The goal of an antimalarial treatment policy is to efficiently use available antimalarial medicines to maximize the reduction in mortality and morbidity due to malaria. The guiding principle of a rational antimalarial treatment policy is to provide safe, effective, good quality and affordable antimalarial medicines at the same time as promoting rational drug use to minimize development of antimalarial drug resistance.
As part of a global strategy to address the rapid development of resistance in malaria and enhance efficacy, WHO recommends that antimalarial medicines should always be used in combination, preferably with an artemisinin partner (artemisinin-based combination therapy - ACT)24. There are several challenges to be met in using these combination treatments. Currently, other than one fixed-dose artemisinin-based combination, the rest of the available combination treatments have to be taken as co-administered separate tablets. Another challenge to disease management is ensuring that patients adhere to the therapeutic dose combinations and to the full treatment schedules so that their use is optimal.
24 Antimalarial Drug Combination Therapy. Report of a WHO Technical Consultation, 4-5 April 2001. Geneva, WHO, 2001 (WHO document reference WHO/CDS/RBM/2001.35).
The concept of prepackaging treatment courses stratified by age or weight groupings has been a major contribution to enhancing rational drug use25. Prepackaging is defined as “blister packing of a course of treatment into a sealed primary packing of aluminium/PVC with individual doses in easily recognizable subunits”. This is of particular importance to malaria as significant proportions of disease treatment takes place without contact with a health worker. Even in the case of single medicines (monotherapies) which are still being used in some situations, evidence has shown that unit-dose packaging stratified by age or weight groups significantly improves adherence to treatment26. As more countries start adopting ACTs, these challenges call for greater attention to be paid to pre-packaging of antimalarial medicines.
25 Yeboah-Antwi. Impact of pre-packaging anti-malarial drugs on cost to patients and compliance with treatment. Bulletin of the World Health Organization, 2001, 79(5), 381-488.
26 Ansah E K, Gyapong J O, Agyepong I A, and Evans D B. Improving adherence to malaria treatment for children: the use of pre-packed chloroquine tablets vs. chloroquine syrup. Tropical Medicine and International Health, 2001, 6(7), 496-504.
Antimalarial combination medicines are relatively new products with which manufacturers, regulatory authorities and health care professionals have limited experience. It is also expected that as demand for ACTs increases, there will be a corresponding increase in multiple and generic sources of these medicines. An overview of existing antimalarial medicines shows an array of products with varying standards of packaging and consumer information provided in the inserts.
Below are the excepts from a report of WHO technical consultation on the recommended norms and standards for prepackaging antimalarial medicines held in Geneva, September 2003.
The two main components of packaging are lidding material and the forming film. The lidding material is made of a barrier layer (e.g. aluminium foil) and usually has a print primer on one side and a sealing agent on the other side that gets in contact with the dosage form. Whereas the forming film may be single film, coated or laminate. There are at present no standard procedures and machines to detect minimum quality of the aluminium foil and there are large variations on the foil quality. However, aluminium strip packaging remains the commonest one used but may not be suitable for all the products.
The quality of the packaged product is significantly improved when it is done with Polyvinyl Chloride (PVC) or Polyvinylidene Chloride (PVDC). It is also important to ensure that the forming film is leak proof and hence leak integrity must be tested and ensured. The following should also be taken in consideration in pre-packaging antimalarial medicines:
- Protection from light and moisture as appropriate for different products. Select packaging materials based on the nature of the product to be blistered, registration information and technical specification of supplier (i.e. select coloured PVC/PVDC foil in case of light and humidity sensitive antimalarial medicines).
- Compatibility of the packaging materials with the product to be packed.
- Ensure that there are no possible interactions of the material to be used and the dosage form.
- The design of the blister should be user friendly i.e. one treatment course per blister with easily identifiable dose subunit and it should function properly (performance) i.e. the product should be easily removal from the blister.
Minimal regulatory requirements
Pharmaceutical products must meet safety and quality standards consistently according to the required specifications. There must be a quality assurance system or program to ensure that all batches produced meet the required specifications. Licensing the manufacturing facility should be based on compliance with Good Manufacturing Practices(GMP)standards as part of quality assurance. The products should be well labelled as required by the regulatory authorities for proper identification and follow up.
Specifications for labelling, label inserts and information
Information on the product label and inserts has focused on satisfying the drug regulatory requirements and not on the consumer. There is need to keep the consumers in mind when designing the packs. It is therefore recommended to have two separate inserts - one for the prescribers and the other for the consumer. This is very important because a significant amount of antimalarial medicines are being sold over the counter(OTC). The following are the expected minimum contents for prepackaging any antimalarial medicines as course of treatment:
a) Blister pack, which is here called a Primary Pack
b) Mandatory regulatory information Package insert
c) Secondary pack, which is the pack that contains the blister packs
d) Consumer information insert and instruction/information prepared by qualified IEC personnel
All packaging should be labelled with the following minimum information:
Primary Pack (Blister Pack):
- Manufacturer's name of the product
- The generic name and strength of active ingredient
- Dosage instructions for the consumer
- The batch number, manufacturing and expiry dates (expiry date of combination pack should be that of component expiring earliest)
- Manufacturer identification
Mandatory regulatory information Package insert
It is recommended to follow the guidelines clearly outlined in the WHO Blue Book (WHO publication WHO/DMP/ RGS/98.5). These usually include the name of each active ingredient, indications of use of the product and name and address of the manufacturer.
Labelling of secondary packs are also recommended to follow WHO guidelines (WHO publication WHO/DMP/ RGS/98.5).
Consumer information insert
One of the main objectives of pre-packaging is to improve consumer compliance. To achieve this, local cultural issues and preferences need to be taken into account by ‘identifying with the customer’, so instructions should be developed from this perspective.
The consumer insert, which should be clear and simple, should not only inform but also educate through good communication. Good consumer inserts designed for interactive use inspire providers to explain well, and enhance understanding and adherence. This is to ensure that the consumers are able to use medicines in the pack correctly and are able to understand how medicines should be taken, the need for a full course, and implications for NOT taking a full course.
The following make up the recommended minimum information that should be part of the consumer information insert in factual and patient-friendly wording:
- Name of the medicine, dosage form, strength and pack size of the product.
- A clear indication for use of the medicine (e.g. “this is a drug for fever/malaria”).
- A clear description of the disease (e.g. “malaria is caused by mosquitoes that carry germs/parasites but is a curable disease”).
- It should advise on the need to treat early and complete the treatment course. (e.g. “the earlier you treat with right drug the better” and “the longer the parasite is in body, the higher the chance to kill” OR phrases like “The full treatment is needed to kill all the germs and parasites, if not, malaria will come back again”).
- The need to use the right dose for the right age or weight and ensuring that adequate treatment is received (e.g. “If the child vomits, give tablet to replace one which is lost”).
- Information on what to do if the situation becomes worse or does not improve (e.g. “If you become more sick during or after completion of treatment, see a trained health worker”).
- Information on the adverse effects, contra-indications, precautions and any appropriate warnings should be given.
In situations where the blister pack is in an individual box, it is recommended that the following information be included on the box:
- Identification as a malaria drug for specific age/size group (e.g. use of color, symbols like a mosquito, logo, portrayal of fever country context).
- Instructions on how to take the medicine stating clearly that the prepack is for use for a single malaria attack and all the medicine should be finished for complete cure.
- Mandatory Regulatory information (drug, batch number, expiry date etc.)
If the blister pack does not have its own individual box, then the information above should be on the blister pack itself.