Pharmaceutical Drug Recall

There has been an increasing trend in the number of prescribed and OTC drug recall over the last few years due to labelling issues, medication mix-ups, and life-threatening adverse effects etc. while not all recalls are dangerous. It is surprising that some recalls are such that it distresses the mind. I have long experience in formulation but till now I have not been able to understand how it is possible that the potency of ?drugs is found to be less after testing by FDA, although we put the ingredients on 100% basis and secondly how the potency of drugs is not maintained as per labelled shelf life even when we use the overdose in several products as per requirement. The same happens with dissolution testing, the product passes in the factory and when the FDA tests the market samples it is found to be non-compliant.

We have mentioned the reference of Indian FDA regulation in this paper, more or less there is similar regulations in every country.

Drug recall is incubus for pharmaceutical companies as it affects the reputation of the company. The most common reason for product recalls is related to manufacturing, the company did not followed the current good manufacturing practice guidelines for manufacturing the products. Another reason involves safety/efficacy affined which suggest that the safety data was not appropriate, or some kind of biasing was involved during drug development time. It is essential to launch the drug in the market after assuring the safety and efficacy of the new intervention so as to minimize drug product recall. Major drug recall list of the history suggests that lots of carelessness is involved during the drug development and manufacturing period.

The long list of drug recall on FDA website is evidence that still industries are not following the standard guidelines issued by FDA. The process of recall execution is followed by FDA and firms in very efficient manner. This execution step is effective enough to protect consumer's health from a particular drug that requires recall. Therefore, even after launch of the drug in the market, it is essential to carry out post market surveillance and investigate the drug performance in the market.

Drug product recall is an action taken to withdraw or remove a batch or an entire production run of drug product from distribution or use to return them to manufacturer. It is usually done due to deficiency in quality, safety and efficacy. In the USA, guidelines for drugs product recall are described under 21 CFR Parts 7, 107 and 1270. In Australia, guidelines for drugs product recall are described under section 65F of trade practices act 1974. In Canada, it includes under section 25 of Natural Health Products Regulations (NHPR). In India it includes under para 27 and 28 of schedule M. In South Africa SAHPRA (South African Health Products Regulatory Authority) guidelines are responsible for regulations of drug product recall.

FDA drug recall and other actions have been classified as the following categories:

• Class I is a situation in which there is a reasonable probability that the use of, or exposure to, a defective product will cause serious adverse health consequences or death and as well as banned under 26A of Drugs and Cosmetics Act 1940.
• Class II is situation in which the use of, or exposure to, a defective product may cause temporary adverse health consequences or where the probability of serious adverse health consequences is remote.
• Class III is a situation in which the use of, or exposure to, a defective product is not likely to cause any adverse health consequences.

How are patients notified of recalls?

These days, it’s common to learn about recalls from news outlets and online articles, but there are many other ways in which recall announcements reach the public. Here are some examples:

• The FDA, manufacturer or dispensing pharmacy may notify patients by telephone, mail, fax or email if a medication has been recalled.
• The manufacturer usually posts recall information on their website.
• The FDA may publicly announce a recall via news and other media.
• The FDA publishes a weekly Enforcement Report of recalls on their website. You can also subscribe to a newsletter to get this report in your email every week.
• The FDA has a Twitter profile, where they announce recalls.

Recall Procedures:

Any batch of a product not meeting the defined quality standards has to be recalled from the market. Recall can be of two types:

• Voluntary Recall and
• Statutory Recall.

?Voluntary Recall:

Voluntary recall can be triggered by any incident that affects the quality, safety and efficacy of the batch/product in question such as

• If the batch or batches are found to be not complying with the regulatory specifications during the post marketing stability study
• If the batch is found to be defective during investigation of market complaint.
• During any failure investigation, if it is observed that the failure under investigation might have adverse quality impact on already released batch (e.g. possibility of contamination, mix-up, degradation etc).
• If any unusual observation is noted during visual inspection of retention samples which indicate an impact on quality of the product after investigation.
• If the post marketing surveillance reports /pharmacovigilance reports indicates that there is serious safety risk associated with the product.

Statutory Recall:

Statutory recall can be triggered in response to the direction or mandate by the Drug Regulatory Authorities (Central/State) in one or more of the situations as follows:

• To recall the drug product/batch, considered to be in violation of the laws, it administers such as not of standard quality etc.
• To recall the banned drugs.
• Labelling and / or Promotional materials, that are considered to be in violation of law.
• Product, violation Rule.

Timelines for Effective Recall System:

Based on the category of risks involved, a timeline of within 24 hours up to a maximum of 72 hours for Class I recall, for class II recall up to a maximum of 10 days and for Class III recall up to a maximum of 30 days is allowed.

The timeline for initiation of recall procedure to commence from the receipt of information as notified by the concerned State/ Central Drugs Control Department under statutory recall or voluntary recall by the manufacturer on its own.

The recall has to be initiated immediately without any prejudice of the outcome of Section 25(3) and Section 25(4) of the Drugs & Cosmetics Act 1940 for adducing the evidence. The timeline for stopping sale/distribution of defective product under Class I shall be ensured within 24 hours and the physical recall being completed within 72 hours. The Class II and Class III recalls shall be ensured up to 10 and up to 30 days respectively.

Mock Recall:

Mock recall shall be carried out for at least one batch of any product, dispatched for sale where maximum distributors are involved, to test the effectiveness of the arrangements of recall. Effectiveness of recall procedure can also be checked by ‘evaluation of a real recall’.

During mock recall traceability shall be performed for at least one of the raw materials used in the batches identified for mock recall.

Mock Recall shall be performed at least once for the longest distribution chain and whenever there is a change in distributor/marketing company.

Records of such mock recall should be maintained by the QA Head of the company.

A mock recall is essentially a practice session that a company should perform to verify its quality systems and controls are effective and fit for purpose.

Mock recalls help employees prepare for a recall. They also indicate to Regulatory Authorities that your recall procedures are fit for purpose and that your quality systems are under control.

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Conclusion:

Many vital stakeholders have legal, ethical, and professional obligations to report issues that could result in a recall. In addition, once a recall is initiated, these key players have additional commitments throughout the process. The FDA, manufacturers, pharmacists, and other healthcare professionals are key players.

The FDA will conduct an Effectiveness Check to determine the success of the recall. The drug will either undergo controlled destruction or reconditioning (i.e. relabelling with the correct label). Status reports are conducted throughout the recall to determine effectiveness.

The root cause of the recall must be addressed and corrected to prevent future occurrences. After all corrective action is acknowledged and carried out, the FDA can terminate the recall.