A recent guidance document released by the US Food and Drug Administration (FDA) that aims to standardize the process for reporting periodic safety update reports to regulators is winning strong support from the pharmaceutical industry's largest trade group, the Pharmaceutical Research and Manufacturers of America (PhRMA), along with a few recommendations to reform the reporting process.
The guidance in question, Providing Postmarket Periodic Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report), is in the process of being developed under the International Conference on Harmonization (ICH), a global regulatory harmonization organization that includes the US, EU and Japan as principal members.
The Periodic Benefit-Risk Evaluation Report (PBRER) format has been under development for several years, and was finalized in November 2012, when ICH received approval from all three core regulatory authorities-the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and Japan's Ministry of Health, Labour and Welfare-to approve the revised E2C PBRER guideline.
The ICH guideline aims to "ensure that the periodic safety update reports for marketed drugs … cover: safety evaluation, evaluation of all relevant available information accessible to marketing authorization holders."
Background: FDA Guidance
FDA's draft guidance is intended to help sponsors and manufacturers interpret the ICH guideline, explaining "the conditions under which applicants can use an alternative reporting format"-that is, PBRER-"in place of the US periodic adverse drug experience report (PADER), US periodic adverse experience report (PAER) or ICH e2C Periodic Safety Update Report (PSUR)."
Companies are currently required to submit to FDA periodic reports using the approved PADER/PAER format for products approved under a New Drug Application (NDA) or a biologics licensing application (BLA), as well as any generic products such as those approved under an abbreviated new drug application (ANDA).
Those reports are to be submitted to regulators every three months for the first three years after a product is first introduced on the market, and annually thereafter. The regulations are intended to make sure that FDA is made aware of any emerging safety problems, such as those not detected during the course of clinical testing or those issues that are more serious than originally thought.
The latest revision "replaces the PSUR with the PBRER for postmarket periodic safety reporting, and describes the recommended format, content, and timing of PBRER submissions," FDA explained.
"Like its predecessor, the PSUR, the harmonized PBRER is intended to promote a consistent approach to periodic postmarket safety reporting among the ICH regions and to enhance efficiency by reducing the number of reports generated for submission to the regulatory authorities," FDA continued. "FDA has initiated the process to adopt the ICH E2C(R2) step 4 guideline as final FDA guidance. We anticipate that some applicants will wish to begin using the PBRER format in the United States before the necessary administrative procedures are completed."
But what does industry think of the guidance? If PhRMA's comments are at all indicative of the broader pharmaceutical industry's thoughts-and they often are-the industry largely supports the measure, albeit with some minor hesitations.
"PhRMA is in support of the overall thrust and intent of the guidance and endorses a number of much needed clarifications to industry sponsors," wrote Michael Gavin, assistant VP of Scientific and Regulatory Affairs at PhRMA in a letter to FDA. "In balance, PhRMA has a few focused comments on the document that aim to enhance the guidance's clarity and usefulness on certain points, and several suggestions for the Agency's consideration in implementing the ICH guideline."
In particular Gavin wrote that the submission of PBRERs could benefit from a multi-year reporting format that allows for "even greater international harmonization."
"Reports covering a longer period of time would not delay notification of significant changes to the benefit-risk profile to FDA, since under the principles of Good Pharmacovigilance Practice, it is expected that applicants will notify FDA (and other worldwide authorities) of any significant changes in the benefit-risk profile immediately, without waiting until the next PBRER is produced and submitted to the Agency," Gavin explained. The present standard is one year, but PhRMA stipulated that even a five-year reporting window would be adequate.
Another recommendation put forth by PhRMA is that industry shouldn't have to submit both an electronic copy and a paper copy of the non-expedited individual case safety reports (ICSRs) if they submit the former.
Gavin also wrote that PhRMA would like to see FDA exhibit some flexibility when it comes to submissions, and allow the submission of periodic postmarket safety reports in either the PBRER or PADER format, depending on the company's preference. That would eliminate the need for waivers.
PhRMA's full statement can be found here.