Drug recall refers to removing or withdrawing a batch of product from distribution or use to be returned to the manufacturer. This action is generally taken when deficiencies are discovered in drug safety, quality, or efficacy. It is important to note that product recall does not include the normal removal of products that have passed their expiry period.
The Organization of Pharmaceutical Producers of India (OPPI)
defines recall as, “An action taken to resolve a problem with therapeutic goods
for which there are established deficiencies in quality, efficacy or safety.”
According to the CDSCO (Central Drugs Standard Control
Organization), quality defects may include drugs that are not of standard
quality, spurious, or adulterated drugs. Safety and efficacy defects include
serious adverse drug reactions and death. Drugs manufactured despite being
prohibited under the Drugs and Cosmetics Act provisions, and products
manufactured under canceled or suspended license may also be recalled from the
market.
Types of Recall
Product recall may be of two types:
(a) Voluntary recall: This refers to situations when
the manufacturer decides on their initiative to recall products where the
safety, efficacy, and quality of a batch is in question. For example:
1. The batch does not comply with regulatory requirements
during the stability study done in the post-marketing phase.
2. An in-house investigation reveals a failure
(cross-contamination or mix-up) that may hurt the quality
of a batch of product that has already been released for distribution.
3. Market complaint investigations show that the entire
batch of distributed products is defective.
4. Visual inspection of retained samples shows evidence of
deterioration that has an impact on product quality.
5. Pharmacovigilance reports indicate a serious safety risk
to those taking the medication.
(b) Statutory recall: These are recalls mandated by
drug regulatory bodies at Central or State levels for one of the following
reasons:
1. The product violates the law – For example, it is not of
standard quality.
2. The formulation contains banned drugs.
3. The labeling of the product or promotional material
violates the law.
4. Product is found to contravene provisions of Schedule J
(it claims to cure a disease/disorder that no drug can claim to do)
Regulatory bodies encourage manufacturers to implement a product recall voluntarily if they discover that any of their products are defective. However, in cases where the regulatory body finds evidence of seriously defective or dangerous products, it may suggest or order a product recall by sending a notice to the concerned company. In case the company does not comply with such an order, legal action may be initiated against the manufacturer.
In cases where the product recall is ordered by the
regulatory body, the concerned company may choose to contest the notice.
However, it is important to do a complete review of the actual situation and
take necessary legal advice before proceeding in this direction.
Recall is Different from Withdrawal
A drug recall is removed from the market due to quality,
safety, or efficacy issues. Drug withdrawal, on the other hand, is a change in
the approval status of the drug by the concerned regulatory authorities. If the
nature and frequency of adverse drug events are such that the risks of a drug
far outweigh its benefits, the regulatory body may decide to withdraw approval
for the manufacturing of such a product, and the manufacturer is informed to
stop producing it.
Reasons for Product Recall
Product recall may have to be carried out if:
• Potentially dangerous/serious product quality issues have
come to light through complaints or other means.
• Mandatory regulations have been violated and come to the
notice of regulatory agencies, who then order a recall.
• Field monitoring studies/other reports show evidence of
tampering with the product.
• New information that comes to light after the distribution
of a product indicates it is unsafe ineffective or dangerous.
Most common reasons for drug recalls:
• cGMP violations.
• Microbial contamination in non-sterile products.
• Failing dissolution test requirements.
• Degradation products/impurities.
• Lack of efficacy.
• Labeling errors (declared strength).
• Lack of assurance of sterility.
• Misbranded drug (therapeutic claims that are unapproved in
promotional literature).
• Lack of drug stability.
• Incorrect outer packaging (correct label on product,
packed in incorrect carton).
Classification of Recall
The CDSCO classifies recalls into three categories:
Class I is the 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 as well as drugs banned
under 26A of the Drugs and Cosmetics Act 1940. Recalls under this class must be
executed to the level of distributor/wholesaler, retailer, and consumer. Public
announcements shall be made using print and electronic media. Timeline for
recall ranges from within 24 hours up to a maximum of 72 hours – stopping the
sale/distribution must be enforced within 24 hours; physical recall must be completed
within 72 hours.
Class II is a 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. These recalls are implemented at the level of distributor/wholesaler
and retailer. The time limit for recall is a maximum of 10 days.
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. Here, recall is executed until the wholesaler level and a time
limit of up to 30 days is permitted.
Banned drugs for which a license is canceled or suspended,
if found to be in the market, shall have to be recalled, being treated as Class
I recall.
Mock Recall
As per CDSCO guidelines, companies must carry out a mock
recall for at least one batch of any one of their products after being
dispatched. It is best to choose a product where maximum distributors are
involved. This helps to evaluate how effective the arrangements are to execute
the product recall. Such a mock recall must also be carried out in the event of
a change in the marketing/distribution partner. Records of mock recalls must be
maintained by the QA department.
USFDA Classification of Product Recalls
Class I: Situations that involve a threat to life.
FDA orders a consumer recall, a 100 % effectiveness check, and requires public
announcements to be made about the hazards of the product.
Class II: Situations that are potentially hazardous
but not life-threatening. FDA orders recall to retail outlets but a 100%
effectiveness check is not mandatory. Depending on the reason for the recall, a
press release may or may not be necessary.
Class III: Situations that do not pose a serious
hazard. Recall is restricted to the wholesale outlets. Effectiveness checks are
not necessary, no press release is required either. Product recall guidelines –
worldwide
|
Country |
Regulatory body |
Guidelines under |
|
USA |
Food &
Drug Administration (FDA) |
21 CFR Parts
7, 107 and 1270. |
|
Australia |
Therapeutic
Goods Administration (TGA) |
Section 65F
of the Trade Practices Act 1974. |
|
UK |
Medicines and
Healthcare products Regulatory Agency (MHRA) |
Sections
2(2), 4, 5, and 7 of the European Communities Act 1972 and Directive
2001/95/EC on general product safety. |
|
South Africa |
Medicine
Control Council |
Section 19
(1) of the Medicines and Related Substances Act, Act 101 of 1965, and
Regulation 43(1) of the Medicines and Related Substances Control Act, Act 101
of 1965. |
|
India |
Central Drugs
Standard Control Organization (CDSCO) |
Para 27, 28
of Schedule M and conditions of license for defective product recall in Rule
74(j) and Rule 78(i) of the Drugs and Cosmetics Act, 1940 and Rules there
under. |
Major drug recalls
|
Product |
Company |
Category |
Year |
Reason For Recall |
|
Fenfluramine/
Phentermine |
Wyeth-Ayerst |
Anti-obesity |
1997 |
Reports of
heart valve defects |
|
Phenylpropanolamine
(PPA) containing drugs |
Many
companies |
Decongestant |
|
Incidents of
hemorrhagic stroke |
|
Baycol |
Bayer |
Anti-cholesterol |
2001 |
Death linked
to rhabdomyolysis |
|
Vioxx |
Merck |
Anti-inflammatory |
2004 |
Linked to
cardiovascular problems |
|
Bextra |
Pfizer |
Anti-inflammatory |
2005 |
Serious
cardiovascular effects and potentially fatal skin conditions |
|
Digitek |
Actavis |
Heart failure
treatment |
2008 |
Double-thickness
tablets containing double the approved dose |
|
Tylenol |
McNeil
Consumer Healthcare |
Pain reliever |
2010 |
The musty odor
of bottles due to preservatives sprayed on pallets where bottles were stored. |
|
Excedrin |
Novartis |
Pain reliever |
2012 |
Suspicion of
mix-up with other products manufactured at the same premises |
|
Velcade |
Takeda
Oncology Company |
Anti-cancer |
2018 |
Particulate
contamination observed after reconstitution |
|
Ranitidine |
Several
companies |
Antacid |
2019 |
Carcinogen
nitroso dimethylamine found at levels crossing USFDA limits |
Product Recall System
Every company is required to have a product recall system in
place to effect a prompt and effective recall in case of serious complaints
regarding defective products. As per cGMP guidelines, product recall activities
must be coordinated and executed by an authorized person who is independent of
the marketing and sales function of the company. The recall approving authority
is generally the Head of the Company (President/Proprietor/Managing Director).
Recall strategy details must include information regarding:
1. Authorized person who will initiate the recall.
2. Nature of communication that will be used to initiate
recall (telephone, email, letters, etc.).
3. Depth of the recall to be instituted (recall from
distributor/wholesaler/hospital/ retailer/general public).
4. Manner of receiving, segregating, and securing storage of
the recalled product.
5. Reconciliation reports to be prepared, at what frequency.
6. Verification of success of recall and report submission
to regulatory authorities.
7. Steps to be taken to avoid re-occurrence of the same
issue with the product.
8. Dealing with recalled products – reworking or destruction
as may be appropriate.