On Oct. 26, 2022, China National Medical Products Administration (NMPA) issued the new Administrative Measures for Drug Recall (hereafter referred to as the Measures), which will take effect on Nov. 1, 2022.
1. MAH as the Main Responsible Entity
Different from the previous version issued in 2007, the new Measures designates drug marketing authorization holders (MAHs), instead of manufacturers, as the main responsible entity for drug recall.
MAHs are required to establish the drug recall system, collect drug quality and safety information, investigate and evaluate potential quality issues and/or other safety risks, and recall the drugs with the issues and risks.
Drug manufacturers, suppliers, and user institutions shall take assisting responsibilities—cooperating with MAH by investigating the drugs, conducting drug recall, sending the feedback for drug recall in time according to the recall plan, as well as controlling and withdrawing the drugs from the market.
2. Scope of Drug Recall
Drug recall means that MAHs recall the marketed drugs that have quality issues or other safety risks endangering human health and life safety due to noncompliant research & development, manufacture, storage & transportation, and/or labeling.
The following two categories are NOT in the scope of drug recall.
1) Drugs that are proved to harm human health and thus seized by medical products administrations.
2) Investigational drugs used in clinical trials.
3. Drug Recall Types: Voluntary and Mandatory
Voluntary recalls are initiated by MAHs upon finding the drug have quality issues or other safety risks.
Mandatory recalls are ordered by the local provincial medical products administration* and to be carried out by MAHs. There are two situations:
1) After investigation and evaluation, the administration deems that MAH should recall the drugs but hasn't made the recall.
2) After reviewing the voluntary recall's result, the administration deems the recall is insufficient.
*Local provincial medical products administration is the provincial-level drug regulator of the province, autonomous region, and municipality directly under the administration of the central government, where the MAH is located.
4. Drug Recall Classification:
According to the degree of quality issues or safety risks, drug recalls are classified into three levels:
Class I: Using this drug may cause or has already caused serious adverse health consequences;
Class II: Using the drug may cause or has already caused temporary or reversible adverse health consequences;
Class III: Using the drug generally does not cause adverse health consequences but the drug should be recalled for other reasons.
5. Drug Recall Steps
For drug recalls, MAHs shall complete the following tasks:
5.1 Releasing the recall information to the public
If the MAH confirms the drug has a quality issue or other safety risks, it shall immediately release the recall information on its official website or pharmaceutical media. The recall information shall include drug name, strength, batch, MAH, manufacturer, recall reason, recall class, etc.
For class I and class II recalls, MAHs shall also apply to publicize the recall information on the website of the local provincial medical products administration.
5.2 Making the recall plan
The recall plan shall include:
Information on the drug's manufacture and sales, and the number of drugs planned to be recalled;
Specific recall measures, including involved organizations, recall scope, and deadline;
The publicizing channel and scope of the recall notification;
The recall's expected effect;
Measures for handling the drugs after recall;
The responsible person's name and contact information.
5.3 Sending recall notifications to involved companies and institutions
After making the recall decision, MAHs shall send the recall notification to manufacturers, distributors, and user institutions within 1 day for class I recalls, 3 days for class II recalls, and 7 days for class III recalls.
The recall notification shall include:
The drug's name, strength, batch, and other basic information;
Recall requirements, such as suspending production, product release, sales, and/or use, reposting the recall notification, etc.
Measures about package label recall, isolated storage, transportation conditions, destruction under supervision, etc.
5.4 Filing recall documents to local regulator
MAHs shall file the drug investigation & evaluation report, recall plan, and recall notification to the local provincial medical products administration. The filing shall be made within 1 day for class I recalls, 3 days for class II recalls, and 7 days for class III recalls after the recall decision.
The investigation & evaluation report on quality issues, adverse reaction/events, and other safety risks shall include:
The drug's name, strength, batch, and other basic information;
Investigation & evaluation result;
5.5 Reporting recall status to the local medical products administration
During the recall, MAHs report the recall status to the local medical products administration every day for class I recalls, evert 3 days for class II recalls, and evert 7 days for class III recalls.
5.6 Keeping drug handling records after recall
MAHs shall report to the local provincial medical products administration and the health department within 10 workdays after completing the recall and specify the recall in the MAH annual report.
If the recalled drugs need to be destructed, the destruction should be supervised by the MAH, the manufacturer, or the county-level or above medical products administration of the area where the recalled drugs are stored, or a notary organization.
The recalled drugs can be returned to the market after appropriate measures according to Good Manufacturing Practices (GMP), Good Supply Practices (GSP), and other regulations on drug quality. For traditional Chinese medical decoction pieces which are not up to the standards but do not affect safety and efficacy, the possible measures can be changing the labels, revising the medical package inserts, repackaging the drugs, or remanufacturing. For remanufactured drug back to the market, their expiration dates shall NOT be extended.
MAHs shall keep detailed drug handling records after recall. The records shall be kept for 5 years and at least 1 year after the drug's expiration date.
6. International Drug Recall by Overseas/Chinese MAHs
To recall drugs manufactured overseas and marketed in China, overseas MAHs shall appoint its local Chinese agent, which should be a legal corporate entity, to carry out the recall and fulfill the same reporting obligation mentioned in section 5.
If MAH has recalled a drug in an overseas country/region and the recalled drug belongs to one of the following three categories, the MAH's local agent shall report the drug name, strength, batch, recall reason, and other information to the local provincial medical products administration in China within 10 workdays since the recall.
1) The drug has the same active ingredient with the drug marketed in China, but can be different in strength, batch, and/or dosage form.
2) The drug is produced on the same production line with the drug marketed in China.
3) Other situations that should be reported to the medical products administration.
Besides the drugs imported to China, Chinese domestic MAHs of drug exported from China shall also report to the destination country/region's drug regulator and purchaser if finding quality issues or other safety risks, and recall the relevant drugs according to the destination country/region's regulations and purchase contract.
7. Punishment for Violations
If MAHs refuse to carry out the mandatory recall ordered by the provincial medical products administration, the MAHs will be liable to a fine more than 5 and less than 10 times of the drugs' value or 100,000 yuan if the drugs' value are less than 100,000 yuan.
If MAHs commits serious violations against the Administrative Measures for Drug Recall, the administration can revoke the drug approval certificate, manufacturing license, and business license, and orders a fine more than 20,000 and less than 200,000 yuan to the legal representative person and other responsible persons.
If the drug manufacturers, suppliers, and medical institutions do not cooperate in the drug recall, they will be fined for more than 100,000 yuan and less than 500,000 yuan.
8. BaiPharm's Comment
Compared to its previous version issued in 2007, the Measures adapts itself to the marketing authorization system launched in 2019 by designating MAH as the main responsibility entity. The Measures is expected to better ensure drug quality and safety with more detailed obligations specified for Chinese domestic and overseas MAHs, as well as overseas MAHs' local agents.
9. BaiPharm's Service
Drug recall is a risk management measure for post-market safety surveillance which is a significant part of pharmacovigilance. BaiPharm offers pharmacovigilance services during the whole drug life cycle. Contact BaiPharm for services include but are not limited to
Development of safety and risk management plans
Data collection, entry and evaluation
Follow-up of safety cases
Preparation and submission of safety report
Chinese and overseas literature retrieval
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