Name, dosage form and strength of the preparation ()

The name of the preparation is usually the title of the BPI. The name of the preparation normally includes the strength of the active substance. When the preparation contains more than one active substance, it may be decided to assign a specific name to the preparation. It may also be necessary to include the batch size (see below) in this title area where a variety of BPIs exist for a specific product formulation.

Batch Size ()

Subsequently, usually the batch size or batch range is mentioned. The latter means that the minimum and maximum batch size are defined, resulting in a more flexible BPI. The batch size can be specified as follows:

• Number (for suppositories, capsules);

• Weight (for ointments, creams);

• Volume (for oral solutions, lotions);

• Volume plus weight between brackets (for solutions with a density unequal to 1);

• Volume plus number of containers between brackets (e.g. eye drops).

Origin/reference ()

Also, it may be useful to refer to the origin of the formulation. This may be a formulary, a scientific publication, information from a manufacturer (e.g. about products that have been withdrawn from the market), or a reference to a proprietary formulation or one from a colleague. It may be useful to mention a version number or date of publication, to give a proper reference.

Authorisation and date of creation ()

The person responsible for the content and implementation of the BPI, usually the pharmacist, places his signature of approval initials to authorise the document. By authorising it, the BPI is released for use. An unauthorised BPI should never be used. Automated systems are normally equipped with a versioning option. In that case the pharmacist authorises the BPI in the computer. Only when this has been done, can the BPI be used for preparation. When the BPI is modified, the authorisation automatically expires and it cannot be used until the new version is authorised.

Together with the authorisation usually the date of creation or modification is mentioned. A version number on the BPI may serve the same purpose. In this way, it will be possible to check if the latest version is used. In automated systems, the system usually records the version number and date of modification automatically.

Batch number and Preparation date ()

A BPI normally leaves some blank space, where the batch number of the preparation and the date of its preparation can be noted during preparation. For a standard extemporaneous preparation the prescription number can be added for traceability. In order to limit the amount of text, the preparation date and batch number can be combined in one number. For example, when the date is mentioned as YYMMDD, an ascending numbering is obtained, which is simply traceable to the date. For larger scale production, an extended batch number is needed for distinguishing different preparations and to obtain a unique batch numbering. It is common to add a number to the date, for example in the form of: 141015-001, 141015-002, 141015-003, etc. Also it is possible to use an alphabetical coding of the months, starting with A for January, B for February and so on. For any system chosen, the important point is that the traceability of each batch is guaranteed.

Reference label ()

Normally, a BPI is provided with a reference label for the label to be used. On a paper BPI the reference label can be stuck directly, in an automated system the label data may be recorded in the master label template. All the relevant data for the preparation should be included on the master label, only variable data fields such as batch number and expiration date should be left blank. According to [2] the following information should be included on the label:

• Name, dosage form and strength of the preparation

• Full qualitative composition and the quantity of the active substance

• Batch number

• Expiry date

• Special storage conditions or handling precautions

• Directions for use, warnings and precautions

• Route of administration

See Sect. 37.​3.​2 for additional information on labelling for the patient.

It is useful to leave some space on the BPI where a copy of the label that will be used for the batch concerned can be attached. Ideally this should be next to the sample label.

Raw materials and packaging materials ()

Subsequently, the BPI provides a list of all active substances and excipients, in a way that defines their identity and quality unambiguously. For example, it should be clear if the free active substance has to be used or the salt form, or, when multiple hydrates exist, which hydrated form is required (see Sect. 23.​1).To define the quality of the raw materials it is advisable to use their pharmacopoeial names wherever possible. Preferably, additional specifications (Functional related characteristics, FRCs) which are not mentioned in the monograph that distinguish between different qualities, are added to the name of the raw material. Examples are the particle size of a solid material, the viscosity of a liquid or a cellulose derivative, or the concentration of a solution. Sometimes a brand name reflects the quality better (e.g. Witepsol H15 instead of Adeps solidus). If confusion may still be possible (crystal water, salt forms), addition of the chemical formula might be useful.

It is also important to include a description of the containers, including size and quantity and if necessary other quality characteristics. Raw materials and containers are mentioned in the same order in which the operator will use them. The reason for this is to help the operator record the batch numbers and signatures on the correct line of the BPR. In automated preparation systems, raw materials usually have to be used in the listed order. Their sequence may depend on the equipment used or the batch size.

The BPI should have space where the identity of the raw materials and packaging materials that have actually been used may be recorded, for example by their batch numbers. This may be done either manually or by an automated system with a barcode reader.

Quantity ()

For each raw material that should be weighed or measured, the needed quantity is listed on the BPI. Excipients which are required on more than one occasion during preparation, may be mentioned separately each time they are needed in the required amount. Also the quantities of the required packaging materials are listed, such as the number of suppository strips.

The quantities listed are given to the accuracy that they need to be measured (see Sect. 29.​1).

It is advisable to specify the balance to be used in the BPI. This ensures the use of a balance with sufficient accuracy for the weighing process.

All amounts are mentioned followed by their units, for example grams (g) or milliliters (mL). Weighing is to be preferred (see Sect. 29.​1.​2) but it may be simpler to work with volumes rather than weights. In that case adequate controls must be in place to ensure that the right volumes have been added. Generally weighing devices can give print-outs of weighings made but volume devices cannot.

Weighed/measured ()

The list of raw materials on the BPI is usually followed by spaces where the operator records the actual quantities which are weighed or measured, including the units. This may be done manually, but the use of an automated system coupled with an electronic balance provides a better opportunity to capture the weighed quantities. With a manual system there should still be a printed record of any weighings made.

Initials and control ()

There is generally space where the preparer can place his initials for each measurement or weighing. During preparation, for each raw material the label on the container is compared with the prescribed material on the BPI, then the source and the batch number are recorded, and the material is weighed or measured. The measured quantity is recorded, the raw material is processed and the preparer places his initials. On the BPI model (Fig. 33.2) a column is reserved for the initials of the operator, marked with the letter ‘O’.

There may also be space for the initials of a second employee, who checks during preparation each weighing or volume measurement. In automated system, the weights are controlled and printed automatically. The validation of the system is a prerequisite. Simple weighing systems cannot monitor the volumes measured, which requires a check by a second employee.

Whatever process is used, the measurements and checks must be verifiable. Obviously, a print out of the balance may be sufficient. It can be attached to the preparation record by the preparer, but it should be understood that this print out alone does not prove which material was weighed. It may be that a system such as barcode scanning needs to be used alongside it if the second check at the time of preparation is to be omitted.

Preparation method ()

The BPI has to provide a clear description of the preparation method, including in process controls and line clearances. All preparation operations are described step-by-step (as unit operations. To improve the readability each step best starts on a new line. If not, all unit operations may be marked separately, to make them easily recognisable. In any case, the essential points of the applied method of preparation, including all in process-controls as well as occupational safety aspects have to be listed.

Also precautions should be stated to prevent any hazards such as fire or damage by corrosive properties of substances.

Packaging process; ()

A description of the packaging process in a separate part of the preparation instruction may be added.

In-process controls ()

In process controls that the operator runs during production are mentioned separately on the BPI. In the BPI model a separate section is reserved for these in-process controls. When applicable these controls are described on the same line as the preparation step to which they apply. In that way the operator is instructed to perform the control immediately after this step. In the description of the preparation, the control moments can be emphasised by mentioning them as ‘check now …’ or ‘record now … “. This should encourage the operator to perform the control at that moment, and not at the end of the preparation. When working in a specific environment, such as laminar air flow (LAF) cabinet, the preparer cannot always interrupt his work to place his initials on a paper record as this would represent poor aseptic practice. In that particular case, a second employee may complete the BPR, and any required signatures can be completed at the end of the process. However, there are also LAF cabinets with built-in display, where the preparer can place his initials electronically.

Automated systems may have obligatory in-process controls, which require that the operator records a result before he is able to proceed to the next step. The nature and extent of the in-process controls are determined in conjunction with the controls on the raw materials before, and in conjunction with the release controls which will follow afterwards. Together these controls ensure the quality of the final product.

If the preparer has to perform a select sampling during preparation, for example to check the content distribution of capsules or suppositories, the sampling method should be described in the preparation text and not under the release controls of the final product. Also the weighings used for a weight control of capsules or suppositories should be mentioned in the preparation text and are part of the preparation process.

Equipment