Quality Assurance
Presentation given by Trlis Eriksen,
WHO Representative, Western Pacific Region
Introduction
I would like to begin by introducing the region I represent. It consists of 35 countries and contains very big variations. From large China with 1.2 billion people down to small Pacific Island countries with only a few thousand people, there are tremendous differences in the health needs of these countries.
The objectives of the pharmaceutical programs of the Western Pacific Region of WHO are:
to ensure, in collaboration with Member States, the continuous supply of drugs and vaccines of acceptable quality and affordable price to the populations by rationalizing the system for selection, procurement, and distribution of drugs and vaccines, as well as by strengthening national capacities for drug and vaccine production and manpower support;
to support Member States in the establishment and implementation of effective national programs for monitoring and maintaining the quality, safety, and efficacy of pharmaceutical products.
Components of Quality Assurance
My presentation here today is on quality assurance (QA). I think we can't talk about drug supply and procurement without putting some emphasis on quality assurance. I'll introduce the topic by giving a few definitions, which are mainly designed for pharmaceutical manufacturers but I think the principles can be applied to the drug supply system as well:
Quality assurance, from the industry point of view, is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use.
Good manufacturing practices for pharmaceutical products (GMP) is that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.
Quality control (QC) is an integral part of GMP, concerned with:
* sampling,
* specification,
* testing,,
* organization,
* documentation,
* release procedures.
The Drug Supply System
Now let's take a look at the drug supply system, itself, and try to identify certain quality assurance activities along the line of supply (see Chart). On one side, we have the manufacture of drugs, drug selection, registration, procurement, storage, distribution and use. On the other side, we have quality assurance activities to ensure products of acceptable quality, safety and efficacy.
Chart. Quality Assurance and the Drug Supply System
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Drug Legislation
A prerequisite for being able to implement these activities is drugs legislation, which should cover the following areas:
* products, activities and personnel;
* the regulatory authority;
* product registration/licensing;
* manufacture, import and export;
* procurement, storage, distribution and sale;
* information, which should include nomenclature, labeling, advertising and promotion;
* enforcement;
* and patents, drug pricing, clinical trials, post-marketing surveillance, monitoring and evaluation.
To be able to enforce legislation, there must be a drugs regulatory authority, whose main duties should be:
Drug Registration (including evaluation of clinical, pharmacological, chemical, pharmaceutical, and toxicological documentation). Some countries don't have the sufficient manpower or infrastructure to do this, but registration should at least be based on the existence of WHO certificates for the products intended for the market. Also, compliance with GMP must be checked at this stage.
Inspection. This is actually ensuring compliance to GMP of local manufacturers, and compliance with other requirements for drug importers, distributors, wholesalers and retail pharmacies.
Quality Control. The ideal thing is to test the drugs before they are actually purchased. This can be done by testing tender samples. It can be done during evaluation during registration or even on samples taken from the market as post-registration testing.
Drug Information Exchange. For countries which don't have sufficient manpower or expertise, I think this is a very important issue because information can be drawn from other countries which have developed proper systems for drug registration. I would like to mention ASEAN, whose pharmaceutical projects include drug information exchange as one important element. This may also be extended into bi-regional technical cooperation between countries in two different areas.
WHO has developed some guiding principles for small national drug regulatory authorities. Their objective should be to provide an overall quality assurance system, which should include a reliable system for manufacturing operations in conformity with accepted norms, a reliable system of licensing of manufacturers and distributors products, official inspection throughout the distribution chain, and official analysis of pharmaceutical products.
WHO Certification Scheme
I mentioned that for countries without necessary manpower and expertise to do drug registration in the ideal way, at least the WHO certification scheme should be implemented. The provisions and objectives of the scheme are to attest to the competent authority of another participating Member State such that:
* a specific product is authorized to be placed on the market within its jurisdiction, or if it is not so authorized, the reason why that authorization has not been accorded should be specified;
* the plant in which the product is produced is subject to inspection at suitable intervals to establish that the manufacturer conforms to GMP as recommended by WHO ant the certifying country;
* and all submitted product information, including labeling, is currently authorized in the country of origin.
Licensing
Licensing of pharmaceutical activities is another important quality assurance aspect. We have already covered manufacturers, but also importers, wholesalers, pharmacies, and other retailers should be licensed by an inspectorate after inspection.
Drug Registration
I just want to list in brief requirements for drug registration. Again, I must say I realize that it is not possible for some countries to do all these activities without the necessary expertise, but I think it's important to put up requirements to suppliers and to manufacturers even though you will not be able to evaluate all the documentation you will see, because the fact that you actually have requirements is an important signal to manufacturers. But anyway, these are the things that ideally should be evaluated during drug registration (see inset). I would highlight maybe stability studies to support claimed shelf life. Also, it is quite important that availability or equivalent studies is documented.
Quality Testing
Quality testing is another topic. Ideally, it should be, in my opinion, done before a drug enters a market, or even before on order has been placed. But I realize that countries have not the capacity to undertake this. However, there are some basic tests introduced by WHO which can be used for a rapid screening for identification. There is an increasing problem all over the world of counterfeiting drugs, and these basic tests quickly disclose counterfeits.
To maintain the quality of drugs of course they have to be stored as recommended by the manufacturer. Sometimes, However, we see some problems with the definition of storage temperature if the temperature range is not specified on the label. I think that this is something that those who procure drugs should specify to the manufacturer that the actual temperature range should be specified.
Distribution
The first-in, first-out principle should be applied and correct quantities should be distributed. Prevention of excess heat, sunlight, and even freezing are important things to consider. I think that people who have gone to rural areas in various countries are sometimes surprised to see either nothing in the stores or excess stock which is just deteriorating.
Monitoring
Here, I am referring to the monitoring of products already on the market. The objective is to establish if the claimed properties are maintained during shelf life. This can be done either by random sampling of drugs from the market, or I thing the better way to do it is to prepare a sample plan based on certain criteria (like stability, the drugs we spend most money on, and maybe also drugs with availability problems) and try to sample those drugs to see if the quality is maintained during shelf life.
Rational Use of Drugs
Mrs. Helling-Borda talked about the rational use of drugs. I think that is also part of quality assurance because it has to do with the quality of the service pr7ovided to the patient, and the correct drug has to be prescribed in the appropriate quantities and the patient has to be informed how to use the drug correctly.
Conclusion
To conclude this speech, I would like to present a slightly modified definition of quality assurance. It is the total arrangements made with the objective of supplying pharmaceutical products, including information of their ration use, of acceptable quality, price, safety, efficacy, incorrect quantity, to all when needed. Thank you.
