Shelf life of preparations

This article sets out the guidelines for the shelf life and the limited useful life of medicines prepared in pharmacies. The shelf life and the limited useful life of compounded pharmaceuticals are no longer than 2 months. As with pharmaceutical compounding, a limited period of use of 2 months after opening also applies to officinal compounding. In addition, in order to determine the shelf life of officinal preparations, a distinction is made between formulas with known stability studies and formulas for which no stability data are available.

The pharmacist is legally obliged to state the expiry date on the label of the magistral and officinal preparations he produces. By expiry date we mean the date after which these preparations may no longer be used. This article attempts to provide an answer to the questions that regularly arise concerning the expiry date and the limited duration of use for medicines prepared in pharmacies.

First of all, we would like to clarify the terms 'shelf life' and 'limited period of use'.

The shelf life is the period between the execution of the preparation and its expiry date. This period only applies to intact, unopened, undamaged packaging and if the storage conditions have been complied with. After this date, degradation of the medicinal product is possible with a reduction of the therapeutic efficacy, or even the formation of toxic substances or substances that can lead to undesirable effects, as a result.

The limited period of use corresponds to the period from the first use until the time when the preparation is no longer allowed to be used. Once started, the shelf life of the preparation will be determined mainly by the risk of microbial contamination and not by the degradation of the active ingredient. The limited duration of use is an important notion for preparations with a low microbiological stability such as certain liquid or semi-solid preparations, in particular preparations containing little or no preservatives.
 

The shelf life of a preparation is determined by:

  • The expiry date of each component of the preparation: The expiry date of each component of the preparation must, of course, be a later date than the expiry date of the preparation, without this extending the expiry date of the preparation. If semi-finished products are used in officinal preparations, such as a ready to use shampoo base, it is best to use a new semi-finished packaging for each batch in order to guarantee the shelf life of the preparations in stock.

  • The stability and physico-chemical compatibility of the components. Unstable raw materials should not be used in the manufacture of officinal preparations. 1] The presence or absence of a preservative

  • The intrinsic stability of the preparation

  • Packaging: the shelf life of both opened and unopened preparations also depends on the choice of packaging. For example, packaging in tubes of dermal preparations significantly improves their microbiological stability and is recommended, especially for preparations without preservatives.

  • Storage conditions

The recommended hygiene measures during manufacture and packaging are also very important to ensure the microbial stability of the preparation in the best possible way.

In Belgium, the Therapeutic Magistral Formulary (TMF), published by the Federal Agency for Medicines and Health Products, is the reference work for magistral preparations. In accordance with the Royal Decree of 21 January 2009 on instructions for pharmacists, the TMF must be present in all pharmacies. The formulas in the TMF have been selected on the basis of their therapeutic efficacy and have been studied in the various pharmaceutical laboratories of the Belgian universities in the field of galenics and stability. The expiry dates mentioned in the monographs of the TMF indicate that it can be expected that the preparation in question will maintain its concentration and activity for a period of time at least equal to the indicated duration, if the preparation is stored under the prescribed conditions.

All preparations must contain not less than 90 % and not more than 110 % of the declared amount of active ingredient1. These limits take into account normal analytical errors, the acceptable variations inherent in the preparation and a certain degree of degradation that is still acceptable.

PHARMACEUTICAL PREPARATIONS

Any medicinal product prepared in a pharmacy according to a prescription for a particular patient is a pharmaceutical preparation. It is therefore by definition an 'ex tempore' preparation. The shelf life and the limited duration of use of magistral preparations will not exceed 2 months, mainly due to microbiological aspects. Since magistral preparations are generally intended for immediate use by the patient for whom they were prescribed, this period of 2 months is reasonable in order to guarantee the patient the use of a preparation of optimum quality for the entire duration of the treatment. Water-based preparations that do not contain any preservatives (aqueous solutions, creams and hydrogels) only have a maximum shelf life of 1 week.

OFFICINAL PREPARATIONS

For official preparations, the situation is slightly different. Official preparations are medicines that are prepared in the pharmacy in accordance with the instructions of a pharmacopoeia or the Therapeutic Magistral Formulary and that are intended for direct delivery to patients of this pharmacy. These preparations are generally made in larger batches and kept in the officina pending their delivery.

As with magistral preparations, officinal preparations also have a limited period of use of 2 months after opening. In order to determine the shelf life of officinal preparations, a distinction is made between preparations whose stability has been studied and described in the literature (TMF, Pharmacopoeias, formularia, etc.), the so-called 'validated formulas' and the non-validated forum modules, i.e. preparations of which the stability has not been studied. For validated formulas, the shelf life mentioned in the reference work is adopted. For the 'non-validated' formulas, the maximum shelf life is described in table 1. These expiry dates for the various galenic forms are indicative. The data in the third column have been taken from the reference book 'Prescription' (ref. 5), which states that for non-validated preparations with uncertain chemical, physical and/or microbiological stability, the shelf life for dry dosage forms is a maximum of 6 months; for liquid and semi-solid preparations with preservatives, this maximum is one month. The data in column 4 taken from an article by Prof. R. Kinget (ref. 1) assume that

  • the active substance(s) is (are) stable and, where necessary, particular attention has been paid to optimising the stability

  • the choice of formulation has a solid basis, which may have been taken from a recognised formularium (FN, FMS, FM3, KAVA - formularium, ...)

  • the hygiene rules were scrupulously complied with before and during preparation

  • the preparation rules were strictly adhered to.

 

In order to optimise the stocks of official preparations, it is best to take into account the shelf life when determining the size of the batch to be manufactured.

As a reminder, the statutory information on the labelling of magistral preparations is compulsory:

  • Name, address and telephone number of the pharmacy;

  • Surname and first name of the pharmacist-owner;

  • Surname and first name of the prescriber;

  • Surname and first name of the patient;

  • Sequence number indicated on the regulation;

  • Quantitative and qualitative composition of the active ingredients (unless otherwise specified by the prescriber);

  • Date of preparation;

  • Posology and preparation instructions;

  • Expiry date and special storage conditions;

  • Limited service life;

  • Labels n° 1 or 2;

  • Preservative.

  • The labelling of the official preparation must include the following information:

  • Name, address and telephone number of the pharmacy;

  • Surname and first name of the pharmacist-owner;

  • Quantitative and qualitative composition of the active ingredients;

  • Date of preparation;

  • Instructions for use of the preparation;

  • Expiry date;

  • Preset values;

  • Limited service life;

  • Preservative.

For the patient's convenience, it is recommended that the limited useful life of the preparation supplied be noted on the packaging at the time of delivery. The patient should also be made aware of the storage conditions of the preparation and the hygiene requirements necessary for the use of certain galenic forms.

NOTE

1. For a number of preparations containing unstable active ingredients such as erythormycin and dithranol, extended limits were set.

REFERENTIES

  1. Kinget R., Storage and use periods for medicinal products prepared in pharmacies. Antwerps Farmaceutisch Tijdschrift, 01 / 07 : 33 - 35.

  2. Royal Decree of 21 January 2009 on education for pharmacists.

  3. Federal Agency for Medicines and Health Products, Therapeutic Magistral Formulary, 1st edition, 2003.

  4. Federal Agency for Medicines and Health Products, Therapeutic Magistracy Formulary, 2nd edition, still to be published.

  5. Bolhuis G.K., Cox H.L.M., Zuidema J., Receptacles. KNMP, The Hague, 1st edition, 1992.

  6. Anonymous, Don't worry (too) about the expiration date. Pharmaceutisch Weekblad, 20 December 2002, 137, nr 51 / 52 : 1830.

  7. Joosten T., retention periods, storage life and expiry dates. Pharmaceutisch Weekblad, 16 December 2005, nr 50 : 1610.

  8. Centre Régional d'Information sur la Mediciamente - Rennes, Dates limits on the use of medicines. Bulletin of information on medicines and pharmacovigilance, November - December 1998, n°80.

  9. Deplazes, Gloor, Möll, Panizzon, Directives concerning the conservation of magistral preparations. 2006. [Internet]. Geraadpleegd op 6 januari op www.magistralrezepturen.ch/pdf/pdf_f/7_1_2_3_F.pdf.

AUTEUR:

Apr. Nathalie Duquet
Service Wetenschappelijke projects
CDSP - CWOA - APB

duquet.nathalie@mail.apb.be

Approved from the pharmaceutical journal for Belgium, 2010 nr. 1