SOP for Global Literature Search and Review

Purpose

ANDA Holders are responsible for screening global scientific literature including for adverse events which are associated with the use of active substances contained in products for which they hold a Marketing Authorization.

The requirements for literature reviewing and case reporting are described in 21 CFR 314.80. According to the FDA Pharmacovigilance legislation:

The Medical Literature searching/reviewing also needs to be conducted for the purpose of ICSRs and periodic Adverse Drug Experience Reports (PADER) and the ongoing safety reviews.

Scope

The scope of this SOP is to describe a procedure for screening, reviewing, assessing and documenting searches of published medical literature for adverse events. This is required for all the molecules of ANDA Holder that fall under Generics Pharmacovigilance system (registered and under process of registration).

Responsibility

• Data entry: Responsible for assessing if the case received is of article or case report. Verifying the country. Performing Primary screening, maintaining trackers.
• QC: Responsible for reviewing the initial assessment and correct the case validity if any missing.
• MR: Responsible for verifying the case validity, reportability and maintaining the respective trackers.

Procedure

Master license list:

• The master license list for XXX products been maintained by XXX Regulatory Affairs department. This list shall be updated whenever there are new ANDA were entered into Market from the company.
• The XXX has to inform the YYY promptly whenever an application for a new Marketing Authorization is submitted/ approval / cancellation of MA within 3 Business days.

Maintenance of the medical literature search list

• The Medical literature search list is maintained by designated pharmacovigilance personnel with review performed on a regular basis, quality check shall be conducted with every update of the product list as part of the monthly compliance monitoring of designated PV activities.
• A template for the medical literature search list is presented in Form 1.
• Any new/additional active substances shall be added to the medical literature search list following notification after through cross reference from the master license list.
• Any active substance for which there is no longer any MA held by one of the ANDA Holder shall, in due course, shall be removed from the Literature search.
• The expiry dates of any remaining batches on the market for the product concerned are to be taken into consideration.

Search in Pubmed and Springer Nature

• Global literature is conducted in terms of Weekly Medical literature searching.
• The service provider or team shall perform weekly searches of the designated medical databases (Pubmed and Springer Nature). Search terms include the recommended International Non-proprietary Name (rINN) and synonyms for each active substance contained in products for which the companies hold a Marketing Authorization. Eg: Paracetamol / Acetaminophen.
• The search from the PubMED is saved as alerts. Alerts are set to run automatically once every week on Tuesday. Search from Springer will be done manually.
• If, alerts are not generated from PubMED, manual search to be done by Literature team on Tuesday. If Tuesday is holiday. Then search to be done on next business day.
• The search shall be made based on the generic name (as well as brand name if provided) ("Substance name"[MeSH Terms] OR "Substance name "[All Fields]) AND ("custom date range”).
• Unless medically relevant, the search shall not be based on particular salt or specific compound for an active ingredient.
• The search shall be broadened or narrowed as per Client requirement with prior agreement.
• Follow-up must be done with respective Authors if suspicious about the validity
• Search details to be recorded in Form 1.
• Articles which do not have minimum safety information are considered as invalid or incomplete articles.

Processing of weekly literature search results

• Weekly alerts received from the PubMed are to be saved under receipt (week) + date (DDMMYYYY) under the active substance named folder.
• Search results from Springer Nature will be assessed and archived in the similar way.
• Screening/DE step: The alerts of PubMED and results of Springer nature will be screened by trained team member to determine:

1. If it is a molecule from the updated approved products list.
2. EMEA website will be referred for IME/DME List
3. Whether it is an Individual case safety report or an article.
4. Country of origin of case/article.
5. Applicant’s country of license.
6. DE comments as “Article was assessed for the validity. Identified as Valid/Non valid”
7. QC Comments as “ No comments” if DE assessment was correct. / as “Wrong assessment” if DE assessment is not accurate. / Respective errors of assessment will be corrected and recorded in form 2.

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• For selecting a literature article as a valid case / ICSR, the literature should have four minimum criteria for case creation. At least, one identifiable reporter, one identifiable patient, one suspected adverse reaction and one suspected medicinal product. Selection of Literature article as valid cases for ICSRs shall be based on the above points and the possibility that the event may be attributed with use of the suspected medicinal product. This should be judged while reviewing the article.
• Medical Review Screening/ MR Step: (to be conducted by a trained medic. Comments shall include whether they are:

1. Identified as an ICSR as per the Marketed list of ANDA Holder
2. Treated as an adverse event/reaction/beneficial effect
3. Excluded if not relevant

• The relevant publications shall also be screen for the following reports apart from standard adverse events:

1. Paediatric use
2. Compassionate supply and named patient use
3. Lack of effect
4. Asymptomatic overdose, misuse and abuse cases
5. Medication errors
6. Pregnancy cases (exposure during pregnancy with no harmful effects)
7. Important non-clinical safety results
8. Occupational exposure
9. Special population (Hepatic, Renal failure conditions etc.)

• The Literature team should inform any adverse events to the respective case processing resources within 4 Calendar days.
• Reports on relevant literature reviews that do not relate to specific adverse events are highlighted for review – for PADER.

Recording weekly medical literature search results

• Every week the literature Search List (form 1) is to be updated to record the number of reports received for the individual drug in that week.
• Electronic copies of all reviewed and marked Literature search copies will be stored electronically.
• Full text articles are to be ordered if the literature case needs to be reported or if further evaluation is required in order to assess completely for validity. PDF copies must be stored in company dive.
• During literature review, if any article requires full text for complete assessment of the report, then the concerned designee shall search in Google or any other websites for procurement of the full text. If any Full texts are with paying option, then YYY shall purchase paid articles upon approval by Client. In this scenario, YYY will send a notification mailer to XXX within 3 business days from the search date for getting the Full text.
• Ordering translation: When the publication is not in English, a translation may be necessary. Translation of any literature articles shall be obtained from Client. It is not always necessary to translate the full article. The translation may be limited to the abstract or pertinent sections of the article as long as it fulfills all the necessary case information. If the case is determined to be valid, full translation will be required. In this kind of scenarios, YYY will approach XXX with e-mail notification for translated document within 3 business days from the search date.
• The cost incurred for procuring the full text article and translation of article in foreign language shall be borne by XXX.

Reporting of Literature Cases

• Provided the literature case has been correctly identified as per the section above, cases must be reported in line with protocols listed in the current version.
• Day 0 in literature search is the day when initial search was conducted. The same was applicable for FUs also.
• Literature Reportable case tracker (form 2) must be filled with results of search.

Abbreviation

ANDA-Abbreviated new drug application.

SRP- Safety Reporting Portal.

MR-Medical Review.

WHO- World health organization.

QC - Quality Check

Annexure

Form 1 – Literature search List

Form 2 – Literature Reportable case Tracker

References

USFDA Guidelines.

Revision History

Nil

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