Guidelines on Packaging for Pharmaceutical Products (WHO TRS 902)

In short: Packaging is part of the medicine, not an afterthought. The WHO guidelines on packaging for pharmaceutical products (Technical Report Series No. 902, Annex 9, 2002) say packaging must contain and protect the product, carry correct information, and not react with the product for the whole shelf life. This article summarises the guideline for packaging staff, QA officers and pharmacy students, and adds the packaging-line controls from EU and US GMP.

Why packaging matters

The summaries below follow the 2002 text. As of October 2026 the WHO publication page for TRS 902 Annex 9 lists it without any note that it has been replaced or revised.

A tablet or injection can meet every specification at release and still fail before it reaches the patient if the pack lets in moisture, light or oxygen, or if the pack itself releases chemicals into the product. The WHO guideline therefore treats packaging materials and systems as subject, in principle, to the same quality assurance requirements as the medicine itself, and points to the WHO GMP guidelines as the quality system to follow.

The guideline also warns that pharmacopoeial and ISO requirements for packaging are only general. Whether a pack is suitable for a particular product can only be shown by packaging and stability studies on that product. Where it quotes the international pharmacopoeia, it adds that precise quantitative standards depend partly on climate and have to be fixed locally.

What good packaging must do

According to the introductory note of the guideline, packaging must:

• protect the product from external influences such as moisture, light, oxygen and temperature changes;
• protect it from biological contamination and physical damage;
• carry the correct information and identification of the product.

The choice of pack and material should also be made so that the pack does not harm the product (through chemical reaction, leaching or absorption) and the product does not harm the pack (by changing its properties or weakening its protective function). These conditions must hold throughout the intended shelf life.

Aspects of packaging (WHO section 1)

General considerations (1.1)

The guideline defines packaging as the collection of components, such as bottle, vial, closure, cap, ampoule or blister, that surround the product from production until use. It lists the aspects to consider: functions of packaging, choice of material, testing of the chosen material, filling and assembling, sterilisation, and storage and stability.

It separates primary components, which touch the product (bottles, vials, closures, blisters), from secondary components, which do not (cartons, aluminium caps). The choice depends on the protection needed, compatibility with the contents, the filling method and cost, and, for over-the-counter products, presentation and ease of use. It also describes two special forms: unit-dose packaging, which helps reduce medication errors, and device packaging such as pre-filled syringes or droppers.

Containment and protection (1.2)

Containment is described as the most basic function. A pack should not leak or allow the product to diffuse or permeate through it, should be strong enough for normal handling, and should not be altered by the formulation inside.

Protection covers light, moisture, oxygen, biological contamination and mechanical damage. The guideline lists the ways primary packaging can interact with a product:

• release of chemicals from pack components;
• release of visible or sub-visible particles;
• absorption or adsorption of product components by the pack;
• chemical reaction between product and pack;
• degradation of pack components in contact with the product;
• effect of the manufacturing process, for example sterilisation, on the container.

It states that only real-time stability studies, covering a period equal to the intended shelf life with the product in its final pack, can show that a pack gives the required protection. Packaging materials should be stored according to GMP, and the pack may have to differ for refrigerated, tropical or light-sensitive products.

Presentation and information (1.3 to 1.6)

Labels and package inserts are the main source of information for the user. The guideline notes that labels should allow identification of each active ingredient by its INN, and that the batch number must allow a product to be traced from manufacture to the patient. After stability has been evaluated, the label can carry a storage statement such as normal storage, 2 to 8 °C without freezing, or freezer conditions.

It also deals with repacking and relabelling (stability data from the manufacturer no longer apply once a medicine is removed from its original pack), patient information leaflets, the role of packaging in patient compliance, tamper-evident and child-resistant designs, and the part packaging design can play in detecting counterfeits.

Packaging materials and closures (WHO section 2)

Closures (2.2) should be as inert as possible and give a complete seal. For parenteral products the usual system is a glass container, an elastomer closure and an aluminium cap. The guideline notes that unsuitable rubber closures are the most frequent cause of incompatibility between pack and drug, and that pharmacopoeial and ISO requirements for rubber closures are minimum requirements; suitability for a given product is shown through stability studies. Caps and overseals (2.2.2) hold the closure in place and give evidence of tampering. Section 2.2.3 covers tamper-evident and child-resistant closures.

Container terms used in the guideline

The glossary of the guideline defines the container types most often met on a packaging line:

The glossary also describes bags, gas cylinders, injection needles, syringes and single-dose containers, and defines “well-closed”, “tightly closed”, “hermetically closed” and light-resistant containers. Read the full glossary in the source document when you need exact wording.

Quality assurance and quality control (WHO section 3)

The guideline says packaging defects such as breakage, printing or ink problems, and errors on labels or inserts can lead to recalls. Packaging processes and equipment need validation or qualification like any other process. Quality control has to follow written procedures, and the guideline lists the basic requirements: trained staff and approved procedures for sampling, inspection and testing of packaging materials; samples taken by approved methods and people; validated test methods; and records of all sampling, inspection and testing, including deviations.

Specifications for packaging materials should state the nature, extent and frequency of routine tests. Typical tests are visual inspection, identification, dimensional, physical, chemical and microbiological tests (3.2.2). Section 3.3 covers self-inspection and supplier audits, and section 4 covers packaging waste and the environment.

Packaging instructions and the packaging line

The WHO text refers to GMP for the detailed packaging-line controls. For these, the current European Union GMP Guide is the clearest reference, and the same expectations appear in US regulations.

Packaging instructions

A revised EU GMP Chapter 4 (Documentation) was put out for stakeholder consultation from 7 July to 7 October 2025. As of October 2026 the EudraLex Volume 4 page still lists the January 2011 version as the current text, so the paragraph numbers below (4.11, 4.19, 4.21) refer to that version. Check them again once a revised chapter is adopted.

EU GMP Part I, Chapter 4 (Documentation, January 2011), paragraph 4.19, says approved packaging instructions should exist for each product, pack size and type. They should include, or refer to:

• the product name, including bulk and finished-product batch number;
• the pharmaceutical form and strength;
• the pack size in number, weight or volume;
• a complete list of packaging materials with quantities, sizes, types and code numbers of their specifications;
• where appropriate, an example of the printed packaging materials showing where the batch number and shelf-life information go;
• line-clearance checks and special precautions before operations begin;
• a description of the packaging operation and the equipment to be used;
• in-process controls with sampling instructions and limits.

Line clearance and line checks

EU GMP Chapter 5 requires the work area, packaging lines, printing machines and other equipment to be clean and free of previous products, materials and documents before packaging starts, using a checklist (paragraph 5.50). The product name and batch number should be shown at each line (5.51), and materials should be checked on delivery to the line for quantity, identity and conformity with the instructions (5.52). Printing of codes and expiry dates must be checked and recorded (5.55), and online checks should cover at least appearance, completeness of packs, correct materials, correct over-printing and line monitors (5.59). Samples taken from the line are not to be returned (5.59).

In the United States, 21 CFR 211.130 requires written procedures for packaging and labelling, physical or spatial separation from other products, checking of packaging and labelling materials before use, and an inspection of the area for line clearance, with results documented in the batch record. 21 CFR 211.134 requires a visual check of a representative sample of finished units for correct labelling, recorded in the batch records.

Reconciliation and batch packaging record

Under EU GMP 5.61, a significant or unusual difference found when reconciling bulk and printed materials against units produced must be investigated and explained before release. Unused batch-coded materials are destroyed and the destruction recorded (5.62). Paragraph 4.21 of Chapter 4 describes the batch packaging record, which includes operator initials, the equipment and lines used, specimens of printed materials where possible, notes on unusual events with authorised deviations, and the quantities issued, used, destroyed or returned.

Record retention: batch packaging records must be kept at least 1 year after the expiry date of the respective product batch (EU GMP Part I, Chapter 4, paragraph 4.11, which also asks for at least 5 years after certification by the Qualified Person where that is longer; 21 CFR 211.180(a)), and longer if local law or the marketing authorisation requires.

Frequently asked questions

What is the difference between primary and secondary packaging?

Primary packaging is in direct contact with the product, such as a bottle, vial, closure or blister. Secondary packaging is not, for example a carton or an aluminium cap. Primary packaging is the main concern for compatibility and stability.

Can a pharmacopoeia alone decide whether a pack is suitable?

No. The WHO guideline treats pharmacopoeial and ISO requirements as general or minimum. Suitability for a product is confirmed by packaging compatibility and real-time stability studies.

Why must labels carry the batch number?

So that a product can be traced from manufacture through distribution to the patient, and affected units can be located in a recall.

Is line clearance only a packaging-department task?

No. It is a documented GMP check before any operation. In packaging it is done against a checklist before a new batch starts and its result is recorded in the batch packaging record.

Related reading

• Good documentation practice for specifications, packaging materials and retention of documents
• Good documentation practices for BMR, BPR, processing and packaging instructions
• SOP for BMR and BPR review

References

1. World Health Organization. Guidelines on packaging for pharmaceutical products. WHO Technical Report Series, No. 902, 2002, Annex 9. who.int/publications/m/item/annex-9-trs-902.
2. European Commission. EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice, Part I, Chapter 4: Documentation (January 2011), paragraphs 4.11, 4.19 and 4.21.
3. European Commission. EudraLex Volume 4, Part I, Chapter 5: Production, paragraphs 5.49 to 5.62 (in operation since 1 March 2015), health.ec.europa.eu.
4. US FDA. 21 CFR 211.130 (Packaging and labeling operations), 21 CFR 211.134 (Drug product inspection) and 21 CFR 211.180(a) (General requirements for records), ecfr.gov.