China’s State Food and Drug Administration recently issued draft guidance on drafting and preparing Periodic Safety Update Reports for drugs and is seeking comments from the public until 16 April 2012.
China’s State Food and Drug Administration (SFDA) issued on 19 March 2012, draft Rules on Drafting Periodic Safety Update Reports for Drugs (Document No. 16) (Draft Rules). The SFDA is soliciting comments from the public, which are due on 16 April 2012.
According to the Preamble, the Draft Rules is “a technical document for guiding drug manufacturers in drafting and preparing Periodic Safety Update Reports, and is also an important basis on which the institutionsmonitoring for adverse drug reactions (ADRs) comment on the Periodic Safety Update Reports.” The Draft Rules set forth several general requirements for drafting a Periodic Safety Update Report, which are presented below. However, theDraft Rules arenot intended to be exhaustive, thus specific issues shall be deliberated and decided based on the actual circumstances.
Also, the Preamble emphasises “[a]s drug manufacturers periodically summarize experience built up in drug safety and the science and technology develop continuously, these Draft Rules will be adjusted from time to time.” The Draft Rules were developed mainly by referring to the ICH E2C(R1) Guideline “Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs”, or PSUR.
I. Basic Principles and Requirements
This section sets forth basic requirements relative to the reporting on compositions containing the same active substance, the data aggregation time, report format, electronic submission and report language.
In particular, drug manufacturers may submit a single PSUR for compositions containing the same active component in the case of a chemical drug and the same prescription composition in the case of a traditional Chinese medicine. A PSUR may be broken down by administration routes, indications (functions) or target populations.
It is noted that “[d]rug manufacturers shall submit PSURs in Chinese. Joint ventures, wholly foreign owned enterprises and foreign drug manufacturers importing drugs may submit PSURs written in English that are uniform within the companies, but meanwhile, shall translate the Company Core Data Sheet and the sections in the reports other than the Line Listings and the Summary Tabulations into Chinese and submit them together with the original English texts.”
II. Main Content
According to the Draft Rules, “[t]he main content of a PSUR includes: basic information on [a] drug, information on marketing within and outside China, information on measures taken for the reason of drug safety, change of drug safety information, estimate on patient exposure, information on reports of ADRs, safety-related study information, other information, drug safety analysis and comment results, and conclusion.”
Information on marketing within and outside China
Disclosure of information on marketing within and outside China is required, including “countries and dates of marketing authorization, current registration status, date of first marketing for sale, trade name, etc., marketing conditions for conditional approval of the drug, especially requirements on safety, approved indications (functions) and special population, the reason why an application for registration is not approved by the competent authority, and any application for registration that is withdrawn by the drug manufacturer because of drug safety or efficacy.” Besides, “[i]f the indications (functions), population, dosage form and dosage of the drug in China are significantly different from those in other countries, it shall be specified.”
Information on measures taken for the reason of drug safety
Measures taken for the reason of drug safety also need to be reported, including: any suspension of production, sale or use, any revocation of drug approval document, failure to approve any further application for registration, restriction of sale, suspension of clinical trials, changes to dosage, target populations or indications (functions), or changing dosage forms or prescriptions. Any other risk control measures that are taken must be reported as well.
Change of drug safety information
Changesin thesafety information presented in drug instructions during the reporting period should be included. The version number and date of the drug instructions on which the report is based, and the version number and date of the drug instructions on which the last report was based, need to be included.
Particularly, if the safety information in the drug instructions in China is significantly different from that in other countries, the drug manufacturer shall explain the reason, state the regional difference and its effect on the overall safety, and state the measures that the drug manufacturer will take or has taken
Estimate on Patient Exposure
Information about patient exposure during the reporting period should be reported as accurately as possible. The patient exposure may be estimated by defined daily dose or by patient-days, number of prescriptions or number of dosage units, but the method used for estimation shall be explained. If the aforesaid methods cannot be used, drug sales may be used for estimation. When necessary, data broken down by sex or age (especially children) should be provided.
When the relevant information, such as spontaneous reports, epidemiology studies and clinical trials, indicates a potential safety problem on the drug, details by country (with locally recommended daily dose) or other factors (e.g., indications or functions, dosage form) should be presented.
When ADR data from clinical studies are included in the PSUR, information such as the corresponding patient exposure, the number of ADR cases and the incidence rate of ADRs should be provided. An explanation and justification should be presented if the number of patients exposed is impossible to estimate or is a meaningless metric.
Information on ADR reports
The draft provides detailed rules regarding the preparation of ADR reports. For individual ADR cases, first reports and follow-up reports on such cases that occur within and outside China during the reporting period shall be reported, including not only those collected by the spontaneous report system, but also those discovered in clinical studies and reported by literature after marketing.
For drugs that are within the new drug monitoring period and within five years of the first importation, all ADRs should be summarised and analysed in the form of line listings and summary tabulations; for other drugs, new or severe ADRs should be summarised and analysed in the forms of line listings and summary tabulations; known general ADRs need only to be summarised and analysed in the form of summary tabulations.
In addition, reports, investigation and disposition of adverse drug events are to be included.
Apart from the above information, safety-related study information is also required to be presented, including completed studies, studies planned or in progress and published studies. Other information such as efficacy-related information, new information after the data cut-off date, risk management programs, thematic analysis reports, etc., is also to be presented in the PSUR.
A translation of the Draft Rules is available upon request.