Pharmaceutical Market Withdrawals and Recalls: Expect the Unexpected

A patient’s path toward heath outcome goals is rarely linear. Even the best treatment plans can become sidetracked, waylaid by interruptions in pharmaceutical supply chains and risks posed by the very pharmaceuticals themselves. Thousands of drugs are withdrawn or recalled from the marketplace annually for any number of reasons. The main differentiator in a manufacturer’s decision to withdraw or recall a product is the risk that product poses to those who take it.

When a drug product is withdrawn or recalled, it requires vigilance: Drug products must be removed from the marketplace, and manufacturers, healthcare providers and pharmacists — all patient-facing entities — must work together to get the job done. It also requires pivots to care plans and constant communication to ensure patients are well-informed of changes and how to handle them.

Market Withdrawals

Products are withdrawn from the marketplace, generally, for one of two reasons: when the manufacturer identifies a minor problem (known in U.S. Food and Drug Administration (FDA) parlance as a “minor violation”) with the product; when the manufacturer rotates stock or discontinues a product, perhaps due to declining sales; or as a result of a more effective drug product receiving a new FDA approval. A market withdrawal may also be initiated when product or manufacturing equipment adjustments are made.

Market withdrawals are only used in instances when there is no evidence FDA laws have been violated by the manufacturer or distributor and when the risk of consumer harm is extremely low.

Product Recalls

Product recalls occur when a drug product is in violation of FDA law.² This may be a problem with its strength or potency, a mislabeling violation or product contamination. Most recalls are voluntary and initiated by the manufacturer, but FDA has statuary authority to request and even require product recalls. FDA will also seize products if recalls are not executed in an approved manner or when the agency determines the violative products are still being manufactured. However, FDA product seizures are rare.

Recalls are classified by the risk the product poses and the likelihood of potential danger to the patient (see FDA Recall Classifications). When determining which classification will be used, FDA looks at a number of variables, including whether any disease or injuries have already occurred that can be attributed to the violative product; whether the recall and subsequent lack of product availability is likely to contribute to negative health outcomes for those who use the product; the degree of seriousness of those negative health outcomes; and any consequences, both immediate and long-term. A medical safety alert is used in place of a recall for violative medical device products. This may include combination drug-device products when the device component presents an unreasonable safety risk.

Recall Plans

The recalling company, typically the manufacturer, is responsible for developing a recall plan, although FDA will guide the recalling company on the specifics of recall requirements. The depth of the recall is dependent on the risks the product poses and how widely the product was distributed.

The recall plan will include customer communication methods and frequency; content and frequency of FDA-required recall status reports; and instructions for product disposal or reconditioning.

The agency will consider terminating the recall only when it determines efforts to warn customers and identify and remove affected lots from the marketplace are complete. FDA will also need confirmation that all affected products were destroyed or reconditioned as required. An analysis of why the violation occurred followed by the implementation of effective corrective actions must also be completed prior to a recall termination.

Communication Is Key

FDA facilitates communication of recalls through weekly enforcement reports found on the agency’s website. Product withdrawals will not be included in FDA’s weekly enforcement report, since these reports include only products found to be in legal violation of FDA regulations (products that have been recalled).

Additional recall notification sources include state boards of pharmacy and state health departments, compounder outsourcing facilities and other vendors in addition to the drug manufacturer itself. FDA recommends manufacturers initiate direct customer communications concerning product recalls only with those who received the affected lots to avoid “recall fatigue.”

Providers and patients also have opt-in communication options for receiving recall notifications such as the Patient Notification System (PNS) led by the Plasma Protein Therapeutics Association and developed with support from the Immune Deficiency Foundation. This PNS, specific to plasma products, requires an online registration and sends alerts via the registrant’s preferred communication method. More information on the PNS can be found at www.patientnotificationsystem.org. The drugs.com database is another opt-in repository of information related to pharmaceuticals, including recalls, and is powered by the American Society of Health-System Pharmacists, IBM Watson and other medical information suppliers.

Should the recalling company wish to issue a public statement regarding the recalled product, FDA requests a draft submission of the proposed warning be first submitted to the agency for its review and comment. FDA will only issue a public warning of a recalled product when urgency dictates the need for additional communication beyond that of the recalling company. However, FDA also notes that it may delay publication of a recall notification in its weekly enforcement reports should the agency determine that a public notification in advance of providers having an opportunity to discuss the recall with their patients may cause unnecessary and harmful anxiety.

Once notification of a withdrawal or recall is received, communication with in-house supply chains that distribute the affected drug must be initiated quickly. Physicians, prescribers, pharmacists and medication administrators will review customers and dispensing records to identify those who have been prescribed the drug. Patients will undoubtedly have questions, so it is important for public-facing providers to be prepared.

Patients should also be encouraged to play a proactive role in keeping track of their drugs, including recording the names and lot numbers of the products they are using. This can help them to quickly determine whether their drugs are affected by a recall, possibly even in advance of outside communication.

If the recalled drug might result in a product shortage, the recalling company is required to explain the situation to its customers, as well as draft a plan to address the shortage. While suitable alternative treatment options are being identified, it is important to remind patients that any changes to medications and dosing should first be discussed with their healthcare professionals.

Identifying Recalled Products

While communication outreach is underway, an inspection of healthcare facilities, storage areas and locations where drugs are prepared or dispensed, including off-site clinics, must be simultaneously conducted. This includes a review of all purchasing records and sample logs to determine if any of the affected drug lots are present in the facilities or on order. A comparison of National Drug Code numbers, lot numbers, etc., will confirm whether the drug in question matches what is on providers’ or patients’ shelves. As part of the recall announcement, drug manufacturers must provide copies of the affected labels and other identifying information. Any identified medications must be removed, returned or destroyed per the instructions found in the recall notice. Additionally, incoming medication shipments should be monitored to prevent recalled products from entering the facility.

Documentation of efforts to identify and recall the affected drugs must be provided to the manufacturer that will in turn prepare an FDA recall compliance report. A facility report will include the date the recall notice was received, the dates any and all subsequent actions were taken and the specifics of those actions, including quantities removed and what was done with them. Communication efforts with prescribers, patients and any other requirements included in the recall notice must also be documented.

FDA, state boards of pharmacy, health departments and other official entities all have an interest in ensuring recalls are conducted in accordance with the FDA-approved plan. All may initiate compliance inspections and recall effectiveness checks and fine entities determined to be out of spec.

Expect the Unexpected

It is best practice for manufacturers to establish and document a recall plan as part of a standard operating procedure (SOP). The plan should cover all aspects of a recall from start to finish and be regularly practiced so the response is automatic when unanticipated issues arise. In short, manufacturers should expect the unexpected.

An effective recall SOP includes and addresses the following key points:

• Name of the person in charge of overseeing the entire recall process. Ideally, that person will be available to orchestrate the recall; however, the SOP should be explicit enough that all staff can easily and independently complete their tasks, reporting their progress up the chain using good documentation practices.
• List of all locations where drugs flow through the system: receiving and inspection areas, floor stocks and automated dispensing stock cabinets, preparation areas, pharmacy carts, clinics and outpatient practices — any area that might hold or dispense pharmaceuticals. And, those locations must be cross-referenced with the affected lot numbers.
• Instructions for identifying affected patients and their providers through a review of dispensing records.
• Location of a designated, quarantined in-house collection area for the recalled product and post-signage so mistakes are not made by unknowing staff.
• Details for a patient notification system (for both inpatients and outpatients), along with a tracking system to confirm when they were contacted, by whom and by what method, as well as the outcome. And, those contacts must be cross-referenced with product dispositions, if applicable, per the manufacturer’s instructions.
• Documentation of the date products were disposed of or returned to the manufacturer.
• Instructions for monitoring incoming shipments to prevent new product from entering the facility.
• Benchmark for what recall success should look like based on risk, per the recall classification.
• An understanding of all applicable laws and compliance with additional state- and/or county-specific requirements. New York state, for example, requires pharmacies to contact patients in the event of a Class I recall within seven days of a recall notice. Often a last line of communication for patients regarding their prescriptions, pharmacies may feel a particular responsibility for timely communications placed upon them.

Be Ready to Respond

There is no time to waste when executing a recall plan. Identification and removal of the affected product, notification of patients and providers, along with documentation of how the recall was executed will demonstrate a facility’s level of compliance. All of these steps are conducted while simultaneously determining appropriate alternative drugs for patients, each unique to their individual needs. The execution of a recall must be seamless and complete to be effective.

Product market withdrawals and recalls are stressful events. But, through a concerted effort and diligent attention to detail, the affected drugs can be quickly removed from circulation, protecting patients from the potential of future harm.