Asia Regulatory Roundup: CFDA Releases Draft Guidance on Data Management (18 October 2016)

Welcome to our Asia Regulatory Roundup, our weekly overview of the top regulatory news in Asia.

TGA Proposes Change to Rare Disease Threshold in Orphan Drug Rethink

The Therapeutic Goods Administration (TGA) of Australia is proposing to change its definition of rare diseases as part of an overhaul of its orphan drug regulation. If implemented, the revised regulations will allow drugs that treat more common diseases to qualify for orphan medicine status, but only if the conditions they target are classed as life-threatening or chronically debilitating.

Currently, TGA classes conditions that affect 2,000 Australians or fewer as rare diseases. TGA is proposing to reset the threshold so that conditions that affect five in 10,000 people are eligible for orphan drug status. This means conditions that affect up to approximately 12,000 Australians would be classified as rare diseases under the revised regulations. Yet, while TGA is looking to relax the threshold, it wants to make the orphan drug classification more stringent in other regards. The proposed regulations limit orphan drug status to diseases TGA views as life-threatening or chronically debilitating.

Both the revised threshold and addition of a stipulation regarding the severity of the condition mirror the criteria set by the European Medicines Agency (EMA), a regulator TGA is increasingly using as a guidepost for its own activities. The mirroring of EMA regulations has enabled TGA to look to Europe for insights into how the changes will affect its orphan drug pathway. From 2011 to 2014, one-fifth of EMA orphan drug designations were for conditions too common to meet TGA’s current threshold. Equally, TGA granted the status to drugs EMA would decline on disease severity grounds. 

TGA expects the increase in applicant numbers facilitated by the new threshold to be balanced out by the disease severity requirement, resulting in the changes having minimal effect on the amount of orphan drug designations it awards. What will change is the type of drugs that receive the status. The idea is ensure drugs for relatively rare, very serious conditions receive special treatment in Australia. Under the current system, the rarity of a condition takes precedence over its severity, a situation that is detrimental to some patients with life-threatening or chronically debilitating conditions.

The proposed changes are part of a broader package of amendments put forward by TGA. Other notable revisions include a change to when drug developers should apply for orphan medicine status. TGA wants firms to apply for the designation when a drug is almost ready to be submitted for approval. As such, the regulator is proposing to make orphan drug designations expire after between three and six months. The change is intended to “discourage premature applications” and ensure data used to support orphan drug filings are current at the time of a marketing application.

Officials are also planning to introduce criteria that encourage the development of orphan drugs that address unmet medical needs or provide significant benefits over existing therapeutic options. 

TGA is accepting feedback on the proposals until 25 November.

TGA Consultation, More

CFDA Releases Draft Guidance on Drug Data Management Practices

China Food and Drug Administration (CFDA) has released draft guidance on drug data management practices. The document is designed to help organizations involved in the development, production and distribution of pharmaceuticals to maintain accurate, timely and traceable data records.

The lengthy document covers everything from the need for senior management to cultivate a culture that values data integrity through to the technical aspects systems need to meet CFDA’s standards. On an organizational level, CFDA is advocating for companies to have structures and procedures that identify risks to data integrity, as well as open and transparent cultures that encourage employees to come forward when they spot a problem. Companies must investigate potential violations in line with their deviation handling procedures, and report issues that affect quality and safety to CFDA.

CFDA seems aware this focus on data integrity may clash with other priorities at the companies it regulates. The agency states commercial, political, financial and organizational pressures must not affect work to ensure the reliability of data. The aforementioned quality culture is one of the ways CFDA thinks companies can achieve this goal. Other recommendations include allocating sufficient human and technical resources to the task and ensuring all staff involved with GXP are trained in data reliability.

The document also covers the establishment of systems that minimize the potential for individuals to compromise data integrity. CFDA wants companies to use signatures that support the identification of who created or modified data. In the case of modifications, the system should require changes to be approved and the reasons for the amendments to be logged. This requirement is part of a set of demands focused on traceability. If an existing computerized system falls short of CFDA’s audit trail requirements, the company must adopt alternative methods to comply with the regulation.

CFDA is accepting comments on the draft until the end of the month.

CFDA Notice (Chinese)

CDSCO Informs Abbott, Glaxo and Pfizer of Outcome of Review of FDC Data

The Central Drugs Standard Control Organization (CDSCO) has contacted 283 drugmakers including Abbott, GlaxoSmithKline and Pfizer about its review of their fixed-dose combination (FDC) products. The review looked at the safety and efficacy of FDCs sold without approval at the national level.

CDSCO and a FDC-focused expert committee conducted the review to assess whether applications filed by companies supported the continued sale of certain products, despite them never having been approved by the Drug Controller General of India (DCGI). In each case, the reviewers have issued either a no objection certificate for the continued manufacturing and marketing of the FDC, a show cause notice or a letter requesting the running of a Phase IV trial.

The notice released publicly by CDSCO lists the companies that have been the subject of review and how many letters they have received, but lacks details of the FDCs assessed and the conclusions reached by the regulator. The notice illustrates the scale of the task undertaken by CDSCO. With the review covering 283 companies, some of which are subject to many assessments, CDSCO sent out close to 1,000 letters detailing its findings.

Publication of the letters moves CDSCO a step closer to its long-standing goal of rationalizing the FDC market in India. In the past, companies introduced FDCs without first securing approval from DCGI. This led to FDCs with questionable safety and therapeutic rationale being available in India. CDSCO wrote to manufacturers in January 2013 seeking data to support the continued use of their FDCs. The letters sent out this week are the result of reviews of data received following that request.

CDSCO Alert, More

TGA Starts Consultation on Planned Changes to NSAID Labels

TGA is proposing to change the labels of nonsteroidal antiinflammatory drugs (NSAIDs) to reflect the risk of miscarriage. The regulator wants to add a line stating NSAIDs should not be used by women who are “likely to become pregnant.”

Currently, the labels for ibuprofen and other NSAIDs state the drugs should not be used in the first six months of pregnancy, unless a doctor advises doing so. Following a review, TGA has concluded there is a known association between non-aspirin NSAIDs and risk of miscarriage. TGA is particularly concerned about the use of NSAIDs around the time of conception.

TGA is accepting comments on the proposal until 22 November.

TGA Consultation, More