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Volume 31, Issue 3
Manufacturers face demands for timely information on clinical studies, product recalls, and approvals.
Secrecy and black-box operations are out; public disclosure is the mantra for regulators and manufacturers alike, as FDA explores more options for communicating agency policies, approval decisions, and concerns about product quality and safety. The drive for greater transparency in agency decision-making fits a range of health policy goals. More information on drug pricing, discounts, and rebates is considered key to limiting payer and patient outlays for prescription drugs. The Federal Open Payments, or “Sunshine”, policy tracks industry payments, gifts, and transactions with healthcare professionals to uncover any industry influence on prescribers. And more timely and complete information on product safety and recalls aims to prevent patient harm, as do efforts to make drug labeling more informative.
A main transparency issue involves public access to clinical study data and results. While industry sponsors of clinical trials are meeting requirements for listing new studies on the ClinicalTrials.gov website, the record is weaker for timely posting of research results for newly approved medical products. The data transparency movement also has prompted biopharma companies to provide scientists and researchers with access to confidential clinical research data and to limit publications to open access journals. Meanwhile, academic researchers have lagged in disclosing clinical research activities, prompting the National Institutes of Health (NIH) to threaten to cancel grants to organizations that fail to meet requirements.
Transparency also is considered important for enhancing drug quality to reduce product recalls and shortages, according to a white paper from the Office of Product Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) (1). As part of efforts to encourage manufacturers to adopt continuous manufacturing and systems to better ensure quality, an OPQ pilot study is exploring strategies with potential to enhance the transparency and consistency of assessments and facilitate team-based review and communication.
Other nations are joining the transparency movement. The China Food and Drug Administration (CFDA) issued draft guidance on policies for disclosing information regarding the acceptance, review, and approval of drug applications. While aiming to keep trade or technical data confidential, CFDA will make public information on active ingredients, dosing, license holder, and patents 60 days following an approval.
Despite expanded information disclosure related to biomedical research, drug marketing, and product safety, stakeholders want to know more about the status of drug applications and FDA’s decision-making process in both rejecting and approving submissions. A main demand-from both consumer activists and free market deregulators-is for access to complete response letters (CRLs) sent to manufacturers that essentially delay or reject an application and outline what additional clinical or manufacturing information is needed to achieve approval. FDA currently posts summaries and reports on newly approved drugs and biologics and has indicated interest in also posting CRLs. But manufacturers strongly oppose such a move as CRLs usually contain trade secrets or confidential information. Current law requires FDA to redact such manufacturing information from public disclosures, and any move to change that policy may require legislative action.
These issues are not new and reflect decades of reviewing and updating FDA policies on public access to information on agency operations and regulated products. A Transparency Initiative launched in June 2009 under former FDA Commissioner Margaret Hamburg and former Principal Deputy Commissioner Joshua Sharfstein has established FDA online “dashboards” that track agency actions and programs, including inspections, recalls, imports, and compliance actions. A “Drug Trials Snapshots” initiative posts data from clinical trials on products approved since January 2015. FDA has expanded access to agency enforcement reports and adverse event data and has made its guidance development process more visible and efficient.
Last year, Sharfstein, now affiliated with the Johns Hopkins Bloomberg School of Public Health, organized a group of experts to produce a Blueprint for Transparency at FDA, which was published March 2017 in a special issue of the Journal of Law, Medicine, and Ethics (2). Among its 18 recommendations for making FDA decisions less opaque, the Blueprint calls for FDA to provide more public information on its evaluation process for new drugs, generics, and biosimilars, including what products are in the review queue and why certain applications are not approved. The rationale is that discussion of unsuccessful R&D would help researchers avoid studies unlikely to succeed, reducing costs and avoiding patient exposure to potential harm. The analysts also seek authority for FDA to correct misleading information issued by manufacturers, such as incomplete factors underlying a CRL, and for the agency to disclose data from clinical trials for approved products when sponsors fail to do so.
Such proposals reflect greatly expanded public access to information on drug testing and production through the Internet, social media, and smart phones-not all of it accurate or unbiased. Consumers and industry competitors can obtain reports of adverse events and enforcement actions, raising questions about the value and impact of limits on what FDA can or cannot disclose about a product or manufacturer.
FDA Commissioner Scott Gottlieb addressed these issues at a January 2018 forum on the Hopkins transparency report. He announced a new pilot to test the impact of FDA posting more data from clinical study reports (CSRs) of approved drugs, asking that sponsors of nine new products voluntarily provide CSR data, protocols, and statistical analysis plans for pivotal studies (3). In addition, FDA aims to better track drug studies from initial Internet posting through FDA approval by adding the ClinicalTrails.gov identifier (NCT) number to all clinical data submitted to the agency.
However, Gottlieb hedged about publishing CRLs, proposing to further explore FDA’s authority to release these documents. While he acknowledged that some information in CRLs might enhance the safe use of already approved products, he noted that redacting proprietary information from these letters is burdensome and questioned the value of disclosing letters that cite manufacturing shortcomings.
Gottlieb also mentioned FDA efforts to inform the public more quickly about adverse events and product recalls, which totaled more than 9000 in 2017, including 1200 involving drugs. Up until now, FDA has delayed recall announcements until it determined whether a safety issue raises serious health consequences, as with a defective anesthesia product, or represents low risk. Now FDA’s Office of Regulatory Affairs (ORA) will include in weekly Enforcement Reports “not-yet-classified” recalls while the months-long classification process continues. FDA issued draft guidance in January 2018 outlining when a manufacturer should issue a public warning about a recall, including timelines and important data to include and what information FDA will post in its reports (4).
Although FDA has authority to require recalls, most drug manufacturers initiate such actions voluntarily, aware that FDA can issue press releases and alerts if companies are slow to act. Recall announcements from companies seem to appear almost weekly, many involving particulates or contamination of sterile injectables. Unfortunately, the failures that lead to drug recalls often create shortages in needed medicines. FDA and manufacturers will be looking to see if the earlier recall listing process generates alarms that turn out to be unnecessary, or if the new policy gets high-risk products off the market more quickly.
2. J.M. Sharfstein et al., The Journal of Law, Medicine, & Ethics, Special Supplement to Vol. 45 (4) 7-23 (Winter 2017).
3. S. Gottlieb, “Fostering Transparency to Improve Public Health," FDA.gov, Jan. 16, 2018,
4. FDA, Guidance for Industry: Product Recalls, Including Removals and Corrections (Office of Regulatory Affairs, Nov. 3, 2003).
Vol. 31, No. 3
When referring to this article, please cite it as J. Wechsler, "FDA Heightens Drive for Transparency," BioPharm International 31 (3) 2018.