNICEF/UNFPA/WB (1999)
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5.3.3 Monitoring and analysing medicine quality problems
A very important role of the DTC is to monitor and analyse all reports of inadequate medicine quality. The problem may present in the following ways:
• visual deterioration of the product as reported by health staff, for example discolouration, fragmentation, leakage, smell
• lack of therapeutic effect
• ADRs.
Once a problem has been reported, it should be investigated (see section 5.4.3) to see if the problem is one of manufacture (including counterfeit), storage, distribution, administration or use. This may involve the following steps:
• Confirming the exact nature of the problem.
• Visually inspecting the product, including the expiry date, the packaging and the labelling.
• Eliciting information concerning the product’s procurement, storage and distribution.
• Observing how the product is administered, for example injection technique, dispensing process, interviewing the patient if necessary to check on compliance.
• Observing how the patient is managed. For example, when dealing with a complaint that a hypoglycaemic drug is not effective, one might do a patient chart audit to check (1) how the drug was being prescribed, and (2) what was the evidence about poor blood sugar control. A prescriber could not claim that a drug was ineffective if blood or urinary sugar was not monitored.
• Analysis of the product. A product may be analysed first using basic (less expensive) tests, which can screen out counterfeit medicines or those of very poor quality. If the product passes such a screen, but has been the subject of complaints about quality, it should be subjected to further full pharmacopoeial (more expensive) tests in a properly equipped laboratory. See annex 5.1 for basic tests.
• Reporting to the national regulatory authority drug products found to be of poor quality on receipt from the manufacturer or supplier.
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BOX 5.2 GOOD STORAGE AND DISTRIBUTION PRACTICES
• Documented drug distribution and control procedures are in place, for example
- procedures for inventory control and management
- minimum and maximum safety stock levels
- visual inspection of all medicines, their packaging and labelling, on arrival at the facility.
• Facilities/departments use pre-defined re-ordering quantities (or methods for calculating drug quantities) for drug orders from the store to avoid shortage and stock-outs.
• Storage conditions should be adequate to maintain the quality of the medicines and free from factors that can cause the deterioration of drug products:
- Appropriate medicines only are stocked in hospital patient care areas (VEN analysis important).
- Manufacturers’ storage instructions are followed; if no special instructions are given, use ‘normal storage conditions’ (temperature 15-25 ° C).
- Storage areas are clean and dry.
- Medicines are arranged either alphabetically or by therapeutic category.
- Repackaging is avoided wherever possible and done only by staff trained to do it; likewise, pre-packaged drugs for individual patients are prepared only by trained staff.
• The expiry date is one important assurance of drug quality. Drugs should be stored according to a first-expiry, first-out policy and there must be a mechanism to dispose of expired medicines. For medicines with the same expiry date, a first-in first-out policy should be followed.
• Narcotics and other controlled drugs should be stored in a separate area locked by two keys, each key controlled by a different person.
• Transport is speedy and conditions are sufficient to maintain medicine quality. In particular, cold-chain procedures should be documented and strictly enforced.
• Appropriate dispensing procedures are in place, for example containers, labelling, patient information and counselling.
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Quality problems are likely to be more serious in medicines that are inherently unstable or have a narrow therapeutic index (narrow range for effective serum levels). These medicines are listed in table 5.2. The same drug product produced by different manufacturers may have differences in bioavailability and therefore be non-bioequivalent. It is much harder to ensure bioequivalence between products where the drug has a narrow therapeutic index. An additional quality factor to consider in drug selection and management is the varying stability of different forms of oral medicines. Generally speaking, solid forms are more stable than liquid forms, especially in tropical or humid conditions. Syrups and injections that are in powder form are more stable than those in liquid form.
Decreasing stability of oral drugs: |
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tablets |
capsules |
suspensions |
syrups and solutions |
Table 5.2 Drugs with known potential bioavailability or stability problems
Bioavailability problems |
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Stability problems |
aminophylline |
furosemide |
nitrofurantoin |
acetylsalicylic acid tablets |
ampicillin |
glibenclamide |
oestrogens |
amoxycillin tablets |
carbamezepine |
glyceryl trinitrate |
phenytoin |
ampicillin tablets |
chloramphenicol |
griseofulvin |
prednisolone |
penicillin V tablets |
chloroquine |
hydrochlorthiazide |
quinidine |
retinol tablets |
chlorpromazine |
iron sulfate |
rifampicin |
paracetamol liquid |
digitoxin |
isosorbide dinitrate |
spironolactone |
penicillin V suspension |
dihydroergotamine |
levodopa |
theophylline |
ergometrine injection |
ergotamine |
methotrexate |
L-thyroxine |
methylergometrine injection |
erythromycin |
methyldopa |
warfarin |
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Source: Managing Drug Supply (MSH 1997), p.273.
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