Handling quality defects of medicines

A quality defect in a medicinal product can result in harm of patient or insufficient  treatment. If a quality defect is identified, it may be crucial to halt further sales and, if necessary, notify the health or veterinary services and patients. It may also be necessary to weigh the benefits of the medicinal product against the risks of using a product with a quality defect and, in some cases, accept that the medicinal product remains on the market despite the defect.

Examples of quality defects include errors with the medicinal product itself, deviations from the approved Marketing Authorisation (MA), such as deviations from specifications,  the manufacturer of the active pharmaceutical ingredient (API) or the medicinal product fail to fulfil the Good Manufacturing Practice (GMP) requirements , incorrect labelling, damage to packaging, or dosing equipment that could affect the use of the medicinal product.

Definitions

Quality Defect: All batches of finished medicinal products released by the Qualified Person (QP) where the quality of the medicinal products is found not to comply with the marketing authorisation. For medicinal products without a marketing authorisation in Norway but marketed under compassionate use named patient, it means the products do not meet the expected quality, including failure to meet the manufacturer's specifications.

Recall: All batches of finished medicinal products released by the QP, regardless of storage location, which are made unavailable to the market either temporarily or permanently. This includes placing the product in quarantine and possibly returning it to the MA holder, wholesaler, or manufacturer.

Reporting Obligation to the Norwegian Medical Products Agency (NOMA)

NOMA must be informed about notifications exchanged between parties in the medicinal product distribution chain regarding matters, observed or suspected, that may result in a recall or otherwise represent a quality defect that could pose a risk or disadvantage to the end user of a medicinal product. NOMA also requires a brief explanation of the causes of the observed problem, to the extent that the cause is known or presumed.

Reporting to NOMA should be in writing, possibly supplemented by other forms of contact if the situation warrants it.

The term "medicinal product distribution chain" includes actions following the manufacturer’s release of the medicinal product for sale (Qualified Person release) up to the point the medicinal product is dispensed to the end user.

The reporting obligation for quality defects does not include issues related to the pharmacological or toxicological properties of the active ingredient or the medicinal product; the requirement to report quality defects is not intended to cover adverse event reporting or lack of efficacy for most medicinal products ("safety" and "efficacy"). See more information about adverse event reporting.

Management and reporting related to observed lack of effect of a medicinal product are described in GVP module VI.

Those importing medicinal products to Norway, often the responsible MA holder, must have a system for receiving quality defect reports from both domestic and international sources. For reports that could affect medicinal products on the Norwegian market or impact the supply situation in Norway, NOMA shall be informed.

Wholesalers and pharmacies suspecting a quality defect in a medicinal product (with the limitations described above) must contact the MA holder and NOMA. If the product is marketed under  compassionate use named patient , the supplier of the medicinal product and NOMA should be contacted.

Norwegian manufacturers who become aware of a quality defect in one of their medicinal products (including API and intermediates) must ensure that NOMA is informed, regardless of whether the medicinal product is intended for the Norwegian or foreign market.

Contact information

For urgent quality defect cases that need to be reported outside of NOMA's opening hours, call +47 992 89 679 (Director of NOMA).

During NOMA’s opening hours, use the switchboard number+47 22 89 77 00, which will transfer you to the on-duty case handler. Written information must also be provided even if contact is made by phone.

In all cases mentioned above, reports should be sent to: rapidalert@noma.no.

Reporting Procedures

The MA holder is responsible for informing all their customers if one or more batches of medicinal products are to be recalled. If it is deemed necessary for the recall to include pharmacies, the MA holder is responsible for ensuring that this occurs.

If a wholesaler is notified by the MA holder, manufacturer, another wholesaler, or authorities that a batch of medicinal products is to be recalled, the wholesaler must immediately place the medicinal products in quarantine and inform other wholesalers to whom they have sold the medicinal products, ensuring that the recall notification has reached the buyer. If it is deemed necessary for the recall to include pharmacies, the wholesaler must ensure that the recall notification reaches pharmacies and other retailers to whom they have sold the medicinal products.

Quality defects deemed serious enough to warrant notifying patients via mass media should be initiated by the MA holder in consultation with NOMA.

The notification to affected customers should include:

• Product number
• Trade name
• Dosage form
• Strength
• Batch number
• Batch size
• Description of the quality defect
• How and where the defect was discovered
• Consequences/risks
• Classification of the quality defect
• The extent of the recall - which levels in the distribution chain should be involved

The notification should be designed so that the recipient can forward it in its entirety to their customers (pharmacy/retailer) if necessary, to avoid delays. The notification should be clearly marked "Kvalitetssvikt" (Quality Defect). NOMA shall receive a copy of all notifications about the recall of medicinal products.

In Norway, further notification to pharmacies is usually handled by the three major pharmaceutical wholesalers through agreements with the company responsible for the import of the medicinal product.

Companies that distribute medicinal products to pharmacies directly, without involving the three major wholesalers or without having an agreement with them for recall from pharmacies , must ensure they have their own system for notification and recall. The same applies to companies selling medicinal products  outside pharmacies, LUA- outlets

MA holders and manufacturers must inform NOMA by email about quality defects preferably before or at least simultaneously with the information sent to relevant wholesalers.

MA holders and manufacturers for centrally authorised medicinal products within the EU, where quality defects shall also be reported to the European Medicines Agency (EMA), may use the same form when informing NOMA.

Manufacturers are responsible for ensuring that all their customers receive notification if there is a quality defect in the delivered medicinal products. The manufacturer must ensure that authorities in the countries where the medicinal products are intended to be marketed are informed.

NOMA shall receive a copy of any notification about initiating a recall.

In all cases mentioned above, reports should be sent to: rapidalert@noma.no .

Report Form (in Norwegian only)

Follow-Up on Quality Defects and Recalls

If the medicinal product is recalled as described above, NOMA shall within one month  receive a report from the MA holder/manufacturer/wholesaler about the causes of the quality defect and what preventive and corrective actions the notifier has planned or implemented to prevent recurrence.

The report should also include an reconciliation  of the recalled products .

NOMA’s Role

NOMA ensures that necessary measures to stop the sale, etc., are implemented and assists when it is relevant to notify the public through the media. If necessary, NOMA may enforce a recall.

Requirements for internal procedures at wholesalers and MA holders, including classification of quality defects

The wholesaler must handle all reports of suspected or confirmed quality defects affecting medicinal products the wholesaler has imported to Norway. This applies regardless of whether the medicinal product has a marketing authorisation or not. Reports may come from manufacturers, other wholesalers, patients, doctors, NOMA, or others reporting suspected or confirmed quality defects to the wholesaler.

The reports should be handled by a person designated by the wholesaler’s management. The responsibility should be set out in a job description, and the individual should have a regular deputy, ensuring that there is always (24/7) someone at the wholesaler to handle reports of suspected or confirmed quality defects. A written procedure for registering and handling reports of suspected or confirmed quality defects in medicinal products should be established. Reports should be forwarded to the manufacturer/MA holder. If necessary, additional information should be obtained from the complainant regarding the background of the report.

Guidance for MA holders/manufacturers/wholesalers on classifying quality defects:

Batch-Specific Variations

In some exceptional cases, it may be necessary and desirable for the MA holder to apply for batch-specific variations when produced, non-QP-released individual batches deviate from the approved MA application, for example, due to production problems and it is desirable to keep the product on the marked.

Reporting of other deviations

The following deviations must also be reported to NOMA via rapidalert@noma.no:

• Quality defects in pharmacy-compounded medicinal products must always be reported directly to the NOMA; see guidance for deviations in pharmacy manufacturing (in Norwegian only).
• Information about suspected and confirmed falsified  medicinal products on the Norwegian market or manufactured by a Norwegian manufacturer intended for other markets.
• Information about medicinal products stolen during transport, burglary, or robbery from wholesalers, MA holders, or manufacturers.
• Significant losses of narcotics from wholesalers, MA holders, and manufacturers in accordance with § 15 of the Narcotics Regulation.

NOMA participates in an international cooperation where authorities mutually have the responsibility to notify each other of situations where there is a risk of reintroducing medicinal products with unknown history, such as stolen medicinal products reintroduced back into the legal distribution chain. Such products are by definition referred to as falsified medicines.

European cooperation

As part of the EEA cooperation, Norway has the same obligations as EU countries to notify each other of quality defects in medicinal products. A serious quality defect discovered in another EEA country will therefore quickly be communicated to NOMA and vice versa. Such notification systems have been established for various product groups within the EEA area due to the principle of free movement of goods. The notification system for medicinal products also includes countries outside the EEA (PIC/S and countries with an MRA agreement).

Mock recall

NOMA expects the recall procedure to be verified annually.

The test should, at a minimum, include the following:

• Review of the internal procedure/SOP
• Review of NOMA's information on measures to take in case of quality defects in medicinal products
• Check that internal communication procedures provide the desired response
• Check that the contact information for external partners is up-to-date and functional
• Check that in a hypothetical recall scenario, all affected products and/or batches can be traced

A report with conclusions that includes  necessary changes or proposals for improvements should be prepared.

After having checked NOMA's contact information on this website , it is not necessary to verify contact details by calling the provided phone number or email address. Neither calls nor emails should be sent to NOMA  due to the mock recall .

The report from the mock recall must be archived by the company and must be available during inspection.

Reports from patients, doctors, veterinarians, or other healthcare professionals

If a patient, doctor, veterinarian, or other healthcare professional discovers a defect or deviation in a medicinal product, it may be useful to know how to file a complaint about the product. The first point of contact should be the nearest pharmacy or store where the product was purchased, as they are obligated to receive  the complaint.

Examples of defects that may lead to a complaint:

• Damaged medicinal product (e.g., broken tablets, capsules with holes, etc.)
• Incorrect appearance, colour, smell, taste, or consistency of the medicinal product
• Breached inner packaging
• Precipitate in a liquid medicinal product
• Defects in technical components (e.g., syringe nozzles, syringes, applicators)
• Incorrect text on packaging or package leaflet

Stores selling certain medicinal products outside pharmacies (LUA) must keep a record of complaints regarding medicinal products they have sold. Complaints must be investigated, and potential defects and quality issues must be reported to the MA holder, wholesaler,  or manufacturer.

Pharmacies must keep a record of complaints regarding medicinal products dispensed by the pharmacy. Complaints must be investigated, and in case of defects or quality issues, a report must be sent to the medicinal product's MA holder or manufacturer.

As a patient, doctor, veterinarian, or other healthcare professional, one can also contact the MA holder  directly,. Contact information for the MA holder is typically provided on the medicinal product's package leaflet.

When filing a complaint, it is important to provide the exact product name (including strength, package size, batch, or lot number), where the product was purchased, and describe the specific defect. Often, it may be relevant to include the package, so the MA holder can forward it to the manufacturer for investigation. Once the complaint has been investigated, it is expected that the manufacturer or MA holder provides feedback through the distribution chain, or directly to the complainant. If the MA holder identifies a quality defect in the medicinal product, they are obligated to report it to NOMA.

If the patient, doctor, veterinarian, or other healthcare professional has contacted the pharmacy, wholesaler, MA holder, or manufacturer and has not received a response to the complaint, they may contact NOMA. NOMA will follow up on the case if the quality defect fulfils the criteria to be notified.